Synthesis of Substituted β‐Functionalised Styrenes by Microwave‐Assisted Olefin Cross‐Metathesis and Scalable Synthesis of Apremilast

Abstract Preparation of diversely substituted β‐functionalised styrenes by microwave‐assisted olefin cross‐metathesis (CM) is described. This method can be also employed in the synthesis of β‐deuterated α,β‐unsaturated sulfones from inexpensive allylbenzenes, though unprecedented one‐pot isomerisation/deuteration/cross‐metathesis sequence. One of such obtained CM products has been utilised in a new scalable synthesis of Apremilast ( 6 ), a potent and orally active phosphodiesterase 4 and tumour necrosis factor‐α inhibitor. The same strategy was used in synthesis of an optical antipode of 6 , ent‐Apremilast.