2-Substituted azetidines, asymmetric

In 2002, the asymmetric synthesis of 3-substituted 3-hydroxy-p-lactams has been reported to be realized by metal-mediated l,3-butadien-2-ylation reactions between 1,4-dibromo-2-butyne and optically pure azetidine-2,3-diones [64]. This latter starting material was prepared via Staudinger reaction followed by sequential transesterification and Swem oxidation (Scheme 15), [65]. 

Indium-promoted reaction of l,4-dibromo-2-butyne with carbonyl compounds gives 1,3-butadiene derivatives via the allenic indium intermediates (Scheme 56).220 Similar indium-mediated l,3-butadien-2-ylation reactions of optically pure azetidine-2,3-diones have been investigated in aqueous media, offering a convenient asymmetric entry to the 3-substituted 3-hydroxy-/ -lactam moiety (Equation (40)). The diastereoselectivity of the addition reaction is controlled by the bulky chiral auxiliary at Q4 221 222... 

The glycol-cleavage oxidation has been utilized in numerous synthetic works, for example, the total syntheses of dipiperidine alkaloids virgidivarine and virgiboidine [1348], total synthesis ofresolvinE2 [1349], synthesis of a-substituted oxazolochlorin aminals or acetals from mera-tetraaryldihydroxychlorins [1350], asymmetric synthesis of l-(2- and 3-haloalkyl)azetidin-2-ones [1351], synthesis of 2-hydroxy-1,4-oxazin-... 

Scheme 12) (during the preparation of this manuscript, a new asymmetric reaction was reported [55]) [56]. A similar mechanism was proposed and benzobicyclo [2,2,2]octenone 63 was isolated in high yield (77-97%) and ee (80-93%). Thus far, this is a unique example of an intermolecularcarboacylatiOTi of alkenes via C-C bond activation. One year later, Louie and co-workers reported a nickel-catalyzed cycloaddition of 1,3-dienes with 3-azetidin(Mies and 3-oxetanones [57]. In their report, the combination of Ni(cod)2 and monodentate phosphine P(p-tolyl)3 was found to successfully couple 1,3-dienes and 3-azetidinones/3-oxetanones and afford eight-membered heterocycles in medium to good yield. It is interesting to note that only 2,3-substituted dienes were suitable substrates, primarily because of sterics (Scheme 13). 

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