Hydrogen-Free Alkene Reduction in Continuous Flow

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.

In Situ Generation of Diimide from Hydrazine and Oxygen: Continuous‐Flow Transfer Hydrogenation of Olefins

“…Herein, we present a highly intensified and catalyst‐free method for the in situ generation of diimide from hydrazine monohydrate (N 2 H 4 ⋅H 2 O) and molecular oxygen in continuous‐flow mode. The diimide generated by this novel gas–liquid flow system is applied to the selective reduction of a variety of alkenes to provide the corresponding alkanes in excellent yields and high selectivity 12. Notably, the high surface‐to‐volume area in combination with high‐temperature/high‐pressure conditions (novel process windows)13 results in remarkably short reaction times (10–30 min) employing only 4–5 equivalents of the hydrazine precursor.…”

In Situ Generation of Diimide from Hydrazine and Oxygen: Continuous‐Flow Transfer Hydrogenation of Olefins

“…Notably, the computational results provided valuable guidance prior to experimental assessment of the reactivity (Table 1; see also Table S4). Most of the chosen substrates (1-5, 7, 9) underwent total consumption without any need for reoptimization from the conditions used for allylbenzene, whereas some other olefins required a larger excess of hydrazine (6,8,10), or a combination of more hydrazine, longer reaction times, and slightly increased temperatures (11,12). In terms of selectivity, olefins containing nitro groups (1, 3) resulted in the desired products in near quantitative yields.…”

“…The diimide generated by this novel gasliquid flow system is applied to the selective reduction of a variety of alkenes to provide the corresponding alkanes in excellent yields and high selectivity. [12] Notably, the high surface-to-volume area in combination with high-temperature/high-pressure conditions (novel process windows) [13] results in remarkably short reaction times (10-30 min) employing only 4-5 equivalents of the hydrazine precursor.…”

The assembly and use of continuous flow systems for chemical synthesis

“…Furthermore, fluorination using SF 6 , 43 biocatalysis, 44 controlled polymer growth, 45 and a range of synthetic transformations have been mediated on 'in-lab' constructed systems. 16,[46][47][48][49][50][51][52][53][54][55][56] As with traditional organic synthesis, a range of accessories is required for continuous-flow synthesis. Typically, systems are operated with a back pressure regulator to ensure fluid homogeneity as it proceeds through the reactor; no back pressure can decrease fluid residence times due to lack of resistance (Fig.…”