WO2018189157A1

WO2018189157A1 - Methods for preparing a boronic acid or a boronic ester

Info

Publication number: WO2018189157A1
Application number: PCT/EP2018/059121
Authority: WO
Inventors: Varinder Aggarwal; Alexander FAWCETT; Eddie Myers
Original assignee: University of Bristol
Current assignee: University of Bristol
Priority date: 2017-04-12
Filing date: 2018-04-10
Publication date: 2018-10-18
Anticipated expiration: 2019-10-12
Also published as: GB201705897D0

Abstract

Methods are disclosed for converting a carboxylic acid by using a diboron reagent to convert the carboxylic acid or imide ester derivative of a carboxylic acid to a boronic ester. The method may involve providing an imide ester, such as a phthalimide ester, of a carboxylic acid, and treating the imide ester with a diboron reagent, thereby forming a boronic ester. The diboron reagent may be selected from bis(catecholato)diboron, B2(OH)4 or a mixture thereof, optionally in the presence of catechol.

Description

METHODS FOR PREPARING A BORONIC ACID OR A BORONIC ESTER

The present invention relates to methods for converting carboxylic acids into boronic acids or esters, more particular to methods for borylation of carboxylic acids and even more particularly to methods for decarboxylative borylation of carboxylic acids.

Carboxylic acids are among the most prevalent class of organic molecules found in Nature and thus methods for the conversion of the carboxyl functional group into other functional groups are highly sought after. In contrast, the isoelectronic boronic acids are hardly found in Nature at all, yet arguably bear the most versatile functional group available to the synthetic organic chemist.

Boronic acids and their ester derivatives can be converted into almost any functional group in one step, through either transition-metal-mediated coupling reactions, 1,2-metallate rearrangements, or deborylative nucleophilic addition.

Therefore, the conversion of carboxylic acid groups into the highly versatile boronic acid moiety would facilitate more rapid diversification of this important class of feedstock molecules. Also, boronic acids are important target molecules in their own right. Specifically, they share a number of features with carboxylic acids that make them potent bioisosteres in medicinal chemistry. For example, boronic acids form hydrogen bonds of similar geometries to carboxylic acids, despite their lower acidity, and they can switch reversibly between stable tricoordinate and tetracoordinate forms, thus allowing them to mimic the tetrahedral intermediates involved in, for example, the enzymatic hydrolysis of amide group. A straightforward method for converting libraries of bioactive carboxylic acids into the corresponding boronic acids would lead to enhanced screening libraries and would facilitate bioisosteric lead optimisation.

Although the decarboxylative borylation of carboxylic acid derivatives has not previously been described, reaction conditions for decarbonylative borylation of carboxylic derivatives have recently been disclosed. However, these transformations, which involve the oxidative addition of a catalytically active Ni(0) or Rh(I) species into the C-0 , C-S, or C-N bond of an ester, thioester, or amide derivative, respectively, only give high yields for carboxylic acid derivatives bearing sp² carbon centers. When these conditions have been applied to simple carboxylic acid derivatives bearing sp³ carbon centers, the yields have been low.

It is an aim of the present invention to provide improved synthetic methods and more particularly methods for borylation of carboxylic acids.

In first and second aspects, the present invention accordingly provides a method as set out in claim 1 and a method as set out in claim 2, respectively.

Preferred, advantageous and optional aspects of the invention are set out in claims 3 to 16. In a third aspect, the present invention additionally provides a method as set out in claim 17, with the optional aspect as set out in claim 18.

In a fourth aspect, the present invention provides a method as set out in claim

19.

The invention is illustrated, but not limited, by the following examples.

Preliminary Studies

Using N-hydroxyphthalimide ester 1 as our test substrate as a solution in N,N- dimethylformamide (DMF; 0.1 M) with CS2CO3 (1.5 equivalent) and the diboron reagent, bis(catecholato)diboron (B₂cat₂, 1.00 equivalent), under the illumination of blue LED light for 14 hours, followed by a workup that involved adding pinacol and NEt₃, so as to effect ligand exchange to form the more stable pinacol boronic ester, we obtained the desired boronic ester 2 in a noteworthy 8% yield. Carrying out the reaction with B₂cat₂ in the absence of CS2CO3 delivered boronic ester 2 in 69% yield.

A solvent screen revealed that the amide-based solvents were effective for this transformation, with the use of N,N-dimethylacetamide (DMAc) being marginally better than DMF. Increasing the amount of B₂cat₂ in increments from 1.00 equivalent to 2.00 equivalents revealed that a slight excess of the reagent (1.25 equivalents; 91% yield) was optimal; there was a slight drop in yield with larger amounts. The transformation conducted in the dark delivered the desired product in 5% yield. Light from a regular white bulb placed in the vicinity of the reaction vessel was effective at increasing yield (91 yield), ambient light also led to efficient reaction (43% yield). The transformation was moderately sensitive to concentration (0.1 M being optimal) the reaction was complete within 4 hours. Investigation of reaction setup showed that although the reaction was tolerant of small amounts of water, the presence of 0₂ was detrimental and therefore conducting the reaction under an inert atmosphere (N₂ or Ar) was advantageous for higher yields.

Reaction Scope The substrate scope of the transformation was broad.

Primary carboxylic acids, including a benzylic substrate and substrates bearing heteroatoms, heterocycles (thiophene, indole), β-positioned alkenes, alkynes, esters, carbon-bromine bonds, and perfluoroalkyl chains, were converted into the corresponding primary pinacol boronic esters in good to high yields. The isolation of these products was facile, for example, a quick filtration through a plug of silica gel, or washing with mild aqueous base being sufficient for providing material of high purity.

Secondary carboxylic acids, either as part of an acyclic chain or as part of a carbo- or heterocycle of a variety of ring sizes (cyclohexyl, cyclopentyl, cyclopropyl, 2,2,2-bridged bicyclic, pyranyl), and containing functional groups, such as difluoromethylene, a carbamate, and an ester, were converted into the corresponding boronic esters in good to high yield.

We also investigated a number of carbocyclic substrates containing two stereogenic centers, at least one of which bears the carboxylic acid moiety. Here, the boronic ester products were obtained with varying levels of diastereo selectivity, depending on the relative position of substituents and ring size. For example, although the 1,3-substituted cyclopentane, 17, was obtained with low levels of

diastereo selectivity, the 1,2-subsitututed cyclohexane 21 (derived from the corresponding dicarboxylic acid) and 1,2-disubstituted cyclopropane 15 were obtained in 90: 10 and 98:2 d.r., respectively. Tertiary carboxylic acids, in which the three carbon atoms are tied back into a ring structure, for example adamantyl, cubyl, and bicyclo[l . l . l]pentyl carboxylic acids, were transformed into the corresponding boronic esters in good yield. Notably, over one gram of adamantyl pinacol boronic ester 25 was prepared in a single reaction, thus showing that the conditions are suitable for preparing significant quantities of material for further applications.

Boronic acids derived from stearic, oleic, lithocholic, pinonic, gibberellic, and arachidonic acids were obtained in moderate to good yields (Figure 2d).

Transformation of the bis(N-hydroxyphthalimide ester) of succinic acid gave the corresponding l,2-bis(boronic ester) 39 in 41% yield.

Fenbufen, a protected form of glutamic acid, and indometacin were converted into the corresponding boronic esters in moderate to good yields. These examples highlight that the transformation is also tolerant of free hydroxy groups, silyl ethers, and ketones.

Examples of the invention will be further described below.

1. General Procedures

1.1 Synthesis of N-Hydroxyphthalimide (NHPI) Esters

o

r.t., overnight

General Procedure A: N-Hydroxyphthalimide (1.0 eq), DMAP (0.1 eq.) and, if solid, carboxylic acid (1.0 eq.) was added to a round-bottomed flask. Dichloromethane (0.1

M) and, if liquid, carboxylic acid (1.0 eq) were then added, followed by DIC (1.0 eq.).

The reaction mixture was allowed to stir at room temperature overnight, before concentrating under reduced pressure. The crude residue was directly purified by flash- column chromatography (S1O2; typically DCM with either pentane or Et₂0) to yield pure NHPI ester. If solid and not pure, the NHPI ester can be recrystallized from DCM/MeOH or EtOAc to give pure material.

1.2 Conditions 1: Decarboxylative Borylation of Alkyl Carboxylic Acids

General Procedure B: NHPI ester (1.0 eq., 0.13 mmol) and B₂cat₂ (40 mg, 1.25 eq., 0.16 mmol) were carefully weighed into a flame-dried 7 mL vial containing a small magnetic stirrer bar. DMAc (1.3 mL, 0.1 M) was added and then the headspace of the vial was purged with a gentle stream of argon for approximately 10 seconds. The vial was tightly sealed and stirred under blue LED irradiation for 14 h. Pinacol (63 mg, 0.53 mmol, 4 eq.) was dissolved in Et₃N (0.45 mL), added to the reaction mixture and stirred for 1 h. For workup, the reaction mixture was transferred into a vial containing EtOAc (15 mL), H₂0 (3 mL), NH₄C1 (saturated aqueous solution, 3 mL). After vigorously shaking and allowing the two layers to separate, the top organic layer was carefully removed with a pipette. This was repeated twice more with EtOAc (5 mL). The organic layers were combined and concentrated under reduced pressure. The crude residue was directly purified using a short silica gel column to yield the desired boronic ester.

Alternative workup: The crude reaction mixture was diluted with Et₂0 (10 mL) and washed with NaOH (aqueous, 0.10 M, 6 mL), and then the aqueous layer was extracted with Et₂0 (10 mL). The combined organic layers were washed with NaOH (aqueous, 0.10 M, 6 mL) and water (6 mL), then dried over MgS0₄, filtered and concentrated under reduced pressure to yield the desired boronic ester.

Notes: Solvent: Also works in DMF, DMPU, DMI, NMP and tetramethylurea. Starting material: Also works with the tetrachlorophthalimide. 1.3 Conditions 2: Decarboxylative Borylation of Alkyl Carboxylic Acids with Catalytic Catechol or B₂cat₂

General procedure C (catalytic B₂cat₂): NHPI ester (50 mg, 1.0 eq., 0.13 mmol), B₂cat₂ (3 mg, 0.10 eq., 0.013 mmol) and B₂(OH)₄ (18 mg, 1.50 eq., 0.195 mmol) were carefully weighed into a flame-dried 7 mL vial containing a small magnetic stirrer bar. DMAc (1.3 mL, 0.1 M) was added and then the headspace of the vial was purged with a gentle stream of argon for approximately 10 seconds. The vial was tightly sealed and stirred under blue LED irradiation for 14 h. Pinacol (63 mg, 0.53 mmol, 4 eq.) was dissolved in Et₃N (0.45 mL), added to the reaction mixture and stirred for 1 h. The reaction mixture was transferred into a vial containing EtOAc (15 mL), H₂0 (3 mL), NH₄C1 (saturated aqueous solution, 3 mL). After vigorously shaking and allowing the two layers to separate, the top organic layer was carefully removed with a pipette. This was repeated twice more with EtOAc (5 mL). The organic layers were combined and concentrated under reduced pressure. The crude residue was directly purified using a short silica gel column to yield the desired boronic ester.

Notes: Solvents: Also works in DMF, DMPU, DMI, NMP and tetramethylurea. Diboron source: Also works with 0 - 100% B₂cat₂ and 95 - 150% B₂(OH)₄. Starting material: Also works with the tetrachlorophthalimide.

General procedure D (catalytic catechol):

NHPI ester (50 mg, 1.0 eq., 0.13 mmol), catechol (4.5 mg, 0.50 eq., 0.065 mmol) and B₂(OH)₄ (18 mg, 1.50 eq., 0.195 mmol) were carefully weighed into a flame-dried 7 mL vial containing a small magnetic stirrer bar. DMAc (1.3 mL, 0.1 M) was added and then the headspace of the vial was purged with a gentle stream of argon for approximately 10 seconds. The vial was tightly sealed and stirred under blue LED irradiation for 14 h. Pinacol (63 mg, 0.53 mmol, 4 eq.) was dissolved in Et₃N (0.45 mL), added to the reaction mixture and stirred for 1 h. The reaction mixture was transferred into a vial containing EtOAc (15 mL), H₂0 (3 mL), NH₄C1 (saturated aqueous solution, 3 mL). After vigorously shaking and allowing the two layers to separate, the top organic layer was carefully removed with a pipette. This was repeated twice more with EtOAc (5 mL). The organic layers were combined and concentrated under reduced pressure. The crude residue was directly purified using a short silica gel column to yield the desired boronic ester. Notes: Solvents: Also works in DMF, DMPU, DMI, NMP and tetramethylurea. Diboron source: Also works with 5 - 100% catechol and 95 - 150% B₂(OH)₄. Starting material: Also works with the tetrachlorophthalimide.

1.4 Conditions 3: Decarboxylative Borylation of a-Amino Carboxylic Acids with Pyridine Derivatives and No Light

General procedure E:

NHPI ester (48 mg, 1.0 eq., 0.13 mmol), B₂cat₂ (16 mg, 0.10 eq., 0.065 mmol) and B₂(OH)₄ (12 mg, 1.0 eq., 0.13 mmol) were carefully weighed into a flame-dried 7 mL vial containing a small magnetic stirrer bar. DMAc (1.3 mL, 0.1 M) and 4- methoxypyridine (29 μί, 2.0 eq., 0.26 mmol) were added and then the headspace of the vial was purged with a gentle stream of argon for approximately 10 seconds. The vial was tightly sealed and stirred at room temperature for 14 h. Pinacol (63 mg, 0.53 mmol, 4 eq.) and glacial acetic acid (0.03 mL) was added to the reaction mixture and stirred for 4 h. The reaction mixture was transferred into a vial containing EtOAc (15 mL), H₂0 (3 mL), NH4CI (saturated aqueous solution, 3 mL). After vigorously shaking and allowing the two layers to separate, the top organic layer was carefully removed with a pipette. This was repeated twice more with EtOAc (5 mL). The organic layers were combined and concentrated under reduced pressure. The crude residue was directly purified using a short silica gel column to yield the desired boronic ester. Notes: Solvents: Also works in DMF, DMPU, DMI, NMP, tetramethylurea, MeCN, DCM, DME, Et20, 1,4-dioxane, acetone, EtOAc, hexane, toluene, THF, chloroform. Diboron source: Also works with 5 - 100% B₂cat₂ and 95 - 150% B₂(OH)₄. Additive: Also works with DMAP, pyridine, DABCO, DBU, quinuclidine, TMG, TBD, MTBD, 2-picoline, 4-picoline, 3-picoline, imidazole, K₂C0₃, AcOH, triethylamine, 4- cyanopyridine, 4-phenylpyridine. Starting material: Also works with the tetrachlorophthalimide .

2. Substrate Scope

2.1.1 Substrate Scope: Primary

2-Benzyl-4,4,5,5-tetramethyl-l,3,2-dioxaborolane (3)

General Procedure A General Procedure B

NHPI

.OH NHPI, DIC, DMAP 1 .25 eq. B₂cat₂, DMAc Bpin cnr DCM, r.t., overnight 59, 85% blue LEDs,14 h cr 3, 83%

then pinacol Et₃N, 1 h

Activation: The carboxylic acid (1.30 g, 10.0 mmol) was coupled with N- hydroxyphthalimide according to General Procedure A. The crude residue was purified by flash column chromatography (Si0₂; 90:10 hexane:EtOAc) to afford the corresponding NHPI ester 59 (2.28 g, 85%) as a white solid. m.p.: 54 - 58 °C (DCM/MeOH)

TLC: R_f = 0.24 (90: 10 hexane:EtOAc) ^lU NMR (400 MHz, CDC1₃) δ 7.89 - 7.84 (m, 2H, phthalimide ArH), 7.79 - 7.74 (m, 2H, phthalimide ArH), 7.40 - 7.30 (m, 5H, ArH), 4.00 (s, 2H, CH₂) ppm

¹³C NMR (101 MHz, CDCI3) δ 167.8 (C=0), 161.9 (C=0), 134.9 (phthalimide ArCH), 131.6 (ArC), 129.4 (ArCH), 129.0 (phthalimide ArC), 127.9 (ArCH), 124.1 (phthalimide ArCH), 37.8 (ArCH₂) ppm (ArC of phenyl ring not observed)

HRMS (m/z) (ESI) calc'd for Ci₆HnN0₄Na [M+Na]⁺: 304.0580, found: 304.0591

IR (solid state) m_ax: 1736, 1363, 1184, 1133, 1060, 969 and 876 cm^"1

Borylation: NHPI ester 59 (37 mg, 0.13 mmol) was borylated according to General Procedure B. The crude reside was purified by flash column chromatography (Si0₂; 80:20 pentane:Et₂0) to afford boronic ester 3 (24 mg, 83%) as a colorless oil.

TLC: Rf = 0.77 (95:5 pentane:Et₂0)

¾ NMR (400 MHz, CDCI3) δ 7.26 - 7.10 (m, 5H, ArH), 2.29 (s, 2H, CH₂Bpin), 1.23 (s, 12H, Bpin) ppm

¹³C NMR (101 MHz, CDC ) δ 138.8 (ArC), 129.1 (ArCH), 128.4 (ArCH), 125.0 (ArCH), 83.6 (C(CH₃)₂), 24.9 (C( H₃)₂) ppm

All data matched that reported in the literature.

