Chemoselective Reduction of Sterically Demanding N,N-Diisopropylamides to Aldehydes
Peihong Xiao, Zhixing Tang, Kai Wang, Hua Chen, Qianyou Guo, Yang Chu, Lu Gao* and Zhenlei Song*
*Key Laboratory of Drug-Targeting of Education Ministry and
Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan
University, Chengdu 610064, P. R. China, Email: lugao
scu.edu.cn,
zhenleisongscu.edu.cn
P. Xiao, Z. Tang, K. Wang, H. Chen, Q. Guo, Y. Chu, L. Gao, Z. Song, J. Org. Chem., 2018, 83, 1687-1700.
DOI: 10.1021/acs.joc.7b02868
see article for more reactions
Abstract
In a sequential one-pot process for the conversion of sterically demanding N,N-diisopropylamides to aldehydes, amides are activated with EtOTf to form imidates, which are reduced with LiAlH(OR)3 [R = t-Bu, Et] to give aldehydes by hydrolysis of the resulting hemiaminals. The non-nucleophilic base 2,6-DTBMP remarkably improves reaction efficiency. The reaction tolerates various reducible functional groups, including aldehyde and ketone.
see article for more examples
proposed reaction mechanism
Key Words
reduction of amides, lithium tri-tert-butoxyaluminum hydride
ID: J42-Y2018
