TY  - JOUR
AB  - The access towards chiral nitriles remains crucial in the synthesis of several pharmaceuticals. One approach is based on metal-catalyzed dehydration of chiral aldoximes, which are generated from chiral pool-derived aldehydes as substrates, and the use of a cheap and readily available nitrile as co-substrate and water acceptor. Dehydration of N-acyl alpha-amino aldoximes such as N-Boc-l-prolinal oxime catalyzed by copper(II) acetate provides access to the corresponding N-acyl alpha-amino nitriles, which are substructures of the pharmaceuticals Vildagliptin and Saxagliptin. In this work, a detailed investigation of the formation of the amide as a by-product at higher substrate loadings is performed. The amide formation depends on the electronic properties of the nitrile co-substrate. We could identify an acceptor nitrile which completely suppressed amide formation at high substrate loadings of 0.5 m even when being used with only 2 equivalents. In detail, utilization of trichloroacetonitrile as such an acceptor nitrile enabled the synthesis of N-Boc-cyanopyrrolidine in a high yield of 92% and with full retention of the absolute configuration. © 2021 The Authors. Published by Wiley-VCH GmbH.
DA  - 2021
DO  - 10.1002/open.202100230
LA  - eng
PY  - 2021
TI  - Process Development of the Copper(II)-Catalyzed Dehydration of a Chiral Aldoxime and Rational Selection of the Co-Substrate
UR  - https://nbn-resolving.org/urn:nbn:de:0070-pub-29598735
Y2  - 2024-11-22T13:39:51
ER  -