CZ305478B6 - Sterically protected vicinal threo-diamines of high fluorophilicity - Google Patents

Abstract

In the present invention, there is disclosed a process for preparing vicinal N,N´-diarylated threo-diamines, modified by two polyfluoroalkyl substituents containing six perfluorinated carbon atoms and two-carbon non-fluorinated link separating the perfluorinated chain from the parent ethylene diamine skeleton. Preparation process thereof is characterized in that 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluoroctyl iodide reacts with tert-butyl lithium and in situ produced 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluoroctyl lithium is then stereoselectively added to a suitable N,N´-diarylethane-1,2-diimine, which contains sterically demanding aryl substituents such as 2,4,6-trimethylphenyl or 2-tert-butylphenyl.

Description

Sterically hindered vicinal threo-diamines with high fluorophilicity

Technical field

The invention relates to a process for the preparation of vicinal (N, N'-diarylated) Areo-diamines modified with two polyfluoroalkyl substituents containing six perfluorinated carbon atoms and a bicarbonate non-fluorinated linker separating the perfluorinated chain from the parent ethylenediamine skeleton. This solution results in high fluorophilicity of the resulting diamines and sufficient steric hindrance to allow the formation of NHC (nitrogen heterocyclic carbene) ligands with sufficient stability and subsequent transition metal complexes allowing their recycling by fluorine separation techniques.

BACKGROUND OF THE INVENTION

Vicinal diamines are frequently used ligands in transition metal chemistry. Of particular importance are diamines modified on both nitrogen atoms by bulky aryl groups such as 2,4,6-trimethylphenyl, 2,6-diisopropylphenyl, 2-isopropylphenyl and the like. Such diamines can be transformed to dihydroimidazoline salts which are readily deprotonated to relatively stable NHC (nitrogen heterocyclic carbene) ligands. These ligands have excellent complexing properties that often replace phosphine ligands in modern transition metal complexes. One of their most important applications is the field of ruthenium catalysts for alkene metathesis, where substitution of the tricyclohexylphosphine ligand for the 1,3-dimesitylimidazolidin-2-ylidene carbene ligand leads to a significant increase in catalyst stability and activity (2nd generation Grubbs catalyst and Hoveyd-Grubbs catalyst 2). generation) ¹ .

Modifications of the imidazolidine ring of the NHC ligand by polyfluoroalkylated ligands at positions 1 and 3 are very rare. Furstner et al. reported the synthesis of a ruthenium complex modified with an asymmetric NHC ligand containing one mesityl and one linear polyfluoroalkylated chain, but its catalytic activity was not studied ² . Skalický et al. have found that imidazoline salts modified with two linear polyfluoro- or polyfluoropolyoxaalkyl chains can be transformed in situ into NHC ligands complexing silver ions, but these ligands are not sufficiently stable to complex ruthenium ³ .

Modifications of the imidazolidine ring at positions 4 and 5 by polyfluoroalkylated ligands are not known. However, vicinal diamines modified with non-fluorinated aryl ⁴ , alkyl ⁵ or alkoxysilylalkyl ⁶ groups were synthesized to obtain reactivity-modified catalysts, silica-immobilized catalysts or chiral alkene metathesis catalysts. These modifications always resulted in mixtures of stereoisomers which had to be subsequently separated by crystallization or column chromatography. The only known stereoselective modification is the modification with sterically bulky tert-butyl groups which, due to steric hindrance, resulted in the formation of exclusively racemic diamine ⁷ ' ⁸ . Although this type of diamine has been transformed into the corresponding NHC ligands and their silver complexes, it is not known to convert them to ruthenium alkene metathesis catalysts.

SUMMARY OF THE INVENTION

The disadvantages of the known vicinal diamines mentioned above consist either in the high steric hindrance of tert-butyl groups preventing further transformations into ruthenium complexes or in the low stereoselectivity of the processes using non-fluorinated linear or aryl substituents and which do not allow separation of NHC ligands and transition metal complexes prepared therefrom. by means of fluorine separation methods, it removes the invented novel process for the preparation of highly fluorinated vicinal diamines, which consists in that the parent molecule of ethylenedi-amine is modified on both nitrogen atoms with sterically demanding aryl ligands such as mesityl or 2-tert-butylphenyl and on both carbon atoms, polyfluoroalkyl substituents containing six perfluorinated carbon atoms and a bicarbonate, non-fluorinated linker.

The present invention relates to the reaction of 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl iodide with tert-butyllithium and the subsequent in-situ stereoselective addition of 3,3,4,4, 5,5,6,6,7,7,8,8,8-tridecafluorooctyllithium to the appropriate N, N -diarylethane-1,2-diimine containing sterically demanding aryl substituents such as 2,4,6-trimethylphenyl (mesityl) ) or 2-tert-butylphenyl.

