Fischer chromium carbenes in organic synthesis: Metathesis reactions of Fischer carbene complexes with isonitriles

Since their discovery in 1964, interest in the chemistry of Fischer carbene complexes has increased rapidly in response to their expanding synthetic potential. These organometallic reagents are crucial synthetic intermediates for the synthesis of a variety of biologically important molecules including {dollar}beta{dollar}-lactam and quinone compounds. Functionalized aromatic amines and nitrogen heterocycles were synthesized through a facile electrocyclization of N- and C-dienylketenimine intermediates, formed via metathesis of isonitriles with carbene complexes.; Metathesis of various isonitriles with a series of dienylcarbene complexes yielded demetallated C-dienylketenimine intermediates. ortho-Alkoxy aromatic amines were formed via thermally-induced 6{dollar}pi{dollar}-electrocyclizations of these ketenimines. The aminobenzannulation reaction provides a general, efficient, chemo- and regioselective synthesis of biologically important amine moieties.; Nitrogen heterocycles were synthesized through a similar metathesis and electrocyclization pathway. Pyridine derivatives were formed via a metal-templated electrocyclization of N-dienylketenimine intermediates which result from the metathesis of cis-dienylisonitriles with simple carbenes. Reactions involving aromatic carbene complexes yielded demetalled pyridines while alkylcarbene reactions formed chromium-bound pyridine complexes.; trans-Dienylisonitriles also reacted with simple carbenes to yield nitrogen heterocycles. These metathesis reactions resulted in the immediate formation of (pyrrolinylidene)carbene complexes via cyclization of the N-dienylketenimine intermediates at {dollar}-{dollar}90{dollar}spcirc{dollar}C. These carbene complexes yielded substituted pyrrole moieties upon reduction with lithium borohydride.; Application of Fischer carbenes to the synthesis of biologically relevant molecules has necessitated the synthesis of unusual carbene complexes. Thus, two new synthetic approaches to Fischer carbene complexes were developed. A cesium fluoride-modified Fischer synthesis yielded functionalized (alkoxy)carbenes directly from lithium chromaacylate intermediates. In addition, imidazol-2-ylidene metal carbenes were synthesized from free carbene compounds and Group VI metal pentacarbonyl fragments.; Nitrile metathesis, alkyne metathesis, Pauson-Khand, and trimethylenemethane reactions of Fischer carbene complexes as well as the biological relevance of the imidazol-2-ylidene carbenes were explored.