1352791-76-4Relevant articles and documents
Asymmetric synthesis of functionalized bicyclic β-amino alcohols by cascade hydrometallation-cyclization-reduction of glycinyl-substituted alkenylsulfoximines - Application to the synthesis of an aggrecanase inhibitor mimic
Acikalin, Serdar,Raabe, Gerhard,Runsink, Jan,Gais, Hans-Joachim
experimental part, p. 5991 - 6008 (2012/01/05)
The treatment of exocyclic alkenylsulfoximines, which carry an α-glycinyl group at the allylic position, with HAliBu2 caused cascade hydroalumination-cyclization-reduction and delivered the corresponding enantio- and diastereopure sulfoximine-substituted bicyclic β-amino alcohols with a bicyclo[3.3.0]octane and bicyclo[4.3.0]nonane skeleton in high yields. Three consecutive stereogenic C atoms of the bicyclic β-amino alcohols were generated in the cascade reactions with high diastereoselectivities. Application of the hydroalumination-cyclization- reduction to a ketal-substituted six-membered exocyclic alkenylsulfoximine afforded the corresponding sulfoximine-substituted β-amino alcohol with aketal-functionalized bicyclo[4.3.0]nonane skeleton. Reduction of a sulfoximine-substituted β-amino alcohol gave the parent β-amino alcohol, whereas its oxidative deamination afforded the corresponding sulfonyl-substituted β-amino alcohol. The treatment of a sulfoximine-substituted β-amino alcohol with chloro- and iodoformates stereoselectively furnished the corresponding chloro- and iodo-substituted β-amino alcohols. Finally, the feasibility of a dehydration and elimination of sulfoximine-substituted β-amino alcohols with formation of the corresponding amino-substituted alkenylsulfoximine and allylic amine was demonstrated. An enantio- and diastereopure protected aggrecanase inhibitor mimic was synthesized in high yield starting from the sulfoximine-substituted bicyclic β-amino alcohol with a bicyclo[4.3.0]nonane skeleton and (R)-2-(3-benzyloxy)benzyl-4-tert-butoxy-4-oxobutanoic acid. Coupling of both building blocks gave the corresponding succinamide, the tert-butoxycarbonyl group of which was converted into the corresponding O-benzyl-hydroxycarbamoyl group. The treatment of glycinyl-substituted alkenylsulfoximines with HAliBu2 gave from a cascade hydroalumination-cyclization-reduction sulfoximine-substituted bicyclic β-amino alcohol in high yields and diastereoselectivities. Coupling of a bicyclic β-amino alcohol with a chiral succinic acid derivative afforded a protected aggrecanase inhibitor mimic.