4,4,5,5-Tetramethyl-2-(thiophen-3-ylmethyl)-l,3,2-dioxaborolane (4)

General Procedure A General Procedure B ^γ^γ-^0Η NH PI, DIC, DMAP j/ 1 .25 eq. B₂cat₂, DMAc ^jj ^BPⁱⁿ

S-^ ^ DCM, r.t., overnight gg QJO/_O blue LEDs,14 h 4 ₅₇o/_o en pinacol ^Et3N , 1 h Activation: The carboxylic acid (500 mg, 3.52 mmol) was coupled with N- hydroxyphthalimide according to General Procedure A. The crude residue was purified by flash column chromatography (Si0₂; 20:80 pentane:DCM) to afford the corresponding NHPI ester 60 (878 mg, 87%) as a colorless oil.

TLC: R_f = 0.36 (20:80 pentane:DCM) ^lU NMR (400 MHz, CDC1₃) δ 7.90 - 7.86 (m, 2H, phthalimide ArH), 7.81 - 7.77 (m, 2H, phthalimide ArH), 7.36 - 7.32 (m, 2H, ArH), 7.14 - 7.12 (m, 1H, ArH), 4.03 (s, 2H, CH₂) ppm

¹³C NMR (101 MHz, CDCI3) δ 167.3 (C=0), 161.9 (C=0), 135.0 (phthalimide ArCH), 130.9 (ArC), 129.0 (phthalimide ArC), 128.3 (ArH), 126.4 (ArH), 124.1 (phthalimide ArCH), 123.9 (ArH), 32.6 (CH₂) ppm

HRMS (m/z): (ESI) calc'd for Ci₄H₉N0₄SNa [M+Na]⁺: 310.0144, found: 310.0145

IR (neat) m_ax: 3103, 1786, 1735, 1357, 1185, 1063, 974, 876 and 783 cm^"1

Borylation: NHPI ester 60 (38 mg, 0.13 mmol) was borylated according to General Procedure B. The crude reside was purified by flash column chromatography (Si0₂; 90: 10 pentane:Et₂0) to afford boronic ester 4 (17 mg, 57%) as a colorless oil. Note: Product volatile! Product unstable on silica gel.

TLC: Rf = 0.34 (90: 10 pentane:Et₂0)

¾ NMR (400 MHz, CDCI3) δ 7.20 (dd, / = 4.7, 3.0 Hz, 1H, ArH), 6.95 - 6.93 (m, 2H, ArH), 2.28 (s, 2H, CH₂), 1.25 (s, 12H, C(CH₃)₂) ppm

¹³C NMR (101 MHz, CDC ) δ 137.7 (ArC), 129.6 (ArCH), 124.9 (ArCH), 120.2 (ArCH), 83.6 (C(CH₃)₂), 24.9 (C( H₃)₂) ppm

All data matched that reported in the literature.

l-Methyl-3-((4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)methyl)-lH-indole (5)

then pinacol Et₃N, 1 h

Activation: The carboxylic acid (500 mg, 2.64 mmol) was coupled with N- hydroxyphthalimide according to General Procedure A. The crude residue was purified by flash column chromatography (Si0₂; 20:80 pentane:DCM) to afford the corresponding NHPI ester 61 (809 mg, 92%) as a white solid. m.p.: 120 - 122 °C (DCM/MeOH) TLC: R_f = 0.26 (20:80 pentane:DCM)

¾ NMR (400 MHz, CDC1₃) δ 7.89 - 7.84 (m, 2H, phthalimide ArH), 7.78 - 7.74 (m, 2H, phthalimide ArH), 7.64 (d, / = 7.9 Hz, 1H, NCH), 7.31 (d, / = 8.1 Hz, 1H, ArH), 7.25 (t, J = 7.5 Hz, 1H, ArH), 7.18 - 7.15 (m, 2H, ArH), 4.14 (s, 2H, CH₂), 3.77 (s, 3H,

¹³C NMR (101 MHz, CDCI3) δ 168.2 (C=0), 162.1 (C=0), 137.0 (ArC), 134.9 (phthalimide ArCH), 129.1 (phthalimide ArC), 128.2 (ArCH), 127.5 (ArC), 124.1 (phthalimide ArCH), 122.2 (ArCH), 119.6 (ArCH), 118.9 (NCH), 109.5 (ArCH), 104.4 (ArC), 32.9 (NCH₃), 28.1 (CH₂) ppm

HRMS (m/z): (ESI) calc'd for Ci₉Hi₄N0₄Na [M+Na]⁺: 357.0846, found: 357.0853

IR (solid state) m_ax: 3074, 2917, 1729, 1187, 1061, 970, 876, 736, 693 and 518 cm^"1

Borylation: NHPI ester 61 (45 mg, 0.13 mmol) was borylated according to General Procedure B. The crude reside was purified by flash column chromatography (Si0₂; 70:30 pentane:Et₂0) to afford boronic ester 5 (25 mg, 69%) as a colorless oil.

TLC: R_f = 0.40 (70:30 pentane:Et₂0)

¾ NMR (400 MHz, CDC ) δ 7.61 (d, / = 7.9 Hz, 1H, ArH), 7.27 (d, / = 8.2 Hz, 1H, ArH), 7.21 (t, / = 7.5 Hz, 1H, ArH), 7.09 (t, / = 7.4 Hz, 1H, ArH), 6.94 (s, 1H, NCH), 3.74 (s, 3H, NCH₃), 2.34 (s, 2H, CH₂), 1.29 (s, 12H, C(CH₃)₂) ppm ¹³C NMR (101 MHz, CDCb) δ 137.1 (ArC), 128.9 (ArC), 126.7 (NCH), 121.3 (ArCH), 119.3 (ArCH), 118.3 (ArCH), 110.2 (ArC), 109.0 (ArCH), 83.5 (C(CH₃)₃), 32.7 (CH₃), 25.0 (C(CH₃)₂) ppm

All data matched that reported in the literature. 2-(4-Bromobutyl)-4,4,5,5-tetramethyl-l,3,2-dioxaborolane (6)

General Procedure A General Procedure B

f en pinacol ^t3N , 1

Activation: The carboxylic acid (2.37 g, 13.1 mmol) was coupled with N- hydroxyphthalimide according to General Procedure A. The crude residue was purified by flash column chromatography (Si0₂; 90: 10 hexane:EtOAc) to afford the corresponding NHPI ester 62 (4.10 g, 96%) as a white solid. m.p.: 53 - 56 °C (DCM/MeOH)

TLC: R_f = 0.24 (90: 10 hexane:EtOAc)

¾ NMR: (400 MHz, CDC1₃) δ 7.91 - 7.86 (m, 2H, phthalimide ArCH), 7.81 - 7.77 (m, 2H, phthalimide ArCH), 3.46 (t, / = 5.9 Hz, 2H, CH₂C=0), 2.72 (t, / = 7 Hz, 2H, CH₂Br), 2.07 - 1.92 (m, 4H, 2xCH₂) ppm

¹³C NMR: (101 MHz, CDCI3) δ 169.2 (C=0), 162.0 (C=0), 134.9 (phthalimide ArCH), 129.0 (phthalimide ArC), 124.1 (phthalimide ArCH), 32.7 (CH₂C=0), 31.5 (CH₂), 30.2 (CH₂Br), 23.3 (CH₂) ppm HRMS (m/z): (ESI) calc'd for Ci₃Hi₂BrN0₄Na [M+Na]⁺: 347.9842, found: 347.9840

IR (solid state) m_ax: 1738, 1374, 1186, 1138, 1065, 968 and 858 cm^"1

Borylation: NHPI ester 62 (44 mg, 0.13 mmol) was borylated according to General Procedure B. The crude reside was purified by flash column chromatography (Si0₂; 80:20 pentane:Et₂0) to afford boronic ester 6 (23 mg, 67%) as a colorless oil. Note: Product volatile!

¾ NMR: (400 MHz, CDCI3) δ 3.40 (t, / = 7.4 Hz, 2H, CH₂Br), 1.87 (p, / = 7.4 Hz, 2H, CH2CH₂Br), 1.54 (p, / = 7.4 Hz, 2H, CH2CH₂Bpin), 1.24 (s, 12H, C(CH₃)₂), 0.79 (t, J = 1.4 Hz, 2H, CH₂Bpin) ppm

¹³C NMR: (101 MHz, CDC1₃) δ 83.2 (C(CH₃)₂), 35.5 (CH₂Br), 33.8 (CH₂), 25.0 (C(CH₃)₂), 22.9 (CH₂) ppm All data matched that reported in the literature.

4,4,5,5-Tetramethyl-2-(pent-4-yn-l-yl)-l,3,2-dioxaborolane (7)

General Procedure A General Procedure B

Activation: The carboxylic acid (0.23 mL, 2.0 mmol) was coupled with N- hydroxyphthalimide according to General Procedure A. The crude residue was purified by flash column chromatography (Si0₂; 90:10 hexane:EtOAc) to afford the corresponding NHPI ester 63 (360 mg, 70%) as a white solid. m.p.: 48 - 52 °C (DCM/MeOH) TLC: Rf = 0.28 (90: 10 hexane:EtOAc)

¾ NMR: (400 MHz, CDC1₃) δ 7.90 - 7.85 (m, 2H, phthalimide ArH), 7.81 - 7.76 (m, 2H, phthalimide ArH), 2.83 (t, / = 7.1 Hz, 2H, CH₂C=0), 2.37 (td, / = 7.1, 2.6 Hz, 2H, ≡CCH₂), 2.03 (t, / = 2.6 Hz,≡CH), 2.00 (p, / = 7.1 Hz, 2H,≡CCH₂CH₂) ppm

¹³C NMR: (101 MHz, CDCI3) δ 169.2 (C=0), 162.0 (C=0), 134.9 (phthalimide ArCH), 129.0 (phthalimide ArC), 124.1 (phthalimide ArCH), 82.6 (≡CH), 70.0 (≡C), 29.8 (CH₂C=0), 23.5 (≡CCH₂ H₂), 17.8 (≡CCH₂) ppm

HRMS (m/z): (ESI) calc'd for Ci₄HnN0₄Na [M+Na]⁺: 280.0580, found: 280.0573

IR (solid state) m_ax: 3273, 1741, 1182, 1062, 969 and 876 cm^"1

Borylation: NHPI ester 63 (33 mg, 0.13 mmol) was borylated according to General Procedure B. The crude reside was purified by flash column chromatography (Si0₂; 95:5 pentane:Et₂0) to afford boronic ester 7 (15 mg, 59%) as a colorless oil. Note: Product volatile!

TLC: R_f = 0.80 (95:5 pentane:Et₂0) ^lU NMR: (400 MHz, CDC1₃) δ 2.19 (td, / = 7.5, 2.6 Hz, 2H,≡CH₂), 1.93 (t, / = 2.6 Hz, 1H,≡CH), 1.65 (p, / = 7.5, 2H,≡CH₂CH₂), 1.24 (s, 12Η, C(CH₃)₂), 0.89 (t, J = 7.5 Hz, 2H, CH₂Bpin) ppm

¹³C NMR: (101 MHz, CDCI3) δ 84.7 (≡CH), 83.1 (C(CH₃)₂), 68.3 (≡C), 24.9

(C(CH₃)₂, 23.3 (≡CCH₂ H₂), 20.8 (≡CCH₂) ppm

LRMS (m/z) (EI) 179 ([M-Me]⁺, 36%), 194 ([M+H⁺]⁺, 3%). Despite repeated attempts, a HRMS could not be obtained.

IR (CHCb) max: 3297, 2979, 2936, 1374, 1318, 1233, and 1145 cm^"1

tert-Butyl-(R)-2-((4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2- yl)methyl)pyrrolidine-l-carboxylate (8)

Activation: The carboxylic acid (500 mg, 2.18 mmol) was coupled with N- hydroxyphthalimide according to General Procedure A. The crude residue was purified by flash column chromatography (Si0₂; 98:2 DCM:Et₂0) to afford the corresponding NHPI ester 64 (628 mg, 77%) as a colorless oil that crystallized over several days to give a white amorphous solid.

TLC: R_f = 0.21 (98:2 DCM:Et₂0)

¾ NMR (400 MHz, CDC1₃) δ 7.93 - 7.71 (br m, 4H, phthalimide ArCH), 4.31 - 4.08 (br m, NCH), 3.48 - 3.09 (br m, 3H, NCH₂ and C *tP =0), 2.83 - 2.60 (br m, CH^aH^bC=0), 2.24 - 2.09 (br m, CH¾^b), 2.01 - 1.78 (br m, CH₂ and CffH*³) ppm

¹³C NMR (126 MHz, CDC1₃) δ 167.6 and 167.5 (C=0), 162.0 (C=0), 154.5 and 154.2 (C=0), 134.9 and 134.8 (phthalimide ArCH), 129.0 (phthalimide ArC), 124.1 (phthalimide ArCH), 80.2 and 79.7 (OC(CH₃)₃), 54.2 and 54.1 (NCH), 46.9 and 46.5 (CH₂C=0), 36.3 and 35.2 (CH2), 31.2 and 30.3 (CH2), 28.6 (C(CH₃)₃), 23.8 and 23.0 (CH₂) ppm (Doubling up of signals due to presence of rotamers)

HRMS (m/z) (ESI) calc'd for

[M+Na]⁺: 397.1370, found: 397.1372

IR (solid state) m_ax: 2973, 2893, 1739 (C=0), 1698 (C=0), 1678 (C=0), 1365, 1165, 1108, 1081, 956, 877, 697 and 519 cm^"1

Borylation: NHPI ester 64 (50 mg, 0.13 mmol) was borylated according to General Procedure B. The crude reside was purified by flash column chromatography (Si0₂; 95:5 pentane: acetone) to afford boronic ester 8 (34 mg, 81%) as a colorless oil.

TLC: Rf = 0.34 (60:40 pentane:Et₂0) *H NMR (400 MHz, CDC1₃) δ 4.01 - 3.82 (br m, 1H, NCH), 3.45 - 3.21 (br m, 2H, NCH₂), 2.06 - 1.94 (m, 1H, CH¾^b), 1.87 - 1.77 (m, 1Η, CffH*³), 1.75 - 1.66 (m, CH¾^b), 1.63 - 1.36 (br m, 2Η, CffH*³ and CH^Bpin), 1.43 (s, 9Η, OC(CH₃)₃), 1.21 (s, 6Η, C(CH₃)₂), 1.20 (s, 6Η, C(CH₃)₂), 1.04 - 0.81 (br m, 1Η, Cff^Bpin) ppm

¹³C NMR (101 MHz, CDC1₃) δ 154.6 and 154.4 (C=0), 83.0 (C(CH₃)₂), 78.9 (OC(CH₃)₃), 54.3 (NCH), 46.5 and 46.3 (NCH₂), 33.4 and 33.1 (CH2), 28.7 (OC(CH₃)₃), 25.0 and 24.8 (C(CH₃)₂), 23.8 and 23.3 (CH₂) ppm (Doubling up of signals due to presence of rotamers)

HRMS (m/z): (ESI) calc'd for Ci₆H₃iNB0₄ [M+H]⁺: 312.2344, found: 312.2341 IR (neat) max: 2975, 1691 (C=0), 1365, 1166, 1 141, 1108 and 848 cm^"1

4,4,5,5-Tetramethyl-2-(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-l,3,2- dioxaborolane (9)

General Procedure A General Procedure B

Activation: The carboxylic acid (500 mg, 2.23 mmol) was coupled with N- hydroxyphthalimide according to General Procedure A. The crude residue was purified by flash column chromatography (S1O₂; 5: 1 petroleum ether 40-60:EtOAc) to afford the corresponding NHPI ester 65 (690 mg, 84%) as a white solid. m.p.: 104 - 106 °C (DCM/MeOH)

TLC: Rf = 0.50 (3: 1 petroleum ether 40-60:EtOAc) ¾ NMR (400 MHz, CDC1₃) δ 7.90 - 7.85 (m, 2H, Ar-H), 7.80 - 7.76 (m, 2H, Ar-H), 3.02 (t, / = 7.7 Hz, 2H, CH₂), 2.68 - 2.52 (m, 2H, CH₂) ppm

¹³C NMR (101 MHz, CDC ) δ 167.7 (C=0), 161.6 (C=0), 134.9 (HCAT), 128.8 (CAT), 124.1 (HCAT), 26.3 (t, / = 23.3 Hz, CH₂), 22.9 (t, / = 4.8 Hz, CH₂) ppm. The carbon atoms bearing fluorine atoms were observed (see NMR spectrum) but were not assigned.

