Structural diversification of the aminobicyclo[4.3.0]nonane skeleton using alkynylsilyl-derived allylic trichloroacetimidates?

Organic & Biomolecular Chemistry Pub Date: 2017-03-14 DOI: 10.1039/C7OB00456G

Abstract

The amino substituted bicyclo[4.3.0]nonane is a molecular scaffold found in a wide range of natural products and medicinal agents. Despite this, synthetic methods for the general preparation of this structural motif are sparse. Here we evaluate a diastereoselective approach for the preparation of vinylsilyl derived aminobicyclo[4.3.0]nonanes using a one-pot multi-bond forming process involving a Pd(II)-catalysed Overman rearrangement, a Ru(II)-catalysed ring closing enyne metathesis reaction, followed by a hydrogen bonding directed Diels–Alder reaction. We show that a benzyldimethylsilyl-substituted alkene analogue is amenable to further functionalisation and the late stage generation of diverse sp3-rich, drug-like aminobicyclo[4.3.0]nonane scaffolds with up to six stereogenic centres.

Graphical abstract: Structural diversification of the aminobicyclo[4.3.0]nonane skeleton using alkynylsilyl-derived allylic trichloroacetimidates
Recommended Literature