β-Aminosubstituted α,β-Unsaturated Fischer Carbene Complexes as Precursors for Complex Oligocyclic Molecules - Basics and Applications

Abstract

Under the optimized conditions, a wide range of β-Aminosubstituted α,β-unsaturated Fischer carbene complexes were easily prepared in a four-step one-pot operation. Reaction of Fischer carbene complexes with alkynes affords versatile adducts, from which complicated skeletons of natural product analogues and interesting molecules are accessible. Tricyclic adducts with highly regio- and diastereoselectivity were prepared in 15-91% yields by the reaction of pentacarbonyl[(2E)-3-cyclohexenyl-3-dimethylamino-1-ethoxy-2-propen-1-yliden]chromium, or its tungsten analogues, with alkynes. The mechanism and limitations of the formation of tricyclic adducts and their unusual photophysical properties were studied in detail. The formal [3+2] cycloadditions of Fischer carbene complexes with different alkynes, including diynes and enynes, performed in pyridine afforded highly substituted 5-dimethylamino-3-ethoxy-cyclopentadienes (sometimes also their regioisomers), generally in medium to good yields. The factors of the product distribution between cyclopentadienes, their second regioisomers and the dimethylamino-migration products have been well studied. The steric bulk of the substituents either in the Fischer carbene complexes were found to have more influence than in the applied alkynes. However, electronic effects of applied alkynes do not play an important role. The dimethylamino-migration products arise from 5-dimethylamino-3-ethoxy-cyclopentadienes with a 1,2-migration via the bridged zwitterionic intermediate. Upon heating Fischer carbene complexes with conjugated dienynes in pyridine at 80 °C, bis- and tri-annulated benzene derivatives were obtained. This new cascade reaction of Fischer carbene complexes proceeds with much milder condition than the traditional methods. Linear triquinanes and their analogs have been prepared from (2'-oxocycloalkyl)methyl-substituted Fischer carbene complexes and alkynes followed by a subsequent hydrolysis. Their structures were determined to be cis,anti,cis, cis, syn,cis and cis,anti,trans. Generally, cis,anti,cis isomers were also obtained as major products. Cycloadducts are obtained as dominating isomers with a ratio of ca. 75 : 20 : 5. Under the same conditions, the aldol condensation of (2'-oxocycloalkanyl)ethyl substituted cyclopentenones in presence of hydrochloric acid at 60 °C led to the cyclization products, which can be regarded as the B-C-D rings in the steroid-like molecules, in good to excellent yields (77-88%). Preparation of the steroid-like molecules should be achievable from the Fischer carbene complex with bicyclic dienynes by a formal [3+2] cycloaddition, a sequential 6π-electrocyclization, hydrogen shifts and a finally hydrolysis in a one-pot operation. Another steroid-like molecules should be synthesized from the reaction of (2'-oxodecalenyl)butyl substituted Fischer carbene complex with various alkynes and a subsequent hydrolysis.