Zirconium-catalyzed Asymmetric Carboalumination of Alkenes (ZACA reaction): It's development and application to the synthesis of deoxypolypropionates and other chiral compounds
Abstract
In this thesis work, an extensive study was carried out on the synthesis of deoxypolypropionates via zirconium-catalyzed asymmetric carboalumination of alkenes. Three major protocols were developed and discussed. (1) The ZACA (Zr-catalyzed Asymmetric Carboalumination) reaction based on 3-buten-1-ol were developed. By higher alkylalumination of unprotected 3-butene-1-ol, the (R)- or (S)-3-methyl-1-alkanol could be produced with 95% enantiopurity in 90% yield in one step. An efficient 3-step protocol was developed based on this method for the construction of α-monoheterofunctional deoxypolypropionates. (2) ZACA reaction based on styrene combined with the in situ negishi cross-coupling tandem process were developed. This method provide an efficient protocol to the synthesis of α,ω-diheterofunctional deoxypolypropionates starting with anti-dimethyl motif. (3) We discovered the “One-Pot” conversion of inexpensive free allyl alcohol to (R)- or (S)-2-methyl-1-propanol (with or without TBS-protection) with 91% enantiopurity in 82% yield. An efficient protocol was developed based on this method for the construction of α,ω-diheterofunctional deoxypolypropionates starting with syn-dimthyl motifes. Natural products synthesized with our novel protocols were discussed, for example the major acid component of preen-gland wax of graylag goose, Anser anser; C5-C13 fragment of (-)-callystatin A; key intermediates for the synthesis of ionomycine and doliculide. In the fifth charpter, the ZACA reaction of the 1,4-pentadiene was discussed.
Degree
Ph.D.
Advisors
Negishi, Purdue University.
Subject Area
Organic chemistry
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