Highly Enantioselective Addition Of Terminal Alkynes To Aldehydes Catalyzed By A New Chiral Sulfonamide Alcohol/Ti(OⁱPr)₄/Et₂Zn/R₃N Catalyst System

Asymmetric carbon-carbon bond formation is an area of intense research in organic chemistry.One of the most powerful methods for the catalytic asymmetric generation of carbon-carbon bonds is the enantioselective addition of organometallic reagents to aldehydes or ketones.The catalytic asymmetric alkynylzinc addition to aldehydes has recently generated a tremendous amount of interest because the addition can provide a very convenient route to the corresponding chiral secondary propargylic alcohols which have been identified as versatile building blocks for fine chemicals,pharmaceuticals,and natural products.While the vast majority of current alkynylation protocols focus solely on the addition of phenyl acetylene to aldehydes, there have been some significant advances to generalize the alkyne.For the possible further transformations of functionalized group,the asymmetric addition of functionalized alkynes to carbonyls should have more potential applications than phenylacetylene for the synthesis of complex bioactive natural products.Herein,we report a highly enantioselective catalyst system for the enantioselective addition of various terminal alkynes to aldehydes.(1)Some simple derivatives 8-11 of natural amino acids were successfully synthesized and used as chiral ligands in the catalytic asymmetric addition of trimethylsilylacetylene and ethynylcyclohexene to aldehydes.Ligand 8 gave high enantioselectivity and chemical yield while other ligands seemed to be inefficient. 1-heptyne was at fist time used as the nucleophile in the asymmetric addition of alkynes to aldehydes catalized by sulfonamide alcohol/Ti(Oⁱpr)₄/ZnEt₂ system.(2)With use of N,N-diisoproylethylamine(DIPEA)as an additive,the transfer of alkynyl to aldyhyde proceeded smoothly,in only two hours,to give the desired propargylic alcohols in high yield and up to＞99%ee in the enantioselective addition of terminal alkynes to aldehydes. (3)Tertiary amine base(R₃N)was introduced inβ-sulfonamide alcohol(8)/ Ti(OⁱPr)₄/ZnEt₂ system,the addition of which greatly facilitated the formation of the alkynylzinc reagents and significantly improved our primary catalytic system.