Stereoselective Access to Silicon-Stereogenic Silacycles via the Carbene-Catalyzed Desymmetric Benzoin Reaction of Siladials

Abstract

The catalytic asymmetric synthesis of silicon-stereogenic organosilicon compounds has been a long-standing challenging task and was recently accomplished through a handful of transition-metal-catalyzed approaches. Herein we report an organocatalytic desymmetrization strategy for constructing optically active silicon-stereogenic silacycles. In the presence of a chiral N-heterocyclic carbene (NHC) catalyst, two identical formyl groups on the tetrasubstituted silanes are successfully discriminated to undergo stereoselective intramolecular benzoin reactions, affording enantioenriched dibenzo­[b,f]­silepin-10-ones featuring carbon- and silicon-stereogenic centers at the 1,4-positions, respectively. This catalytic process can be readily expanded to the gram scale, and the products can be further converted to other valuable molecules. DFT calculations were also conducted to unveil the reaction mechanism and the origins of the stereoselectivities.

Advancements in N-heterocyclic carbenes (NHCs) catalysis for benzoin reactions: A comprehensive review from past to present

“…In a recent study, Liu and coworkers [88] developed a desymmetric organocatalyzed method for the synthesis of siliconstereogenic silacycles with optical activity. This catalytic process is effective in the presence of a chiral NHC 114 catalyst for the synthesis of enantiomerically enriched dibenzo[b,f]silepin-10-ones containing 1,4-carbon-and siliconstereogenic centers from a wide range of silicon-centered diaromatic aldehydes (Schemes 11-13).…”

Remote Electronic Tuning of Chiral N‐Heterocyclic Carbenes

“…The intramolecular version of this reaction is an attractive transformation because it can access cyclic α‐hydroxy ketone, a useful chiral building block for the preparation of biologically important compounds. While the intramolecular reactions involving aldehydes and ketones are well‐established, [11c,36] the reports using dialdehyde were rare, probably because of unstable nature of dialdehyde [11d,37] . We anticipated that if stereo divergent synthesis of inosose is realized via intramolecular cross‐benzoin condensation of dialdehyde readily available from alditols, the thus‐obtained polyols can be used as chiral building blocks for a divergent synthesis of structurally important cyclitols (Scheme 11).…”

Highly Enantioselective Construction of Multifunctional Silicon‐Stereogenic Silacycles by Asymmetric Enamine Catalysis

“…On the other hand, although organocatalysis is well established as the third pillar of asymmetric catalysis, [7] its potential to construct Si‐stereocenter is largely unexplored. To date, only four protocols have been reported, namely, the chiral Brønsted base mediated intramolecular oxa‐Michael reaction by Matsubara and Asano, [8] the elegant chiral Brønsted acid catalyzed rearrangement of bis(methallyl)silanes by List et al., [9] and the NHC catalysis realized annulation of siladials by the groups of Chi [10a] and Xu [10b] (Scheme 1B). These meaningful works, together with the fact that different organocatalytic patterns activate different functionalities, outline an attractive feature of using organocatalysis to creat Si‐stereocenters, a broad scope of prochiral substrates for desymmetric reactions can be employed and readily convertible functionalities, such as alkene, formyl and carbonyl groups, can be incorporated into the final products.…”