DETAILED DESCRIPTION OF THE INVENTION

Example 1

i-BuLi

Et ₂ O, -78 ° C

Scheme 1

To a solution of 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl iodide (1, 3.24 g, 6.84 mmol) in anhydrous diethyl ether was at -78 ° A solution of tert-butyllithium in pentane (1.7 M, 8.55 mL, 14.53 mmol) was added via syringe. After stirring for 20 minutes at -78 ° C, N, N'-dimesitylethane-1,2-diimine (2a, 0.50 g, 1.71 mmol) was added portionwise. The mixture was allowed to stir for 4 h at -78 ° C, slowly warmed to 0 ° C and quenched with saturated aqueous ammonium chloride solution (1 mL). To the mixture was added 20 mL of water, the organic layer was separated and the aqueous organic layer was extracted with diethyl ether (3 x 15 mL). The combined organics were dried perfectly. MgSO ₄ , the desiccant was removed by filtration and the solvent was removed on a rotary evaporator (40 ° C / 5 kPa / Ι h). Desired threole, 1,1,2,2,3,3,4,4,5,5,6,6,13,13,14,14,15,15,16,16,17,17,18,18 18-hexakosafluor-N, ^{N /} -dimesityloktadekan-9,10-diamine (3a, 1.36 g, 80.5%, white crystalline solid, mp 85-86 ° C) was obtained by column chromatography of the residue (eluent: hexane (dichloromethane 4: 1). 1 H NMR (299.97MHz, CDCl ₃ ): δ 1.55-1.72 (m, 2H, CH ₂ CHHCH (NHAr)), 1.92 (s, 12H, O-CH 3), 1.97-2 19 (m, 4H, CHHCH 2 CH (NHAr)), 2.25 (s, 6H, t-CH ₃ ), 2.55-2.80 (m, 2H, CHHCH ₂ CH (NHAr)), 2, 87 (br m, 2H, NH), 3.14 (md, _{1H H} = 10 Hz, 2H, CH), 6.75 (s, 4H, Ar-CH) ppm. ¹⁹ F NMR (282.23 MHz, CDCl 3): δ -81.4 (t, VF-F = 10 Hz, 6F, CF 3), -114.9 (m, 4F, CF 2 CH 2), -122.4 (m, 4F (CFCF2CH2), -123.4 (m, 4F, CF3CF2CF2CF2), -123.9 (m, 4F, CF3CF2CF2), -126.7 (m, 4F, CF3CF2) ppm. ¹³ C NMR (75.44 MHz, CDCl 3): δ 18.6 (o-CH ₃ , 4C), 20.5 (CHCH ₃ , 2C), 21.7 (m, CF ₂ CH ₂ CH ₂ , 2C), 29.2 (t, ² JF = 22 Hz, CF 2 CH 2, 2 C), 57.1 (CH, 2 C), 105-123 (m, 8 x CF 2, 8 C), 117.4 (qt, 2 '). ./FC = 288 Hz, ² ./PC = 33 Hz, CF ₃ , 2C), 118.7 (tt, = 255 Hz, ² /., _C = 31 Hz, CF ₂ CH ₂ , 2C), 128.7 (Ar-C, 4C), 130.0 (Ar-CH, 4C), 131.4 (Ar-C, 2C), 140.5 (Ar-C, 2C) ppm.

MS (ESI), m / z (%): 990 [M + H] < + ^> (100), 854 [M-MesNH2] ⁺ (20). HRMS (ESI) calcd for C 36 H ₃₅ F ₂₆ N ₂ ([M + H] ⁺⁾ 989.2380, found 989.2383.

