Fischer carbene complexes: Synthesis and application in organic synthesis.

摘要

Fischer carbene complexes are versatile intermediates for organic synthesis, but their synthesis can be challenging. Ile standard Fischer method of preparation involves addition of a hard anion to a metal carbonyl followed by alkylation of the resultant metal acylate with a reactive alkylating reagent. However, the alkylation step can be quite problematic. We developed a new method to prepare acyclic and cyclic aza, oxa, and thia substituted carbene complexes by simple protonation of vinyl ate complexes. This method solves the alkylation problem encountered in the standard Fischer synthesis. Reaction of M(CO) ₅-TBF and vinylzinc chlorides, generated from deprotonation of vinyl ethers, vinyl thioethers and imines with t-butyllithium. followed by zinc-lithium exchange, forms vinyl ate complexes by adding to the metal of M(CO)₅ -THF, which are then converted to the carbene complexes by protonation at the carbon or nitrogen atoms. Use of vinylzinc halides is critical for successful results, since vinyllithiums, hard Lewis bases, always add to a hard Lewis acid, a carbonyl carbon of M(CO)₅-THF. Optimization of the reaction conditions led to the discovery that freshly prepared ZnCl ₂ solution in THF is critical for high yields of the carbene complexes. In most cases, the yields of the carbene complexes prepared by this method are higher than those by other methods and some carbene complexes prepared by this method cannot be synthesized by other methods.; The synthesis of indolocarbazoles; containing hydrogen-bonding functionality mimicking the pharmacophore contained within bioactive indolocarbazole natural products is achieved. The indolocarbazoles are prepared via palladium catalyzed cross coupling of indoles followed by photochemical and thermal annulation reactions of chromium carbene complexes.