Regio‐ and Stereospecific 1,3‐Allyl Group Transfer Triggered by a Copper‐Catalyzed Borylation/ortho‐Cyanation Cascade

Abstract

A copper-catalyzed borylation/ortho-cyanation/allyl group transfer cascade has been developed. Initiated by an unconventional copper-catalyzed electrophilic dearomatization, this process features a regio-and stereospecific 1,3-transposition of the allyl fragment enabled by an aromatization-driven Cope rearrangement. This method provides an effective means for the construction of adjacent tertiary and quaternary stereocenters with excellent diastereocontrol. Keywordscopper; cyanation; C-C activation; dearomatization; sigmatropic rearrangement Since its discovery in 1940, [1] the Cope rearrangement has been widely utilized as a powerful tool for the construction of complex molecular architectures. [2] Using the chairlike six-membered transition state as the dominant stereocontrol element, this venerable transformation allows for the efficient creation of well-defined stereochemical arrays in a predictable fashion. Due to the reversible nature of this sigmatropic rearrangement, the use of substrates featuring ring strain or possessing specialized substitution patterns (e.g., oxyCope) [2] represents the most commonly employed tactics to drive the reaction towards the desired rearranged products. In this context, the development of alternative strategies to facilitate the Cope rearrangement is pivotal to its further advancement as a synthetically useful transformation.We previously reported that the capture of a vinylarene-derived benzylcopper species with an electrophilic cyanating reagent led to the highly selective formation of a dearomatized intermediate. [3,4] Very recently, the elegant work of Montgomery has expanded the scope of this transformation to simple styrenes. [5] A related borylative bromine recycling strategy was pioneered by Schomaker and coworkers, [6] which has been shown to proceed via a similar mechanism. [6d] Based on these precedents, we envisioned that the catalytic generation of a semibenzene intermediate (III) could serve as a generic platform for the development of a broad spectrum of novel rearrangement reactions, including the Cope rearrangement (Scheme 1). In contrast to conventionally applied strategies, this process Correspondence to: Yang Yang, yang89@mit.edu. HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript utilizes aromatization as the crucial driving force for the rearrangement of these previously difficult-to-access dearomatized intermediates. As detailed in Scheme 1, interception of the transient benzylcopper intermediate II generated from 2-allylstyrene I with an electrophile would provide the dearomatized intermediate III.Enabled by the rearomatizing Cope rearrangement, the subsequent 1,3-transposition of the allyl unit would be expected to proceed in a completely regio-and stereospecific fashion, affording densely functionalized products bearing two adjacent stereocenters. Notably, the selective cleavage of the allyl fragment from an aromatic moiety and the subsequent allyl group shuttling achieved in this cascade remained une...

Copper Mediated Chemo‐ and Stereoselective Cyanation Reactions

“…This methodology provided an efficient technique for the tertiary and quaternary stereocenters formation with high diastereocontrol (See Figure 58). [67] …”