Studies On The Reactions Of Propargylic Alcohol-Type Compounds And The Synthetic Applications

Propargylic alcohols and their derivatives are widely used as synthetic building blocks. During my Ph. D. study, I focused my attention on the carbometallation of3-aryl-substituted propargylic alcohols with Grignard reagents and Sn2’-or SN2-type coupling of4-ethynyl-oxetan-2-one with Grignard reagents, as well as their synthetic application.The whole dissertation can be divided into two parts:Part I:CuCl-Mediated carbometallation reaction of3-aryl-substituted secondary propargylic alcohols with Grignard reagents and its synthetic application.(1) We have achieved a highly regio-and stereoselective Cu(Ⅰ)-catalyzed carbometallation of3-aryl-substituted secondary propargylic alcohols with Grignard reagents followed by treatment with various electrophiles, affording stereodefined polysubstituted allylic alcohols. The alkyl, aryl, vinyl, and allyl groups from the Grignard reagents could be introduced to the2-position of the propargylic alcohols to form5-membered cyclic organometallic intermediates. Optically active allylic alcohols may be prepared without obvious racemization.(2) Sonogashira coupling of (Z)-3-iodoalk-2-en-l-ols with terminal propargyl alcohols affords4-alkyn-2-ene-1,6-diols, which undergo a cyclization-eliminaton-aromatization reaction catalyzed by Au(PPh3)Cl/AgOTf to provide polysubstituted2-(1-alkenyl)furans or a cyclization-coupling-eliminaton-aromatization reaction catalyzed by Pd(II) to provide polysubstituted2-(1,4-alkadienyl)-furans in moderate to excellent yields. The reaction is quite general:Different alkyl and aryl groups may be introduced into the3-,4-, and5-positions of the2-(1-alkenyl)furans or2-(1,4-alkadienyl)furans. The introduction of such substituents with C=C bond(s) to the furans will provide further opportunity for elaboration.Part Ⅱ:Catalytic highly regioselective coupling of 4-(trimethylsilylethynyl)-oxetan-2-one with Grignard reagents and its application.(1) A highly regio-and stereoselective SN2’-type coupling reaction of4-ethynyl-oxetan-2-ones with Grignard reagents affording β-allenoic acids. After a few steps,4,5-allenoic acids may be prepared. With a newly sterically demanding electrophilic iodination reagent optically active γ-butyrolactones were formed highly selectivily from these4,5-allenoic acids. The reaction shows high efficiency of axial chirality transfer and excellent Z/E selectivity providing chiral α,γ-disubstituted, β,γ-disubstituted, and y-butyrolactones to give very high diastereomeric and enantiomeric excess. The reaction has been successfully utilized in the synthesis of naturally occurring compounds (+)-cis-whisky lactone,(+)-cis-3-methyl-4-decanolide, and (-)-(R)-Z-5-(oct-l-enyl)oxacyclopentan-2-one.(2) On the other hand, we have achieved an Fe-catalyzed SN2coupling reaction of various optically active4-ethynyl-oxetan-2-ones with different Grignard reagents affording chiral4-alkynocic acids in good yield and excellent regio-selectivity. The products are readily to be protected by BnBr, followed by treating with TBAF and an asymmetric allenylation reaction with (R)-or (S)-diphenyl(pyrrolidin-2-yl)methanol and aldehydes to provide optically active4,5-allenoates.