Direct asymmetric alkynylation

Scheme 3.20 Direct asymmetric alkynylation and proposed reaction pathway.

One of the severest challenges of asymmetric synthesis is the direct enantioselective construction of quaternary stereogenic centers. Brian Pagenkopof of the University of Texas has reported (Chem. Communications 2003 2592) that alkynyl aluminum reagents will open a trisubstituted epoxide such as 10 at the more substituted center, with inversion of absolute configuration. As the epoxide 10 is available in high from 9 by the method of Yian Shi of Colorado State (J. Am. Chem. Soc. 119 11224, 1997), this opens a direct route to quaternary cyclic stereogenic centers. 

A dramatic application was the asymmetric synthesis of epibatidine 70 by Simpkins.18 Diels-Alder reaction of the deactivated pyrrole 63 with the alkynyl sulfone 64 gave the bicyclic core 65 of epibatidine. Selective reduction gave the compound 66 needed for epibatidine, but in racemic form. A directed lithiation (chapter 7) and sulfonation led to achiral bis sulfone 67. 

Alkynylzinc reagents. The direct alkynylation of aldehydes is subject to asymmetric induction in the presence of a chiral base such as (-l-)-Af-methylephedrine. Addition to the C=N bond of A-tosylimines and nitrones by this procedure is also successful. ... 

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