Studies towards the total synthesis of palau'amine. Formation of 4,5-dihydropyrrole-2-carboxylate intermediates by alkene-enamide ring-closing metathesis

A highly functionalized 4,5-dihydropyrrole-2-carboxylate is assembled by alkene-enamide ring-closing metathesis. Subsequent intramolecular azomethine imine dipolar cycloaddition provides a triazacyclopenta[cd]pentalene intermediate of potential use in a total synthesis of palau'amine.     

Efficient and practical synthesis of N-acetyl enamides from ketoximes by unique iron catalytic system

A new procedure for the iron-catalyzed synthesis of enamides from ketoximes was developed, and its mechanism was proposed. A unique reduction system, with the concerted use of KI and Na₂S₂O₄, was involved. The reaction exhibited a wide substrate scope and gave good yields in a short reaction time. The procedure is operationally simple and also applicable for the large-scale synthesis.     

Stereoselective reductions of N-Boc-hexahydro-1H-indolin-5(6H)-ones

We report the divergent effects of a 3a-methyl and 3a-phenyl substituent on the chemoselectivity and stereoselectivity of reduction of the enamide moiety of N-Boc-hexahydro-1H-indolin-5(6H)-ones. Under ionic reduction conditions (triethylsilane/trifluoroacetic acid) the enamide group of 3a-methyl-N-Boc-hexahydro-1H-indolin-5(6H)-one was reduced to afford exclusively a cis ring-fused product. For the 3a-phenyl substituted analogue more forcing conditions (sodium cyanoborohydride at pH 2-2.5) were required and resulted in the selective reduction of the enamide group to give a trans ring-fused product as well as reduction of the ketone group.     

Friedel–Crafts alkylation of 2-naphthols with enamides and enethers induced by catalytic amount of triarylaminium salt

A novel and efficient regioselective Friedel–Crafts alkylation reaction of 2-naphthols with electron-rich enamides or enethers initiated by catalytic amounts of stable radical cation triarylaminium salt has been developed. The processes occur under mild conditions.     

Synthesis of nitrogen-containing heterocycles using exo- and endo-selective radical cyclizations onto enamides

The effect of positional change of the carbonyl group of enamides on Bu₃SnH-mediated alkyl radical cyclization leading to five-, six-, seven-, and eight-membered nitrogen-containing heterocycles was examined. A 5-exo cyclization is generally preferred over a 6-endo ring closure in systems having an alkyl radical center on the enamide-acyl side chain, whereas enamides having an alkyl radical center opposite to the acyl side chain predominantly gave 6-endo cyclization products. These results suggest that the exo or endo selectivity of radical cyclization onto the alkenic bond of enamides can be controlled by positional change of the carbonyl group. For an understanding of these selectivities, heat of formation for each transition state was calculated. 6-endo-Selective radical cyclization was applied to the radical cascade, enabling a concise synthesis of a cylindricine skeleton. A 7- or 8-endo alkyl radical cyclization, however, predominated over a corresponding 6- or 7-exo ring closure regardless of the positional change of the carbonyl group of enamides.