| Research Abstract |
We report herein the highly stereoselective construction of three contiguous stereogenic centers in tandem Michael addition and Meerwein-Ponndorff-Verley (MPV) reduction of the α,β-unsaturated ketones with chiral mercapto alcohol. The reaction of α,β-unsaturated ketones with (-)-10-mercaptoisobornenol in the presence of Me_2AlCl involved asymmetric protonation at ctposition in the Michael addition step and 1,i-hydride shift to reduce carbonyl group. Since the mercapto alcohol behaves as a chiral template during the tandem reaction proceeds, the conformation of the Michael adducts (10-membered transition-state) was rather restricted to control the stereochemistry of the products. The reaction of, α,β-disubstituted vinyl phenyl ketone with (-)-10-mercaptoisobornenol afforded excellent results accompanying the stereoselective construction of three contiguous chiral carbons in the absence ofadditives. On the other hand, the range of the stereoselectivities of the reaction choosing α,β-disubstituted vinyl alkyl ketone as a substrate was potently affected by the pH values of additives. After being scrutinized many additives, pentafluorobenzoic acid (pKa 1.7) provided the best result to afford the high stereoselectivity. Furthermore, isoborneol moiety that is the chiral auxiliary in the reaction was removed by taking advantage of Wagner-Meerwein rearrangement to afford enatiomerically pure 1,3-mercapto alcohols with three contiguous chiral centers. Whisky lactones and cognac lactones were facilely prepared in optically pure form by using the tandem reaction mentioned above. In addition, we succeeded in preparing odorless thiols (Dodesyl-SH) and odorless sulfides (Dodesyl-S-Me), which carry 10 carbons as the alkyl chain, on the basis of the fact (-)-10-mercapto-isobornenol smells faint. Corey-Kim and Swern oxidations, dealkylation with AlCls-thiols combination, and reductive work up of ozonolysis became,attainable under odorless conditions by using the odorless reagents
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