CN112125803B - Preparation of homoallylic alcohol compound, synthetic method and application thereof - Google Patents

Preparation of homoallylic alcohol compound, synthetic method and application thereof Download PDF

Info

Publication number
CN112125803B
CN112125803B CN202010985993.8A CN202010985993A CN112125803B CN 112125803 B CN112125803 B CN 112125803B CN 202010985993 A CN202010985993 A CN 202010985993A CN 112125803 B CN112125803 B CN 112125803B
Authority
CN
China
Prior art keywords
alcohol compound
nmr
cdcl3
homoallylic
aldehyde
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN202010985993.8A
Other languages
Chinese (zh)
Other versions
CN112125803A (en
Inventor
石磊
厉熙宇
李富盛
林爽杰
陈昱清
史彩哲
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Dalian University of Technology
Original Assignee
Dalian University of Technology
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Dalian University of Technology filed Critical Dalian University of Technology
Priority to CN202010985993.8A priority Critical patent/CN112125803B/en
Publication of CN112125803A publication Critical patent/CN112125803A/en
Application granted granted Critical
Publication of CN112125803B publication Critical patent/CN112125803B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
    • C07C69/73—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
    • C07C69/732—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids of unsaturated hydroxy carboxylic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
    • C07C29/36—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring increasing the number of carbon atoms by reactions with formation of hydroxy groups, which may occur via intermediates being derivatives of hydroxy, e.g. O-metal
    • C07C29/38—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring increasing the number of carbon atoms by reactions with formation of hydroxy groups, which may occur via intermediates being derivatives of hydroxy, e.g. O-metal by reaction with aldehydes or ketones
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C33/00—Unsaturated compounds having hydroxy or O-metal groups bound to acyclic carbon atoms
    • C07C33/40—Halogenated unsaturated alcohols
    • C07C33/46—Halogenated unsaturated alcohols containing only six-membered aromatic rings as cyclic parts
    • C07C33/48—Halogenated unsaturated alcohols containing only six-membered aromatic rings as cyclic parts with unsaturation outside the aromatic rings
    • C07C33/483—Monocyclic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
    • C07C41/01—Preparation of ethers
    • C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
    • C07C41/30—Preparation of ethers by reactions not forming ether-oxygen bonds by increasing the number of carbon atoms, e.g. by oligomerisation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C43/00—Ethers; Compounds having groups, groups or groups
    • C07C43/02—Ethers
    • C07C43/03—Ethers having all ether-oxygen atoms bound to acyclic carbon atoms
    • C07C43/14—Unsaturated ethers
    • C07C43/178—Unsaturated ethers containing hydroxy or O-metal groups
    • C07C43/1787—Unsaturated ethers containing hydroxy or O-metal groups containing six-membered aromatic rings and having unsaturation outside the aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
    • C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
    • C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D307/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
    • C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D309/10—Oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
    • C07D333/54—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
    • C07D333/60—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J17/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, having an oxygen-containing hetero ring not condensed with the cyclopenta(a)hydrophenanthrene skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
    • C07J9/005—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane containing a carboxylic function directly attached or attached by a chain containing only carbon atoms to the cyclopenta[a]hydrophenanthrene skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/02—Systems containing only non-condensed rings with a three-membered ring

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Steroid Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

The invention provides a homoallylic alcohol compound, a synthetic method and application thereof, belonging to the field of organic chemistry. Under the protection of inert gas at room temperature and in the presence of an organic photosensitizer, a titanium catalyst and an electron donor, aldehyde or ketone reacts with the 1, 3-butadiene derivative and halogenated alkane under the irradiation of blue light to obtain the homoallyl alcohol compound with high selectivity. The method has the advantages of mild reaction conditions, short reaction steps, simple post-treatment, and high stereoselectivity and regional selection of reaction products. Meanwhile, the method can be used for derivatization of natural products.

