Cooperative Catalysis for the Highly Diastereo- and Enantioselective [4+3]-Cycloannulation of ortho-Quinone Methides and Carbonyl Ylides.

Arun Suneja,Christoph Schneider,Henning Jakob Loui

doi:10.1002/anie.201913603

Arun Suneja, Christoph Schneider + Show 1 more

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https://doi.org/10.1002/anie.201913603

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Abstract

We describe herein a highly diastereo‐ and enantioselective [4+3]‐cycloannulation of ortho‐quinone methides and carbonyl ylides to furnish functionalized oxa‐bridged dibenzooxacines with excellent yields and stereoselectivity in a single synthetic step. The combination of rhodium and chiral phosphoric acid catalysis working in concert to generate both transient intermediates in situ provides direct access to complex bicyclic products with two quaternary and one tertiary stereogenic centers. The products may be further functionalized into valuable and enantiomerically highly enriched building blocks.

Highlights

We describe a highly diastereo- and enantioselective [4+3]-cycloannulation of ortho-quinone methides and carbonyl ylides to furnish functionalized oxa-bridged dibenzooxacines with excellent yields and stereoselectivity in a single synthetic step
The combination of a transition-metal catalyst and a Lewis acid or organocatalyst to activate two different substrates for a given reaction has attracted significant interest among synthetic organic chemists recently since it potentially enables highly efficient and/or unprecedented complex chemical transformations in a one-pot operation.[4]. The success of this strategy relies upon the simultaneous activation of two reacting partners by two different catalysts that operate in concert in two distinct catalytic cycles.[4c]. A prominent early example is the work of Hu, Gong, and co
Workers on cooperative Rh-/chiral phosphoric acid catalyzed multicomponent reactions of a-diazoesters, alcohols, and imines, which were converted into a-hydroxy b-amino esters with excellent enantio- and diastereocontrol.[5]

Summary

Introduction

We describe a highly diastereo- and enantioselective [4+3]-cycloannulation of ortho-quinone methides and carbonyl ylides to furnish functionalized oxa-bridged dibenzooxacines with excellent yields and stereoselectivity in a single synthetic step. We envisioned that a chiral phosphoric acid would form hydrogen-bonded o-QM A starting from ortho-hydroxy benzylalcohol 1 in one catalytic cycle, while in a second and separate catalytic cycle, carbonyl ylide B would be generated through Rh-catalyzed decomposition of a a-diazoester 2 tethered to an aryl ketone (Scheme 1).

Results

Conclusion