ABSTRACT
An enantioselective formal synthesis of the alkaloid (-)-cephalotaxine has been completed, using an alkylidene carbene 1,5-CH insertion reaction as a key step to construct the spiro[4.4]azanonane core D/E-ring system. A Heck-type cyclization was used to close the tetrahydroazepine C-ring and a selective epoxidation-rearrangement sequence was used to elaborate the E-ring.
Subject(s)
Alkaloids/chemical synthesis , Harringtonines/chemical synthesis , Alkaloids/chemistry , Crystallography, X-Ray , Cyclization , Harringtonines/chemistry , Homoharringtonine , Molecular Conformation , Molecular Structure , StereoisomerismABSTRACT
The desymmetrisation of centrosymmetric molecules by enantioselective carbon-carbon bond formation has been reported for the first time. A bimetallic zinc catalyst developed by Trost was exploited in the desymmetrisation of a centrosymmetric dialdehyde. The approach was successful with a range of ketone nucleophiles and was uniformly highly diastereoselective (>98:<2). The yield and the enantioselectivity of the reaction varied as a function of the ketone used, and the desymmetrised products were obtained in up to 74 % yield and 97 % ee (ee=enantiomeric excess). The desymmetrisation of centrosymmetric molecules by enantioselective carbon-carbon bond formation is an efficient and convergent synthetic approach which is likely to find wide application in synthesis, particularly in the total synthesis of natural products with embedded centrosymmetric fragments.