Description

Preparation of homoallylic alcohol compound, synthetic method and application thereof
Technical Field
The invention belongs to the field of organic synthesis, and relates to a homoallyl alcohol compound, a synthesis method and application thereof.
Background
Homoallylic compounds are important components in the synthesis of various drugs and natural substances with biological activity. The addition of allyl metal complexes to the carbonyl group is one of the most efficient methods for obtaining homoallyl alcohols, which has prompted the rapid development of synthetic and pharmaceutical chemistry over the last decades. However, the preparation process which relies on preactivated allylhalohydrocarbons and stoichiometric amounts of metal reducing agents is cumbersome and uneconomical, which limits its use. Therefore, the simple, economical and environment-friendly synthetic method of the homoallylic alcohol compound is developed, and the homoallylic alcohol compound is applied to the synthesis of natural substances with biological activity, and has great promotion effect on synthetic chemistry and pharmaceutical chemistry.
Disclosure of Invention
The invention provides a homoallylic alcohol compound, a synthetic method and application thereof. Under the conditions of room temperature and inert gas protection, illumination, organic photosensitizer, titanium catalyst and electron donor, the halogenated alkane, the 1, 3-butadiene derivative and aldehyde or ketone react to obtain the homoallyl alcohol compound with high selectivity.
The technical scheme adopted by the invention is as follows:
a homoallylic alcohol compound has the following structure:
Figure BDA0002689245700000011
wherein R is1、R2、R4、R5、R6And R7Each independently selected from hydrogen, C1-C8 alkyl, phenyl, substituted phenyl, naphthyl, benzyl, or heterocyclyl; the substituent in the substituted phenyl is selected from halogen, C1-C3 alkyl, C1-C3 alkoxy, hydroxyl, C1-C3 alkoxycarbonyl and amino; r3Is C3-C9 alkyl.
The invention also provides a synthetic method of the homoallylic alcohol compound, and the synthetic route is as follows:
Figure BDA0002689245700000021
the method comprises the following steps: under the conditions of room temperature and inert gas protection, illumination, organic photosensitizer, titanium catalyst and electron donor, halogenated alkane 1 reacts with 1, 3-butadiene derivative 2 and aldehyde or ketone 3 in a solvent to obtain a homoallylic alcohol compound 4; wherein R is1、R2、R3、R4、R5，R6，R7Substituent andas in claim 1.
The organic photosensitizer may be 4 CzIPN.
The titanium catalyst may be titanocene dichloride (Cp)2TiCl2)。
The electron donor may be diethyl 2, 6-dimethyl-1, 4-dihydro-3, 5-pyridinedicarboxylate (HE).
The molar ratio of the halogenated alkane 1, the 1, 3-butadiene derivative 2, the aldehyde or ketone 3, the organic photosensitizer, the titanium catalyst and the HE is 2.0:2.0:1.0:0.01:0.05: 2.0.
The solvent is Tetrahydrofuran (THF).
Based on homoallylation of various compounds and high yield derivatization of natural active substances (such as lithocholic acid and estrone), the method of the invention can be applied to derivatization of natural substances with biological activity, and has a promoting effect on the development of synthetic chemistry and pharmaceutical chemistry.
The method has the advantages of mild reaction conditions, short reaction steps, simple post-treatment, environmental friendliness, suitability for aldehyde ketone and aldehyde ketone reaction substrates, high reaction yield and high selectivity. Meanwhile, the reaction has better application in derivatization of natural active substances.
Drawings
FIG. 1 is a schematic representation of Cp2TiCl2 quenched 4 CzIPN.
FIG. 2 schematic representation of HE quenching 4 CzIPN.
FIG. 3 schematic representation of BrCF2COOEt quenching 4 CzIPN.
Fig. 4 is a schematic diagram of a light/dark experiment.
In the figure: i0 is fluorescence intensity without addition of quencher; i is the fluorescence intensity after addition of the quencher.
Detailed Description
The technical solution of the present invention will be further described in detail with reference to the following specific examples.
Exploration test of reaction conditions: (taking the example of the reaction of 1a, 1, 3-butadiene and 3a to give 4 a)
Typically, the reaction was carried out by reacting compound 1a (2.0mmol), compound 2(2.0mmol), compound 3a (1.0mmol), and Cp2TiCl2(0.05mmol), 4CzIPN (0.01mmol), HE (2.0mmol) and 5mL THF are mixed, and the reaction is irradiated by a 10W 450nm LED lamp for 5h at room temperature under the protection of inert gas, and a thin layer plate (TLC) monitors the complete disappearance of the raw material 3a (5 h); the solvent was dried by spin-drying and column chromatography (eluent petroleum ether/ethyl acetate 20/1) gave colorless liquid 4 a.
