Modified Polonovski Reaction, a Versatile Synthetic Tool

Recent synthetic applications of' the modified Polonovski reaction are reviewed.In particular, the mechanistic consequences of the reaction are discussed.Designing the synthesis of a complex organic molecule such as several alkaloids often involves the strategist in questions of formidable difficulty.It can be argued that many of the greatest achievements of synthetic organic chemistry have come within the past two decades, and one can only presume that an increasing rate of new syntheses (sensu stricto, see ref. 1) will be achieved in the future.Of vital importance to the development of new efficient and elegant syntheses is the discovery of new selective chemical transformations, the unit processes which the organic chemist uses as "building blocks" in designing and executing a synthetic strategy and plan in detail.Piperidine unit is an abundant feature of several natural products, as exemplified by corynantheidine 1, (2)-20-epiuleine 3, histrionicotoxin 3, Y-pelletierine 4 and morphine 5 in Chart 1.Beyond doubt, the achievement of the correct substitution pattern in the piperidine ring has been 3 a vexed p r o b l m 2 The development of the modified Polonovski reaction has provided a versatile approach to various substituted piperidine systems, in offering a general method of constructing a 5,6-dihydropyridinium system 5 which is susceptible to the attack of carbon nucleophiles in a desired conjugated addition manner.In addition to being a useful means of preparing the dihgdropyridine equivalent 5, the modified Polonovski reaction is also amenable to generating cr-aminonitriles, srnthons of wide applicability in both nucleophilic and electrophilic reactions. I POLONOVSKI REACTION 1-1 MechanismAlready in 1927,Max and Michel Polonovski observed that tertiary amines can be demethylated by treating the corresponding N-oxide L with acid anh~dride.~The main products of the reaction were found to be the N-acylated N-demethylamine 8 and formaldehyde (Equation 1).