Lactones from nucleophilic addition

In 1973, the group led by Prof. Adinolfi synthetized the antibiotic LL-Z1271a (63) [81] starting from ketolactone 139, obtained, in turn, by degradation of the diterpene marrubiin (9% overall yield). This synthesis basically consists of the formation of the 5-lactone C ring by nucleophilic addition to carbonyl group and subsequent lactonization (Scheme 11).. 

Anomeric C-arylation by nucleophilic addition of suitable aryl anions to a lactone, followed by Lewis acid catalyzed reduction of the resulting hemiacetal, has been used in the synthesis of (—)-altholactone from D-gulonolactone [297]. 

A cycloheptenone precursor to the (+)-Prelog-Djerassi lactonic acid has been synthesized stereoselectively from cyclohepta-1, 3-diene using a nucleophilic addition-reactivation-nucleophilic addition sequence on iron complexes to introduce the required... 

The Baeyer-Wlliger oxidation of ketones affords esters (from open-chain ketones) and lactones (from cyclic ketones), respectively. It is typically carried out using nucleophilic oxidants, such as peracids or dihydrogen peroxide in the presence of bases (29). Nucleophilic oxidants are required because the first step of the reaction mechanism is the addition of the peroxidic oxidant to the ketone s carbonyl function, affording the so-called Criegee-intermediate (Scheme 10). The subsequent cleavage of the 0 0 bond in the latter, and the concerted shift of yield the ester (lactone) product. In enzymatic Baeyer-Vlliger oxidations, flavin hydroperoxides such as 26 act as the nucleophilic oxidant (30). 

Oxy-y-butyrolactones are substructural units in many biologically interesting natural products, accessible by nucleophilic addition of the enolates of tert-butyl acetate on epoxy pentuloses. The hthium enolate of ferf-butyl acetate is reacted with the epoxy ketose 50 (generated from 49) in a mixture of THF/HMPA (3 1) to afford 51 and 52. However, the frans-oriented isomer 52 can only be converted to the desired lactone 54 on treatment with TFA in CH2CI2 at room temperature for 30 min [18] (Scheme 11). 

Our first climbing route, or synthetic path, to aureothin, relied on the reduction of lactone 17, prepared by the condensation of the anion of 18 with aldehyde 15, an approach entailing nucleophilic addition and subsequent lactonization (Scheme 11). We envisioned the conversion of 17 into aureothin (1), either by the direct reduction of the lactone moiety into the cyclic ether or by the cyclization of the diol resulting from the exhaustive reduction of the lactone. 

The use of carbon nucleophiles stabilized by SR groups has been a feature of sulphur chemistry for many years now, and this year has seen additional uses for these versatile reagents. Thus the carbanion CH(SPh)2 adds in a 1,2-manner to 2-methylacrolein giving the allyl alcohol (175), which is then converted to the activated diene (176) by standard methodology. The latter has been used in studies towards the total synthesis of the Rubradirin antibiotics. The related anion ArC(SPh)2 also adds to a,/3-unsaturated systems however, in the case of lactone (177) conjugate addition is observed. If the initial ion from (177) is trapped with benzylic bromides then frans-butyrolactones (178) are obtained in good yield. ... 

---