The reaction equation is as follows:
Figure BDA0002689245700000031
Figure BDA0002689245700000032
Figure BDA0002689245700000041
as shown in the table, the boundary conditions of the reaction were investigated, and it was found that the target product was obtained in different yields under all other possible reaction conditions. Finally, the optimal reaction conditions are determined as follows: 4CzIPN is used as photosensitizer and Cp in Tetrahydrofuran (THF) solvent under the protection of inert gas at room temperature2TiCl2As catalyst, HE as electron donor, and irradiation with 450nm LED lamp.
Example 1:
Figure BDA0002689245700000042
the experimental procedures and purification were carried out according to the search experiment. RF 0.4(EA: PE 1:3), eluent: petroleum ether/ethyl acetate 20/1, 92% yield, product was a colorless liquid.1H NMR(400MHz,CDCl3)δ7.35–7.27(m,2H),7.24–7.17(m,3H),5.71(dt,J＝17.2,9.8Hz,1H),5.23–5.08(m,2H),4.28(q,J＝7.1Hz,2H),3.62(dt,J＝8.3,4.2Hz,1H),2.88–2.58(m,2H),2.51–2.41(m,1H),2.40–2.24(m,2H),2.01(s,1H),1.84–1.65(m,2H),1.34(t,J＝7.2Hz,3H).13C NMR(101MHz,CDCl3)δ164.08(t,J＝33.0Hz),141.62,135.77,128.35,128.29,125.84,118.55,116.57(dd,J＝249.2,248.7Hz),72.91,62.67,43.59(dd,J＝4.3,2.3Hz),36.24,35.89(t,J＝22.7Hz),32.05,13.73.19F NMR(377MHz,CDCl3)δ-101.44(dt,J＝261.5,15.0Hz,1F),-105.06(dt,J＝260.7,17.9Hz,1F).HRMS-ESI(m/z)[M+Na]+calculated for C17H22F2NaO3,335.1435,found 335.1431.
Example 2:
Figure BDA0002689245700000051
by using
Figure BDA0002689245700000052
Replacement of
Figure BDA0002689245700000053
The experimental procedures and purification were carried out according to the search experiment. RF 0.4(EA: PE 1:3), eluent: petroleum ether/ethyl acetate 20/1, 71% yield, product was a colorless liquid.1H NMR(400MHz,CDCl3)δ5.75(dt,J＝18.3,9.3Hz,1H),5.24–4.97(m,2H),4.26(q,J＝7.1Hz,2H),2.76(dd,J＝9.0,4.2Hz,1H),2.53(dq,J＝9.1,4.6Hz,1H),2.47–2.16(m,2H),1.87(s,1H),1.32(t,J＝7.1Hz,3H),1.01–0.83(m,1H),0.68–0.40(m,2H),0.37–0.10(m,2H).13C NMR(101MHz,CDCl3)δ164.13(t,J＝32.7Hz),136.55,118.19,116.15(dd,J＝251.7,248.9Hz),78.85,62.64,44.22(dd,J＝4.9,2.5Hz),35.87(t,J＝22.8Hz),15.17,13.81,3.12,2.73.19F NMR(377MHz,CDCl3)δ-101.43(dt,J＝261.5,15.0Hz,1F),-105.04(dt,J＝260.7,17.9Hz,1F).HRMS-ESI(m/z)[M+Na]+calculated for C12H18F2NaO3,271.1122,found 271.1137.
Example 3:
Figure BDA0002689245700000054
by using
Figure BDA0002689245700000055
Replacement of
Figure BDA0002689245700000056
The experimental procedures and purification were carried out according to the search experiment. RF 0.4(EA: PE 1:3), eluent: petroleum ether/ethyl acetate 20/1, 74% yield, product was a colorless liquid.1H NMR(400MHz,CDCl3)δ5.77–5.51(m,1H),5.22–5.12(m,3H),4.27(q,J＝7.1Hz,2H),4.21(dd,J＝9.0,6.5Hz,1H),2.38(ddt,J＝12.9,6.2,2.9Hz,1H),2.34–2.22(m,1H),2.21–2.07(m,1H),1.76(d,J＝1.4Hz,3H),1.73(dd,J＝3.3,1.4Hz,1H),1.69(d,J＝1.4Hz,3H),1.34(t,J＝7.2Hz,3H).13C NMR(101MHz,CDCl3)δ164.10(t,J＝32.8Hz),137.74,136.95,124.51,119.11,116.06(dd,J＝252.0,249.0Hz),69.95,62.70,44.94(dd,J＝4.7,2.7Hz),35.33(t,J＝22.9Hz),25.93,18.48,13.89.19F NMR(377MHz,CDCl3)δ-100.34(t,J＝14.8Hz),-101.04(t,J＝14.6Hz),-104.02(t,J＝18.0Hz),-104.71(t,J＝17.8Hz).HRMS-ESI(m/z)[M+Na]+calculated for C13H20F2NaO3,285.1278,found 285.1268.
Example 4:
Figure BDA0002689245700000061
by using
Figure BDA0002689245700000062
Replacement of
Figure BDA0002689245700000063
The experimental procedures and purification were carried out according to the search experiment. RF 0.4(EA: PE 1:3), eluent: petroleum ether/ethyl acetate 20/1, 77% yield, the product was a colorless liquid.1H NMR(400MHz,CDCl3)δ5.87–5.76(m,1H),5.02–4.97(m,2H),4.20(q,J＝7.1Hz,2H),3.23–3.19(m,1H),2.39–2.12(m,2H),2.02(d,J＝6.9Hz,1H),1.26(t,J＝7.2Hz,3H),0.85(s,9H).13C NMR(101MHz,CDCl3)δ165.76,164.41–163.51(m),136.87(s),117.11(s),116.07(dd,J＝251.8,248.4Hz),62.47(s),39.56(dd,J＝4.9,2.1Hz),38.99(t,J＝22.2Hz),35.84(s),26.48(s),13.71(s).19F NMR(377MHz,CDCl3)δ-100.30(t,J＝14.7Hz),-100.99(t,J＝14.7Hz),-105.79(dd,J＝20.4,17.0Hz),-106.49(dd,J＝20.6,16.9Hz).HRMS-ESI(m/z)[M+Na]+calculated for C13H22F2NaO3,287.1435,found 287.1426.
Example 5:
Figure BDA0002689245700000071
by using
Figure BDA0002689245700000072
Replacement of
Figure BDA0002689245700000073
The experimental procedures and purification were carried out according to the search experiment. RF 0.4(EA: PE 1:3), eluent: petroleum ether/ethyl acetate 15/1, 79% yield, the product was a colorless liquid.1H NMR(400MHz,CDCl3)δ7.42–7.09(m,5H),5.55(dt,J＝17.1,9.7Hz,1H),5.17–4.91(m,2H),4.48(d,J＝6.4Hz,1H),4.16(qd,J＝7.2,1.9Hz,2H),2.60(dq,J＝8.9,6.6Hz,1H),2.18(s,1H),2.15–2.02(m,2H),1.23(t,J＝7.2Hz,3H).13C NMR(101MHz,CDCl3)δ164.00(t,J＝32.8Hz),141.19,136.44,128.42,128.02,126.71,119.47,118.61–112.81(m),75.96,62.75,45.97(dd,J＝4.6,2.7Hz),35.47(t,J＝23.0Hz),13.86.19F NMR(377MHz,CDCl3)δ-100.90(t,J＝14.9Hz),-101.59(t,J＝15.0Hz),-104.48(t,J＝17.6Hz),-105.17(t,J＝17.7Hz).HRMS-ESI(m/z)[M+Na]+calculated for C15H18F2NaO3,307.1122,found 307.1118.
