Cinchona‐Derived Picolinamides: Effective Organocatalysts for Stereoselective Imine Hydrosilylation

Abstract

Picolinamide-cinchona organocatalysts for the successful enantioselective reduction of ketomines were developed. For the first time, a new type of chiral Lewis base, a cationic species, is reported to efficiently organocatalyze the addition of trichlorosilane to imines. Excellent yields with good to high enantioselectivities (up to 91 %) were obtained in the reduction of differently substituted substrates. Noteworthy,

Stereoselective Reduction of Imines with Trichlorosilane Using Solid-Supported Chiral Picolinamides

“…Compound 2a was obtained as brownish oil (1.04 mmol, 77% yield). All analytical data are in agreement with literature [24]. 1 H-NMR (300 MHz, CDCl 3 ) δ H 8.88 (br s, 1H), 8.70 (d, J = 4 Hz, 1H), 8.46 (d, J = 4 Hz, 1H), 8.03–7.96 (m, 2H), 7.75 (d, J = 3 Hz, 1H), 7.71–7.66 (m, 1H), 7.42 (d, J = 4 Hz, 1H), 7.34–7.26 (m, 2H), 5.80–5.69 (m, 1H), 5.62 (br s, 1H), 5.01–4.91 (m, 2H), 3.94 (s, 3H), 3.44–3.36 (m, 1H), 3.33–3.23 (m, 2H), 2.81–2.68 (m, 2H), 2.27 (br, 1H), 1.66–1.48 (m, 4H), 0.96–0.88 (m, 1H).…”

“…The use of polystyrene-supported catalyst C afforded chiral amine 7a in 95% yield but very low ee of 23% (entry 3); this was probably due to an incomplete conversion of primary amine 4 into C [23]. Gratifyingly, upon using polystyrene supported catalyst D , the reaction proceeded in quantitative yield and 90% ee (entry 4), a result comparable to the one obtained with the homogeneous catalyst [24]. Lowering the catalyst loading to 10 mol % did not alter the reaction outcome (entry 5), while using 5 mol % of D resulted in slightly lower ee (entry 6).…”

HMPA-Catalyzed Transfer Hydrogenation of 3-Carbonyl Pyridines and Other N-Heteroarenes with Trichlorosilane

“…Trichlorosilane with a Lewis base as an activator is a well-known unsaturated double bond reduction method. Its strength has been well demonstrated by others and ourselves in terms of asymmetric reduction of double bonds [31,32,33,34,35,36,37,38]. However, to the best of our knowledge, the reduction of pyridines by use of this system still presents a great challenge, and no successful protocol has been reported.…”

The Development of Organocatalytic Asymmetric Reduction of Carbonyls and Imines Using Silicon Hydrides

“…In 2014, Burke and Benaglia developed cinchona-derived picolinamides as chiral Lewis base organocatalysts for the enantioselective reduction of ketimines. [80] The cinchona-picolinamide 44 promoted the reduction in high yields (up to 99 % ee) and good enantioselectivities (up to 91 % ee) (Scheme 16a). Remarkably, high turnover frequencies were achieved at a catalytic loading of only 1 mol%.…”