Polonovsky reaction

Acylation. Aliphatic amine oxides react with acylating agents such as acetic anhydride and acetyl chloride to form either A[,A/-diaLkylamides and aldehyde (34), the Polonovski reaction, or an ester, depending upon the polarity of the solvent used (35,36). Along with a polar mechanism (37), a metal-complex-induced mechanism involving a free-radical intermediate has been proposed. 

Several groups have contributed pieces to the puzzle of how this reaction proceeds and understanding of the events that transpire has evolved with time. While on the surface, this reaction looks analogous to the Polonovsky reaction (5 —> 6) or the Pummerer... 

A very surprising sulfone formation has been investigated by Oae and coworkers . On heating p-toluenesulfinic acid with dimethylaniline in ethanol for 15 h, the reaction mixture shown in equation 100 has been obtained. Obviously, the observed products arise from an equilibrium between the sulfinic acid and its pseudo-anhydride (disulfide trioxide), which is able to attack the amine nitrogen and degrade the tertiary amine corresponding to a Polonovsky reaction . 

The spirobenzylisoquinoline 171b derived from berberine (15) (Section IV,A,1) was oxidized with m-chloroperbenzoic acid to the /V-oxide 389, which was treated with trifluoroacetic anhydride to afford dehydrohydrastine (370) in 56% overall yield (Scheme 71) through the Polonovski reaction (187). Holland et al. (188,189) reported the reverse reaction from dehydrophthalides to spirobenzylisoquinolines, namely, 370 was reduced with diisobutylalu-minum hydride to give a mixture of two diastereoisomeric spirobenzylisoquinolines 320 and 348 via the enol aldehyde. This reaction was applied to synthesis of various spirobenzylisoquinoline alkaloids such as (+)-sibiricine (352), ( + )-corydaine (347), (+ )-raddeanone (354), ( )-yenhusomidine (359), (+ )-ochrobirine (343), and ( )-yenhusomine (323). 

Also, a mixture of ( )-3-epi-18,19-dihydroantirhine (203) and its C-20 epimer (204) has been obtained (138) by hydrogenation and subsequent deacetylation of 206, prepared earlier via a modified Polonovski reaction (101). 

An interesting transformation was discovered by Sakai and Shinma (181) during the chemical investigation of corynanthe alkaloid (V-oxides. Polonovski reaction and sodium cyanoborohydride reduction of hirsuteine A-oxide (331) gave corynantheine (52) and 3-isocorynantheidine (65), the latter likely formed by reduction of the conjugated iminium intermediate 334. 

The observed acid-catalysed conversion of complestatin (289) into chloropeptin L (291) has been envisioned" " as proceeding through a cyclopropyl intermediate (290) (see Scheme 94). An intramolecular oxygen-transfer reaction illustrated in Scheme 95 has been proposed" to explain hydroxylation of the aromatic nucleus, viz. formation of (292), during the course of a modified Polonovski reaction on galanthamine. 

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. 

Application of the modified Polonovski reaction to catharanthine p-ep-oxide (73) afforded leurosine (74) in 6% (75) or 20% yield (70-74), thus... 

The relatively facile formation of anhydrovinblastine (42) by the modified Polonovski reaction, and the poor yields experienced on coupling of other catharanthine derivatives, made anhydrovinblastine an attractive precursor for the preparation of additional binary alkaloids, including vinblastine itself (50,57). Hydrogenation to 20 -deoxyleurosidine (61a), formation of its Af -oxide (78), and reaction with trifluoroacetic anhydride led to the enamine 59 (Scheme 23). Oxidation of this enamine with thal-... 

In another search for an alternative to Potier s modified Polonovski reaction of catharanthine A-oxide (45), it has now been found that anhy-drovinblastine (42) can be generated directly, in 77% yield, from a reaction of catharanthine and vindoline in 0.01 N acid, promoted by ionized ferric salts, followed by reduction with sodium borohydride (Scheme 30) (Wl). Remarkably, the cation radical 106 generated by Fe(III), in accord with other simple amine oxidations by Lindsay Smith and Mead (102), resulted in isoquinuclidine fragmentation and coupling to vindoline at 0°C, without the conformational inversion observed in the modified Polonovski reaction at that temperature (see Scheme 15). Other metal oxidants or ligand-bound Fe(lll) did not promote the coupling reaction. It will be of interest to see if the overwhelming competition of C-5-C-6 bond... 

Phosphoryl-stabilized anions, 25, 2 Photochemical cycloadditions, 44, 2 Photocyclization of stilbenes, 30, 1 Photooxygenation of olefins, 20, 2 Photosensitizers, 20, 2 Pictet-Spengler reaction, 6, 3 Pig liver esterase, 37, 1 Polonovski reaction, 39, 2... 

Another example is provided by the application of the modified Polonovski reaction to A3-piperideines. Treatment of amine oxides (141) with trifluoroacetic anhydride results in the formation of iminium ion (142). These compounds can behave as useful synthetic intermediates, reacting with a number of nucleophiles such as cyanide ion (80JA1064). 

POLONOVSKI REACTION. Demethylation of tertiary (or Heterocyclic) amine A-oxides on treatment with acetyl chloride or acetic anhydride 1o give A-acylated secondary amines and formaldehyde, along with (9-acylated aminophenols as a result of a side reaction. 

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