Search

A novel and highly enantioselective synthesis of hydroxyalkynyl esters and ethers through the asymmetric addition of alkynyl esters or ethers to aldehydes promoted by a cyclopropyl amino alcohol based zinc catalyst has been developed. The method afforded a library of new enantioenriched hydroxyalkynol esters and ethers (up to 93% yield; 95% ee), and it was compatible with a broad range of functional groups. Moreover, it could be used in the synthesis of carbon-chain-elongated enantioenriched hydroxyalkynol esters and (2R,5R)-musclide-A1, a cardiotonic potentiating principle from musk.

The first total syntheses of 9-epoxyfalcarindiol 1a and its diastereomer 1b have been achieved. Central to our approach were the Zn-cyclopropane-based amino alcohol catalyzed enantioselective alkynylation of acrolein, the diastereoselective addition of a diynic ester to an epoxy aldehyde, and the asymmetric Sharpless epoxidation of allylic alcohol catalyzed with L-(+)-diethyl tartrate and Ti(OiPr)4.

The first total syntheses of two marine natural products, (R)-strongylodiols C and D, with 99% ee were achieved. The key steps of the strategy include the zipper reaction of an alkyne, the asymmetric alkynylation of an unsaturated aliphatic aldehyde catalyzed with Trost's ProPhenol ligand, and the Cadiot-Chodkiewicz cross-coupling reaction of a chiral propargylic alcohol with a bromoalkyne.

The enantioselective Henry reaction between nitromethane and various aldehydes catalyzed by chiral amino alcohol–Zn complex was described. The resulting β-nitroalcohols were obtained in high yields and with moderate to good enantiomeric excesses.

The method can be applied to aromatic, aliphatic, and α,β-unsaturated aldehydes to give the corresponding propargylic alcohols.

The synthetic value of the present method is demonstrated by preparation of marine allynols (X).

Asymmetric catalysis: A highly enantioselective and efficient procedure for the amino alcohol-zinc-catalyzed addition of 1,3-diynes to various aromatic, α,β-unsaturated, and aliphatic aldehydes has been developed. The present catalytic system was successfully applied in the concise synthesis of natural products such as (S)-strongylodiols A and B (see scheme).

Aromatic as well as aliphatic aldehydes undergo the Henry reaction with nitromethane under catalysis of an in situ generated chiral amino alcohol—Zn complex to give the corresponding β-nitroalcohols in moderate to good enantioselectivity.

The method can be applied to aromatic, aliphatic, and α,β-unsaturated aldehydes to give the corresponding propargylic alcohols.