No abstract

The first continuous hydrogenation that requires neither H 2 nor metal catalysis generates diimide by a novel reagent combination. The simple flow reactor employed minimizes residence time by enabling safe operation at elevated temperature.Herein we report the first continuous method for H 2 -free hydrogenation 1 via diimide (diazene, HN=NH 1) 2 generated from the new reagent combination of N,Obistrifluoroacetylhydroxylamine 2 and hydroxylamine (Scheme 1). This transformation proceeds with significantly reduced reaction times relative to batch reductions, enjoys a wide substrate scope with excellent functional group compatibility, and features a userfriendly flow reactor easily constructed from commercial components.(1) Pioneering flow hydrogenation protocols and instrumentation have been developed. Homogeneous: (a) Newton, S.; Ley, S. V.; Arcé, E. C.; Grainger, D. M. Adv. Synth. Catal. 2012, 354, 1805 Mercadante, M. A.; Kelly, C. B.; Lee, C. X.; Leadbeater, N. E. Org.

[reaction: see text] The total synthesis of the interleukin-1beta converting enzyme inhibitor EI-1941-2 was achieved utilizing tandem oxidation/oxa-electrocyclization/oxidation to access a key alpha-pyrone intermediate. Support for the tandem reaction mechanism was obtained by evaluation of a stepwise oxidation protocol.

A H2‐free continuous flow hydrogenation protocol is presented.

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