¹⁹F NMR (377 MHz, CDCb) δ -80.8, -114.6, -121.8, -122.8, -123.3, -126.1 ppm

HRMS (m/z) (ESI) calc'd for Ci₇H₈Fi₃NNa0₄ [M+Na]⁺: 560.0138, found: 560.0139

IR (solid state) m_ax: 1744, 1225, 1136, 1073, 965 and 877 cm^"1

Borylation: NHPI ester 65 (70 mg, 0.13 mmol) was borylated according to General Procedure B. The crude reside was purified by flash column chromatography (Si0₂; 10: 1 petroleum ether 40-60:Et₂O) to afford boronic ester 9 (31 mg, 50%) as a colorless oil. Note: product unstable on silica gel.

TLC: R_f = 0.75 (3: 1 petroleum ether 40-60:EtOAc)

¾ NMR (400 MHz, CDCb) δ 2.25 - 2.01 (m, 2H, CH₂), 1.18 (s, 12H, 2xOC(CH₃)₂), 1.02 - 0.88 (m, 2H, CH₂) ppm

¹³C NMR (101 MHz, CDCb) δ 83.6 (OC(CH₃)₂), 25.7 (t, / = 23.4 Hz, CF2CH2), 24.7 (OC(CH₃)₂) ppm. The carbon atoms bearing fluorine atoms were observed (see NMR spectrum) but were not assigned.

¹⁹F NMR (377 MHz, CDCb) δ -80.91, -116.12, -122.00, -122.91, -123.57, -126.20 ppm

HRMS (m/z): (ESI) calc'd for Ci₄Hi₆BFi₃Na0₂ [M+Na]⁺: 497.0931, found: 497.0947 IR (neat) m_ax: 2984, 1385, 1235, 1195, 1141, 1072 and 847 cm^" -1

2-(But-3-en-l-yl)-4,4,5,5-tetramethyl-l,3,2-dioxaborolane (10)

General Procedure B

51 then pinacol Et₃N, 1

Activation: NHPI ester 51 was prepared according to a known procedure (36). Borylation: NHPI ester 51 (33 mg, 0.13 mmol) was borylated according to General Procedure B. The crude reside was purified by flash column chromatography (S1O2; 95:5 pentane:Et₂0) to afford boronic ester 10 (14 mg, 56%) as a colorless oil. Note: the intermediate alkyl radical undergoes radical ring opening, and the product is volatile!

TLC: Rf = 0.29 (95:5 pentane:Et₂0) ¾ NMR: (400 MHz, CDC1₃) δ 5.88 (ddt, /= 17.0, 10.2, 7.3 Hz, 1H, CH=), 5.03 - 4.95 (m, 1H, =CH^aH^b), 4.92 - 4.87 (m, 1H, =C I?^>), 2.17 (app q, /= 7.3 Hz, 2H, CH₂CH=), 1.24 (s, 12H, C(CH₃)₂), 0.88 (t, J = 7.3 Hz, 2H, CH₂Bpin) ppm

¹³C NMR: (101 MHz, CDCI3) δ 140.8 (=CH), 113.3 (=CH₂), 83.1 (C(CH3)₂), 28.1 (CH₂), 25.0 (C( H₃)₂) ppm All data matched that reported in the literature.

Methyl 5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)pentanoate (11)

General Procedure B

then pinacol t₃N, 1

Activation: NHPI ester 66 was prepared according to a known procedure. Borylation: NHPI ester 66 (40 mg, 0.13 mmol) was borylated according to General Procedure B. The crude reside was purified by flash column chromatography (Si0₂; 4: 1 petroleum ether 40-60:Et₂O) to afford boronic ester 11 (13 mg, 41%) as a colorless oil. TLC: Rf = 0.65 (1: 1 petroleum ether 40-60:EtOAc) ^lU NMR (400 MHz, CDC1₃) δ 3.67 (s, 3H, CO2CH3), 2.32 (t, / = 7.2 Hz, 2H, CH₂), 1.70 - 1.60 (m, 2H, CH₂), 1.50 - 1.40 (m, 2H, CH₂), 1.27 (s, 12H, 2xOC(CH₃)₂), 0.80 (t, J = 8.0 Hz, 2H, CH₂Bpin) ppm

¹³C NMR (101 MHz, CDCI3) δ 174.2 (C0₂CH₃), 82.9 (OC(CH₃)₂), 51.4 (C0₂CH₃), 33.9 (CH₂), 27.5 (CH₂), 24.8 (OC(CH₃)₂), 23.6 (CH₂) ppm

All data matched that reported in the literature.

2-(4-Bromophenethyl)-4,4,5,5-tetramethyl-l,3,2-dioxaborolane (12)

General Procedure B

1 .25 eq. B₂cat₂, DMAc

blue LEDs,14 h

then pinacol Et₃N, 1 h Activation: The carboxylic acid (500 mg, 2.18 mmol) was coupled with N- hydroxyphthalimide according to General Procedure A. The crude product was filtered quickly through a short column (~5 cm silica gel). After concentrated to a -10 mL solution, 30 mL of MeOH was added. The precipitate was collected by filtration and washed with 10 mL of MeOH to afford the corresponding NHPI ester 67 (530 mg, 65%) as a white solid. m.p.: 154 - 156 °C (DCM/MeOH)

TLC: R_f = 0.38 (3 : 1 petroleum ether 40-60:EtOAc)

¾ NMR (400 MHz, CDC1₃) δ 7.84 - 7.79 (m, 2H, Ar-H), 7.74 - 7.68 (m, 2H, Ar-H), 7.36 (d, / = 8.1 Hz, 2H, Ar-H), 7.06 (d, / = 8.1 Hz, 2H, Ar-H), 2.98 (t, J = 7.3 Hz, 2H, CH₂), 2.88 (t, / = 7.2 Hz, 2H, CH₂) ppm ¹³C NMR (101 MHz, CDC1₃) δ 168.6 (C=0), 161.8 (C=0), 138.1 (CAT), 134.8 (HCAT), 131.8 (HCAT), 130.1 (HCAT), 128.8 (CAT), 124.0 (HCAT), 120.6 (CAT), 32.4 (CH₂), 29.9 (CH₂) ppm

HRMS (m/z): (ESI) calc'd for Ci₇Hi₂BrNNa0₄ [M+Na]⁺: 395.9842, found: 395.9854 IR (solid state) m_ax: 1789, 1741, 1487, 1371, 1070, 964, 877 and 821 cm^"1

Borylation: NHPI ester 67 (49 mg, 0.13 mmol) was borylated according to General Procedure B. The crude reside was purified by flash column chromatography (Si0₂; 10: 1 petroleum ether 40-60:Et₂O) to afford boronic ester 12 (29 mg, 72%) as a colorless oil. TLC: Rf = 0.68 (3: 1 petroleum ether 40-60:EtOAc)

¾ NMR (400 MHz, CDCI3) δ 7.29 (d, / = 8.3 Hz, 2H, Ar-H), 7.01 (d, / = 8.3 Hz, 2H, Ar-H), 2.67 - 2.55 (t, / = 8.1 Hz, 2H, CH₂), 1.14 (s, 12H, 2xOC(CH₃)₂), 1.03 (t, / = 8.1 Hz, 2H, CH₂) ppm

¹³C NMR (101 MHz, CDC ) δ 143.3 (CAT), 131.1 (HCAT), 129.8 (HCAT), 119.1 (CAT), 83.1 (OC(CH₃)₂), 29.4 (CH₂), 24.8 (OC(CH₃)₂) ppm

HRMS (m/z) (ESI) calc'd for Ci₄H₂₀BBrNaO₂ [M+Na]⁺: 333.0635, found: 333.0647 IR (neat) max: 2976, 1679, 1369, 1315, 1140, 967 and 827 cm^"1

3-(2-(4,4,5,5-Tetramethyl-l,3,2-dioxaborolan-2-yl)ethyl)pyridine (95):

94, 46% 95, 16%

Activation: The carboxylic acid (500 mg, 3.31 mmol) was coupled with N- hydroxyphthalimide according to General Procedure A. The crude residue was purified by flash column chromatography (Si0₂; 70:30 pentane: acetone) to afford the corresponding NHPI ester 94 (447 mg, 46%) as a pale yellow solid. Note: product unstable on silica gel. m.p.: I l l - 115 °C (cryst. EtOAc)

TLC: Rf = 0.21 (pentane: acetone 70:30) ¾ NMR: (400 MHz, CDC1₃) δ 8.54 (d, / = 2.3 Hz, 1H, Ar-H), 8.50 (dd, / = 4.9, 1.6 Hz, 1H, Ar-H), 7.87 (dd, / = 5.5, 3.1 Hz, 2H, 2xAr-H), 7.78 (dd, / = 5.5, 3.1 Hz, 2H, 2xAr-H), 7.60 (ddd, / = 7.8, 2.3, 1.6 Hz, 1H, Ar-H), 7.26 (dd, / = 7.8, 4.9 Hz, 1H, Ar- H), 3.11 (t, / = 7.4 Hz, 2H, pyridyl-CH₂), 2.99 (t, / = 7.4 Hz, 2H, CH2CO2R) ppm

¹³C NMR: (101 MHz MHz, CDCI3) δ 168.6 (C0₂R), 161.9 (2xCO), 149.9 (HCAT), 148.4 (HCAT), 136.0 (HCAT), 134.9 (2XHCAT), 134.6 (CAT), 129.0 (2XCAT), 124.1 (2XHCAT), 123.7 (HCAT), 32.4 (CH2CO2R), 27.9 (pyridyl-CH₂) ppm

HRMS (m/z) (ESI) calc'd for Ci6Hi₂N₂Na04 [M+Na]⁺: 319.0689, found: 319.0692

IR (neat) max: 3100, 3055, 2943, 2324 (br.), 1812, 1783, 1742, 1714, 1188 and 1079 cm^-1 Borylation: NHPI ester 94 (77 mg, 0.26 mmol) was borylated according to General Procedure B. The crude reside was purified by flash column chromatography (Si0₂; 90: 10 hexane:acetone) to afford boronic ester 95 (10 mg, 16%) as a colorless oil. Note: product unstable on silica gel.

TLC: R_f = 0.54 (pentane: acetone 80:20) ¾ NMR: (500 MHz, CDCI3) δ 8.48 (d, J = 1.1 Hz, 1H, Ar-H), 8.41 (dd, / = 4.8, 1.2 Hz, 1H, Ar-H), 7.52 (ddd, / = 7.7, 1.7, 1.2 Hz, 1H, Ar-H), 7.18 (dd, / = 7.7, 4.8 Hz, 1H, Ar-H), 2.74 (t, J = 8.0 Hz, 2H, CH₂), 1.21 (s, 12H, 4xCH₃), 1.14 (t, / = 8.0 Hz, 2H, CH₂) ppm

¹³C NMR: (126 MHz, CDC ) δ 149.9 (HCAT), 147.2 (HCAT), 139.6 (HCAT), 135.6 (HCAT), 123.3 (HCAT), 83.4 (2xOC(CH₃)₂), 27.3 (pyridyl-CH₂), 24.9 (4xCH₃) ppm

HRMS (m/z): (ESI) calc'd for Ci₃H₂₀BNNaO₂ [M+Na]⁺: 256.1482, found: 256.1480 IR (neat) m_ax: 2978, 2929, 1575, 1479, 1422, 1372, 1311, 1144, 968, 849 and 714 cm^-1

2.1.2 Substrate Scope: Secondary

tert-Butyl 4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)piperidine-l- carboxylate (2)

General Procedure B

0

Activation: NHPI ester 1 was prepared according to a known procedure.

Borylation: NHPI ester 1 (50 mg, 0.13 mmol) was borylated according to General Procedure B. The crude reside was purified by flash column chromatography (Si0₂; 75:25 pentane:Et₂0) to afford boronic ester 2 (35 mg, 87%) as a colorless oil. TLC: Rf = 0.28 (75:25 pentane:Et₂0)

¾ NMR (400 MHz, CDC1₃) δ 3.85 - 3.70 (m, 2H, NCH^aH^b), 2.95 - 2.88 (m, 2H, NCffH*³), 1.65 - 1.60 (m, 2Η, CH¾^b), 1.51 - 1.38 (m, 2Η, CffH¹³), 1.43 (s, 9Η, OC(CH₃)₃), 1.22 (s, 12H, C(CH₃)₂), 1.06 (m, 1H, CHBpin) ppm

¹³C NMR (126 MHz, CDC1₃) δ 155.0 (C=0), 83.3 (C(CH₃)₂), 79.1 (OC(CH₃)₃), 45.0 (NCH₂), 28.6 (OC( H₃)₃), 27.1 (CH₂), 24.9 (C(CH₃)₂) ppm

All data matched that reported in the literature. tert-Butyl 4-(6-methyl-4,8-dioxo-l,3,6,2-dioxazaborocan-2-yl)piperidine-l- carboxylate (13)

General Procedure B

0

Activation: NHPI ester 1 was prepared according to a known procedure.

Borylation: NHPI ester 1 (50 mg, 0.13 mmol) was borylated according to General Procedure B but with a modified workup. After the 14 h stir under irradiation with blue LEDs methyliminodiacetic acid (MIDA, 79 mg, 0.53 mmol, 4.0 eq.) was added and the reaction mixture was stirred for 24 h at 60 °C (oil bath). The reaction mixture was transferred into a vial containing EtOAc (15 mL) and H₂0 (6 mL). After vigorously shaking and allowing to two layers to separate, the top organic layer was carefully removed with a pipette. This was repeated twice more with EtOAc (5 mL). The organic layers were combined and concentrated under reduced pressure. The crude reside was purified by flash column chromatography (Si0₂; THF) to afford boronic ester 13 (24 mg, 53%) as a white amorphous solid. Note: The THF must be BHT free.

¾ NMR (500 MHz, CDC1₃) δ 4.07 - 4.04 (br m, 2H, NCH¾^b), 3.95 (d, / = 16.9 Hz, 2H, C^CHTi), 3.78 (d, / = 16.9 Hz, 2H, C^OTH*³), 2.93 (s, 3Η, NCH₃), 2.73 - 2.60 (br m, 2H, NCffH¹³), 1.61 - 1.58 (br m, 2Η, CH¾^b), 1.44 (s, 9Η, C(CH₃)₃), 1.31 - 1.19 (m, 2H, C tP), 0.93 (tt, / = 12.3, 3.2 Hz, CHBpin) ppm

¹³C NMR (126 MHz, CDC1₃) δ 169.0 (C=0), 155.4 (C=0), 79.4 (OC(CH₃)₃), 63.2 (C=O H₂), 46.4 (NCH₃), 28.6 (C( H₃)₃), 27.9 (CH₂) ppm. NCH₂ not observed.

HRMS (m/z) (ESI) calc'd for Ci₅H₂₅BN₂Na0₆ [M+Na]⁺: 363.1701, found: 363.1697 IR (solid state) m_ax: 2924, 2853, 1752, 1676, 1288, 1163, 1111 and 1030 cm^"

2-(4,4-Difluorocyclohexyl)-4,4,5,5-tetramethyl-l,3,2-dioxaborolane (14)

O General Procedure A Q General Procedure B

then pinacol Et₃N, 1 h ^F Activation: The carboxylic acid (250 mg, 1.52 mmol) was coupled with N- hydroxyphthalimide according to General Procedure A. The crude residue was purified by flash column chromatography (Si0₂; 75:25 pentane:Et₂0) to afford the corresponding NHPI ester 68 (417 mg, 89%) as a white solid. m.p.: 109 - 112 °C (DCM/MeOH) TLC: Rf = 0.19 (90: 10 pentane:EtOAc)

¾ NMR (400 MHz, CDC1₃) δ 7.91 - 7.87 (m, 2H, phthalimide ArCH), 7.82 - 7.77 (phthalimide ArCH), 2.92 - 2.85 (m, 1H, CHC=0), 2.26 - 2.04 (m, 6H, CH¾^b x2 and CH₂ x2), 1.97 - 1.84 (m, 2H, CWl x2) ppm

¹³C NMR (126 MHz, CDCI3) δ 170.6 (C=0), 162.0 (C=0), 135.0 (phthalimide ArCH), 129.0 (phthalimide ArC), 124.1 (phthalimide ArCH), 122.3 (t, / = 241.3 Hz, CF₂), 37.9 (CHC=0), 32.2 (t, / = 24.8 Hz, CF2 H2), 25.1 (t, / = 5.1 Hz, CH₂) ppm

¹⁹F NMR: (377 MHz, CDCI3) δ -95.6 (d, / = 239.8 Hz), -98.4 (d, / = 239.8 Hz)

HRMS (m/z): (ESI) calc'd for

[M+Na]⁺: 332.0705, found: 332.0708

IR (solid state) max: 2973, 2948, 1809, 1782, 1740 (C=0), 1374, 1360, 1147, 1114, 1115, 1079, 981, 947, 875 and 697 cm^"1

Borylation: NHPI ester 68 (40 mg, 0.13 mmol) was borylated according to General Procedure B. The crude reside was purified by flash column chromatography (Si0₂; 95:5 pentane:Et₂0) to afford boronic ester 14 (21 mg, 66%) as a colorless oil.

