Rhodium(Ⅰ)-catalyzed Ring Expansion Of Alkylideneazetidines And Its Asymmetric Catalysis

Domino reactions provide a simple,convenient and economical method for the synthesis of complex compounds.α,β-unsaturated compounds are among the most important building blocks in synthetic chemistry,and they are also common substrates for domino reactions catalyzed by transition metals.The domino"conjugate addition-electrophilic reactions"ofα,β-unsaturated compounds catalyzed by transition metals have been well developed and applied to the synthesis of complex compounds.In recent decades,inert bond activation catalyzed by transition metal has developed rapidly,which provides the conditions for the emergence of domino"conjugate addition-inert bond activation"mode.Only a few reports of conjugated addition combined with inert bond activation demonstrate the great potential of the synthesis strategy for building complex compounds.However,the synthesis strategy also faces the challenge that it is difficult to achieve accurate regulation of reactive intermediates.As a result,the strategy can only be applied to the special forms,such as the C-C bond activation of small rings and C(sp~2)-H bond activation.Based on the previously established domino conjugate addition/β-C cleavage/protonation,we proposed a reaction model of selective C(sp~3)-H bond activation guided by N atom coordination over rhodium catalyst.Using this reaction model,it is possible to realize domino conjugate addition-C(sp~3)-H bond activation reaction,and thus realize the ring expansion transformation of alkylideneazetidines to dihydropyrroles.In this paper,the rhodium(I)-catalyzed ring expansion of 2-(azetidin-3-ylidene)acetates was achieved by optimizing the key factors affecting the reaction,such as ligands and oxidants.Mechanistic investigations suggest a novel domino"conjugate addition/N-directedα-C(sp~3)–H activation"process.The asymmetric catalysis of the ring expansion transformation is realized by using Quinox P*with excellent enantioselectivities.The applications of dihydropyrrole products achieve convenient synthesis of multi-substituted functional pyrrolidines with excellent diastereoselectivities.