The application of [gamma-(silyloxy)allylidene]ditin to the efficient synthesis of the chromophore of the neocarzinostatin dihydroxycyclopentene-based dienediyne core
Résumé
1-(tert-Butyldimethylsilyl)oxy-3,3-bis(tributylstannyl)propene (5), a versatile gem-dimetallic allylic synthon accessible through various synthetic routes, has been condensed with (trimethylsilyl)propiolaldehyde to give the fully functionalised acyclic vinyltin compound 9h, which is a precursor of the complex dihydroxycyclopentene sub-unit of neocarzinostatin chromophore (NCS) 1. Subsequent transformation into the geminal (E)-alpha-chloro-(Z)-alpha-iodovinylic intermediate 20, followed by a palladium-catalysed carbometallation/cyclisation reaction including in situ trapping with either (tributylstannyl) acetylene or the more functionalised 3,3-diethoxy-1 1-(tributylstannyl) prop-1-yne delivered the corresponding alkyne-substituted 4-chloro-1,2-bis(silyloxy)cyclopent-3-enes 21 or 22, respectively. Chlorocyclopentene 21 was subsequently easily transformed into the target dienediyne adduct 23 by Sonogashira condensation with trimethylsilylacetylene. This diastereoselective process is efficient with only six steps and an overall 26 % yield from the allylic ditin precursor 5. More than just an NCS building block, the final acyclic dihydroxycyclopentene-based dienediyne is also a seco analogue of the NCS chromophore. ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006).