New Methods of Preparing Cyclopentenone Ketals: The Photosolvolysis of 3-Alkoxypyridinium Tetrafluoroborates

Abstract

A new base catalysed method of ketal formation is reported, such that substituted cyclopentenone ketals are prepared from 3-alkoxypyridinium tetrafluoroborate salts.The photochemical properties of aromatic compounds are a source of amazement to many organic chemists. In particular the metaphotocyclo addition 1 has often been described as the reaction that leads to the greatest increase in molecular complexity. This light induced reaction between an aromatic ring and an olefin was concurrently discovered in 1966 by Wilzbach and Kaplan 2 and also by Bryce-Smith, Gilbert and Orger. 3 The metaphotocycloaddition has been very elegantly utilised by Wender for the synthesis of a number of key natural products, such as (±)-a-cedrene 4 and (±)-modhephene (4) 5 (Scheme 1). Scheme 1As yet there have been no reports of heteroaromatic compounds being involved with similar reaction sequences, although Wilzbach, Kaplan and Pavlik 6 reported an unusual photohydration reaction of pyridinium ions in 1972. These workers described how the irradiation of an alkaline solution of N-methylpyridinium chloride 5 led to the formation of a bicyclic aziridinyl alcohol 7. It was proposed that the reaction proceeded via an azabenzvalene 6 cation that was subsequently captured by water from the least hindered face. Scheme 2A renaissance of interest in this reaction has led to some important discoveries by Mariano 7 and Burger. 8,9 Mariano reported the results of photosolvolysis of various pyridinium salts and subsequent solvolytic aziridine ring opening of the products. 7 Burger then reported how this reaction could be used for b-lactam synthesis 8 and, more recently, has shown how polyhydroxylated aminocyclopentanes 9 can be made. We were intrigued to know what effect an electron donating group at the 3 position on the pyridine ring would have on the photosolvolysis of pyridinium salts. We reasoned that the incipient cation would be very stable and should be readily captured by the solvent to form a geminal bisalkoxy species. To test our hypothesis various 3-alkoxypyridinium salts 8 were irradiated in different solvents using a 400 W medium pressure mercury vapour lamp with a pyrex filter. Analysis of the different products showed that a series of cyclopentenone ketal derivatives 9 had been made (Scheme 3). Scheme 3The pyridinium salts were made according to standard literature procedures, starting from either 3-hydroxypyridine or 3-hydroxy-6-methylpyridine 10. The hydroxyl group was initially protected as an ether 11 using an alkyl halide. 10 In order to introduce larger alkyl groups at the 6 position of the pyridine ring, the 6-methylpyridine derivative was metallated using LDA and quenched with an appropriate alkyl halide. 11 The pyridine species were quaternised by heating in neat alkyl bromide or iodide inside a sealed tube and, after filtration, the pyridinium halides 13 were converted to the tetrafluoroborate salts 14 using silver carbonate and fluoroboric acid. Chloride 6,8,9 and perchlorate 7 salts have previously been used for photos...

The synthetic potential of pyridinium salt photochemistry

“…Other interesting observations have come from investigations reported by Penkett and Simpson in 1999. 33,34 As shown in Scheme 18, these workers observed that irradiation of alcoholic solutions of 1,6-dialkyl-3alkoxypyridinium tetrafluoroborates 59 containing NaOH leads to modestly to highly efficient (41-92%) production of the bicyclic ketals 61. Several features of these processes give additional insight into mechanistic and synthetic issues.…”

Pyridinium Salt Photochemistry in a Concise Route for Synthesis of the Trehazolin Aminocyclitol, Trehazolamine

“…In addition, these workers showed that the products of these reactions undergo stereocontrolled, acid-promoted ring opening with a variety of nucleophiles (H 2 O, CH 3 OH, HOAc, HSAc). Since that time, a number of informative studies of these processes have been described. − Also, unique applications of the bicyclic-aziridine ring forming and opening sequence to the synthesis of aminocyclitols, − polyhydroxylated indolizidines, and amino-aldopentoses 15 have been reported.…”