Carbene-catalysed reductive coupling of nitrobenzyl bromides and activated ketones or imines via single-electron-transfer process.
Benzyl 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.
Division of Chemistry &Biological Chemistry, Nanyang Technological University, School of Physical &Mathematical Sciences, Singapore 637371, Singapore.
Bao-Sheng
BS
Li
Division of Chemistry &Biological Chemistry, Nanyang Technological University, School of Physical &Mathematical Sciences, Singapore 637371, Singapore.
Yuhuang
Y
Wang
Division of Chemistry &Biological Chemistry, Nanyang Technological University, School of Physical &Mathematical Sciences, Singapore 637371, Singapore.
Rupert S J
RS
Proctor
Division of Chemistry &Biological Chemistry, Nanyang Technological University, School of Physical &Mathematical Sciences, Singapore 637371, Singapore.
Yuexia
Y
Zhang
Division of Chemistry &Biological Chemistry, Nanyang Technological University, School of Physical &Mathematical Sciences, Singapore 637371, Singapore.
Richard D
RD
Webster
Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Huaxi District, Guiyang 550025, China.
Song
S
Yang
Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Huaxi District, Guiyang 550025, China.
Baoan
B
Song
Division of Chemistry &Biological Chemistry, Nanyang Technological University, School of Physical &Mathematical Sciences, Singapore 637371, Singapore.|Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Huaxi District, Guiyang 550025, China.
Yonggui Robin
YR
Chi
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