Stereoselective copper-catalyzed heteroarene C–H functionalization/Michael-type annulation cascade with α-diazocarbonyls

Abstract

A stereoselective, copper-catalyzed, arene C(sp2)–H functionalization/Michael-type annulation reaction involving α-diazocarbonyl compounds has been developed. The method features low catalyst loadings, high yields, and excellent regio and stereoselectivity, in the synthesis...

Recent Progress on Copper-Catalyzed C–C Bond Formation via C(sp2)–H Insertions Using Diazo and Related Compounds

“…Very recently, Grover’s group demonstrated an elegant approach for the Cu(II)-catalyzed C(sp 2 )–H bond functionalization and cascade annulation of heteroaromatic compounds (Scheme 30 ). 48 They commenced their investigation by utilizing functionalized indoles containing alkynyl-ester electrophiles 66 and α-diazocarbonyl compounds 38 as starting materials in the presence of a catalytic amount of Cu(tfacac) 2 . Differently substituted ester moieties on the indole substrates delivered the desired annulated products 67a – d in good to moderate yields.…”

“…Based on mechanistic findings, Grover suggested that the copper catalyst played a dual role in this transformation. 48 The diazocarbonyl compound 38a was initially activated by the copper salt to produce the reactive carbenoid intermediate 72 , which then produced the copper intermediate 73 via C(sp 2 )–H functionalization of substrate 66 . The enolate (derived from a carbonyl compound) and the alkyne electrophile 74 were both activated by the copper catalyst and underwent a 5- exo -dig syn addition, resulting in the formation of cyclized intermediate 75 .…”