Studies on Stereoselective Addition of Substituted 1,1-Dimetalloids to Aldehydes and Aldimines

Abstract

The design and synthesis of new metalloid compounds are highly important in modern synthetic chemistry because it allows the development of new synthetic methodologies for the preparation of synthetically useful compounds. In particular, the preparation and utilization of 1,1-diboryl or 1,1-borylsilyl compounds is an interesting area of research because of their propensity to undergo sequential transformations to form highly complex molecules. In this research, we have developed unprecedented strategies to develop a variety of stereoselective reactions utilizing 1,1-dimetalloids, such as 1,1-diborylalkanes, allylic 1,1-diboryl, and allylic 1,1-borylsilyl compounds, exploiting different modes of activation. In chapter I, we describe the development of a copper-catalyzed diastereoselective addition reaction between diborylmethane and N–tert-butanesulfinyl aldimines. In this study, the combination of copper bromide as a catalyst and lithium tert-butoxide as a base facilitates the addition of diborylmethane to N–tert-butanesulfinyl aldimines with excellent diastereoselectivtiy, affording a broad range of a-aminoboronates in good-to-excellent yield. Based on the stereoselectivity observed in the reaction, we proposed that the reaction proceeds via a boron-chelating chair-like transition state. The application of the reaction toward the synthesis of a highly potent antitubercular reagent is also described. In chapter II, we disclose a new strategy for the preparation of allylic 1,1-diboryl compounds. The allylic 1,1-diboryl compound was prepared via an iridium-catalyzed olefin transposition reaction of a homoallylic 1,1-diboronate, which can be easily prepared from diborylmethane. The reaction proceeds with complete stereoselectivity and the (E)-allylic-1,1-allylboronate ester was obtained under mild conditions. To demonstrate is synthetic application, we performed the chemo- and stereoselective allylboration of the allylic-1,1-diboronate ester with a range of aldehydes and cyclic aldimines. The allylboration reaction with aldehydes proceeded via a chair-like transition state to provide anti-5,6-disubstituted oxaborinin-2-ols, whereas the reaction with cyclic aldimines afforded δ-borylhomoallylic amines via a half chair-like transition state. An asymmetric version of the reaction was also developed using (R)-3,3′-bis(2,4,6-triisopropylphenyl)-1,1′-binaphthyl-2,2′-diyl hydrogenphosphate ((R)-TRIP) as a catalyst. These reactions show a broad substrate scope with excellent functional group compatibility. Further synthetic manipulations of the as-obtained products including carbon-carbon, carbon-oxygen, and carbon-halogen bond forming reactions have also been demonstrated. In chapter III, a chemo- and stereoselective allylboration reaction of aldehydes using an (E)-a-silyl-allylboron reagent and chiral phosphoric acid is disclosed. Previously, 1,1-bismetallic allylation reagents bearing two non-identical organometallic centers on the same sp3 carbon atom have been studied using a chirality transfer strategy. However, their catalytic asymmetric variants have been rarely reported. In this study, we found that the allylboration of aldehydes using (E)-a-silyl-allylboron reagents proceeds with excellent diastereo- and enantioselectivity in the presence of (R)-TRIP via kinetic resolution.