Example 6:
Figure BDA0002689245700000074
by using
Figure BDA0002689245700000075
Replacement of
Figure BDA0002689245700000076
The experimental procedures and purification were carried out according to the search experiment. RF 0.4(EA: PE 1:3), eluent: petroleum ether/ethyl acetate 15/1, 81% yield, product was a colorless liquid.1H NMR(400MHz,CDCl3)δ7.40–7.31(m,2H),6.34(d,J＝1.8Hz,1H),5.61(dt,J＝17.0,9.7Hz,1H),5.22–5.05(m,2H),4.54(d,J＝6.1Hz,1H),4.23(q,J＝7.2Hz,2H),2.70–2.56(m,1H),2.33–2.02(m,2H),1.29(td,J＝7.2,1.3Hz,3H).13C NMR(101MHz,CDCl3)δ164.04(t,J＝32.7Hz),143.42,140.08,136.46,125.99,119.33,115.99(dd,J＝251.9,249.3Hz),108.64,68.96,62.79,44.78(dd,J＝4.7,2.6Hz),35.25(t,J＝23.0Hz),13.80.19F NMR(377MHz,CDCl3)δ-101.04(t,J＝15.0Hz),-101.74(t,J＝15.0Hz),-104.57(t,J＝17.9Hz),-105.26(t,J＝17.9Hz).HRMS-ESI(m/z)[M+Na]+calculated for C13H16F2NaO4,297.0914found 297.0899.
Example 7:
Figure BDA0002689245700000081
by using
Figure BDA0002689245700000082
Replacement of
Figure BDA0002689245700000083
The experimental procedures and purification were carried out according to the search experiment. RF 0.4(EA: PE 1:2), eluent: petroleum ether/ethyl acetate 10/1% yield, the product being a colorless liquid.1H NMR(400MHz,CDCl3)δ5.67–5.50(m,1H),5.22–5.03(m,2H),4.23(q,J＝7.2Hz,2H),3.80–3.61(m,4H),2.53–2.35(m,1H),2.28–2.04(m,2H),1.85–1.70(m,2H),1.69–1.57(m,1H),1.42–1.33(m,1H),1.31(t,J＝7.2Hz,3H).13C NMR(101MHz,CDCl3)δ164.02(t,J＝32.7Hz),135.97,119.46,116.22(dd,J＝251.8,248.7Hz),69.76,63.36,63.34,62.66,49.07(dd,J＝5.1,2.2Hz),35.44,34.32,33.18(t,J＝22.9Hz),13.77.19F NMR(377MHz,CDCl3)δ-100.53–-101.42(m,1F),-104.73–-105.65(m,1F).HRMS-ESI(m/z)[M+Na]+calculated for C13H20F2NaO4,301.1227,found 301.1219.
Example 8:
Figure BDA0002689245700000084
by using
Figure BDA0002689245700000085
Replacement of
Figure BDA0002689245700000086
The experimental procedures and purification were carried out according to the search experiment. RF 0.4(EA: PE 1:3), eluent: petroleum ether/ethyl acetate 15/1, 62% yield, product was a colorless liquid.1H NMR(400MHz,CDCl3)δ7.11(d,J＝8.5Hz,2H),6.83(d,J＝8.6Hz,2H),5.67(dt,J＝17.0,9.9Hz,1H),5.23–5.10(m,2H),4.26(q,J＝7.2Hz,2H),3.79(s,3H),2.70–2.58(m,2H),2.49–2.35(m,2H),2.28–2.09(m,1H),1.77–1.68(m,2H),1.56(s,1H),1.33(t,J＝7.2Hz,3H),1.22(s,3H).13C NMR(101MHz,CDCl3)δ164.13(t,J＝34.2Hz),157.81,136.69,134.24,129.21,119.52,115.76(dd,J＝280.8,250.3Hz),113.89,72.98,62.69,55.25,48.08(dd,J＝4.6,2.6Hz),41.28,34.43(t,J＝22.9Hz),28.66,24.72,13.87.19F NMR(377MHz,CDCl3)δ-100.49–-101.72(m,1F),-104.39–-105.58(m,1F).HRMS-ESI(m/z)[M+Na]+calculated for C19H26F2NaO4,379.1697,found 379.1703.
Example 9:
Figure BDA0002689245700000091
by using
Figure BDA0002689245700000092
Replacement of
Figure BDA0002689245700000093
The experimental procedures and purification were carried out according to the search experiment. RF 0.4(EA: PE ═ 1:3), eluent: petroleum ether/ethyl acetate 15/1, 61% yield, the product was a colorless liquid.1H NMR(400MHz,CDCl3)δ7.35–7.25(m,4H),7.24–7.15(m,1H),5.43(dt,J＝18.4,9.5Hz,1H),5.17–5.01(m,2H),4.13(qd,J＝7.1,3.4Hz,2H),2.63–2.48(m,1H),2.33(tdd,J＝16.2,14.6,2.1Hz,1H),1.91(s,1H),1.89–1.74(m,1H),1.51(s,3H),1.21(t,J＝7.2Hz,3H).13C NMR(101MHz,CDCl3)δ164.34(t,J＝32.7Hz),144.62,136.80,128.07,127.19,125.81,119.44,116.16(dd,J＝249.4,237.7Hz),75.03,62.58,49.89(dd,J＝4.6,2.8Hz),34.24(t,J＝22.9Hz),26.85,13.81.19F NMR(377MHz,CDCl3)δ-100.07–-101.84(m,1F),-104.26–-105.78(m,1F).HRMS-ESI(m/z)[M+Na]+calculated for C16H20F2NaO3,321.1278,found 321.1281.
Example 10:
Figure BDA0002689245700000101
by using
Figure BDA0002689245700000102
Replacement of
Figure BDA0002689245700000103
The experimental procedures and purification were carried out according to the search experiment. RF 0.4(EA: PE 1:3), eluent: petroleum ether/ethyl acetate 15/1, 52% yield, the product was a colorless liquid.1H NMR(400MHz,CDCl3)δ7.89–7.77(m,1H),7.77–7.65(m,1H),7.40–7.27(m,2H),7.15(s,1H),5.69(dt,J＝17.2,9.8Hz,1H),5.30–5.19(m,2H),4.19(p,J＝7.3Hz,2H),2.78–2.65(m,1H),2.60–2.44(m,1H),2.43(s,1H),2.19–1.98(m,1H),1.68(s,3H),1.26(t,J＝7.2Hz,3H).13C NMR(101MHz,CDCl3)δ163.95(t,J＝32.8Hz),150.24,139.48,139.43,136.08,124.28,124.20,123.45,122.19,120.72,120.37,116.00(dd,J＝252.2,249.4Hz),74.76,62.67,50.15(dd,J＝4.3,3.0Hz),34.57(t,J＝23.1Hz),27.58,13.75.19F NMR(377MHz,CDCl3)δ-101.51(ddd,J＝261.1,16.7,13.4Hz,1F),-104.41(ddd,J＝260.3,19.0,15.3Hz,1F).HRMS-ESI(m/z)[M+Na]+calculated for C18H20F2NaO3S,377.0999,found 377.0999.
Example 11:
Figure BDA0002689245700000104
by using
Figure BDA0002689245700000105
