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Rapid Generation and Safe Use of Carbenes Enabled by a Novel Flow Protocol with In‐line IR spectroscopy
Author(s) -
Müller Simon T. R.,
Murat Aurélien,
Maillos Delphine,
Lesimple Patrick,
Hellier Paul,
Wirth Thomas
Publication year - 2015
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201500416
Subject(s) - diazo , flow chemistry , extraction (chemistry) , chemistry , decomposition , aryl , flow (mathematics) , combinatorial chemistry , materials science , chromatography , process engineering , organic chemistry , catalysis , physics , alkyl , mechanics , engineering
A powerful new continuous process for the formation and use of donor/acceptor‐substituted carbenes is described. The safety profile of diazo group transfer on methyl phenylacetate was determined including kinetic studies in batch and in flow using in‐line IR analysis. Batch work‐up and liquid chromatography were circumvented by developing an optimized liquid/liquid flow separation method providing aryl diazoacetates in high purity. Fast screening of reaction conditions in flow with in‐line IR analysis allowed rapid reaction optimization. Finally, a multistep process of diazo group transfer, extraction, separation and subsequent diazo decomposition combined with multiple XH insertion reactions was established.