Synthesis of Asymmetric Allenes with Chiral Copper Nucleophiles

Significance

Optically active allenes possessing axial chirality can be prepared through a 1,4-addition of nucleophiles to optically active propargylic acceptors. Herein, the authors illustrate an alternative route to these compounds. Organocuprates bearing a chiral sulfinyl auxiliary are added to propargylic electrophiles allowing for the formation of both axial chirality and a stereocenter. High diastereoselectivity is observed, and the yields indicate a complete kinetic resolution of the racemic propynylmesylates. Since the synthesis of enantiopure propargylic nucleophiles is challenging, this alternative strategy presents a useful route to asymmetric allenes.

Review

K. M. Brummond, J. E. DeForrest Synthesis 2007, 795-818.

Comment

Benzylic organometallic reagents bearing a chiral sulfinyl group and a prochiral center are known to add to electrophiles generating two stereocenters (Chem. Eur. J. 2007, 13, 6179). Their S_N2′ addition to propynylbromides and propynylmesylates works well to give rise to chiral ­allenes with an α-stereocenter. Intriguingly, chiral resolution of the racemic propynylmesylate 2 is observed. Upon reaction with cuprate 1, the two isomers of 2 lead to the same product 3 with different rates. This demonstrates that one isomer reacts preferentially and that racemization of the propargylic stereocenter occurs under the reaction conditions. Although the yields show that ­racemization prior to S_N2′ addition is limited, in terms of potential dynamic kinetic resolution the results are very promising.