TLC: R_f = 0.51 (pentane:Et₂0 85: 15) ¾ NMR (400 MHz, CDCb) δ 1.99 (m, 2H), 1.85 - 1.52 (m, 6H), 1.23 (s, 12H, 4xCH₃), 0.97 (m, 1H, CHBpin) ppm

¹³C NMR (101 MHz, CDCb) δ 123.9 (t, / = 240.5 Hz, CF₂), 83.4 (2xOC(CH₃)₂), 34.5 (t, / = 23.2 Hz, 2xCH₂CF₂), 24.9 (4xCH₃), 24.4 (m, 2xCH₂CH₂CF₂) ppm ¹⁹F NMR: (377 MHz, CDCb) δ -91.6 (d, / = 234 Hz), -98.7 (d, / = 234 Hz)

MS (m/z): Despite repeated attempts, a HRMS or LRMS could not be obtained by any means.

IR (neat) m_ax: 2925, 2854, 1454, 1330, 1144 and 847 cm^"1

4,4,5,5-Tetramethyl-2-(tra«s-2-phenylcyclopropyl)-l,3,2-dioxaborolane (15)

General Procedure A General Procedure B

69, 82% 15, 60%

98:2 d.r.

Activation: The carboxylic acid (1.00 g, 6.17 mmol) was coupled with N- hydroxyphthalimide according to General Procedure A. The crude residue was purified by flash column chromatography (Si0₂; 80:20→ 60:40 pentane:Et₂0) to afford the corresponding NHPI ester 69 (1.55 g, 82%) as a white solid. m.p.: 116 - 119 °C (Et₂0)

TLC: R_f = 0.34 (pentane:Et₂0 70:30)

¾ NMR: (400 MHz, CDCb) δ 7.90 (m, 2H, 2xAr-H), 7.79 (m, 2H, 2xAr-H), 7.34 (m, 2H, 2xAr-H), 7.27 (m, 1H, Ar-H), 7.28 (m, 2H, 2xAr-H), 2.79 (ddd, / = 9.1, 6.9, 4.0 Hz, 1H, PhCH), 2.23 (ddd, / = 8.4, 5.2, 4.0 Hz, 1H, CHC0₂R), 1.83 (ddd, / = 9.1, 5.2, 4.9 Hz, 1H, CH¾^b), 1.64 (ddd, / = 8.4, 6.9, 4.9 Hz, 1H, CH¾ ppm ¹³C NMR: (101 MHz, CDC1₃) δ 169.8 (C0₂R), 162.1 (2xCO), 138.6 (CAT), 134.8 (2XHCAT), 129.1 (2XCAT), 128.8 (2XHCAT), 127.3 (HCAT), 126.5 (2XHCAT), 124.1 (2XHCAT), 28.4 (PhCH), 21.1 (CHCO2R), 18.6 (CH₂) ppm

HRMS (m/z): (ESI) calc'd for Ci₈Hi₃NNa0₄ [M+Na]⁺: 330.0737, found: 330.0748 IR (neat) m_ax: 3065, 3031, 1806, 1778, 1738, 1467, 1401, 1360, 1186, 1100 and 877 cm

Borylation: NHPI ester 69 (40 mg, 0.13 mmol) was borylated according to General Procedure B. The crude reside was purified by flash column chromatography (Si0₂; 95:5 pentane:Et₂0) to afford boronic ester 15 (19 mg, 60%) as a colorless oil. TLC: Rf = 0.35 (pentane:Et₂0 95:5)

¾ NMR: (400 MHz, CDC ) δ 7.24 (m, 2H, 2xAr-H), 7.14 (m, 1H, Ar-H), 7.08 (m, 2H, 2xAr-H), 2.11 (ddd, / = 8.1, 5.5, 5.2 Hz, 1H, PhCH), 1.26 (s, 6H, 2xCH₃), 1.24 (s, 6H, 2xCH₃), 1.16 (ddd, / = 8.1, 6.8, 3.7 Hz, 1H, CH¾^b), 1.01 (ddd, / = 9.5, 5.2, 3.7 Hz, 1H, CH¾, 0.31 (ddd, / = 9.5, 6.8, 5.5 Hz, 1H, CHBpin) ppm ¹³C NMR: (101 MHz, CDCb) δ 143.5 (CAT), 128.4 (2XHCAT), 125.8 (2XHCAT), 125.7 (HCAT), 83.3 (2xOC(CH₃)₂), 24.9 (2xCH₃), 24.8 (2xCH₃), 22.0 (PhCH), 15.2 (CH₂) ppm

HRMS (m/z): (EI) calc'd for C15H21BO2: 244.1635, found: 244.1634

IR (neat) max: 3027, 2978, 2931, 1419, 1357, 1321, 1217, 1144 and 860 cm^"1 All data matched that reported in the literature.

2-(2,3-Dihydro-lH-inden-2-yl)-4,4,5,5-tetramethyl-l,3,2-dioxaborolane (16)

O General Procedure B

Activation: NHPI ester 70 was prepared according to a known procedure.

Borylation: NHPI ester 70 (40 mg, 0.13 mmol) was borylated according to General Procedure B. The crude reside was purified by flash column chromatography (S1O₂; 5: 1 petroleum ether 40-60:Et₂O) to afford boronic ester 16 (17 mg, 53%) as a colorless oil.

TLC: Rf = 0.68 (3: 1 petroleum ether 40-60:EtOAc)

¾ NMR (400 MHz, CDC1₃) <5 7.16 - 7.11 (m, 2H, Ar-H), 7.08 - 7.00 (m, 2H, Ar-H), 3.05 - 2.83 (m, 4H, 2xCH₂), 1.80 (p, / = 9.9 Hz, 1H, CHBpin), 1.19 (s, 12H, 2xOC(CH₃)₂) ppm ¹³C NMR (101 MHz, CDCI3) δ 144.4 (CAT), 125.8 (HCAT), 124.1 (HCAT), 83.2

(OC(CH₃)₂), 35.1 (CH₂), 24.7 (OC(CH₃)₂) ppm

All data matched that reported in the literature.

Methyl (lR)-3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)cyclopenti

carboxylate (17)

General Procedure B

in .r.

Activation: NHPI ester 71 was prepared according to a known procedure.

Borylation: NHPI ester 71 (42 mg, 0.13 mmol) was borylated according to General Procedure B. The crude reside was purified by flash column chromatography (Si0₂; 70:30 pentane:Et₂0) to afford boronic ester 17 (28 mg, 82%, 1.4: 1 d.r.) as a colorless oil.

TLC: R_f = 0.36 (70:30 pentane:Et₂0) ¾ NMR (400 MHz, CDC1₃) δ 3.64 and 3.64 (s, 3H C=OOCH₃), 2.82 - 2.67 (m, 1H, CHC=0), 2.12 - 1.35 (m, 7H, CHBpin and CH₂ x3), 1.22 and 1.21 (s, 12H, C(CH₃)₂) ppm

¹³C NMR (101 MHz, CDCI3) δ 177.3 and 177.0 (C=0), 83.2 and 83.1 (C(CH₃)₂), 51.7 and 51.6 (C=OOCH₃), 45.2 and 44.3 (CHC=0), 33.3 and 32.3 (CH₂), 31.3 and 30.5 (CH₂), 28.9 and 27.9 (CH₂), 24.9 and 24.8 (C(CH₃)₂) ppm

HRMS (m/z): (ESI) calc'd for Ci₃H₂₃BNa0₄ [M+Na]⁺: 277.1584, found: 277.1580

IR (neat) m_ax: 2977, 2952, 2872, 1733, 1381, 1315, 1197, 1143, 973 and 858 cm^"1

2-Cyclododecyl-4,4,5,5-tetramethyl-l,3,2-dioxaborolane (18)

Activation: NHPI ester 72 was prepared according to a known procedure.

Borylation: NHPI ester 72 (46 mg, 0.13 mmol) was borylated according to General Procedure B. The crude reside was purified by flash column chromatography (Si0₂; 10: 1 petroleum ether 40-60:Et₂O) to afford boronic ester 18 (34 mg, 89%) as a colorless oil.

TLC: Rf = 0.54 (10: 1 petroleum ether 40-60:EtOAc)

¾ NMR (400 MHz, CDC1₃) δ 1.45 - 1.20 (m, 22H, l lxCH₂), 1.16 (s, 12H, 2xOC(CH₃)₂), 1.04 - 0.94 (m, 1H, CHBpin) ppm

¹³C NMR (101 MHz, CDC1₃) δ 82.7 (OC(CH₃)₂), 24.9 (CH₂), 24.7 (OC(CH₃)₂), 24.2 (CH₂), 24.1 (CH₂), 23.4 (CH₂), 23.4 (CH₂), 23.3 (CH₂) ppm

HRMS (m/z): (ESI) calc'd for Ci₈H₃₅BNa0₂ [M+Na]⁺: 317.2626, found: 317.2628

IR (neat) max: 2928, 2848, 1469, 1305, 1144, 967, 858 and 708 cm^"1 2-(Heptan-2-yl)-4,4,5,5-tetramethyl-l,3,2-dioxaborolane (19)

General Procedure A General Procedure B

ien pinacol t₃N, 1

Activation: The carboxylic acid (1.44 g, 10.0 mmol) was coupled with N- hydroxyphthalimide according to General Procedure A. The crude residue was purified by flash column chromatography (Si0₂; 5: 1 petroleum ether 40-60:EtOAc) to afford the corresponding NHPI ester 73 (2.81 g, 97%) as a colorless oil.

TLC: Rf = 0.51 (3: 1 petroleum ether 40-60:EtOAc)

¾ NMR (400 MHz, CDC1₃) δ 7.78 - 7.73 (m, 2H, Ar-H), 7.70 - 7.65 (m, 2H, Ar-H), 2.80 - 2.67 (m, 1H, CH), 1.79 - 1.66 (m, 1H, CH₂), 1.58 - 1.47 (m, 1H, CH₂), 1.41 - 1.33 (m, 2H, CH₂), 1.29 - 1.19 (m, 7H, 2xCH₂ + CH₃), 0.90 - 0.76 (m, 3H, CH₃) ppm

¹³C NMR (101 MHz, CDC1₃) δ 172.7 (C=0), 161.9 (C=0), 134.6 (HCAT), 128.9 (CAT), 123.8 (HCAT), 37.1 (CH), 33.6 (CH₂), 31.5 (CH₂), 26.4 (CH₂), 22.4 (CH₂), 16.9 (CH₃), 13.9 (CH₃) ppm

HRMS (m/z): (ESI) calc'd for Ci₆Hi₉NNa0₄ [M+Na]⁺: 312.1206, found: 312.1201 IR (neat) Vma_X: 2931, 1739, 1466, 1363, 1185, 1047, 876 and 710 cm^"1

Borylation: NHPI ester 73 (38 mg, 0.13 mmol) was borylated according to General Procedure B. The crude reside was purified by flash column chromatography (Si0₂; 10: 1 petroleum ether 40-60:Et₂O) to afford boronic ester 19 (27 mg, 92%) as a colorless oil. TLC: R_f = 0.54 (10: 1 petroleum ether 40-60:EtOAc) ^lU NMR (400 MHz, CDC1₃) <5 1.38 - 1.15 (m, 20H, 8xCH₂ + 2xOC(CH₃)₂), 0.95 - 0.86 (m, 4H, CHBpin + CH₃), 0.80 (t, J = 6.9 Hz, 3H, CH₃) ppm

¹³C NMR (101 MHz, CDC1₃) δ 82.7 (OC(CH₃)₂), 33.2 (CH₂), 32.0 (CH₂), 28.6 (CH₂), 24.7 (OC(C¾)₂), 24.7 (OC(CH₃)₂), 22.6 (CH₂), 15.5 (CH₃), 14.0 (CH₃) ppm All data matched that reported in the literature. 4,4,5,5-Tetramethyl-2-(tetrahydro-2H-pyran-4-yl)-l,3,2-dioxaborolane (20)

General Procedure B

0

Activation: NHPI ester 74 was prepared according to a known procedure. Borylation: NHPI ester 74 (36 mg, 0.13 mmol) was borylated according to General Procedure B. The crude reside was purified by flash column chromatography (Si0₂; 3: 1 petroleum ether 40-60:Et₂O) to afford boronic ester 20 (9 mg, 32%) as a colorless oil. Note: the product is unstable on silica gel.

TLC: Rf = 0.48 (3: 1 petroleum ether 40-60:EtOAc) ¾ NMR (400 MHz, CDC1₃) δ 3.76 (dt, / = 11.2, 3.9 Hz, 2H, OCH₂), 3.48 - 3.34 (m, 2H, OCH2), 1.59 - 1.51 (m, 4H, 2xCH₂), 1.23 - 1.15 (m, 13H, CHBpin + 2xOC(CH₃)₂) ppm

¹³C NMR (101 MHz, CDCI3) δ 83.1 (OC(CH₃)₂), 68.8 (OCH₂), 27.6 (CH₂), 24.7

All data matched that reported in the literature.

l,2-Bis(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)cyclohexane (21)

then pinacol Et₃N, 1 h 91 :9 d.r.

Activation: The carboxylic acid (500 mg, 3.24 mmol) was coupled with N- hydroxyphthalimide according to General Procedure A with all reagents doubled in quantity. The crude residue was purified by flash column chromatography (Si0₂; DCM) to afford the corresponding NHPI ester 75 (709 mg, 47%) as a white solid. m.p.: 188 - 192 °C (DCM/MeOH)

¾ NMR (400 MHz, CDC1₃) δ 7.89 - 7.85 (m, 2H, phthalimide ArH), 7.79 - 7.75 (m, 2H, phthalimide ArH), 3.28 - 3.21 (m, 2H, CHC=0), 2.44 - 2.37 (br m, 2H, CHCH¾^b x2), 1.94 - 1.87 (br m, 2Η, CH¾^b x2), 1.84 - 1.75 (br m, 2Η, CHCH¾^b x2), 1.53 - 1.46 (br m, 2Η, CH^ x2) ppm

¹³C NMR (101 MHz, CDCI3) δ 170.3 (C=0), 161.8 (C=0), 134.8 (phthalimide ArCH), 129.2 (phthalimide ArC), 124.1 (phthalimide ArC), 41.7 ( HC=0), 28.4 (CH₂CHC=0), 24.4 ( H₂CH₂CHC=0) ppm HRMS (m/z) (ESI) calc'd for C₂₄Hi₈N₂Na0₈ [M+Na]⁺: 485.0955, found: 485.0955

IR (solid state) m_ax: 2937, 2862, 1783, 1734, 1468, 1358, 1186, 1123, 1082, 997, 970, 876, 693 and 518 cm^"1

Borylation: NHPI ester 75 (62 mg, 0.13 mmol) was borylated according to General Procedure B with double the amount of B₂cat₂. The crude reside was purified by flash column chromatography (Si0₂; 90: 10 pentane:Et₂0) to afford boronic ester 21 (30 mg, 67%, 91 :9 d.r.) as an amorphous white solid.

