ABSTRACT
A concise, organocatalytic, enantioselective route to the γ-lactam core of the oxazolomycins was developed. Key steps include a Lewis base-catalyzed, Michael proton transfer-lactamization organocascade, a one-pot N-methylation and diastereoselective α-alkylation, a diastereotopic group-selective reduction, a substrate-directed allylic hydroxylation, and a lanthanide-mediated organolithium addition to append the side chain. A formal synthesis of (+)-neooxazolomycin via interception of a Kende intermediate, accessed in 10 steps (previously 24 steps from α-d-glucose), enabled confirmation of the relative and absolute stereochemistry.
Subject(s)
Bridged Bicyclo Compounds, Heterocyclic/chemical synthesis , Oxazoles/chemistry , Oxazoles/chemical synthesis , Pyrrolidinones/chemistry , Spiro Compounds/chemistry , Alkylation , Bridged Bicyclo Compounds, Heterocyclic/chemistry , Catalysis , Molecular Structure , StereoisomerismABSTRACT
The first total synthesis of trichoaurantianolides C and D is described. An enantiocontrolled pathway leads to rapid construction of the tricyclic carbon skeleton and establishes the trans-dimethyl geometry of the quaternary bridgehead carbons via a reductive cyclization. Application of the π-allyl Stille cross-coupling leads to a nonracemic allylic alcohol as a prerequisite for the introduction of asymmetry in the cycloheptane system. Two strategies have been examined for elaboration of the unsaturated tetrahydrofuranyl ring from a common tricyclic intermediate. These efforts reveal a number of unanticipated issues of reactivity and significant stereochemical requirements for a novel acyloin rearrangement as well as the elimination and cyclodehydration of chiral α-hydroxy ketones. Key reactions leading to completion of the synthesis include the stereoselective addition of isopropenyllithium TMEDA complex and a facile chemoselective oxidation with selenium dioxide.
