Facial selectivity azomethine ylides

This attractive protocol for the asymmetric addition of a, p-unsaturated esters to A-metalated azomethine ylides was further developed using C(2) symmetrical imidazoladine stereodirecting units in an extensive study into the effects of reaction conditions and substituent effects on the facial selectivity of the reaction (36). Both... 

In synthetic efforts toward the DNA reactive alkaloid naphthyridinomycin (164), Gamer and Ho (41) reported a series of studies into the constmction of the diazobicyclo[3.2.1]octane section. Constmction of the five-membered ring, by the photolytic conversion of an aziridine to an azomethine ylide and subsequent alkene 1,3-dipolar cycloaddition, was deemed the best synthetic tactic. Initial studies with menthol- and isonorborneol- tethered chiral dipolarophiles gave no facial selectivity in the adducts formed (42). However, utilizing Oppolzer s sultam as the chiral controlling unit led to a dramatic improvement. Treatment of ylide precursor 165 with the chiral dipolarophile 166 under photochemical conditions led to formation of the desired cycloadducts (Scheme 3.47). The reaction proceeded with an exo/endo ratio of only 2.4 1 however, the facial selectivity was good at >25 1 in favor of the desired re products. The products derived from si attack of the ylide... 

The near perfect facial and endo/exo selectivities observed were reconciled by assuming that the reaction proceeded through the highly ordered endo transition state 173, in which both the azomethine ylide and the approaching dipolarophile are coordinated to the lithium cation (Fig. 3.10). Alternative endo transition state models that would allow for the observed stereochemical outcome of the cycloaddition do not permit an efficient and sterically less imposing environment for the relevant functionalities. 

The only concern is die cis stereochemistry of die cycloadduct O. If die planar azomethine ylide adopts the least sterically hindered W geometry, then the cis isomer will be produced as a pair of enantiomers. The use of d.v-stilbenc as the dipolarophile to obtain die all-cis geometry in one step would require that only die endo transition state produces product. Although endo transitions are favored in 1,3 dipolar cycloadditions, mixtures of diastereomers from the exo and endo transition states are usually formed. Catalytic hydrogenation has a higher facial selectivity and is much more likely to give a single diastereomer. 

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