TLC: Rf = 0.31 (90: 10 pentane:Et₂0)

¾ NMR (400 MHz, CDCI3) δ 1.72 - 1.62 (br m, 4H, CH₂ x2), 1.25 - 1.17 (m, 4H, CH₂ x2), 1.21 (s, 24H, C(CH₃)₂), 1.01 - 0.94 (br m, 2H, CHBpin) ppm ¹³C NMR (101 MHz, CDCI3) δ 82.8 (C(CH₃)₂), 28.5 (CH₂), 27.3 (CH₂), 25.0 (C(CH₃)₂), 24.8 (C(CH₃)₂) ppm

HRMS (m/z): (ESI) calc'd for Ci₈H₃₄B₂Na0₄ [M+Na]⁺: 359.2542, found: 359.2543 IR (solid state) max: 2977, 2918, 2848, 1370, 1312, 1138, 972 and 861 cm^"1 2-((9s,10s)-9,10-Dihydro-9,10-ethanoanthracen-ll-yl)-4,4,5,5-tetramethyl-l,3,2- dioxaborolane (22)

Activation: The carboxylic acid (52) (500 mg, 2.00 mmol) was coupled with N- hydroxyphthalimide according to General Procedure A. The crude residue was purified by flash column chromatography (S1O2; 40:60 pentane:DCM) to afford the corresponding NHPI ester 76 (677 mg, 86%) as a white solid. m.p.: 180 - 184 °C (DCM/MeOH)

TLC: R_f = 0.29 (30:70 pentane:DCM) ¾ NMR (400 MHz, CDC1₃) δ 7.89 - 7.82 (m, 2H, phthalimide ArH), 7.78 - 7.74 (m, 2H, phthalimide ArH), 7.52 - 7.48 (m, 1H, ArH), 7.41 - 7.37 (m, 1H, ArH), 7.35 - 7.25 (m, 2H, ArH), 7.18 - 7.1 1 (m, 4H, ArH), 4.90 (d, / = 2.3 Hz, 1H, CHCHC=0), 4.42 (t, J = 2.6 Hz, 1H, CHCH₂), 3.30 - 3.26 (m, 1H, CHC=0), 2.22 - 2.12 (m, 2H, CH₂) ppm

¹³C NMR (101 MHz, CDCI3) δ 170.2 (C=0), 162.0 (C=0), 143.5 (ArC), 143.4 (ArC), 141.9 (ArC), 138.6 (ArC), 134.8 (phthalimide ArCH), 129.1 (phthalimide ArC), 126.8 (ArCH), 126.7 (ArCH), 126.2 (ArCH), 126.1 (ArCH), 125.9 (ArCH), 124.1 (phthalimide ArCH), 123.9 (ArCH), 123.8 (ArCH), 123.2 (ArCH), 47.2 (CHCHC=0), 43.7 (CHCH₂), 41.8 (CHC=0), 31.4 (CH₂) ppm

HRMS (m/z): (ESI) calc'd for C₂5Hi₇NNa0₄ [M+Na]⁺: 418.1050, found: 418.1048 IR (solid state) m_ax: 3024, 2954, 1743 (C=0), 1466, 1087, 996, 964, 762 and 695 cm^"1

Borylation: NHPI ester 76 (53 mg, 0.13 mmol) was borylated according to General Procedure B. The crude reside was purified by flash column chromatography (Si0₂; 98:2 pentane:Et₂0) to afford boronic ester 22 (23 mg, 53%) as an amorphous white solid. TLC: R_f = 0.21 (95:5 pentane:Et₂0) ¾ NMR (400 MHz, CDC1₃) δ 7.28 - 7.24 (m, 4H, ArH), 7.10 - 7.01 (m, 4H, ArH), 4.47 (d, / = 2.3 Hz, 1H, CHCHBpin), 4.33 (t, / = 2.6 Hz, 1H, CHCH₂), 1.90 (ddd, / = 11.8, 5.4, 2.5 Hz, 1H, CH¾^b), 1.82 (app td, / = 11.8, 2.5 Hz, 1H, CffH¹³), 1.43 (ddd, / = 10.7, 5.4, 2.5 Hz, 1H, CHBpin), 1.12 (s, 6H, C(CH₃)₂), 1.02 (s, 6H, C(CH₃)₂) ppm ¹³C NMR (101 MHz, CDC1₃) δ 145.2 (ArC), 144.3 (ArC), 143.9 (ArC), 142.8 (ArC), 125.7 (ArCH), 125.5 (ArCH), 125.4 (ArCH), 125.1 (ArCH), 124.3 (ArCH), 123.4 (ArCH), 123.3 (ArCH), 122.8 (ArCH), 83.4 (C(CH₃)₂), 45.7 (CHCHBpin), 44.6 (CHCH₂), 29.6 (CH₂), 24.9 (C(CH₃)₂) ppm

HRMS (m/z) (ESI) calc'd for C₂₂H25BNa02 [M+Na]⁺: 355.1844, found: 355.1837 IR (solid state) v_max: 2982, 2940, 2870, 1458, 1366, 1315, 1249, 1138, 981, 854, 753, 743 and 701 cm^"1

4,4,5,5-tetramethyl-2-(2,2,3,3-tetramethylcyclopropyl)-l,3,2-dioxaborolane (23)

General Procedure A Q General Procedure B

then pinacol Et₃N, 1 h

Activation: The carboxylic acid (500 mg, 3.52 mmol) was coupled with N- hydroxyphthalimide according to General Procedure A. The crude residue was purified by flash column chromatography (Si0₂; 40:60 pentane:DCM) to afford the corresponding NHPI ester 77 (740 mg, 73%) as a white solid. m.p.: 78 - 80 °C (DCM/MeOH)

TLC: Rf = 0.21 (40:60 pentane:DCM) ¾ NMR (400 MHz, CDC1₃) δ 7.89 - 7.84 (m, 2H, phthalimide ArCH), 7.78 - 7.74 (m, 2H, phthalimide ArCH), 1.52 (s, 1H, CHC=0), 1.30 (s, 6H, CH₃ x2), 1.27 (6H, CH₃ x2) ppm

¹³C NMR (101 MHz, CDC1₃) δ 167.8 (C=0), 162.6 (C=0), 134.7 (phthalimide ArCH), 129.2 (phthalimide ArC), 124.0 (phthalimide ArCH), 33.4 (C(CH₃)₂), 32.4 (CHC=0), 23.4 (CH₃), 16.5 (CH₃) ppm HRMS (m/z): (ESI) calc'd for Ci₆Hi₇NNa0₄ [M+Na]⁺: 310.1050, found: 310.1052

IR (solid state) v_max: 2950, 2924, 1773, 1731, 1467, 1357, 1094, 1021, 997, 977, 877, 847, 783 and 691 cm^"1

Borylation: NHPI ester 77 (38 mg, 0.13 mmol) was borylated according to General Procedure B. The crude reside was purified by flash column chromatography (S1O2; 95:5 pentane:Et₂0) to afford boronic ester 23 (25 mg, 83%) as an amorphous white solid.

TLC: Rf = 0.60 (80:20 pentane:Et₂0) ^lU NMR (400 MHz, CDC1₃) δ 1.21 (s, 12H, Bpin C(CH₃)₂), 1.15 (s, 6H, C(CH₃)₂ x2), 1.14 (s, 6H, C(CH₃)₂ x2), -0.46 (s, 1H, CHBpin) ppm

¹³C NMR (101 MHz, CDC1₃) δ 82.5 (Bpin C(CH₃)₂), 27.2 (C(CH₃)₂, 25.0 (Bpin C( H₃)₂), 24.7 (CH₃), 19.9 (CH₃) ppm

HRMS (m/z): (ESI) calc'd for Ci₃H₂₅BNa0₂ [M+Na]⁺: 247.1842, found: 247.1840

IR (solid state) max: 2979, 2925, 2867, 1418, 1396, 1343, 1311, 1235, 1142, 1106, 857 and 706 cm^"1

2.1.3 Substrate Scope: Tertiary

4,4,5,5-Tetramethyl-2-(l-phenylcyclopropyl)-l,3,2-dioxaborolane (24)

Activation: NHPI ester 78 was prepared according to a known procedure.

Borylation: NHPI ester 78 (40 mg, 0.13 mmol) was borylated according to General Procedure B. The crude reside was purified by flash column chromatography (Si0₂; 80:20 pentane:Et₂0) to afford boronic ester 24 (29 mg, 91 ) a colorless oil. TLC: Rf = 0.59 (70:30 pentane:Et₂0)

¾ NMR (400 MHz, CDC1₃) δ 7.28 - 7.21 (m, 4H, ArH), 7.14 - 7.10 (m, 1H, ArH), 1.21 (s, 12H, C(CH₃)₂), 1.11 (q, / = 3.5 Hz, 2H, CH₂), 0.91 (q, / = 3.5 Hz, 2H, CH₂) ppm ¹³C NMR (101 MHz, CDC ) δ 145.0 (ArC), 129.1 (ArCH), 128.1 (ArCH), 125.4 (ArCH), 83.5 (C(CH₃)₂), 24.7 (C( H₃)₂), 13.5 (CH₂) ppm

All data matched that reported in the literature.

2-((3r,5r,7r)-Adamantan-l-yl)-4,4,5,5-tetramethyl-l,3,2-dioxaborolane (25)

General Procedure B

25, 74% ₍₆₉ ^o/₀ 1 .1 1 g) Activation: NHPI ester 79 was prepared according to a known procedure.

Borylation: NHPI ester 79 (43 mg, 0.13 mmol) was borylated according to General Procedure B. The crude reside was purified by flash column chromatography (Si0₂; 80:20 pentane:Et₂0) to afford boronic ester 25 (26 mg, 74%) an amorphous white solid.

Gram Scale Borylation: NHPI ester 79 (2.0 g, 6.15 mmol) and B₂cat₂ (1.83 g, 7.68 mmol) were carefully weighed into a flame-dried Schlenk tube containing a small magnetic stirrer bar. DMAc (12.3 mL, 0.5 M) was added and then the headspace of the vial was purged with a gentle stream of argon for approximately 30 seconds. The tube was sealed and stirred under blue LED irradiation for 14 h. Pinacol (2.91 g, 24.59 mmol) was dissolved in Et₃N (4.14 mL) and added to the reaction mixture and stirred for 1 h. The reaction mixture was transferred into a separating funnel containing EtOAc

(40 mL), H₂0 (20 mL), NH₄C1 (saturated aqueous solution, 20 mL). After vigorously shaking and allowing to two layers to separate, the organic layer was collected. This was repeated twice more with EtOAc (40 mL). The organic layers were combined, dried over MgS0₄, and concentrated under reduced pressure. The crude residue was purified by flash column chromatography (Si0₂; 80:20 pentane:Et₂0) to afford boronic ester 25

(1.1 lg, 69%) as an amorphous white solid. ^lU NMR (400 MHz, CDC1₃) δ 1.91 - 1.71 (br m, 15H, CH x3 and CH₂ x6), 1.21 (s, 12H, C(CH₃)₂) ppm

¹³C NMR (101 MHz, CDCI3) δ 82.7 (C(CH₃)₂), 38.1 (CH₂), 37.7 (CH₂), 27.7 (CH), 24.8 (C(CH₃)₃) ppm All data matched that reported in the literature.

4,4,5,5-Tetramethyl-2-(4-pentylbicyclo[2.2.2]octan-l-yl)-l,3,2-dioxaborolane (26)

80, 84% then pinacol Et₃N, 1 h 26, 83%

Activation: The carboxylic acid (500 mg, 2.23 mmol) was coupled with N- hydroxyphthalimide according to General Procedure A. The crude residue was purified by flash column chromatography (Si0₂; 20: 1 petroleum ether 40-60:EtOAc) to afford the corresponding NHPI ester 80 (690 mg, 84%) as a white solid. m.p.: 121 - 123 °C (DCM/MeOH)

TLC: R_f = 0.24 (10: 1 petroleum ether 40-60:EtOAc) ¾ NMR (400 MHz, CDC1₃) δ 7.86 - 7.82 (m, 2H, Ar-H), 7.77 - 7.72 (m, 2H, Ar-H), 2.07 - 1.92 (m, 6H, 3xCH₂), 1.53 - 1.39 (m, 6H, 3xCH₂), 1.35 - 1.07 (m, 8H, 4xCH₂), 0.87 (t, / = 7.1 Hz, 3H, CH₃) ppm

¹³C NMR (101 MHz, CDC1₃) δ 174.0 (C=0), 162.1 (C=0), 134.6 (HCAT), 129.1 (CAT), 123.9 (HCAT), 41.2 (CH₂), 38.7 (C), 32.8 (CH₂), 30.4 (C), 30.1 (CH₂), 28.5 (CH₂), 23.4 (CH₂), 22.7 (CH₂), 14.1 (CH₃) ppm

HRMS (m/z): (ESI) calc'd for C₂₂H27NNa04 [M+Na]⁺: 392.1832, found: 392.1832

IR (neat) m_ax: 2917, 2855, 1774, 1738, 1369, 1183, 1139, 980, 876 and 734 cm^"1

Borylation: NHPI ester 80 (48 mg, 0.13 mmol) was borylated according to General Procedure B. The crude reside was purified by flash column chromatography (Si0₂; 10: 1 petroleum ether 40-60:Εί₂Ο) to afford boronic ester 26 (33 mg, 83%) as an amorphous white solid.

TLC: Rf = 0.51 (10: 1 petroleum ether 40-60:EtOAc)

¾ NMR (400 MHz, CDC1₃) δ 1.52 - 1.41 (m, 6H, 3xCH₂), 1.26 - 1.08 (m, 24H, 6xCH₂ + 2xOC(CH₃)₂), 0.98 - 0.89 (m, 2H, CH₂), 0.79 (t, / = 7.2 Hz, 3H, CH₃) ppm

¹³C NMR (101 MHz, CDC1₃) δ 82.6 (OC(CH₃)₂), 42.2 (CH₂), 32.9 (CH₂), 30.7 (CH₂), 29.8 (C), 27.4 (CH₂), 24.6 (OC(CH₃)₂), 23.1 (CH₂), 22.7 (CH₂), 14.1 (CH₃) ppm

HRMS (m/z): (ESI) calc'd for Ci₉H₃₅BNa0₂ [M+Na]⁺: 329.2626, found: 329.2641

IR (neat) m_ax: 2925, 2855, 1750, 1383, 1306, 1145, 1125 and 849 cm^"1

Methyl 4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)cubane-l-carboxylate (27)

Activation: NHPI ester 81 was prepared according to a known procedure.

Borylation: NHPI ester 81 (47 mg, 0.13 mmol) was borylated according to General Procedure B. The crude reside was purified by flash column chromatography (Si0₂; 60:40 pentane:Et₂0) to afford boronic ester 27 (18 mg, 46%) an amorphous solid.

TLC: R_f = 0.42 (50:50 pentane:Et₂0)

¾ NMR (400 MHz, CDC1₃) δ 4.31 - 4.27 (m, 3H, CH), 4.04 - 3.99 (m, 3H, CH), 3.69 (s, 3H, C=OOCH₃), 1.25 (s, 12H, C(CH₃)₂) ppm ¹³C NMR (126 MHz, CDC1₃) δ 172.6 (C=0), 83.2 (C(CH₃)₂), 55.3 (CC=0), 51.5 (C=OO H₃), 49.8 (CH), 45.1 (CH), 24.8 (C( H₃)₂) ppm

HRMS (m/z): (ESI) calc'd for Ci₆H₂iBNa0₄ [M+Na]⁺: 311.1428, found: 311.1420 IR (solid state) m_ax: 2976, 1715, 1429, 1395, 1307, 1224, 1142, 1085 and 845 cm^"1

2-(Bicyclo[l.l.l]pentan-l-yl)-4,4,5,5-tetramethyl-l,3,2-dioxaborolane (28) n

Activation: The carboxylic acid (110 mg, 0.98 mmol) was coupled with N- hydroxyphthalimide according to General Procedure A. The crude residue was purified by flash column chromatography (S1O2; 60:40 pentane:Et₂0) to afford the corresponding NHPI ester 82 (187 mg, 74%) as an amorphous white solid.

TLC: R_f = 0.23 (50:50 pentane:DCM) ¾ NMR (500 MHz, CDC1₃) δ 7.89 - 7.86 (m, 2H, phthalimide ArH), 7.80 - 7.76 (m, 2H, phthalimide ArH), 2.55 (s, 1H, CH), 2.33 (s, 6H, CH₂) ppm

¹³C NMR (126 MHz, CDCI3) δ 164.7 (C=0), 162.0 (C=0), 134.8 (phthalimide ArCH), 129.1 (phthalimide ArC), 124.1 (phthalimide ArCH), 52.5 (CH₂), 40.0 (CC=0), 29.3 (CH) ppm HRMS (m/z): (ESI) calc'd for Ci₄HnNNa0₄ [M+Na]⁺: 280.0580, found: 280.0594

IR (solid state) max: 3001, 2887, 1776, 1736, 1372, 1185, 1039, 875, 789, 692, 606 and 518 cm^"1

Borylation: NHPI ester 82 (34 mg, 0.13 mmol) was borylated according to General Procedure B. The crude reside was purified by flash column chromatography (Si0₂; 90: 10 pentane:Et₂0) to afford boronic ester 82 (11 mg, 42%) a colorless oil (due to the product's volatility, a small amount of pentane remained). Note: product is volatile and unstable on silica.

TLC: Rf = 0.24 (90: 10 pentane:Et₂0)

¾ NMR (500 MHz, CDC ) δ 2.48 (s, 1H, CH), 1.95 (s, 6H, CH₂), 1.22 (s, 12H, C(CH₃)₂) ppm ¹³C NMR (126 MHz, CDC1₃) δ 83.3 (C(CH₃)₂), 52.0 (CH₂), 34.7 (CH), 24.9 (C(CH₃)₂) ppm

HRMS (m/z): (EI) calc'd for CnHi₉BNa0₂ [M+Na]⁺: 217.1372, found: 217.1369 IR (neat) m_ax: 2923, 1399, 1317, 1216, 1135, 852 and 662 cm^"1

2.1.4 Substrate Scope: Natural Products and Drugs

2-Heptadecyl-4,4,5,5-tetramethyl-l,3,2-dioxaborolane (29)

O General Procedure A Q General Procedure B

^^OH NHPI, DIC, DMAP "^^NHPI 1 -25 eq. B₂cat₂, DMAc "^ Bpin

Stearic acid ^DCM> ^{r t} > ^ονθΓη'9^η1 83, 71 % blue LEDs,14 h 29, 84%

^en pinacol Et₃N, 1 h

Activation: Stearic acid (1.0 g, 3.52 mmol) was coupled with N-hydroxyphthalimide according to General Procedure A. The crude residue was purified by flash column chromatography (Si0₂; 60:40 pentane:DCM) to afford the corresponding NHPI ester 83 (1.07 mg, 71%) as a white solid.

