Carbene-catalysed reductive coupling of nitrobenzyl bromides and activated ketones or imines via single-electron-transfer process

Organocatalysis Science :Chemistry [Science] Synthetic Chemistry Methodology Q 540 01 natural sciences Article Science::Chemistry 0104 chemical sciences
DOI: 10.1038/ncomms12933 Publication Date: 2016-09-27T11:14:23Z
ABSTRACT
AbstractBenzyl bromides and related molecules are among the most common substrates in organic synthesis. They are typically used as electrophiles in nucleophilic substitution reactions. These molecules can also be activated via single-electron-transfer (SET) process for radical reactions. Representative recent progress includes α-carbon benzylation of ketones and aldehydes via photoredox catalysis. Here we disclose the generation of (nitro)benzyl radicals via N-heterocyclic carbene (NHC) catalysis under reductive conditions. The radical intermediates generated via NHC catalysis undergo formal 1,2-addition with ketones to eventually afford tertiary alcohol products. The overall process constitutes a formal polarity-inversion of benzyl bromide, allowing a direct coupling of two initially electrophilic carbons. Our study provides a new carbene-catalysed reaction mode that should enable unconventional transformation of (nitro)benzyl bromides under mild organocatalytic conditions.
SUPPLEMENTAL MATERIAL
Coming soon ....
REFERENCES (44)
CITATIONS (87)