A Continuous Flow Solution to Achieving Efficient Aerobic Anti‐Markovnikov Wacker Oxidation

Abstract

An aerobic anti-Markovnikov Wacker oxidation for the flow-synthesis of arylacetaldehydes is reported. In the process, flow chemistry techniques have provided a means to control and minimise the over-oxidation of sensitive products. The reaction showed general applicability to various functionalised styrenes and provided a process capable of a multi-gram scale.

Chemical reaction engineering, process design and scale-up issues at the frontier of synthesis: Flow chemistry

“…The latter sensibly improved selectivity at quantitative conversion [36]. Styrenes were also synthesized in flow by the same group from different aryl iodides and ethylene [37], as well as unsymmetrical stylbenes [38].…”

Liquid phase oxidation chemistry in continuous-flow microreactors

“…A continuous-flow aerobic anti-Markovnikov Wacker oxidation of styrenes using molecular oxygen as oxidant. 166 Kappe et al constructed a continuous-flow reactor for the preparation of acetophenone and benzoic acid from ethyl benzene. 167 The combination of CoBr2 (2.5 mol%) in combination with Mn(OAc)2 (2.5 mol %) in acetic acid was used as active catalytic system.…”

The Use of Gases in Flow Synthesis

“…68 A conventional 'tube in tube' 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 Oxygen has also used in continuous flow aerobic anti-Markovnikov Wacker oxidation. 69 Optimisation of the reaction temperature, oxygen pressure and water content was performed to achieve a good conversion and selectivity towards the desired aldehyde product. The reaction was successfully performed on a selection of styrenes possessing both electron withdrawing as 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 …”