TLC: Rf = 0.32 (50:50 pentane:DCM)

¾ NMR (400 MHz, CDC1₃) δ 7.91 - 7.86 (m, 2H, phthalimide ArH), 7.81 - 7.76 (m, 2H, phthalimide ArH), 2.66 (t, / = 7.5 Hz, 2H, CH₂C=0), 1.78 (p, / = 7.5 Hz, CH₂CH₂C=0), 1.44 (p, / = 7.5 Hz, CH₂CH₂CH₂C=0), 1.37 - 1.21 (m, 26H, CH₂ xl3), 0.88 (t, / = 7.0 Hz, 3H, CH₃) ppm

¹³C NMR (101 MHz, CDC1₃) δ 169.8 (C=0), 162.1 (C=0), 134.8 (phthalimide ArCH), 129.1 (phthalimide ArC), 124.1 (phthalimide ArCH), 32.1 (CH₂C=0), 31.1 (CH₂), 29.8 - 29.7 (CH₂ x9), 29.5 (CH₂), 29.3 (CH₂), 29.0 (CH₂), 24.8 (CH₂), 22.8 (CH₂), 14.3 (CH₃) ppm All data matched that reported in the literature.

Borylation: NHPI ester 83 (57 mg, 0.13 mmol) was borylated according to General Procedure B. The crude reside was purified by flash column chromatography (Si0₂; 90: 10 pentane:Et₂0) to afford boronic ester 29 (41 mg, 84%) as colorless oil. TLC: Rf = 0.56 (90: 10 pentane:Et₂0)

¾ NMR (400 MHz, CDC1₃) δ 1.43 - 1.17 (m, 30H, CH₂ xl5), 1.24 (s, 12H, C(CH₃)₂), 0.88 (t, J = 6.8 Hz, 3H, CH₃), 0.76 (t, / = 7.7 Hz, 2H, CH₂Bpin) ppm

¹³C NMR (101 MHz, CDC1₃) δ 83.0 (C(CH₃)₂), 32.6 (CH₂), 32.1 (CH₂), 29.9 - 29.5 (CH₂ x9), 25.0 (C(CH₃)₂), 24.2 (CH₂), 22.9 (CH₂), 14.3 (CH₃) ppm HRMS (m/z): (ESI) calc'd for C₂₃H48B0₂ [M+H]⁺: 367.3746, found: 367.3745

IR (neat) m_ax: 2922, 2853, 1377, 1316, 1145, 968, 847 and 735 cm^"1

tert-Butyl(((3R,8R,95,105,13R,145,17R)-10,13-dimethyl-17-((R)-4-(4,4,5,5- tetramethyl-l,3,2-dioxaborolan-2-yl)butan-2-yl)hexadecahydro-lH- cyclopenta[a]phenanthren-3-yl)oxy)dimethylsilane (30)

Activation: Crude TBS protected lithocholic acid (55) (2.45 g, 5.0 mmol) was coupled with N-hydroxyphthalimide according to General Procedure A. The crude residue was purified by flash column chromatography (Si0₂; 95:5 hexane:EtOAc) to afford the corresponding NHPI ester 84 (1.37 g, 43% over two steps) as a white solid. m.p.: 194 - 198 (DCM/MeOH)

TLC: R_f = 0.55 (90: 10 hexane:EtOAc) ^lU NMR (400 MHz, CDC1₃) δ 7.91 - 7.86 (m, 2H, phthalimide ArH), 7.80 - 7.76 (m, 2H, phthalimide ArH), 3.58 (app tt, / = 11.0, 4.7 Hz, 1H, CHOTBS), 2.76 - 2.65 (m, 1H, CH¾^bC=0), 2.64 - 2.53 (m, 1Η, CffH^O), 1.98 - 1.72 (m, 6Η), 1.58 - 0.86 (m, 20Η), 0.98 (d, / = 6.3 Hz, CHCH3), 0.90 (s, 3Η, CH₃), 0.89 (s, 9H, SiC(CH₃)₃), 0.67 (s, 3H, CH₃), 0.06 (s, 6H, Si(CH₃)₂) ppm

¹³C NMR (101 MHz, CDC1₃) ^ 170.2 (C=0), 162.1 (C=0), 134.8 (ArCH), 129.1 (ArC), 124.1 (ArCH), 73.0 (CHOTBS), 56.5, 56.1, 42.9 (C), 42.4, 40.3, 40.3 (C), 37.1 (C), 36.0, 35.7 (C), 35.4, 34.7 (C), 31.2 (CH₂), 30.9 (CH₂), 28.3 (CH₂), 28.2 (CH₂), 27.5 (CH₂), 26.5 (CH₂), 26.1 (SiC( H₃)₃), 24.4 (CH₂), 23.5, 21.0 (CH₂), 18.5 (SiC(CH₃)₃), 18.4, 12.2 (CH₃), -4.4 (Si(CH₃)₂) ppm

HRMS (m/z) (ESI) calc'd for CssHsvBNOsSiNa [M+Na]⁺: 658.3898, found:

658.3888

IR (neat) m_ax: 2930, 2860, 1744, 1065, 835 and 781 cm^"1 [α]£⁴: +20 (c = 1.0, CHC ) Borylation: NHPI ester 84 (83 mg, 0.13 mmol) was borylated according to General Procedure B. The crude reside was purified by flash column chromatography (Si0₂; 95:5 pentane:Et₂0) to afford boronic ester 30 (54 mg, 72%) as an amorphous white solid.

TLC: Rf = 0.38 (pentane:Et₂0 95:5) ¾ NMR (400 MHz, CDC ) δ 3.57 (dddd, / = 10.9, 10.7, 4.7, 4.5 Hz, 1H, CHOTBS), 1.95 (m, 1H), 1.90 - 1.70 (m, 4H), 1.59 - 1.50 (m, 3H), 1.48 - 1.28 (m, 8H), 1.28 - 1.17 (m, 15H), 1.16 - 0.98 (m, 6H), 0.98 - 0.75 (m, 17H), 0.69 - 0.54 (m, 4H), 0.05 (s, 6H, Si(CH₃)₂) ppm

¹³C NMR (101 MHz, CDCb) δ 82.9 (2xOC(CH₃)₂), 73.0 (CHOTBS), 56.6 (CH), 56.2 (CH), 42.9 (C^w), 42.5 (CH), 40.4 (CH), 40.3 (CH₂), 37.8 (CH), 37.1 (CH₂), 36.1 (CH), 35.8 (CH₂), 34.8 (C^w), 31.2 (CH₂), 29.9 (CH₂), 28.4 (CH₂), 27.5 (CH₂), 26.6 (CH₂), 26.2 (SiC(CH₃)₃), 25.0 (OC(CH₃)₂), 24.9 (OC(CH₃)₂), 24.4 (CH₂), 23.6 (CH₃), 21.0 (CH₂), 18.5 (CH), 18.2 (CH₃), 12.2 (CH₃), -4.4 (Si(CH₃)₂) ppm HRMS (m/z): (ESI) calc'd for C₃₅H₆₅BNa0₃Si [M+Na]⁺: 595.4695, found: 595.4690 IR (neat) m_ax: 2927, 2856, 1470, 1370, 1312, 1251, 1146, 1095, 835 and 774 cm^"1 [α ⁴: + 17 (c = 1.0, CHC1₃)

(3R,5R,8R,95,105,13R,145,17R)-10,13-Dimethyl-17-((R)-4-(4,4,5,5-tetramethyl- l,3,2-dioxaborolan-2-yl)butan-2-yl)hexadecahydro-lH- cyclopenta[a]phenanthren-3-ol (31)

Activation: The carboxylic acid (1.00 g, 2.66 mmol) was coupled with N- hydroxyphthalimide according to General Procedure A. The crude residue was purified by flash column chromatography (S1O2; 80:20→ 60:40 pentane:EtOAc) to afford the corresponding NHPI ester 85 (418 mg, 30%) as a white solid. m.p.: 161 - 163 °C (EtOAc)

TLC: Rf = 0.42 (pentane:EtOAc 50:50) ¾ NMR: (400 MHz, CDC1₃) δ 7.88 (m, 2H, 2xAr-H), 7.78 (m, 2H, 2xAr-H), 3.62 (dddd, / = 11.1, 11.0, 4.7, 4.6 Hz, 1H, CHOH), 2.71 (ddd, / = 15.9, 9.6, 4.8 Hz, 1H, CH H^bC0₂R), 2.58 (ddd, / = 15.9, 9.0, 6.9 Hz, 1H, CH^aH¾0₂R), 2.05 - 1.93 (m, 2H), 1.91 - 1.83 (m, 2H), 1.81 - 1.70 (m, 2H), 1.66 (m, 1H), 1.61 - 1.46 (m, 4H), 1.44 - 1.36 (m, 5H), 1.35 - 1.21 (m, 4H), 1.19 - 1.02 (m, 5H), 1.01 - 0.95 (m, 4H), 0.92 (s, 3H, CH₃), 0.67 (s, 3H, CH₃) ppm

¹³C NMR: (101 MHz, CDC1₃) δ 170.2 (C0₂R), 162.1 (2xCO), 134.8 (2XHCAT), 129.1 (2XCAT), 124.1 (2XHCAT), 72.0 (CHOH), 56.6 (CH), 56.0 (CH), 43.0 (C^w), 42.2 (CH), 40.6 (CH), 40.3 (CH₂), 36.6 (CH₂), 36.0 (CH), 35.5 (CH₂), 35.4 (CH), 34.7 (C^w), 30.9 (CH₂), 30.7 (CH₂), 28.3 (CH₂), 28.2 (CH₂), 27.3 (CH₂), 26.6 (CH₂), 24.3 (CH₂), 23.5 (CH₃), 21.0 (CH₂), 18.4 (CHCH₃), 12.2 (CH₃) ppm

HRMS (m/z): (ESI) calc'd for C₃₂H₄₃NNa0₅ [M+Na]⁺: 544.3033, found: 544.3032

IR (neat) max: 3366 (br.), 2928, 2863, 1816, 1788, 1741, 1467, 1365, 1067 and 732 cm^"1

[a]²,⁴: + 18 (c 1.0, CHC1₃)

All data matched that reported in the literature.

Borylation: NHPI ester 85 (68 mg, 0.13 mmol) was borylated according to General Procedure B. The crude reside was purified by flash column chromatography (Si0₂; 60:40 pentane:Et₂0) to afford boronic ester 31 (52 mg, 87%) as a white solid. m.p.: 159 - 161 °C (Et₂0)

TLC: Rf = 0.24 (pentane:Et₂0 50:50)

¾ NMR: (400 MHz, CDC1₃) δ 3.61 (dddd, / = 11.1, 11.0, 4.7, 4.6 Hz, 1H, CHOH), 1.96 (m, 1H), 1.91 - 1.70 (m, 4H), 1.65 (m, 1H), 1.60 - 1.46 (m, 3H), 1.45 - 1.28 (m, 7H), 1.28 - 1.17 (m, 15H), 1.17 - 0.94 (m, 7H), 0.91 (s, 3H, CH₃), 0.88 (d, / = 6.5 Hz, 3H, CHCHs), 0.79 (ddd, / = 15.8, 10.7, 5.1 Hz, 1H, CffH^bBpin), 0.68 - 0.56 (m, 4H, CH₃ & CH^aH¾pin) ppm

¹³C NMR: (101 MHz, CDC1₃) δ 82.9 (2xOC(CH₃)₂), 72.0 (CHOH), 56.7 (CH), 56.1 (CH), 42.8 (C^w), 42.3 (CH), 40.6 (CH), 40.4 (CH₂), 37.8 (CH), 36.7 (CH₂), 36.0 (CH), 35.5 (CH₂), 34.7 (C^w), 30.7 (CH₂), 29.9 (CH₂), 28.4 (CH₂), 27.4 (CH₂), 26.6 (CH₂), 25.0 (OC(CH₃)₂), 24.9 (OC(CH₃)₂), 24.4 (CH₂), 23.5 (CH₃), 21.0 (CH₂), 18.2 (CHCH₃), 12.2 (CH₃) ppm

HRMS (m/z): (ESI) calc'd for C₂₉H₅iBNa0₃ [M+Na]⁺: 481.3829, found: 481.3827 IR (neat) max: 3346 (br.), 2974, 2929, 2864, 1448, 1369, 1311, 1144 and 732 cm^"1 [a] ⁶: +21 (c 1.0, CHC1₃) 4,4,5,5-Tetramethyl-2-((4Z,7Z,10Z,13Z)-nonadeca-4,7,10,13-tetraen-l-yl)-l,3,2- dioxaborolane (32)

General Procedure A General Procedure B

NHPI, DIC, DMAP 1 .25 eq. B₂cat₂, DMAc , Bpin arachidonic acid DCM, r.t., overnight 86, 74% blue LEDs,14 h 32, 58%

then pinacol Et₃N, 1 h

Activation: The carboxylic acid (100 mg, 0.33 mmol) was coupled with N- hydroxyphthalimide according to General Procedure A. The crude residue was purified by flash column chromatography (Si0₂; 90: 10 pentane:Et₂0) to afford the corresponding NHPI ester 86 (110 mg, 74%) as a colorless oil.

TLC: R_f = 0.15 (pentane:Et₂0 90: 10)

¾ NMR: (400 MHz, CDC1₃) δ 7.88 (m, 2H, 2xAr-H), 7.78 (m, 2H, 2xAr-H), 5.50 - 5.29 (m, 8H, 8xCH), 2.87 - 2.80 (m, 6H, 3XCHCH2CH), 2.68 (t, / = 7.4 Hz, 2H,

CH2CO2R), 2.24 (td, / = 7.3, 7.1 Hz, 2H, ClMCT^CChR), 2.05 (td, / = 7.0, 6.9 Hz,

2H, C4H9CH2CH), 1.87 (tt, / = 7.4, 7.3 Hz, 2H, CH2CH2CO2R), 1.40 - 1.22 (m, 6H,

3xCH₂), 0.88 (t, J = 6.8 Hz, 3H, CH₃) ppm

¹³C NMR: (101 MHz, CDC ) δ 169.6 (C0₂R), 162.0 (2xCO), 134.8 (2XHCAT), 130.6

(CH), 129.8 (CH), 129.1 (2XCAT), 128.7 (CH), 128.5 (CH), 128.3 (CH), 128.2 (CH),

128.0 (CH), 127.7 (CH), 124.1 (2XHCAT), 31.6 (CH₂), 30.5 (CH2CO2R), 29.5 (CH₂),

27.3 (C4H9CH2CH), 26.3 (CH2(CH₂)2C0₂R), 25.8 (3xCHCH₂CH), 24.7

(CH2CH2CO2R), 22.7 (CH₂), 14.2 (CH₃) ppm

HRMS (m/z): (ESI) calc'd for C₂8H₃₅NNa04 [M+Na]⁺: 472.2458, found: 472.2460 IR (neat) m_ax: 3012, 2927, 2856, 1816, 1789, 1743, 1467, 1367, 1185, 1081 and 877 cm^-1

Borylation: NHPI ester 86 (58 mg, 0.13 mmol) was borylated according to General

Procedure B. The crude reside was purified by flash column chromatography (Si0₂;

95:5 pentane:Et₂0) to afford boronic ester 32 (29 mg, 58%) as a colorless oil.

TLC: R_f = 0.50 (pentane:Et₂0 95:5) ^lU NMR: (400 MHz, CDC1₃) δ 5.48 - 5.24 (m, 8H, 8xCH), 2.92 - 2.73 (m, 6H, 3XCHCH2CH), 2.06 (app. p, J^app- = 7.0 Hz, 4H, 2xCHCH₂CH₂), 1.48 (tt, J = 7.8, 7.7 Hz, 2H, CH₂CH₂Bpin), 1.41 - 1.27 (m, 6H, 3xCH₂), 1.24 (s, 12H, 4xCH₃), 0.89 (t, / = 6.8 Hz, 3H, CH₃), 0.80 (t, / = 7.9 Hz, 2H, CH₂B(OR)₂) ppm ¹³C NMR: (101 MHz, CDC1₃) δ 130.5 (CH), 130.2 (CH), 128.6 (CH), 128.5 (CH), 128.0 (CH), 128.0 (CH), 127.9 (CH), 127.6 (CH), 82.9 (2xOC(CH₃)₂), 31.5 (CH₂), 29.8 (CHCH₂CH₂), 29.3 (CH₂), 27.2 (CHCH₂CH₂), 25.6 (3xCHCH₂CH), 24.8 (4xCH₃), 24.1 (CH₂CH₂Bpin), 22.6 (CH₂), 14.1 (CH₃) ppm

HRMS (m/z): (EI) calc'd for C₂₅H₄₃B0₂: 386.3356, found: 386.3338 IR (neat) m_ax: 3012, 2927, 2858, 1371, 1316, 1140, 968 and 846 cm^"1

l-([l,l'-Biphenyl]-4-yl)-3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)propan-l- one (33)

General Procedure B

1 .25 eq. B₂cat₂, DMAc

blue LEDs.14 h

fie" pinacol Et₃N, 1 h

Activation: Fenbufen (1.0 g, 3.93 mmol) was coupled with N-hydroxyphthalimide according to General Procedure A. The crude product was filtered quickly through a short column (~5 cm silica gel). After concentrated to a -15 mL solution, 30 mL of MeOH was added. The precipitate was collected by filtration and washed with 10 mL of MeOH to afford the corresponding NHPI ester 87 (1.42 g, 91%) as a light pink solid. Note: The product is not stable on silica gel. m.p.: 165 - 168 °C (DCM/MeOH)

TLC: Rf = 0.50 (1 : 1 petroleum ether 40-60:EtOAc) ^lU NMR (400 MHz, CDC1₃) δ 8.00 (d, / = 8.1 Hz, 2H, Ar-H), 7.85 - 7.79 (m, 2H, Ar- H), 7.75 - 7.67 (m, 2H, Ar-H), 7.62 (d, / = 8.1 Hz, 2H, Ar-H), 7.55 (d, / = 7.4 Hz, 2H, Ar-H), 7.39 (t, / = 7.5 Hz, 2H, Ar-H), 7.33 (t, / = 7.4 Hz, 1H, Ar-H), 3.43 (t, / = 6.9 Hz, 2H, CH₂), 3.10 (t, J = 6.9 Hz, 2H, CH₂) ppm ¹³C NMR (101 MHz, CDC ) δ 196.0 (C=0), 169.3 (C=0), 161.8 (C=0), 146.1 (CAT), 139.7 (CAT), 134.8 (CAT), 134.7 (HCAT), 128.9 (HCAT), 128.9 (CAT), 128.7 (HCAT), 128.3 (HCAT), 127.3 (HCAT), 127.2 (HCAT), 124.0 (HCAT), 33.2 (CH₂), 25.5 (CH₂) ppm

HRMS (m/z): (ESI) calc'd for C₂4Hi₇NNa0₅ [M+Na]⁺: 422.0999, found: 422.1004

IR (neat) m_ax: 2920, 1741, 1682, 1360, 1186, 1083, 877 and 765 cm^"1 Borylation: NHPI ester 87 (52 mg, 0.13 mmol) was borylated according to General Procedure B. The crude reside was purified by flash column chromatography (Si0₂; 4: 1 petroleum ether 40-60:Et₂O) to afford boronic ester 33 (13 mg, 30%) as a colorless oil.

