Alkyne Addition to aldehyde

Jiang has expanded the Carreira method of alkyne addition to aldehydes to include other ligands and Zn(II) salts (Eq. 13) [17]. Thus use of stoichiometric quantities of Zn(II) difluoromethane sulfonate salt and (lS,2S)-3-(tert-butyldi-methylsilyloxy)-2-N,N-dimethylamino-l-(p-nitrophenyl)propane-l-ol (3) in the addition reaction can afford propargylic alcohols in high ee. Difluoromethanesul-fonic acid is prepared from 3,3,4-,4-tetrafluoro[1.2]oxathietane the amino alcohol has been used in the synthesis of chloramphenicol and is also readily accessible. Application of a combination of this same amino alcohol ligand with Zn(OTf)2 has also been shown to afford products in high yield and ee in addition reactions (Eq. 14) [18]. 

Scheme 7.31 Asymmetric alkyne addition to aldehydes using BINOL.

Jiang has subsequently reported the use of amino alcohol 319 in Zn-cata-lyzed enantioselective alkyne additions to aldehydes [192]. In an important development of the method, the substrate scope was expanded also to include non-enolizable a-ketoesters, such as 318 (Equation 22) [193]. 

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