Asymmetric Syntheses and Applications of Propargylic Alcohols and Amines

Ying, Jun, Chemistry - Graduate School of Arts and Sciences, University of Virginia
Pu, Lin, Department of Chemistry, University of Virginia

Chiral propargylic alcohols and amines are important building blocks for the synthesis of numerous pharmaceuticals, biologically active compounds and natural products. A number of catalytic systems have been reported for the highly enantioselective alkynylation of aldehydes and imines to access chiral propargylic alcohols and amines.
Using the chiral propargylic alcohols prepared from the asymmetric alkyne addition to aldehydes catalyzed by the BINOL-Ti(OiPr)4-Et2Zn-Cy2NH catalyst system, we have prepared a series of chiral propargylic triene-ynes with high enantiomeric purity (up to 92% ee). We have found that these compounds can undergo an efficient one-pot Rh(I)-catalyzed domino PK/DA cycloaddition to generate the multicyclic products with high chemoselectivity and stereoselectivity (up to 94% ee). These products contain the core structure of mangicol A, a natural product possessing significant anti-inflammatory activity.
A series of chiral propargyl 2,4-hexadienyl ethers are also found to undergo a highly chemo- and stereoselective PK/DA cycloaddition to generate the tetracyclic products (up to 88% ee). This strategy is very efficient for the asymmetric synthesis of polycyclic compounds such as polyquinanes.
A 3,3’-di(1-diphenylmethylpiperazinyl)methyl H8BINOL compound has been developed to catalyze the asymmetric reaction of both alkyl and aryl alkynes with N-(diphenylphosphinoyl)imines in the presence of Et2Zn and Ti(OiPr)4. It exhibits unprecedented high enantioselectivity (up to 85% ee) for the alkyl alkyne addition to the N-(diphenylphosphinoyl)imines.
A Au(III)-catalyzed regiospecific hydration of N-(diphenylphosphinoyl) propargylic amines has been developed to produce various β-amino ketones under mild conditions. The high enantiomeric purity of a chiral N-(diphenylphosphinoyl) propargylic amine (85% ee) is maintained after the hydration which makes method useful for the asymmetric synthesis of chiral β-amino ketones.

PHD (Doctor of Philosophy)
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