AAA in KAT/DYKAT processes: first- and second-generation asymmetric syntheses of (+)- and (-)-cyclophellitol.
Kinetic resolutions and kinetic asymmetric transformations (KAT) as well as dynamic kinetic resolutions and dynamic kinetic asymmetric transformations (DYKAT) are important synthetic protocols. The feasibility of KAT and DYKAT processes for asymmetric allylic alkylations (AAA) is explored utilizing a single substrate--conduritol B tetraesters. Both processes can be performed resulting in excellent enantioselectivity. The impact of nucleophile and leaving group on the effectiveness of each is outlined. The ability to differentiate the various hydroxyl groups is also described. For this purpose, 4-tert-butyldimethylsiloxy-2,2-dimethylbutyric acid was developed as a nucleophile. The utility of effecting KAT/DYKAT processes through the Pd-catalyzed AAA reaction is demonstrated by efficient syntheses of both enantiomers of the potent glycosidase inhibitor cyclophellitol.
Trost
B M
BM
Department of Chemistry, Stanford University, CA 94305-5080, USA. bmtrost@stanford.edu
Patterson
D E
DE
Hembre
E J
EJ
D000363:Agaricales / Q000737:chemistry; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry; D002384:Catalysis; D003511:Cyclohexanols / Q000138:chemical synthesis* / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D008722:Methods; D012211:Rhenium / Q000737:chemistry; D013237:Stereoisomerism; D001617:beta-Glucosidase / Q000037:antagonists & inhibitors
D019380:Anti-HIV Agents; D003511:Cyclohexanols; D004791:Enzyme Inhibitors; C063285:cyclophellitol; D012211:Rhenium; D001617:beta-Glucosidase