Replacement of
Figure BDA0002689245700000106
The experimental procedures and purification were carried out according to the search experiment. RF 0.4(EA: PE 1:3), eluent: petroleum ether/ethyl acetate 10/1, 55% yield, the product was a colorless liquid.1H NMR(400MHz,CDCl3)δ7.39–7.26(m,7H),7.22–7.15(m,3H),5.73(dt,J＝17.3,9.7Hz,1H),5.19–5.05(m,2H),4.58(d,J＝2.3Hz,2H),3.68–3.51(m,3H),2.80(ddd,J＝13.7,9.8,5.8Hz,1H),2.65(ddd,J＝13.7,9.6,6.7Hz,1H),2.44(tt,J＝9.0,4.5Hz,1H),2.29–2.00(m,2H),1.84–1.65(m,2H),1.60(d,J＝5.1Hz,1H).13C NMR(101MHz,CDCl3)δ141.90,137.33,137.11,128.50,128.41,128.03,127.88,125.87,118.02,73.70,72.85,70.59(t,J＝32.7Hz),43.94(t,J＝3.2Hz),36.42,34.99(t,J＝22.9Hz),32.20.19F NMR(377MHz,CDCl3)δ-100.33–-101.35(m,1F),-101.45–-102.44(m,1F).HRMS-ESI(m/z)[M+Na]+calculated for C22H26F2NaO2,383.1799,found 383.1797.
Example 12:
Figure BDA0002689245700000111
by using
Figure BDA0002689245700000112
Replacement of
Figure BDA0002689245700000113
The experimental procedures and purification were carried out according to the search experiment. RF 0.4(EA: PE 1:3), eluent:petroleum ether/ethyl acetate 20/1, 59% yield, product was a colorless liquid.1H NMR(400MHz,CDCl3)δ7.29(t,J＝7.6Hz,2H),7.25–7.15(m,3H),5.87(dt,J＝56.8,3.4Hz,1H),5.72–5.55(m,1H),5.19(dd,J＝44.4,13.7Hz,2H),3.53(dd,J＝7.4,3.9Hz,1H),2.98–2.53(m,2H),2.05(h,J＝4.9,4.1Hz,1H),1.90–1.58(m,5H),1.55–1.42(m,1H).13C NMR(101MHz,CDCl3)δ141.93,137.32,128.42,125.88,119.04,117.67(t,J＝238.9Hz),77.32,77.00,76.68,73.01,49.88,36.57,32.12,32.08(t,J＝20.7Hz),23.11.HRMS-ESI(m/z)[M+Na]+calculated for C15H20F2NaO,277.1380,found 277.1384.
Example 13:
Figure BDA0002689245700000114
by using
Figure BDA0002689245700000115
Replacement of
Figure BDA0002689245700000116
The experimental procedures and purification were carried out according to the search experiment. RF 0.4(EA: PE 1:3), eluent: petroleum ether/ethyl acetate 20/1, 58% yield, product was a colorless liquid.1H NMR(400MHz,CDCl3)δ7.42–7.35(m,2H),7.33–7.27(m,3H),5.74(ddd,J＝17.2,10.3,9.3Hz,1H),5.38–5.13(m,2H),3.69–3.51(m,1H),2.98–2.69(m,2H),2.44–2.20(m,2H),2.19–2.09(m,1H),1.98–1.77(m,4H),1.53(s,9H).13C NMR(101MHz,CDCl3)δ173.11,142.13,137.66,128.43,128.34,125.75,118.62,80.22,72.63,50.05,36.52,33.27,32.13,28.07,25.88.HRMS-ESI(m/z)[M+Na]+calculated for C19H28NaO3,327.1936,found 327.1936.
Example 14:
derivatization of lithocholic acid
Lithocholic acid is a secondary bile acid, also known as cholalic acid, 3 a-dihydroxy -carboxylic acid, and is present in higher vertebrate bile. The molecular structure of the bile acid contains both hydrophilic groups and hydrophobic groups, so that the spatial configuration of the bile acid has two properties of hydrophilicity and hydrophobicity, and the bile acid has strong interfacial activity. Meanwhile, lithocholic acid has more pharmacological activities, such as: inhibiting tumor growth, selectively killing breast cancer cells, and selectively inhibiting the activity of mammalian DNA polymerase.
The steps of the derivatization of lithocholic acid in the invention are as follows:
first, reaction of lithocholic acid with p-hydroxybenzaldehyde derivatizes lithocholic acid to aldehyde:
Figure BDA0002689245700000121
and reacting the derived aldehyde with 1, 3-butadiene and ethyl difluorobromoacetate to obtain the homoallyl alcohol compound derived from lithocholic acid.
Figure BDA0002689245700000122
And (3) derivatization of lithocholic acid to obtain a homoallyl alcohol compound. RF 0.4(EA: PE 1:3), eluent: petroleum ether/ethyl acetate 5/1% yield, the product being a colorless liquid.1H NMR(400MHz,CDCl3)δ7.31(d,J＝8.5Hz,2H),7.06(d,J＝8.5Hz,2H),5.69–5.55(m,1H),5.24–5.06(m,2H),4.59(d,J＝6.0Hz,1H),4.24(q,J＝6.6,6.2Hz,2H),3.61(dt,J＝11.0,6.2Hz,1H),2.73–2.53(m,2H),2.53–2.40(m,1H),2.37–2.27(m,1H),2.25–2.09(m,2H),2.01–1.72(m,6H),1.72–1.46(m,7H),1.44–1.34(m,5H),1.34–1.23(m,7H),1.19–1.02(m,5H),0.97(d,J＝6.3Hz,3H),0.91(s,3H),0.66(s,3H).13C NMR(101MHz,CDCl3)δ172.69,163.95(t,J＝32.7Hz),150.33,138.63,136.12,128.30,127.68,121.48,119.55,115.90(dd,J＝250.3,249.5Hz),75.39,71.83,62.76,56.45,55.89,45.81(dd,J＝4.3,2.3Hz),42.73,42.02,40.37,40.12,36.36,35.79,35.33,35.32(t,J＝28.5Hz),34.52,31.32,30.89,30.46,29.07,27.13,26.37,24.17,23.33,23.06,20.78,18.27,13.84,12.03.HRMS-ESI(m/z)[M+Na]+calculated for C39H56F2NaO6681.3943, found 681.3936 example 15:
derivatization of estrone
Estrone, also known as feminone, is a white crystalline powder, soluble in ethanol and insoluble in water. Is obtained from pregnant woman urine or livestock ovary. It is the original hormone secreted by female animal ovary, has been used in clinic, is an important medical intermediate, is the intermediate of hormone ethinylestradiol for No. 1 contraceptive, and is mainly used for treating uterine hypoplasia, menstrual disorder, climacteric disturbance and the like.
