Organometallic scaffolding as a practical approach to diversity-oriented synthesis: Stereo- and regiocontrolled sequential functionalization of pyranylalkylidene allylmolybdenum complexes.

摘要

Organometallic enantiomeric scaffolding is a powerful and versatile tool for enantiocontrolled bond construction. Tp(CO)2allylmolybdenum complexes of pyrans and piperidines are noteworthy examples of this approach to synthesis. A streamlined procedure for the construction of the key eta 3(2,3,4)-5-oxopyranyl molybdenum complex was developed, facilitating scale up, and making these scaffolds more available to the synthetic community.;The key scaffold was derivatized to include an alkylidene moiety that provided new opportunities for synthesis of heterocyclic skeletons and stereochemical relationships not accessible with existing methods. An unprecedented intermolecular 1,5-Michael reaction of this substrate was evaluated for its scope and mechanism, whereby the addition of alkoxide nucleophiles to neutral allyl molybdenum complexes is apparently favorable, and likely goes through an anionic molybdenum intermediate.;The products of this reaction were studied for use in a novel and general sequential functionalization protocol, whereby iterative leaving group abstraction/nucleophilic addition sequences afford highly substituted pyran architectures with divergent, yet predictable regiochemical outcomes, notably those bearing 2,6- trans and 2,2,6-functionality. Other highlights include a [5+2] cycloaddition reaction to 5,6-disubstituted pyranyl complexes, and hetero Diels-Alder reaction to form spiroketals.;The full utility of the method is ultimately demonstrated by the synthesis of highly functionalized enantiomerically pure pyran rings bearing functionality equipped for further manipulations.