Nickel-catalyzed intermolecular reductive couplings of alkynes and aldehydes ; Enantioselective synthesis of (-)-terpestacin and structural revision of siccanol using catalytic stereoselective fragment couplings and macrocyclizations

Abstract

I. Nickel-Catalyzed Intermolecular Reductive Coupling of Alkynes and Aldehydes. Alkynes and aldehydes were coupled reductively in a single catalytic reaction to yield di- and trisubstituted allylic alcohols with high stereoselectivity and regioselectivity. In most cases, a 1:1 ratio of alkyne to aldehyde was sufficient for efficient coupling. The yield and regioselectivity were strongly dependent on the phosphine ligand, but the allylic alcohols formed were invariably the products of cis addition to the alkyne. [Image] ... II. Enantioselective Synthesis of (-)-Terpestacin and Structural Revision of Siccanol Using Catalytic Stereoselective Fragment Couplings and Macrocyclizations. (-)-Terpestacin (1), (naturally occurring enantiomer) and (+)-1 -epi-terpestacin (2) were prepared using catalyst-controlled, stereoselective intermolecular reductive couplings of alkyne 9 and aldehyde 10. Related to enantioselective methods developed in our laboratory, these stereoselective fragment couplings were instrumental in confirming that "siccanol" is not 11-epi-terpestacin, but in fact is (-)-terpestacin itself.