The steps of the derivatization of estrone in the invention are as follows:
firstly, reacting estrone with 2- (2-bromoethyl) -1, 3-dioxane to derive estrone into an acetal compound, and hydrolyzing into aldehyde:
Figure BDA0002689245700000141
and reacting the derived aldehyde with 1, 3-butadiene and ethyl difluorobromoacetate to obtain the homoallyl alcohol compound derived from the estrone.
Figure BDA0002689245700000142
A homoallylic alcohol compound derived from estrone derivatization. RF 0.4(EA: PE 1:2), eluent: petroleum ether/ethyl acetate 10/1, 62% yield, product was a colorless liquid.1H NMR(400MHz,CDCl3)δ7.19(d,J＝8.6Hz,1H),6.70(dd,J＝8.6,2.7Hz,1H),6.63(d,J＝2.5Hz,1H),5.85(ddd,J＝17.0,10.4,8.7Hz,1H),5.29–5.16(m,2H),4.66(dt,J＝9.4,3.6Hz,1H),4.21–3.98(m,2H),2.93–2.82(m,2H),2.65–2.57(m,2H),2.55–2.45(m,1H),2.43–2.33(m,1H),2.27–1.93(m,8H),1.91–1.82(m,1H),1.65–1.44(m,7H),0.91(s,3H).13C NMR(101MHz,CDCl3)δ171.47,156.66,137.82,134.29,132.29,126.37,118.63,114.39,112.17,78.20,77.20,63.48,50.40,48.00,43.96,40.04,38.35,35.86,32.73,31.57,29.63,27.06,26.52,25.90,24.66,21.57,13.84.HRMS-ESI(m/z)[M+Na]+calculated for C27H34NaO4,445.2355,found 445.2352.
Example 16: fluorescence quenching experiments, as shown in fig. 1, 2 and 3.
In FIG. 1, the Stern-Volmer equation: f0/F＝1+Kqτ0[Q]，Kqτ0＝2032L/mol，τ0＝557ns，Kq＝3.65×109L/(mol*s)；
In FIG. 2, the Stern-Volmer equation: f0/F＝1+Kqτ0[Q]，Kqτ0＝22L/mol，τ0＝557ns，Kq＝3.95×107L/(mol*s)
In FIG. 3, the Stern-Volmer equation: f0/F＝1+Kqτ0[Q]，Kqτ0＝17L/mol，τ0＝557ns，Kq＝3.05×107L/(mol*s)。
The emission intensity of all experiments was recorded using an Edinburgh FS920 fluorescence spectrophotometer. All 4CzIPN solutions were excited at 468nm and emission intensities were collected at 500-800 nm. In a typical experiment, 4CzIPN (10)-5M) adding a proper amount of quenching agent into the THF solution, placing the solution into a spiral top 4.5cm quartz test tube, degassing by nitrogen, and collecting the emission spectrum of a sample. The results show that Cp2TiCl2HE and BrCF2CO2Et has better inhibition effect on photo-excitation of 4 CzIPN.
Example 17: light/dark experiment scheme, as shown in FIG. 4
To a solution containing 3a (250mg, 1.86mmol, 1.0 eq) according to standard procedures.
HE(945mg，3.73mmol，2.0eq.)，Cp2TiCl2(46.3g, 0.19mol, 0.1eq.), 1,3, 5-trimethoxybenzene (104.5mg, 0.62mmol, 0.33eq.) and 4CzIPN (7.3mg, 0.0093mmol, 1.0% mol) in THF were added 1, 3-butadiene derivative (3.0M in toluene, 1.25mL, 3.73mmol) and ethyl difluorobromoacetate (757mg, 480. mu.L, 3.73mmol, 2.0 eq.). The reaction mixture was stirred at room temperature under illumination by 10W 450nm LED lamp with on-off indicator. At different time points, 400 μ Ι _ of reaction mixture was collected and concentrated under vacuum. Using 1,3, 5-trimethoxybenzene as an internal standard by1H NMR calculated scoreAnd (6) analyzing the result.
Figure BDA0002689245700000151
According to the above experimental results, the reaction mechanism is as follows:
Figure BDA0002689245700000161
first, bromofluoroacetic acid ethyl ester is substituted with IrIIIThe complex is reduced to generate alkyl free radicals. The resulting alkyl radical can be rapidly added to butadiene to form allyl radical 2, which is then further reduced. At the same time, TiIVIs covered with another IrIIIReduced to TiIII. Ir of strong oxidizing agentsIVThe material is subsequently reduced to Ir by HEIIIAnd produces HE +, which can further participate in excluded electron transfer events because the coordination of Ti is already fully occupied. Final generation pyH+。TiIIIThe allyl group 2 can be captured to form a nucleophilic hydroxy-allyl titanium complex 1, which is subsequently coupled to a carbonyl group. Warp pyH+Hydrolyzing to obtain iso-alcohol, and releasing free TiIV. Finally, the catalyst is cycled in IrIIIAnd TiIVIs turned off by the SET. In view of proton coupling electron transfer process and TiIIIBoth generate carbonyl radicals and the radical-radical coupling pathway II does proceed (at least for electron deficient substrates). In general, the anti-selectivity of homoalcohols can be explained by the Ziegler-Traxler transition state. In this case, however, no non-cyclic transition state is possible.
Therefore, the method for synthesizing the homoallylic alcohol compound can be used for derivatization of natural substances, and natural products comprise natural substances with biological activity such as estrone, lithocholic acid and the like.
The foregoing is a preferred embodiment of the present invention and modifications, without departing from the principles of the invention, will be apparent to those skilled in the art and are intended to be within the scope of the invention.

