87494-97-1Relevant academic research and scientific papers
Rearrangements in the acid-catalyzed formation of lactones from 2-hydroxynorbornane-2-acetic acid derivatives and related compounds
Yates, Peter,Kaldas, Magdy
, p. 2491 - 2501 (2007/10/02)
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 50percent 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 50percent 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 50percent 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.