TLC: Rf = 0.63 (1 : 1 petroleum ether 40-60:EtOAc) ¾ NMR (400 MHz, CDCb) δ 8.08 (d, 7 = 8.3 Hz, 2H, Ar-H), 7.70 (d, / = 8.3 Hz, 2H, Ar-H), 7.65 (d, / = 7.6 Hz, 2H, Ar-H), 7.50 (t, / = 7.4 Hz, 2H, Ar-H), 7.42 (t, / = 7.3 Hz, 1H, Ar-H), 3.21 (t, / = 7.0 Hz, 2H, CH₂), 1.29 (s, 12H, 2xOC(CH₃)₂), 1.13 (t, / = 7.0 Hz, 2H, CH₂Bpin) ppm

¹³C NMR (101 MHz, CDCb) δ 200.1 (C=0), 145.4 (CAT), 140.0 (CAT), 135.7 (CAT), 128.9 (HCAT), 128.5 (HCAT), 128.1 (HCAT), 127.2 (HCAT), 127.1 (HCAT), 83.1 (OC(CH₃)₂), 33.7 (CH₂), 24.8 (OC(CH₃)₂) ppm

HRMS (m/z) (ESI) calc'd for C₂iH₂₅BNa0₃ [M+Na]⁺: 359.1792, found: 359.1788 IR (neat) max: 2972, 1745, 1679, 1369, 1313, 1221, 1137, 1074, 966 and 763 cm^"1 (4-Chlorophenyl)(5-methoxy-2-methyl-3-((4,4,5,5-tetramethyl-l,3,2- dioxaborolan-2-yl)methyl)-lH-indol-l-yl)methanone (34)

Activation: NHPI ester 88 was prepared according to a known procedure. Borylation: NHPI ester 88 (67 mg, 0.13 mmol) was borylated according to General Procedure B. The crude reside was purified by flash column chromatography (Si0₂; 95:5 pentane: acetone) to afford boronic ester 34 (28 mg, 47%) a colorless oil.

TLC: Rf = 0.31 (70:30 pentane:Et₂0) ^lU NMR (400 MHz, CDC1₃) δ 7.64 (d, / = 8.6 Hz, 2H, ArH), 7.45 (d, / = 7.6 Hz, 2H, ArH), 6.93 (d, / = 9.0 Hz, 2H, ArH), 6.65 (dd, / = 9.0, 2.5 Hz, 1H, ArH), 3.84 (s, 3H, OCH3), 2.29 (s, 3H, CH₃), 2.18 (s, 2H, CH₂Bpin), 1.23 (s, 12H, C(CH₃)₂) ppm

¹³C NMR (126 MHz, CDC ) δ 168.3 (C=0), 156.0 (ArC), 138.8 (ArC), 134.7 (ArC), 133.2 (ArC), 132.0 (ArC), 131.2 (ArCH), 131.1 (ArC), 129.1 (ArCH), 1 16.7 (ArC), 115.0 (ArCH), 111.3 (ArCH), 101.7 (ArCH), 83.7 (C(CH₃)₂), 55.8 (OCH₃), 24.9 (C(CH₃)₂), 13.8 (CH₃) ppm

HRMS (m/z): (ESI) calc'd for C₂4H₂7BClNNa0₄ [M+Na]⁺: 462.1618, found:

462.1618

IR (neat) m_ax: 2977, 1676, 1476, 1454, 1321, 1222, 1140, 1088, 1061, 846, 732 cm^"1 (15,25,4aR,4bR,75,9aR,105,10aR)-l-Methyl-8-methylene-13-oxo-10-(4,4,5,5- tetramethyl-l,3,2-dioxaborolan-2-yl)-l,2,5,6,8,9,10,10a-octahydro-4a,l- (epoxymethano)-7,9a-methanobenzo[a]azulene-2,7(4bH)-diyl diacetate (35)

from gibberellic ^acid

Activation: To a solution of Gibberellic acid (346 mg, 1 mmol, 1.0 eq.), acetic anhydride (1.2 g, 12 mmol, 12.0 eq.) and DMAP (12 mg, 0.1 mmol, 0.1 eq) in anhydrous DCM (10 mL) at room temperature was added pyridine (1.6 g, 20 mmol, 20.0 eq.). After the addition, the mixture was allowed to stir for 48 h at room temperature before addition of 10 mL of water. After extraction with DCM (10 mLx2), the organic phase was dried over MgS0₄, filtered and concentrated under reduced pressure to give a colourless oil (450 mg). The crude was used without further purification and was coupled with N-hydroxyphthalimide according to General Procedure A. The crude residue was purified by flash column chromatography (S1O2; 2: 1 petroleum ether 40-60:EtOAc) to afford the corresponding NHPI ester 89 (390 mg, 68%) as a colorless oil. m.p.: 172 - 175 °C

TLC: R_f = 0.60 (1: 1 petroleum ether 40-60:EtOAc)

¾ NMR (400 MHz, CDC1₃) δ 7.85 - 7.80 (m, 2H, Ar-H), 7.76 - 7.72 (m, 2H, Ar-H), 6.32 (d, / = 9.3 Hz, 1H, =CH-), 5.83 (dd, / = 9.3, 3.8 Hz, 1H, =CH-), 5.30 (d, / = 3.8 Hz, 1H, CH-OAc), 5.18 (s, 1H, =CH₂), 5.02 (s, 1H, =CH₂), 3.32 (d, / = 11.1 Hz, 1H), 3.07 (d, / = 11.1 Hz, 1H), 2.83 (dt, / = 15.0, 3.1 Hz, 1H), 2.46 - 2.35 (m, 3H), 2.17 (d, / = 15.0 Hz, 1H), 2.06 - 1.94 (m, 8H), 1.80 - 1.63 (m, 2H), 1.24 (s, 3H, CH₃) ppm ¹³C NMR (101 MHz, CDC1₃) δ 176.4 (C=0), 169.9 (C=0), 168.5 (C=0), 161.5 (C=0), 153.0 (C=0), 134.9 (CH), 133.9 (CH), 129.3 (CH), 128.8 (C), 124.1 (CH), 108.6 (=CH₂), 89.6 (C), 83.8 (C), 70.0, 54.0, 52.1 (C), 51.4 (C), 51.3, 48.0, 42.2 (CH₂), 39.7 (CH₂), 36.1 (CH₂), 21.9, 20.7, 16.9 (CH₂), 14.3 ppm HRMS (m/z) (ESI) calc'd for C₃iH₂₉NNaOio [M+Na]⁺: 598.1684, found: 598.1686

IR (solid state) m_ax: 2948, 1780, 1740, 1369, 1227, 1019, 972, 911 and 730 cm^"1

[α]£⁴: +132 (c = 0.5, CHC )

Borylation: NHPI ester 89 (75 mg, 0.13 mmol) was borylated according to General Procedure B. The crude reside was purified by flash column chromatography (Si0₂; 90: 10 pentane: acetone) to afford boronic ester 35 (16 mg, 24%), which co-eluted with the corresponding H-atom abstraction product 36 (12 mg, 25%), as a colorless oil.

TLC: Rf = 0.31 (80:20 pentane: acetone) ^lU NMR (400 MHz, CDC ) δ 6.25 (d, / = 9.3 Hz, 1H, C=CH), 5.69 (dd, / = 9.3, 3.8 Hz, 1H, C=CH), 5.19 (dd, / = 3.7 Hz, 1H, CHOAc), 5.01 (d, / = 2.1 Hz, 1H, =CH₂), 4.85 (d, / = 2.0 Hz, 1H, =CH₂), 2.89 (d, / = 12.2 Hz, 1H), 2.35 (dt, / = 14.8, 3.1 Hz, 1H), 2.31 - 2.19 (m, 1H), 2.11 - 2.03 (m, 3H), 1.98 (s, 3H, OAc), 1.90 - 1.82 (m, 4H), 1.70 - 1.60 (m, 2H), 1.55 - 1.46 (m, 1H), 1.29 (d, / = 12.2 Hz, 1H), 1.14 (s, 12H, 2xOC(CH₃)₂), 1.02 (s, 3H, CH₃) ppm

¹³C NMR (101 MHz, CDCB) δ 177.6 (C=0), 169.9 (C=0), 169.8 (C=0), 155.2 (C=CH₂), 135.1 (CH), 128.6 (CH), 107.4 (C=CH₂), 91.4 (C), 84.4 (C), 83.8 (OC(CH₃)₂), 70.5 (CHOAc), 53.4 (CH), 52.5 (C), 51.6 (CH), 51.0 (C), 44.7 (CH₂), 40.6 (CH₂), 36.7 (CH₂), 25.2 (OC(CH₃)₂), 24.7 (OC(CH₃)₂), 22.0 (0₂CCH₃), 20.7 (0₂CCH₃), 16.8 (CH₂), 15.0 (CH₃) ppm

HRMS (m/z): (ESI) calc'd for C₂8H₃₇BNa08 [M+Na]⁺: 535.2479, found: 535.2476 IR (neat) m_ax: 2978, 1769, 1736, 1370, 1228, 1141, 1015, 970, 892 and 730 cm^"1 [α]£⁴: -204 (c = 0.2, CHCb) (15,25,4aR,4bR,75,9aR,10aR)-l-Methyl-8-methylene-13-oxo-l,2,5,6,8,9,10,10a- octahydro-4a,l-(epoxymethano)-7,9a-methanobenzo[a]azulene-2,7(4bH)-diyl diacetate (36) m.p.: 193 - 195 °C ¾ NMR (400 MHz, CDC1₃) δ 6.40 (d, / = 9.2 Hz, 1H, C=CH), 5.86 (dd, / = 9.3, 3.8 Hz, 1H, C=CH), 5.34 (d, / = 3.7 Hz, 1H, CHOAc), 5.13 (s, 1H, =CH₂), 4.97 (s, 1H, =CH₂), 2.85 (dd, / = 11.2, 7.9 Hz, 1H), 2.55 (dt, / = 15.2, 3.0 Hz, 1H), 2.43 - 2.34 (m, 1H), 2.34 - 2.27 (m, 1H), 2.21 (dd, / = 10.8, 2.7 Hz, 1H), 2.12 (m, 4H), 2.05 - 1.94 (m, 5H), 1.86 - 1.78 (m, 2H), 1.75 - 1.66 (m, 2H), 1.22 (s, 3H, CH₃) ppm ¹³C NMR (101 MHz, CDC ) δ 177.5 (C=0), 169.8 (C=0), 154.9 (C=CH₂), 134.7 (CH), 128.9 (CH), 106.9 (C=CH₂), 91.6 (C), 84.9 (C), 70.4 (CHOAc), 52.3 (C), 51.0 (CH), 50.4 (CH), 48.2 (C), 46.7 (CH₂), 39.8 (CH₂), 36.8 (CH₂), 34.9 (CH₂), 22.1 (0₂CCH₃), 20.8 (0₂CCH₃), 16.5 (CH₂), 14.5 (CH₃) ppm

HRMS (m/z) (ESI) calc'd for C₂₂H₂6Na06 [M+Na]⁺: 409.1622, found: 409.1630 IR (neat) m_ax: 2939, 1774, 1735, 1369, 1227, 1157, 1019, 964, 896 and 731 cm^"1 [α ⁴: +138 (c = 0.5, CHC1₃)

Glutamic acid derived pinacol boronic ester (37)

O General Procedure B

Activation: Glutamic acid derived NHPI ester 90 was prepared according to a known procedure.

Borylation: NHPI ester 90 (66 mg, 0.13 mmol) was borylated according to General Procedure B. The crude reside was purified by flash column chromatography (Si0₂; 5: 1 petroleum ether 40-60:Εί₂Ο) to afford boronic ester 37 (44 mg, 76%) as a colorless oil.

TLC: Rf = 0.48 (3: 1 petroleum ether 40-60:EtOAc)

¾ NMR (400 MHz, CDC1₃) δ 4.85 (dd, / = 9.9, 5.1 Hz, 1H, CHCO2CH3), 3.70 (s, 3H, CO2CH3), 2.22 (dddd, / = 14.1, 8.9, 7.7, 5.1 Hz, 1H, CH₂), 1.99 (dtd, / = 14.3, 9.5, 6.6 Hz, 1H, CH₂), 1.49 (s, 18H, NBoc₂), 1.24 (s, 12H, 2xOC(CH₃)₂), 0.80 (ddd, / = 9.3, 7.0, 2.3 Hz, 2H, CH₂Bpin) ppm

¹³C NMR (101 MHz, CDC13) δ 171.4 (C=0), 152.2 (C=0), 83.0 (OC(CH₃)₂), 82.7 (OC(CH₃)₃), 59.7 (CHC0₂CH₃), 51.9 (CQ₂CH₃), 27.9 (OC(CH₃)₃), 24.8 (OC(CH₃)₂), 24.1 (CH₂) ppm

HRMS (m/z): (ESI) calc'd for C₂iH₃₈BNa0₈ [M+Na]⁺: 466.2587, found: 466.2587

IR (neat) m_ax: 2978, 1743, 1700, 1367, 1235, 1131, 849 and 781 cm^"1

[α ⁴: -24 (c = 1, CHC1₃)

(Z)-2-(Heptadec-8-en-l-yl)-4,4,5,5-tetramethyl-l,3,2-dioxaborolane (38)

O General Procedure A Q General Procedure B

^=^^oH NHPI, DIC, DMAP ^=^A_NHp| 1.25 eq. B₂cat₂, DMAc v^=^ Bpin oleic acid DCM, r.t., overnight 91 , 77% blue l_EDs,14 h 38, 90%

then pinacol Et₃N, 1 h

Activation: Oleic acid (1.0 mL, 3.15 mmol) was coupled with N-hydroxyphthalimide according to General Procedure A. The crude residue was purified by flash column chromatography (Si0₂; 60:40 pentane:DCM) to afford the corresponding NHPI ester 91 (1.04 g, 77%) as a colorless oil.

TLC: R_f = 0.28 (50:50 pentane:DCM)

¾ NMR (400 MHz, CDC1₃) δ 7.90 - 7.86 (m, 2H, phthalimide ArH), 7.80 - 7.76 (m, 2H, phthalimide ArH), 5.39 - 5.31 (m, 2H, =CH x2), 2.66 (t, / = 7.5 Hz, 2H, CH₂C=0), 2.06 - 1.97 (m, 4H, =CHCH₂ x2), 1.78 (p, J = 7.5 Hz, 2H, CH₂CHC=0), 1.47 - 1.23 (m, 20H, CH₂ xlO), 0.87 (t, / = 7.0 Hz, 3H, CH₃) ppm ¹³C NMR (101 MHz, CDC1₃) δ 169.7 (C=0), 162.1 (C=0), 134.8 (phthalimide ArCH), 130.2 (=CH), 129.8 (=CH), 129.1 (phthalimide ArC), 124.1 (phthalimide ArCH), 32.0 (CH₂), 31.1 ( H2C=0), 29.9 (CH₂), 29.8 (CH₂), 29.7 (CH₂), 29.5 (CH₂), 29.4 (CH₂), 29.2 (CH₂ x2), 28.9 (CH₂), 27.4 (=CHCH₂), 27.3 (=CHCH₂), 24.8 (CH₂CH₂C=0), 22.8 (CH₂), 14.2 (CH₃) ppm

All data matched that reported in the literature.

