Studies in physical organic chemistry

Abstract

The objects of these investigations are: (1) to study the preparation and properties of fulvenes possessing electron-withdrawing substituents at the C-6 position, in relation to the concept of anti-aromaticity, and (2) to explore the stereochemistry and mechanism of the transformation of 2?-N-morpholino-bicyclo[3.3.1]nonan-9-one methiodide to trans-octahydrocoumarin. The thesis entitled "STUDIES IN PHYSICAL ORGANIC CHEMISTRY" is divided into three chapters.

Chapter I describes the preparation and properties of fulvenes having electron-withdrawing substituents at the C-6 position. These fulvenes (1 and 2) were found to be too unstable to be obtained pure. They readily undergo dimerisation, oligomerisation, and polymerisation, and easily react with dienophiles like maleic anhydride or N-phenylmaleimide to give endo (4+2) cycloadducts (3). However, a small amount of exo-adduct (4) was also isolated from the cycloaddition reaction of fulvene (1, X = NO?) with N-phenylmaleimide. The fulvene dimers (5) were also found to be unstable (Scheme I). The dimers have been tentatively proposed to be (4+2) cycloadducts, but their stereo- and regiochemical features have not been determined. The fulvenes were also analysed by E.S.R. spectroscopy to determine whether they possess any triplet-diradical character like the cyclopentadienyl cation. No evidence, however, was found for such triplet character. It is possible, however, that the fulvenes possess thermally accessible, low-lying triplet states, which are not detectable by conventional E.S.R. spectroscopy. Studies have been mostly carried out on fulvenes of type (1).

Chapter II describes mechanistic investigations on the reaction shown in Scheme II. This reaction, reported by Dean et al. in 1968 without much explanation, exhibits total stereoselectivity in that exclusively the trans-lactone (7a) is formed. In principle, the stereoselectivity of the reaction, presumed to be an intramolecular Cannizzaro-type reaction, could be due to two possibilities: (i) axial delivery of hydride with the side-chain equatorial, and (ii) equatorial delivery of hydride with the side-chain axial (Scheme III). Pathway (i) has merit because nucleophiles attack cyclohexanones preferentially from the axial direction; pathway (ii) would be important if the “2-alkyl ketone effect”, by which ?-alkyl groups in cyclohexanones occupy the axial positions more than they do so in cyclohexanes, plays a role. To distinguish between these two mechanisms, the 3,3-dimethyl keto-aldehyde (6b) was prepared and subjected to the above redox reaction. It was found that the reaction of keto-aldehyde (6b) is also stereoselective, yielding trans-lactone (7b). Also, the reaction of (6b) was only half as fast as that of (6a) under similar conditions. This retardation is probably due to 1,3-diaxial interaction with the methyl group in the transition state, and shows that hydride delivery is axial, i.e., pathway (i). Thus, the direction of hydride delivery controls the course of the reaction and ground-state properties (e.g., the 2-alkyl ketone effect) apparently are not important. This conclusion, of course, is to be expected on the basis of the Curtin–Hammett principle. It was also found that the rate of formation of lactone (7) is inversely proportional to temperature. The probable reason for this phenomenon is that the concentration of the 2-axial isomer (which does not react) increases with increase in temperature.

Chapter III describes results of investigations on the mechanism of the reaction shown in Scheme IV. It is well known that quaternary salts undergo nucleophilic substitution very rarely. Therefore, the displacement of the N-methylmorpholinium moiety by hydroxide ion in 2?-N-morpholino-bicyclo[3.3.1]nonan-9-one methiodide (8) to give (9) was surprising. It seemed likely that the reaction was catalysed by intramolecular participation of the keto group, via the pathway shown in Scheme V. Such a mechanism is supported by the fact that the 6-isomer does not undergo the substitution reaction. In fact, the desoxy analogue of (8), i.e., (11), as also 9-methylidene-2?-N-morpholino-bicyclo[3.3.1]nonane methiodide (12) were found to be completely unreactive towards substitution by hydroxide ion, thereby further supporting the proposed keto-participation mechanism (Scheme VI). Attempts to isolate tricyclic intermediates such as (10) were, however, unsuccessful.