New Chiral Route to (-)-Swainsonine via an Aqueous Acylnitroso Cycloaddition Approach

Article abstract of DOI:10.1021/jo00085a026

A new noncarbohydrate-based enantioselective approach to (-)-swainsonine (1) is described, in which the aqueous intramolecular Diels-Alder reaction of a chiral acylnitroso diene has been employed as a key reaction.The intramolecular cycloaddition of the chiral hydroxamic acid 9, available from D-malic acid in 10 steps, with Pr4NIO4 was conducted under the conventional nonaqueous conditions using CHCl3 as a solvent, whereupon intermediacy acylnitroso compound 10 cyclized spontaneously to give the trans- and cis-1,2-oxazinolactams 11 and 12 with a low diastereoselection af 1.3:1 in 76percent combined yield.When the corresponding reaction was performed in water, it led to significant enhancements of trans selectivity of 4.1:1 as well as combined yield (89percent).The trans adduct 11 was subjected to reductive N-O bond cleavage followed by diastereoselective hydroxylation with OsO4 to provide the 1,2-glycol 21, which was then converted to the amino alcohol 25.Intramolecular cyclodehydration of 25 with CBr4/PPh3/Et3N and subsequent deprotection furnished (-)-swainsonine (1).