Application Of Chiral 1,1'-Binaphthols (BINOLs) In The Enantioselective Alkynylzinc Addition To Aldehydes

Optically active propargylic alcohols are very useful and important precursors to many chiral organic compounds including natural products, pharmaceutical compounds and macromolecules. Among various methods to synthesize optically active propargylic alcohols, the asymmetric alkynylation of aldehydes is particularly useful because it simultaneously forms a carbon-carbon bond and a chiral secondary alcohol center in one single step. Significant research has been conducted in this area in recent years.Up to date, there are four efficient systems that catalyze highly enantioselective alkynylzinc addition to aldehydes: the amino alcohol/Zn(OTf)2/Et3N system discovered by Carreira laboratory at ETH in Switzerland, the amino alcohol/Ti(O'Pr)4/Et2Zn system discovered by Wang laboratory at Lanzhou University in China, the BINOL/Ti(O'Pr)4/Me2Zn system discovered by Chan laboratory at the Hong Kong Polytechnic University, and the BINOL/Ti(O'Pr)4/Et2Zn system discovered by Pu laboratory at the University of Virginia in the USA. Among them Carreira's system is only catalytic for the reaction of aliphatic aldehydes. The methods of Wang and Chan are only good for the reaction of aromatic aldehydes. Our system is the only one that exhibits high enantioselectivity for the reaction of aromatic, aliphatic and a,P-unsaturated aldehydes.In this thesis, we explored the application of the BINOL/Ti(OiPr)4/Et2Zn system in the enantioselective alkynylzinc addition to aliphatic aldehydes, on the basis of our discovery for the reaction of aromatic aldehydes. We found that solvent, reaction time and reactants ratio are three key factors affecting the enantioselectivity. We have achieved the highly enantioselective alkynylzinc addition to aliphatic aldehydes byusing the optimal conditions. The results were published in Organic Letters.We then focused on the room temperature enantioselective alkynylzinc addition to aldehydes, in order to extend the application of the BINOL/TXO'PrVEtaZn system to the reaction of functional alkynes. We discovered that in the presence of hexamethylphosphoramide (HMPA), EtiZn, BINOL and Ti(O'Pr)4,various functional alkynes added to various aldehydes at room temperature with good enantioselectivity. The results were published in Proceedings of the National Academy of Sciences (USA).We also synthesized six 3,3'-disubstituted and 6,6'-disubstituted BINOLs, and a main chain BINOL polymer. We investigated their application in the enantioselective alkynylzinc addition to aldehydes, and have obtained useful information for further investigation.