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Total Synthesis of p-Menthenolides

1981; Elsevier BV; Volume: 16; Issue: 12 Linguagem: Inglês

10.3987/r-1981-12-2091

1881-0942

Harold W. Pinnick, Balkrishna S. Bal,

Advanced Synthetic Organic Chemistry

A general approach to both cis-and trans-fused a-methylene -I-butyrolactones has been developed.This includes a new, mild method for the oxidation of a.8-unsaturated aldehydes.In addition, a new method to couple trans-a-methylene hydroxy acids into trans-lactones or, alternatively, cis-lactones has been developed.This strategy has been applied to the total synthesis of both ∧ ~-p -m e n t h e n o l i d e .prepared in 35% (trans) and 21% (cis1 overall yields f r w isopulegol.NUmeTOUS naturally-occurring compounds contain a-methylene y-butyrolactones.2Many of the$e natural products have antitumor activity3 and this has caused much of the interest in developing new methods for the preparation of this functionality.Most of these procedures first form the lactone4 and then introduce the amethylene group;5'6 however, a limited but growing number of methods have been devised for the direct conversion of an olefin into an ~imethylene y-butyrolactone.'unfortunately, many of these approaches are useful for making azther cis-or trans-fused products only, lack regiospecificity, involve exotic reagents or are very inefficrent.We wish to report a new, general method for the preparation of both cis-and trans-fused a-methylene y-butyrolactones from a single precursor.The target molecules in the present study are m-p-menthenolide (1) and G-ementhenalide (21.~h e s e lactones have been prepared in unspecified yield from isopulegol -acetate8 although a similar approach gave the lsomer~c lactone 3 among other product^.^Our synthetic plan is outlined in equation 1. ~sopulegol (4) will he converted first into the alcohol 5 and then the acid 6 as the key precursor for both of the desired products.