Rearrangements in the acid-catalyzed formation of lactones from 2-hydroxynorbornane-2-acetic acid derivatives and related compounds

Abstract

A mixture of the epimeric ethyl 2-hydroxynorbornane-2-acetates (1) on treatment with concentrated sulfuric acid is converted in turn to the lactones of exo-2-hydroxynorbornane-1-acetic acid (4), endo-6-hydroxynorbornane-endo-2-acetic acid (5), and exo-3-hydroxynorbornane-exo-2-acetic acid (6). With trifluoroacetic acid or 50% sulfuric acid, 1 gives 4, but this does not react further. In concentrated sulfuric acid the parent acids of 1 (7) and (E)- and (Z)-(norborn-2-ylidene)acetic acids (8 and 9) and their ethyl esters (10 and 11) give 6 as the infinity product. A mixture of 5-norbornene-endo- and exo-2-acetic acid (30 and 31) on treatment with 50% sulfuric acid gives 4, 5, 6, and exo-2-hydroxynorbornane-syn-7-acetic acid lactone (33). Routes are proposed for the formation of the lactones that involve protonation and carbocation formation followed by rearrangement via Wagner–Meerwein, endo-6,2-hydride, and exo-3,2-hydride shifts in decreasing order of preference. It is postulated that the usual inhibition of the rearrangement of tertiary to secondary norbornyl carbocations is not operative when the third substituent is a carboxymethyl group or its derivatives because of the electron-withdrawing properties of such groups relative to simple alkyl groups. A preliminary study has shown that exo-5-acetyloxy-endo-2-hydroxynorbornane-exo-2-acetic acid (35) with 50% sulfuric acid gives four products that are considered to be the γ-lactones of endo-5-acetyloxy- and endo-5-hydroxynorbornane-1-acetic acid (38 and 39) and exo-2-acetyloxy-1-hydroxy-and 1,2-dihydroxynorbornane-syn-7-acetic acid (40 and 41). Protonation of either the hydroxyl or acetyloxyl group is postulated, giving two carbocations that undergo rearrangements as in the case of 1, together with 3,2-hydroxyl shifts. The structures of the lactones are assigned on the basis of spectroscopy, reactivity, and analogy. The reactions of the lactones, which lead to a variety of hydroxy- and oxonorbornaneacetic acids, illustrate their synthetic potential.