Remote Control of Diastereoselectivity in Intramolecular Reactions of Chiral Allylsilanes

Abstract

During investigations of cyclization reactions between chiral allylsilanes and N-acyliminium ions, it was discovered that a suitably positioned benzyloxy group on the allylsilane component caused a reversal in the diastereoselectivity of these reactions relative to that normally observed with alkylsubstituted allylsilanes. This effect was subsequently observed in two other reaction types. Investigations into this effect led to the proposal of product formation through thermodynamic control facilitated by neighboring group interactions with a transient cationic species. This hypothesis was experimentally supported by the isolation of an intermediate in the proposed mechanistic pathway.The reactions of allylsilanes with electrophilic species, in particular iminium ions, have become standard means for the formation of carbon-carbon bonds. 1-4 This strategy has been enriched by the introduction of chiral allylsilane derivatives, which can afford products with a high degree of stereochemical control. 5-18 Still this strategy has considerable untapped promise, especially when combined with non-standard methods of generating the electrophilic component.Previous work in this laboratory has shown that reactive iminium ions can be prepared through the intramolecular reactions of an aryl imine bearing an NHBoc substituent in the ortho position and that this reaction affords a route to interesting ring systems. 19,20 As an extension of this methodology, we wished to examine chiral silanes in this reaction, with the overall goal being the synthesis of enantiomerically pure products. In this work, a most unexpected outcome was observed: the diastereoselectivity of the reactions can be reversed by the placement of a benzyloxy group γ to the silicon moiety. We have ascertained that this observation holds in at least two other reactions of allylsilanes. These observations will be discussed in the context of kinetic v. thermodynamic control of the stereochemistry of a cationic intermediate in the reaction through neighboring group interactions. Results Preparation of Chiral AllylsilanesInitially, chiral alkenyl silanes 1 and 2, each containing a terminal azido group were prepared in enantiomerically pure form. Thus, enantiomerically pure (S)-1,2,4-butanetriol derived from malic acid was converted into allylic alcohol 3 by a standard series of functional group transformations and protecting group manipulation steps (Scheme 1; see Supporting Information for details). Conversion of this allylic alcohol to alkenyl silane 5a was accomplished by the 1,3-transpositive bis-silylation protocol developed by Ito. 21-23 This process has been shown to proceed with syn relative stereocontrol and with high retention of enantiomeric purity. Conversion of the product 5a to azide 1 was accomplished through straightforward transformations.We synthesized chiral allylsilanes containing more highly functionalized side chains as shown in Scheme 2. The oxygenated allylsilane 2, was originally envisioned as an intermediate en route to martinellin...

Regiodivergent and Stereoselective Hydrosilylation of 1,3‐Disubstituted Allenes

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