Claims (5)

1. A synthetic method of a homoallyl alcohol compound is characterized in that the structural formula is as follows:
Figure FDA0003034181060000011
wherein R is1、R2、R4、R5、R6And R7Each independently selected from hydrogen, C1-C8 alkyl, phenyl, substituted phenyl, naphthyl, benzyl, or heterocyclyl; the substituent in the substituted phenyl is selected from halogen, C1-C3 alkyl, C1-C3 alkoxy, hydroxyl, C1-C3 alkoxycarbonyl and amino; r3Is C3-C9 alkyl;
the synthetic method of the homoallylic alcohol compound comprises the following synthetic route:
Figure FDA0003034181060000012
reacting halogenated alkane with 1, 3-butadiene derivative and aldehyde or ketone in a solvent at room temperature in the presence of inert gas protection, illumination, an organic photosensitizer, a titanium catalyst and an electron donor to obtain a homoallylic alcohol compound;
the organic photosensitizer is 4 CzIPN;
the titanium catalyst is titanocene dichloride;
the electron donor is diethyl 2, 6-dimethyl-1, 4-dihydro-3, 5-pyridinedicarboxylate.
2. The synthesis method according to claim 1, wherein the molar ratio of the haloalkane 1, 3-butadiene derivative 2, aldehyde or ketone 3, the organic photosensitizer, the titanium catalyst and diethyl 2, 6-dimethyl-1, 4-dihydro-3, 5-pyridinedicarboxylate is 2.0:2.0:1.0:0.01:0.05: 2.0.
3. The method of synthesis according to claim 2, wherein the solvent is tetrahydrofuran.
4. The method of synthesizing homoallylic compounds of any of claims 1-3 for derivatization of natural actives.
5. Use according to claim 4, characterized in that: the natural active substances comprise estrone and lithocholic acid.
CN202010985993.8A 2020-09-18 2020-09-18 Preparation of homoallylic alcohol compound, synthetic method and application thereof Active CN112125803B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202010985993.8A CN112125803B (en) 2020-09-18 2020-09-18 Preparation of homoallylic alcohol compound, synthetic method and application thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202010985993.8A CN112125803B (en) 2020-09-18 2020-09-18 Preparation of homoallylic alcohol compound, synthetic method and application thereof