Borylation: NHPI ester 91 (57 mg, 0.13 mmol) was borylated according to General Procedure B. The crude reside was purified by flash column chromatography (Si0₂; 95:5 pentane:Et₂0) to afford boronic ester 38 (44 mg, 90%) as colorless oil. TLC: Rf = 0.55 (95:5 pentane:Et₂0)

¾ NMR (400 MHz, CDCI3) δ 5.39 - 5.30 (m, 2H, =CH x2), 2.05 - 1.98 (m, 4H, =CHCH₂ x2), 1.43 - 1.21 (m, 22Η, CH₂ xl l), 1.24 (s, 12H, C(CH₃)₂), 0.88 (t, / = 7.0 Hz, 3H, CH₃), 0.76 (t, / = 7.7 Hz, 2H, CH₂Bpin) ppm

¹³C NMR (101 MHz, CDC1₃) δ 130.1 (=CH), 130.0 (=CH), 83.0 (C(CH₃)₂), 32.6 (CH₂), 32.1 (CH₂), 29.9 (CH₂ x2), 29.9 (CH₂), 29.7 (CH₂), 29.5 (CH₂ x2), 29.4 (CH₂), 27.4 (=CH H₂), 27.4 (=CHCH₂), 25.0 (C( H₃)₂), 24.2 (CH₂), 22.8 (CH₂), 14.3 (CH₃) ppm

HRMS (m/z): (ESI) calc'd for C₂₃H₄6B0₂ [M+H]⁺: 365.3590, found: 365.3589

IR (neat) m_ax: 2978, 2923, 2854, 1377, 1371, 1316, 1146, 958 and 847 cm^"1

l,2-Bis(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)ethane (39)

Activation: Succinic acid (500 mg, 4.23 mmol) was coupled with N- hydroxyphthalimide according to General Procedure A with all reagents doubled in quantity. The crude residue was purified by flash column chromatography (Si0₂; 98:2 DCM:Et₂0) to afford the corresponding NHPI ester 92 (1.02 g, 59%) as an amorphous white solid.

TLC: R_f = 0.21 (98:2 DCM:Et₂0)

¾ NMR (400 MHz, DMSO-J6) δ 8.00 - 7.93 (m, 8H, phthalimide ArH), 3.21 (s, 4H, CH₂C=0) ppm

¹³C NMR (101 MHz, DMSO-J6) δ 168.8 (C=0), 161.6 (C=0), 135.5 (phthalimide ArCH), 128.1 (phthalimide ArC), 124.0 (phthalimide ArCH), 25.3 (CH₂) ppm

HRMS (m/z): (ESI) calc'd for C₂₀Hi₂N₂NaO₈ [M+Na]⁺: 431.0486, found: 431.0484

IR (solid state) m_ax: 3058, 2939, 1788, 1732, 1467, 1375, 1301, 1186, 1140, 1076, 972, 882, 789, 728, 694, 601 and 519 cm^"1

Borylation: NHPI ester 92 (53 mg, 0.13 mmol) was borylated according to General Procedure B with double the amount of B₂cat₂. The crude reside was purified by flash column chromatography (Si0₂; 100:0→ 90: 10 pentane:Et₂0) to afford boronic ester 39 (15 mg, 41%) as a colorless oil. TLC: R_f = 0.30 (80:20 pentane:Et₂0)

¾ NMR (400 MHz, CDC1₃) δ 1.23 (s, 24H, 8xCH₃), 0.84 (s, 4H, 2xCH₂) ppm

¹³C NMR (101 MHz, CDCI3) δ 83.0 (4xOC(CH₃)₂), 25.0 (8xCH₃), 4.6 (2xCH₂) ppm

All data matched that reported in the literature.

l-((lR,35)-2,2-Dimethyl-3-((4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)methyl) cyclobutyl)ethan-l-one (40)

c/s-pinonic acid ' ⁷ ^ p_inaCol Et₃N, 1 h , 29%

Activation: ds-Pinonic acid (1.0 g, 5.42 mmol) was coupled with N- hydroxyphthalimide according to General Procedure A. The crude residue was purified by flash column chromatography (S1O2; 3: 1 petroleum ether 40-60:EtOAc) to afford the corresponding NHPI ester 93 (1.32 g, 74%) as a white solid. m.p.: 88 - 90 °C

TLC: Rf-= 0.23 (3: 1 petroleum ethenEtOAc) ¾ NMR (400 MHz, CDC1₃) δ 7.82 - 7.77 (m, 2H, Ar-H), 7.74 - 7.69 (m, 2H, Ar-H), 2.85 (dd, / = 10.1, 7.6 Hz, 1H, CH), 2.67 - 2.50 (m, 2H, CH₂), 2.43 (dtd, / = 10.4, 8.4, 6.8 Hz, 1H, CH), 2.13 - 1.89 (m, 5H, CH₂ + CH₃), 1.30 (s, 3H, CH₃), 0.88 (s, 3H, CH₃) ppm

¹³C NMR (101 MHz, CDC1₃) <S 207.0 (C=0), 168.6 (C=0), 161.8 (C=0), 134.7 (HCAT), 128.8 (CAT), 123.9 (HCAT), 53.9 (CH), 43.3 (C), 37.8 (CH), 31.8 (CH₂), 30.1 (CH₃), 30.0 (CH₃), 22.9 (CH₂), 17.2 (CH₃) ppm

HRMS (m/z): (ESI) calc'd for Ci₈Hi₉NNa0₅ [M+Na]⁺: 352.1155, found: 352.1145

IR (solid state) m_ax: 2949, 1785, 1739, 1701, 1356, 1184, 1060, 968 and 876 cm^"1

Borylation: NHPI ester 93 (43 mg, 0.13 mmol) was borylated according to General Procedure B. The crude reside was purified by flash column chromatography (Si0₂; 10: 1 petroleum ether 40-60:Et₂O) to afford boronic ester 40 (10 mg, 29%) as a colorless oil.

TLC: Rf = 0.53 (3: 1 petroleum ether 40-60:EtOAc)

¾ MR (400 MHz, CDC1₃) ^ 2.73 (dd, / = 10.0, 7.7 Hz, 1H, CH), 2.12 - 1.99 (m, 1H, CH), 1.95 (s, 3H, 0=CCH₃), 1.87 - 1.74 (m, 2H, CH₂), 1.20 (s, 3H, CH₃), 1.16 (s, 12H, 2xOC(CH₃)₂), 0.74 (s, 3H, CH₃), 0.71 - 0.60 (m, 2H, CH₂Bpin).

¹³C NMR (76 MHz, CDC1₃) δ 208.3 (C=0), 83.0 (OC(CH₃)₂), 54.7 (CH), 44.1 (C), 38.1 (CH), 30.1 (CH₃), 30.0 (CH₃), 25.2 (CH₂), 24.9 (OC(CH₃)₂), 24.8 (OC(CH₃)₂), 17.3 (CH₃). HRMS (m/z): (ESI) calc'd for C₂₅H₂₇BNa0₃ [M+Na]⁺: 289.1948, found: 289.1945 IR (neat) max: 2975, 1705, 1369, 1317, 1145, 968 and 846 cm^"1 tert-Butyl 3-((tert-butyldimethylsilyl)oxy)-5-(4,4,5,5-tetramethyl-l,3,2- dioxaborolan-2-yl)pentanoate

⁹⁶. ^{61 %} f/ien pinacol EtaN, 1

Activation: The carboxylic acid (577 mg, 1.74 mmol) was coupled with N- hydroxyphthalimide according to General Procedure A. The crude residue was purified by flash column chromatography (Si0₂; 70:30 pentane:Et₂0) to afford the corresponding NHPI ester 96 (508 g, 61%) as a white solid.

¾ NMR (400 MHz, CDC1₃) δ 7.91 - 7.87 (phthalimde ArH), 7.81 - 7.76 (phthalimide ArH), 4.22 (p, / = 6.7 Hz, CHO), 2.76 (t, J = 1.9 Hz, 2H, CH₂C=0), 2.48 (dd, / = 14.9, 5.6 Hz, 1H, C *tP =0), 2.35 (dd, / = 14.9, 6.9 Hz, 1H, CffH^O), 2.10 - 2.01 (m, 1Η, CM¹³), 1.98 - 1.88 (m, 1Η, CffH¹³), 1.45 (s, 9Η, C(CH₃)³), 0.90 (s, 9H, SiC(CH₃)₃), 0.12 (s, 3H, SiCH₃), 0.10 (s, 3H, SiCH₃) ppm

Borylation: NHPI ester 96 (64 mg, 0.13 mmol) was borylated according to General Procedure B. The crude reside was purified by flash column chromatography (Si0₂; 95:5 pentane:Et₂0) to afford boronic ester 40 (43 mg, 77%) as a colorless oil.

TLC: Rf = 0.26 (90: 10 pentane:Et₂0)

¾ NMR (400 MHz, CDC1₃) δ 4.03 (p, / = 5.9 Hz, 1H, CHO), 2.33 (d, / = 6.3 Hz, 2H, CH₂C=0), 1.64 - 1.51 (m, 2H, CH₂), 1.43 (s, 9H, C(CH₃)₃), 1.23 (s, 12H, C(CH₃)₂), 0.86 (s, 9H, SiC(CH₃)₃), 0.82 - 0.72 (2H, CH₂Bpin), 0.06 (s, 3H, SiCH₃), 0.04 (s, 3H, SiCH₃) ppm

2.1.5 Radical Cyclization

2-(Cyclopentylmethyl)-4,4,5,5-tetramethyl-l,3,2-dioxaborolane (53) and 2-(Hex- 5-en-l-yl)-4,4,5,5-tetramethyl-l,3,2-dioxaborolane (54)

General Procedure A General Procedure B

52, 67% 53, 31 % 54, ₄6% Activation: The carboxylic acid (150 mg, 1.17 mmol) was coupled with N- hydroxyphthalimide according to General Procedure A. The crude residue was purified by flash column chromatography (S1O2; 90: 10 hexane:acetone) to afford the corresponding NHPI ester 52 (215 mg, 67%) as a colorless oil.

TLC: Rf = 0.27 (hexane:acetone 80:20) ¾ NMR: (400 MHz, CDC1₃) δ 7.88 (m, 2H, 2xAr-H), 7.78 (m, 2H, 2xAr-H), 5.81 (ddt, / = 17.0, 10.2, 6.7 Hz, 1H), 5.04 (ddt, / = 17.0, 2.2, 1.7 Hz, 1H), 4.98 (ddt, / = 10.2, 2.2, 1.2 Hz, 1H), 2.67 (t, / = 7.4 Hz, 2H, CH2CO2R), 2.12 (dddt, / = 7.4, 6.7, 1.7, 1.2 Hz, 2H, CH2(CH2)3C0₂R), 1.81 (app. p, J^app- = 7.4 Hz, 2H, CH2CH2CO2R), 1.55 (app. p, J^app- = 7.4 Hz, 2H, CH^O^CChR) ppm ¹³C NMR: (101 MHz, CDCI3) δ 169.6 (C0₂R), 162.1 (2xCO), 138.2 (H₂CCHR), 134.9 (2XHCAT), 129.1 (2XCAT), 124.1 (2XHCAT), 115.2 (H₂CCHR), 33.3 (CH₂(CH₂)3C0₂R), 31.0 (CH2CO2R), 28.1 (CH2(CH₂)2C0₂R), 24.2 (CH₂CH₂C0₂R) ppm

HRMS (m/z): (ESI) calc'd for Ci₅Hi₅NNa0₄ [M+Na]⁺: 296.0893, found: 296.0883

IR (neat) m_ax: 3076, 2934, 2865, 1815, 1787, 1738, 1467, 1362, 1185, 1081, and 877 cm^"1

Borylation: NHPI ester 52 (36 mg, 0.13 mmol) was borylated according to General Procedure B. The crude reside was purified by flash column chromatography (Si0₂; 100:0→ 90:10 pentane:Et₂0) to afford a 57:43 mixture of lineancyclized boronic esters 54 and 53 (21 mg, 77%) as a colorless oil. Note: Product volatile! TLC: R_f = 0.55 (pentane:Et₂0 95:5) Linear product (54):

¾ NMR: (400 MHz, CDCb) δ 5.81 (ddt, / = 17.1, 10.1, 6.6 Hz, 1H, H₂CCHR), 4.98 (d, / = 17.1 Hz, 1H), 4.91 (d, / = 10.1 Hz, 1H), 2.04 (td, / = 7.0, 6.6 Hz, 2H, H2CCHCH2), 1.45 - 1.34 (m, 4H, 2xCH₂), 1.24 (s, 12H, 4xCH₃), 0.77 (t, J = 7.3 Hz, 2H, CH₂Bpin) ppm

¹³C NMR: (101 MHz, CDCb) δ 139.3 (H₂CCHR), 114.2 (H₂CCHR), 83.0 (2xOC(CH₃)₂), 33.7 (CH₂(CH₂)₃Bpin), 31.8 (CH₂), 25.0 (4xCH₃), 23.7 (CH₂) ppm

All data matched that reported in the literature.

Cyclized product (53) ¾ NMR: (400 MHz, CDCb) δ 1.95 (m, 1H, CHCH₂Bpin), 1.76 (m, 2H), 1.60 (m, 2H), 1.50 (m, 2H), 1.05 (m, 2H), 0.83 (d, / = 7.4 Hz, 2H, CH₂Bpin)

¹³C NMR: (101 MHz, CDCb) δ 82.9 (2xOC(CH₃)₂), 36.3 (CHCH₂Bpin), 35.2 ((CH₂)₂CHCH₂Bpin), 25.3 ((CH₂CH2)2CHCH₂Bpin), 25.0 (4xCH₃) ppm

All data matched that reported in the literature.

Claims

1. A method for converting a carboxylic acid, the method comprising using a diboron reagent to convert a carboxylic acid or imide ester derivative of a carboxylic acid to a boronic ester.

2. A method for converting a carboxylic acid, the method comprising, providing an imide ester of a carboxylic acid, and treating the imide ester with a diboron reagent, thereby forming a boronic ester.

3. A method as claimed in either claim 1 or claim 2, wherein the diboron reagent is selected from bis(catecholato)diboron, B₂(OH)4 or a mixture thereof.

4. A method as claimed in claim 3, wherein the diboron reagent further comprises catechol.

5. A method as claimed in any one of the preceding claims, wherein the diboron reagent comprises bis(catecholato)diboron and/or B₂(OH)₄ in the presence of catechol

6. A method as claimed in either claim 4 or claim 5, wherein catechol is present in 0.1 to 0.9 equivalents.

7. A method as claimed in any one of the preceding claims wherein the diboron reagent is present in 1.0 to 2.0 equivalents, preferably 1.1 to 2.0 equivalents.

8. A method as claimed in any one of the preceding claims, wherein the imide ester is a phthalimide ester, preferably a phthalimide ester derived from N- hydroxyphthalimide or halogen- substituted N-hydroxyphthalimide, more preferably N-hydroxytetrachlorophthalimide .

9. A method as claimed in any one of the preceding claims, wherein providing an imide ester comprises a step of reacting an N-hydroxyimide with the carboxylic acid, preferably esterifying a N-hydroxyphthalimide or halogen- substituted N- hydroxyphthalimide, more preferably N-hydroxytetrachlorophthalimide with the carboxylic acid.

10. A method as claimed in any one of the preceding claims, further comprising a subsequent step of converting the boronic ester produced by the method into another boronic ester.

11. A method as claimed in claim 10, wherein converting the boronic ester comprises ligand exchange of the boronic ester, preferably with a ligand composition comprising pinacol and/or N-methyliminodiacetic acid (MID A).

12. A method as claimed in any one of the preceding claims, wherein treating the imide ester with the diboron reagent is conducted under illumination.

13. A method as claimed in claim 12, wherein illumination is with light having a component with a wavelength in the range 410 nm to 480 nm.

14. A method as claimed in any one of the preceding claims, wherein the method is conducted in a solvent, preferably an amide solvent, more preferably an amide solvent selected from DMAc, DMF, DMPU, DMI, NMP and tetramethylurea.

15. A method as claimed in any one of the preceding claims, wherein the method is conducted in the presence of an additive, preferably selected from one or more of 4- methoxypyridine, DMAP, pyridine, DABCO, DBU, quinuclidine, TMG, TBD, MTBD, 2-picoline, 4-picoline, 3-picoline, imidazole, K2CO3, AcOH, triethylamine, 4- cyanopyridine, and 4-phenylpyridine.

16. A method as claimed in claim 15, wherein there is no illumination other than, optionally, ambient light.

17. A method for converting a carboxylic acid, the method comprising, providing a phthalimide ester of a carboxylic acid, the phthalimide ester being a derivative of N-hydroxyphthalimide or N-hydroxytetrachlorophthalimide, and treating the phthalimide ester with a diboron reagent selected from

bis(catecholato)diboron and/or B₂(OH)4 and catechol, thereby forming a boronic ester of the carboxylic acid.

18. A method as claimed in claim 17, further comprising converting the boronic ester by ligand exchange of the boronic ester, preferably by treatment with a ligand composition comprising pinacol and/or N-methyliminodiacetic acid (MID A).

19. A method of preparing a boronic acid or a boronic ester, the method comprising the capture of an alkyl radical with a diboron reagent.