Lactonization/benzylic methodology

Mori and Ban reported the novel syntheses of benzolactams and lactones from o-haloarylalkylamines and -alcohols using Pd(OAc)2 and PPh3 in the presence of BU3N under carbon monoxide. As an application of this methodology, they succeeded iu the total synthesis of sendaverine (7, Scheme 3) by very short steps. °i The key step is the formation of isoquinolone 6a by Pd-catalyzed carbonylation of aryl bromide 5a. Pandey later reported the synthesis of benzyl-tetrahydroisoquinolines using a similar proce-dure.f This procedure was also used for the total synthesis of protoberberine alkaloids. ... 

In an extension of the methodology described for the preparation of a-methylenebutyrolactones," it has been found that O-silyl enolates of esters, lactones, and ketones can be smoothly monoalkylated by reactive alkyl halides [e.g. benzylic, allylic, MeOCHzCl, PhSCH(Cl)R] in the presence of small amounts of zinc bromide. This approach could find extensive use especially in cases where direct carbanion methods are unsatisfactory. 

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. ... 

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