Publications (2)

Publication Number Publication Date
CN112125803A CN112125803A (en) 2020-12-25
CN112125803B true CN112125803B (en) 2021-07-13

Family

ID=73841422

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202010985993.8A Active CN112125803B (en) 2020-09-18 2020-09-18 Preparation of homoallylic alcohol compound, synthetic method and application thereof

Country Status (1)

Country Link
CN (1) CN112125803B (en)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110002957B (en) * 2019-04-18 2021-11-30 滁州学院 Method for synthesizing homoallyl alcohol of polysubstituted olefin
CN114656369A (en) * 2022-01-19 2022-06-24 大连理工大学 High allylamine compound, synthesis method and application thereof
CN114591281B (en) * 2022-03-21 2023-09-29 河南师范大学 Preparation method of allyl alcohol compound

Non-Patent Citations (7)

* Cited by examiner, † Cited by third party
Title
《A new synthetic method for γ-butyrolactols by the palladium-catalyzed regioselective oxidation of 1-alken-4-ols》;Junzo Nokami等;《Tetrahedron Letters》;19881231;第29卷(第40期);第5181-5184页（表1中的化合物1b、1c） *
《Enantioselective 1,2-Difunctionalization of 1,3-Butadiene by Sequential Alkylation and Carbonyl Allylation》;Yang Xiong和Guozhu Zhang;《Journal of the American Chemical Society》;20180208;第140卷(第8期);第2735-2738页（ 图1；表1中的化合物4a；图2中的化合物4b-4z、4aa、4ab、4ac） *
《Enantioselective Synthesis of Anti Homoallylic Alcohols from Terminal Alkynes and Aldehydes Based on Concomitant Use of a Cationic Iridium Complex and a Chiral Phosphoric Acid》;Tomoya Miura等;《Journal of the American Chemical Society》;20130725;第135卷(第31期);第11497-11500页（表1中的化合物3aa，表2中的化合物3ab-3ad、3af） *
《Petasis Borono-Mannich Reaction and Allylation of Carbonyl Compounds via Transient Allyl Boronates Generated by Palladium-Catalyzed Substitution of Allyl Alcohols. An Efficient One-Pot Route to Stereodefined α-Amino Acids 》;Nicklas Selander等;《Journal of the American Chemical Society》;20071210;第129卷(第44期);第13723-13731页（图1；表1中的化合物9d、9e） *
《Synthesis of pinacol allylic boronic esters via olefin cross-metathesis between pinacol allylboronate and terminal or internal alkenes》;Yasunori Yamamoto等;《Synlett》;20021231(第1期);第128-130页（Scheme 3中的化合物15a-15c） *
《Transition-Metal-Free Coupling Reaction of Vinylcyclopropanes with Aldehydes Catalyzed by Tin Hydride》;Ryosuke Ieki等;《Chemistry - A European Journal》;20150305;第21卷(第16期);第6295-6300页（表3中的化合物3k-3n） *
Yang Xiong和Guozhu Zhang.《Enantioselective 1,2-Difunctionalization of 1,3-Butadiene by Sequential Alkylation and Carbonyl Allylation》.《Journal of the American Chemical Society》.2018,第140卷(第8期),第2735-2738页. *

Also Published As

Publication number Publication date
CN112125803A (en) 2020-12-25

Similar Documents

Publication Publication Date Title
CN112125803B (en) Preparation of homoallylic alcohol compound, synthetic method and application thereof
Schreiber et al. Structural and synthetic studies of the spore germination autoinhibitor, gloeosporone
Kaneko et al. Synthetic studies of huperzine A and its fluorinated analogues. 1. Novel asymmetric syntheses of an enantiomeric pair of huperzine A
Yamana et al. A convenient synthesis of 2, 2-difluoro enol silyl ethers from chlorodifluoromethyl ketones
CN108727229B (en) Novel process route for modifying fatty acid type PET reagent precursor
Martı́nez-Ramos et al. Highly diastereoselective nucleophilic additions using a novel myrtenal-derived oxathiane as a chiral auxiliary
Wang et al. Synthesis of New Chiral Aryl Diphosphite Ligands Derived from Pyranoside Backbone of Monosacharides and Their Application in Copper‐Catalyzed Asymmetric Conjugate Addition of Diethylzinc to Cyclic Enones
CN111328332B (en) Process for the preparation of bile acids
Wasserman et al. Singley oxygen in synthesis. Formation of antimycin A3 from an oxazole template
CN116444419A (en) Indigo infrared diene structure compound and preparation method thereof
Li et al. Synthesis of 1, 1-disubstituted-2, 6-diarylcyclohexane-4-ones catalyzed by KF/basic Al2O3 under ultrasound
Brown et al. Comparison of cationic rhodium and iridium complexes in directed homogeneous hydrogenation
Hernando et al. Influence of the substitution pattern on the Pb (OAc) 4 mediated oxidative cleavage of steroidal 1, 2-diols
Lee et al. Synthesis of 1, 3-oxazolidines by copper-catalyzed addition of acetone and ethyl diazoacetate to imines
CN113173974A (en) Synthesis method of cyclosporine derivative
Chanu et al. Synthesis of a norsesquiterpene spirolactone/steroidal hybrid by using an environmentally friendly domino reaction as a key step
Chanu et al. The domino chemistry approach to molecular complexity: high-yielding bis-hetero intramolecular Diels–Alder reactions with ketone components
EP1401851A1 (en) Two-stage protective groups for the synthesis of biopolymers
CS212221B2 (en) Method of making the (+) 3a, 7a-trans-4-/7,7-/ethylenedioxy /-oxooktyl/-7a beta-methylperhydroindane-1,5-dion
CN115181013B (en) Preparation method and application of key intermediate of modified fatty acid type PET reagent precursor
CN114656369A (en) High allylamine compound, synthesis method and application thereof
Wells et al. Antitumour benzothiazoles 13.(Diacetoxy) iodobenzene (DAIB) oxidation of 2-(4-hydroxy-3-methoxyphenyl)-benzothiazole and related compounds in the presence of dienophiles.
Osadchii et al. Study of alkaloids from plants of Siberia and Altai: 4. N-Deethylation of diterpene alkaloids of the aconitane type
Lena et al. A practical access into conveniently functionalized, homochiral C-ring system of taxuyunnanine C
Zhen et al. Enolate Additions to a Chiral 3-Hydroxypropionate 2, 3-Dication Equivalent. Enantioselective Synthesis of β, δ-Dihydroxy Esters

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant