Studies of coupling reactions of Fischer carbene complexes with enyne-carbonyl compounds and an approach towards the synthesis of apomorphine alkaloid

The use of Fischer carbene complexes for the synthesis of aporphine natural products and development of different synthetic methodologies based on these reagents has been well studied. The net [5+5]-cycloaddition of gamma-delta unsaturated carbene complexes and ortho-alkynylbenzoyl systems has been employed as a key step toward the synthesis of aporphine natural products. These efforts are exemplified by attempted total synthesis of apomorphine, a treatment for advanced Parkinson's disease. Routes based on 2,6-dialkynylbenzaldehydes, monoalkynylbenzaldehyde, and alkynyl isoquinolones as [5+5]-cycloaddition substrates were examined, which provide diverse methods for the incorporation of the heterocyclic ring. The heterocylic ring of apomorphine was introduced by employing Suzuki-Miyaura cross coupling reaction between products obtained from [5+5]-cycloaddition reaction and organotrifluoroborates followed by sodium iodide initiated deprotection of carbamate group and subsequent cyclization. These exciting reaction series have offered routes to synthesize the apomorphine skeleton in three major steps from the simple alkynylbenzoyl compound in an efficient manner.;A novel method for the efficient construction of highly substituted benzene ring has been developed. This reaction sequence involves the three component synthesis of benzene derivatives through the coupling of Fisher carbene derivatives with enyne imines followed by Diels-Alder reaction with activated alkyne dienophiles, followed by nitrene extrusion. In many cases this process can be accomplished as a one-pot reaction, depending on the reactivity of the dienophile. Varity of substituted benzenes can be synthesized by varying enyne-imine, carbene complexes and dienophiles. This represents a major advance in benzene ring synthesis since they are most commonly prepared through adding groups onto pre-existing benzene derivatives.;Coupling of o-alkynylbenzoyl compounds with Fischer carbene complexes to make an isobenzofuran intermediate followed by trapping of the isobenzofuran intermediate by some activated dienophiles to form a Diels-Alder cycloaddition product was well studied. In the same system, the formation of the alkylidenephthalans was observed when there was an absence of dienophiles. In the absence of dienophiles, it was noticed that the vinyl isobenzofuran intermediate decomposed to afford different derivatives of alkylidenephthalans. The observed process results from the uniquely facile net [1,7] hydride shift. Coupling of enynecarbonyls and carbene complexes is unique in that decomposition of the isobenzofuran to an alkylidenephthalan is too fast for coupling with a third component. The scope, limitation and feasibility of [1,7]-hydride shift of isobenzofuran intermediates were well studied.