Stereoselectivity control in Rh-catalyzed β-OH elimination for chiral allene formation

Stereoselectivity control and understanding in the metal-catalyzed reactions are fundamental issues in catalysis. Here we report sterically controlled rhodium-catalyzed S(N)2'-type substitution reactions of optically active tertiary propargylic alcohols with arylmetallic species affording the non-readily available enantioenriched tetrasubstituted allenes via either exclusive syn- or anti-beta-OH elimination, respectively, under two sets of different reaction parameters. Detailed mechanistic experiments and density functional theory (DFT) studies reveal that the exclusive anti-Rh(I)-OH elimination is dictated by the simultaneous aid of in situ generated boric acid and ambient water, which act as the shuttle in the hydroxy relay to facilitate the Rh(I)-OH elimination process via a unique ten-membered cyclic transition state (anti-TS2_u). By contrast, the syn-Rh(III)-OH elimination in C-H bond activation-based allenylation reaction is controlled by a four-membered cyclic transition state (syn-TS3) due to the steric surroundings around the Rh(III) center preventing the approach of the other assisting molecules. Under the guidance of these mechanistic understandings, a stereodivergent protocol to construct the enantiomer of optically active tetrasubstituted allenes from the same starting materials is successfully developed.

Automated summary

This study reports the synthesis of non-readily available enantioenriched tetrasubstituted allenes through rhodium-catalyzed reactions controlled by steric hindrance. Detailed mechanistic experiments and density functional theory studies reveal the mechanism behind the formation of different stereochemistry under different reaction conditions. A stereodivergent protocol to construct the enantiomer of optically active tetrasubstituted allenes from the same starting materials is successfully developed based on these mechanistic understandings.