Regioselective Anti-Silyllithiation of Propargylic Alcohols

Abstract

Among the known hydrosilylation or carbosilylation conditions of alkynes, anti-addition of the two units across the triple bond is considered rare compared to the syn counterpart. For anti-silylative vicinal difunctionalizations, transition-metal catalysts, such as ruthenium or palladium complexes, are generally required. Accordingly, silyl alkali metals have not been employed for those anti-addition transformations. Here we demonstrate that silyllithiums can add across the triple bond of a series of propargylic alkoxides regioselectively in an anti-fashion. Upon treatment with a variety of electrophiles, the trisubstituted alkenyl lithium intermediates were transformed into highly functionalized β-silyl allylic alcohols with high regiocontrol, eventually providing tri-or tetrasubstituted alkenylsilanes stereoselectively. A classic trick for anti-addition with propargylic alkoxides has transformed anti-silylative functionalizations into a robust and reliable strategy.

Regioselective anti-Silyllithiation of Propargylic Amines

“…Through optimization, we established standard conditions as follows: tert-butyl (3-phenylprop-2-yn-1-yl)carbamate (1a, 0.1 M in toluene), 3.5 equiv PhMe2SiLi (2a, 1.5 M in THF), -40 °C, 3 h. We employed the mixed solvent system previously optimized for the silyllithiation reaction again for this transformation. 13 Table 1 illustrates the yields of 3aa associated with variations in the deviations listed. Under the standard conditions (Entry 1), initial deprotonation of 1a and anti-addition of PhMe2SiLi 2a proceeded to afford the silyllithiated intermediate 4.…”

“…The residue was purified by column chromatography on silica gel (hexane/EtOAc = 5/1) followed by GPC to provide 8 (116.8 mg, 0.225 mmol, 45%) as a white crystalline solid. Mp: 148.9-151.1 °C; [α] 20 D -158.6 (c 1.00, CHCl3); 1 H NMR (600 MHz, CDCl3): δ 7.49-7.47 (m, 3H), 7.31-7.29 (m, 3H), 7.08-6.99 (m, 7H), 6.84 (t, J = 6.9 Hz, 1H), 6.52 (s, 1H), 6.39 (d, J = 7.5 Hz, 1H), 5.56 (brs, 1H), 4.52 (t, J = 9.6 Hz, 1H), 3.55 (d, J = 9.6 Hz, 1H), 2.23 (m, 1H), 1.17 (d, J = 6.9 Hz, 3H), 1.12 (s, 9H), 0.94 (d, J = 6.2 Hz, 3H), 0.36 (s, 3H), -0.32 (s, 3H); 13 C NMR (151 MHz, CDCl3): δ 157.9, 141.9, 140.…”

“…(δ) units, parts per million (ppm) downfield relative to residual CHCl3 (d = 7.26 ppm). Chemical shifts in13 C NMR spectra were recorded in delta (δ) units, parts per million (ppm) downfield relative to CDCl3 (d = 77.16 ppm). The following abbreviations are used for spin multiplicity: s = singlet, d = doublet, t = triplet, m = multiplet, br = broad.…”

“…(R,Z)-N-(2-(Dimethylphenylsilyl)-3-phenylallyl)-2-methylpropane-2-sulfinamide (3fa):GP [from 1f (123.4 mg, 0.52 mmol) with PhMe2SiLi 2a (1.5 M in THF, 1.5 mL, 2.34 mmol, 4.5 equiv), column chromatography with an eluent (CH2Cl2/EtOAc = 1/1)] afforded 3fa as a colorless oil (171.0 mg, 0.460 mmol, 89%). [α] 20 D 19.6 (c 1.00, CHCl3); 1 H NMR (600 MHz, CDCl3): δ 7.50 (s, 1H), 7.47 (m, 2H), 7.33-7.29 (m, 3H), 7.20-7.18 (m, 3H), 7.14-7.12 (m, 2H), 4.00 (dd, J = 13.7, 3.4 Hz, 1H), 3.88 (ddd, J = 13.7, 8.9, 1.4 Hz, 1H), 3.19 (m, 1H), 1.18 (s, 9H), 0.22 (s, 3H), 0.16 (s, 3H);13 C NMR (151 MHz, CDCl3): δ 146.0, 139.1, 139.0, 138.5, 133.9, 129.0, 128.6, 127.91, 127.86, 127.4, 55.9, 53.4, 22.8, -1.18, -1.20; HRMS (APCI-MS, positive) m/z [M+H] + calcd for C21H30NOSSi: 372.1812; found: 372.1824. (Z)-N-(2-(Dimethylphenylsilyl)-3-phenylallyl)benzenesulfonamide (3ga):GP [from 1g (271.1 mg, 0.950 mmol) with PhMe2SiLi 2a (1.5 M in THF, 2.2 mL, 3.33 mmol, 3.5 equiv), column chromatography with an eluent (CH2Cl2 only)] afforded 3ga as a pale yellow oil (328.9 mg, 0.807 mmol, 85%).…”

“…55 (m, 1H), 3.75 (d, J = 6.2 Hz, 2H), 0.13 (s, 6H);13 C NMR (151 MHz, CDCl3): δ 146.3, 140.0, 138.7, 138.5, 136.7, 133.9, 132.7, 129.2 (2C), 128.5, 128.1, 127.9, 127.5, 127.3, 50.7, -1.5; HRMS (APCI-MS, positive) m/z [M+H] + calcd for C23H26NO2SSi: 408.1448; found:408.1433. (Z)-N-(2-(Dimethylphenylsilyl)-3-phenylallyl)methanesulfonamide (3ha): GP [from 1h (210.5 mg, 1.01 mmol) with PhMe2SiLi 2a (1.5 M in THF, 2.3 mL, 3.52 mmol, 3.5 equiv), column chromatography with an eluent (CH2Cl2 only)] afforded 3ha as a white amorphous solid (335.6 mg, 0.971 mmol, 96%).…”