Polonovsky-Potier reaction

Laboratory transformations took advantage of fragmentation of dregamine (30), tabemaemontanine (31), and vobasine (32) as N4 oxide induced by treatment with trifluoroacetic anhydride (Polonovski-Potier reaction) (192) and reductive capture of the intermediate iminium ion (Scheme 1). 

A modification of the Polonovski reaction where trifluoroacetic anhydride is used in place of acetic anhydride. Because the reaction conditions for the Polonovski-Potier reaction are mild, it has largely replaced the Polonovski reaction. 

The iminium salts of 2,3-dihydropyridines are far more stable than the free bases and have been used extensively in the synthesis of alkaloids. N-Benzyl iminium salt 26, formed from the Polonovski-Potier reaction of V-oxide 25, was transformed into enol ether 27, which is a synthon for the unstable AT-benzvl-l, 2-dihvdropyridine 28 (Scheme 5) <2004LOC168>. The same transformation on a similar iminium salt has been used in the formation of macrocyclic marine alkaloids <1995TL2059>. Carbon nucleophiles, such as the silylenol ethers of esters, have been shown to undergo 1,2-addition rather than 1,4-addition to 2,3-dihydropyridinium salts <1999T14995>. 

In the laboratory of J. Kobayashi, the biomimetic one-pot transformation of serratinine into serratezomine A was accomplished using the Polonovski-Potier reaction Serratinine was first treated with m-chloroperbenzoic acid to obtain the A/-oxide, and then excess TFAA was added. The iminium ion was formed in the following fashion the C13 hydroxyl group formed a hemiacetal with the C5 carbonyl group and simultaneously with the formation of the C5-C13 lactone the C4-C5 bond was broken. The iminium ion was then reduced with sodium cyanoborohydride to afford the tertiary amine functionality. Besides serratezomine A, another lactone (between the C8 hydroxyl and C5 carbonyl) was formed in 27% yield. 

The naturally occurring sulfonamide (-)-altemicidin is the first 6-azaindene monoterpene alkaloid isolated as a metabolite of microorganisms. A.S. Kende utilized the Polonovski-Potier reaction in the key step to introduce the carbamoyl enamine functionality. The tertiary amine was oxidized to the A/-oxide by H2O2 followed by treatment with excess TFAA to afford the desired vinylogous trifluoromethyl amide. 

Dihydropyridinium salt 31 was initially selected to check the viability of the proposal. This salt was prepared from tetrahydropyridine 30, which was accessible in six steps from methyl nicotinate, by treatment of the corresponding N-oxide derivative (mixture of two diastereoisomers) under Polonovski-Potier reaction conditions (Scheme 11). Reaction of the crude salt 31 with the sodium salt of diethyl 1,3-acetonedicarboxylate gave a mixture of two diastereoisomeric adducts 32 (two isolable enol forms) and 33 in 87% overall yield, the undesired stereoisomers 32 (axial amino-methyl chain) predominating (69 31 ratio). 

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