-2GB 305478 B6

F 13 ^ 6 ^ t-BuLi

Et ₂ O, -78 ° C

Scheme 2

To a solution of 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl iodide (1, 2.96 g, 6.24 mmol) in anhydrous diethyl ether was at -78 ° A solution of tert-butyllithium in pentane (1.7 M, 7.35 mL, 12.48 mmol) was added via syringe. After stirring for 20 minutes at -78 ° C, ACV-bis (2-di- tert -butylphenyl) ethane-1,2-diimine (2b, 0.50 g, 1.56 mmol) was added portionwise. The mixture was allowed to stir for 4 h at -78 ° C, slowly warmed to 0 ° C and quenched with saturated aqueous ammonium chloride solution (1 mL). To the mixture was added 20 mL of water, the organic layer was separated, and the aqueous organic layer was extracted with diethyl ether (3 x 15 mL). The combined organics were dried perfectly. MgSO ₄ , the desiccant was removed by filtration and the solvent was removed on a rotary evaporator (40 ° C / 5 kPa / Ι h). Desired (Ara) -W, # - bis- (2-di-tert-butylphenyl) 1,1,2,2,3,3,4,4,5,5,6,6,13,13,14, 14,15,15,16,16,17,17,18,18,18-hexacosafluorooctadecane-9,10-diamine (3b, 1.50 g, 96.4%, yellowish oil) was obtained by column chromatography of the residue (eluent hexane / dichloromethane 4: 1). 1 H NMR (299.97 MHz, CDCl ₃ ): δ 1.45 (s, 18H), (CH ₃ ) ₃ CH), 1.73 1.90 (m, 2H, CH ₂ CHHCH (NHAr)), 2 O 2 - 2.44 (m, 6H, CHHCHHCH (NHAr)), 3.87 (d, ³ J _H -h = 3.0 Hz, 4H, NH and CH), 6.74 - 6.82 (m , 4H, Ar-CH), 7.19 (ddd, ³ J '= ⁸ > 5 ^{and 7} ' ^{2 Hz} > ^4j hh =

1.5 Hz, 2H, Ar-CH), 7.32 (dd, 'V _HH λ = ^8Hz, Xh = 1.5 Hz, 2H, Ar-CH ppm. ¹⁹ F NMR (282.23 MHz, CDC13 ): δ -81.3 (tt, ³ F 7F = 9.9 Hz, V _FA = 2.3 Hz, 6F, CF _3), -114.8 (m, 4F, _{CH2 CF2),} -122 5 (m, 4F, CF ₂ CF ₂ CH ₂₎ -123.4 (m, 4F, CF ₃ CF ₂ CF ₂ CF ₂₎ -123.9 (m, 4F, CF ₃ CF ₂ CF ₂₎ , -126.7 (m, 4F, CF ₃ CF ₂ ) ppm ¹³ C NMR (75.44 MHz, CDCl 3): δ 23.1 (m, CF ² CH ² CH ² , 2C), 28.9 (t, 27F- _C) = 22.2 Hz, CF ₂ CH ₂ , 2 C), 30.3 (CH ₃ ) ₃ CH, ₆ C), 34.3 ((CH ₃ ) ₃ CH, 2 C), 55.1 (CH, 2 C), 104-113 (8 x CF ₂ 8C), 111.5 (Ar-CH, 2C), 117.4 (qt, '_c ./ _F = 288 Hz, V _F _. _C = 32.7 Hz, CF _3.2 (C), 118.0 (Ar-CH, 2C), 118.6, (tt, J _{F- C} = 254.2 Hz, ²⁷ F_C = 31.3 Hz, CF ² CH ² , ² C), 127.3 (Ar-CH, 2C), 127.7 (Ar-CH, 2C), 133.4 (Ar-C, 2C), 144.9 (Ar-C, 2C) ppm. MS (APCI), m / z (%): 1017 [M + H] < + ^> (100), 508 [M / 2] < ^{+ >} (45). HRMS (APCI) calc'd for C38H ₃₉ F ₂₆ N ₂ ([M + H] ⁺⁾ 1017.2693, found 1017.2699.

Example 3 and enantiomer

Scheme 3

To a solution of 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl iodide (1.60 g, 6.84 mmol) in anhydrous diethyl ether was at -78 ° A solution of tert-butyllithium in pentane (1.7 Μ, 11.40 mL, 19.40 mmol) was added via syringe. After stirring for 20 minutes at -78 ° C, N, N -bis[4-( tert -butyldiphenylsilyloxy) -2,6-dimethylphenyl]ethane-1,2-diimine (2c, 1, 2, 3, 4, 25 g,

1.71 mmol). The mixture was allowed to stir at -78 ° C for 4 h, slowly warmed to 0 ° C and quenched with saturated aqueous ammonium chloride solution (1 mL). To the mixture was added 20 mL of water, the organic layer was separated and the aqueous organic layer was extracted with diethyl ether (3 x 15 mL). The combined organics were dried perfectly. MgSO ₄ , the desiccant was removed by filtration and the solvent was removed on a rotary evaporator (40 ° C / 5 kPa / Ι h). Desired threo A, N -bis [4- (tert -butyldiphenylsilyloxy) -2,6-dimethylphenyl] 1,1,1,2,2,3,3,4,4,5,5,6,6,13,13 , 14,14,15,15,16,16,17,17,18,18,18-hexacosafluorooctadecane-9,10-diamine (3c, 1.70 g, 71.9%, yellowish oil) was obtained by column chromatography of the residue ( eluent hexane / dichloromethane 4: 1). 1 H NMR (299.97 MHz, CDCl 3): δ 1.09 (s, 18H), (CH ₃ ) ₃ CH), 1.41 1.58 (m, 2H, CH ₂ CHHCH (NHAr)), 1, 70 (s, 12H, o-CH _3), 1.85 - 2.02 (m, 4H, CHHCHHCH (NHAr)), 2.49 - 2.71 (m, 4H, CH ₂ CHHCH (NHAr) and NH 2.95 (md, .delta.)

