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 the low-loading of (1.0 mol% to 500 ppm) Rawal’s quinine-squaramide-catalyst followed by in situ acid-catalysed tert-hydroxy group acetylation constructed the high-yielding chiral bicyclo[3.2.1]octanes in a up to single dr and er through [3+2]-annulations at the ambient conditions. These kind of rare low organocatalyst-loading, asymmetric, one-pot, gram-scale annulations would 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 is highlighting the importance of developing present catalytic protocol for the synthesis of both achiral and chiral version of functionally rich bicyclo[3.2.1]octanes.