Constructing chiral bicyclo[3.2.1]octanes via low-loading organocatalysis

Abstract

Multi-centric ambident 2-hydroxy-3,5-dialkyl-p-quinones selectively reacted with α-alkylnitroethylenes under a low-loading of (1.0 mol% to 500 ppm) Rawal's quinine-squaramide-catalyst, followed by in situ acid-catalysed tert-hydroxy group acetylation to construct high-yielding chiral bicyclo[3.2.1]octanes in up to single dr and er through [3 + 2]-annulations under ambient conditions. These kinds of rare low organocatalyst-loading, asymmetric, one-pot, gram-scale annulations will be highly inspirational to plan a greater number of low-loading organocatalytic asymmetric reactions in both academia and industry. Additionally, bicyclo[3.2.1]octanes are basic skeletons of many natural products and drugs, which highlights the importance of developing the present catalytic asymmetric protocol for the synthesis of both achiral and chiral versions of functionally rich bicyclo[3.2.1]octanes.