9.6 Hz, 2H, CH), 6.31 (s, 4H, Ar-CH), 7.30-7.41 (m, 12H, Ar-CH), 7.68-7.75 (m, 8H, ArCH) ppm. ¹⁹ F NMR (282.23 MHz, CDCl 3): δ -81.4 (t, VF-F = 10 Hz, 6F, CF 3), -114.9 (m, 4F, CF 2 CH 2), -122.4 (m, 4F (CF 2 CF 2 CH 2), -123.4 (m, 4 F, CF 3 CF 2 CF 2 CF 2), -123.9 (m, 4 F, CF 3 CF 2 CF 2), -126.7 (m, 4 F, CF 3 CF 2) ppm. ¹³ C NMR (75.44 MHz, CDCl 3): δ 18.7 (o-CH 3, 4 C),

19.6 ((CH ₃ ) ₃ C, 2C), 21.4 (m, CF ₂ CH ₂ CH ₂ , 2C), 26.8 ((CH ₃ ) ₃ C, 6C), 29.1 (t, ² JF_C) = 22.7 Hz, CF 2 CH 2, 2 C), 56.8 (CH, 2 C), 105-126 (m, 2 x CF 2, 10 x CH 2, 12 C), 120.2 (Ar-C, 4 C), 127, 8 (Si-Ar-CH, 2C), 133.4 (2 x Si-Ar-C, 4C), 135.7 (2 x Si-Ar-CH, 8C), 136.3 (Ar-C, 2C) ), 150.3 (Ar-C, 2C) ppm. MS (ESI), mlz (%): 1469 [M + H] ⁺ (100). HRMS (ESI): calcd for C ₆₆ H ₆₇ F ₂₆ N ₂ O ₂ Si ₂ ([M + H] ⁺ ) 1469.4320, found 1469.4322.

Industrial applicability

The invention is useful as highly fluorinated diamines with a clear relative configuration. The resulting diamines can be used directly as ligands or preferably as intermediates for the preparation of highly fluorinated NHC ligands. Both types of ligands can serve as components of transition metal complexes useful as homogeneous catalysts that can be recycled using fluorine separation methods.

Literature

1. Vougioukalakis, G.C .; Grubbs, R.H. Chem. Roar. 2010, 110, 1746-1787.

2. Furstner, A .; Ackermann, L .; Gabor, B .; Goddard, R .; Lehmann, C.W .; Mynott, R .; Stelzer, F .; Thiel, O. Chem. Eur. J. 2001, 7, 3236-3253.

3. Skalicky, M .; Skalicka, V .; Rybackova M .; Kvicalova, M .; Cvačka J .; Brezinova, A .; Kvicala, J. Organometallics 2012, 31, 1524-1532.

4. Mercer, G.J .; Sturdy, M .; Jensen, D.R .; Sigman, M.S. Tetrahedron 2005, 61, 6418-6424.

5. Obrecht, W .; Muller, J.M .; Nuyken, O .; Berke, H .; Meca, L .; Triscikova, L., US. Pat. 2007/0049700.

6. Monge-Marcet, A .; Pleixats, R .; Cattoen, X .; Wong Chi Man, M.J. Mol. Catal A: Chem. 2012, 357, 59-66.

7. Zinner, S.C .; Herrmann, W.A .; Kiihn, F.E. Tetrahedron: Asymmetry 2008, 19, 1532-1535.

8. Jacquemard, U .; Harpainter, P .; Roland, S. Tetrahedron Lett. 2013, 54, 4-93-4Ί95.

Claims (4)

PATENT CLAIMS 1. A process for the preparation of highly fluorinated vicinal threoamines is characterized in that 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl iodide is reacted with tert-butyllithium and in. 3,3,4,4,5,5,6,6,7,7,8,8,8-tridekafluorooctyllithium formed in the sieve is stereoselectively added to the appropriate N, Ndiarylethan-1, 2-diimine, which contains sterically demanding aryl substituents. The process according to claim 1, wherein the diimine used is N, Nbis (2,4,6-trimethylphenyl) ethane-1,2-diimine. The process according to claim 1, wherein the diimine used is N, Nbis (2-tert-butylphenyl) ethane-1,2-diimine. 4. The process of claim 1 wherein the diimine used is N, Nbis [4- (tert-butyldiphenylsilyloxy) -2,6-dimethylphenyl] ethane-1,2-diimine. End of document