Contrasteric regiocontrol in rhodium-catalyzed hydrogenative couplings of nonsymmetric 1,3-diynes to ethyl glyoxalate

To probe the origins of regioselection in rhodium-catalyzed hydrogenative couplings of 1,3-diynes to ethyl glyoxalate, a series of structurally related nonsymmetric 1,3-diynes, 1a-14a, were prepared and surveyed. Nonsymmetric 1,3-diynes 1a-8a possess different degrees of alkyl substitution at the propargylic carbons. Unusual contrasteric regioselectivity is observed, often with a complete preference for coupling at the diyne terminus proximal to the more substituted propargylic center. Couplings to diynes 9a-14a are meant to probe the effects of heteroatom substitution at the propargylic position vis-à-vis partitioning of regioisomeric coupling manifolds. Heteroatom substitution exerts only a modest influence on the regiochemistry of coupling, except in the case of (trimethylsilyl)methyl-substituted diynes 13a and 14a. The observed trends suggest that substituents at the diyne termini compete for stabilization of intermediate regioisomeric rhodium-alkyne jr-complexes via hyperconjugative interactions, with regio-determining oxarhodacycle formation occurring from the more stable jr-complex.