Enantioconvergent construction of stereogenic silicon via Lewis base-catalyzed dynamic kinetic silyletherification of racemic chlorosilanes

Abstract

Organosilanes possessing an enantioenriched stereogenic silicon center are important in many branches of chemistry, yet they remain challenging to synthesize in a practical and scalable way. Here we report a dynamic kinetic silyletherification process of racemic chlorosilanes with (S)-lactates using 4-aminopyridine as a Lewis base catalyst. This enantioconvergent approach asymmetrically constructs the stereogenic silicon center in a different manner from traditional resolution or desymmetrization. A range of silylethers have been prepared with high diastereoselectivity on up to 10 g-scale, allowing the practical synthesis of diverse enantioenriched organosilane analogs.

Lewis Base-Catalyzed Dynamic Kinetic Asymmetric Transformation of Racemic Chlorosilanes en Route to Si-Stereogenic Silylethers

“…In fact, the 29 Si NMR spectra of the equimolar mixtures of 1a and 3g at either 25 or −45 °C in CH 3 CN only showed a single 29 Si resonance corresponding to 1a, and no new silicon species was observed, while similar intermediates were successfully characterized using a DMAP-type catalyst and racemic chlorosilane in our previous work. 42 The results imply that chlorosilane activation in this case might be both kinetically and thermodynamically disfavored. In addition, we also observed a zero-order with respect to the concentration of both phenol 2f and NEt 3 (Figure 3A-2,A-4), suggesting that Si− O bond formation is faster than chlorosilane activation.…”

“…This hypothesis has been preliminarily confirmed in our previous work using achiral DMAP-type catalyst and (S)-lactate as a stoichiometric chiral substrate (Figure 1C). 42 However, the exploration of a more sophisticated DYKAT strategy, in which a chiral Lewis base catalyst is responsible for the equilibration of two chlorosilane enantiomers, has been pending. Inspired by the achievements in Lewis base-catalyzed kinetic resolution 43−45 or desymmetrization of hydroxy with achiral chlorosilanes to construct a Cstereogenic center, 46−49 we envisioned that such an asymmetric organocatalysis approach might be capable of constructing a Sistereogenic center, if racemic chlorosilanes are employed with achiral alcohols.…”

Copper‐Catalyzed Asymmetric Synthesis of Silicon‐Stereogenic Benzoxasiloles

“…Ring‐opening reactions of chiral benzoxasiloles with various organolithium or Grignard reagents would be ideal approaches to afford chiral tetraorganosilanes bearing benzyl alcohol functional groups. For example, the reactions of benzoxasilole 2 a with methyl or aryllithiums at −78 °C provided tetraorganosilanes 5 a and 5 b in excellent yields with retention of configuration at silicon (Scheme 2a) [15,20,23–24] . In addition, vinyl, alkynyl, and allyl groups substituted tetraorganosilanes 5 c , 5 d , and 5 e were obtained without racemization via ring‐opening with the corresponding Grignard reagents.…”