Pyrrolidines endo-, formation

Zard and coworkers [32] reported a simple approach to create another group of natural products, namely the lycopodium alkaloids [15]. These authors first investigated the reaction of O-benzoyl-N-allylhydroxylamide 3-60 with tributyltin hydride and ACCN in refluxing toluene, which led (after formation of the N-radical 3-61 in a 5-exo-trig/5-exo-trig cyclization) to the undesired pyrrolidine 3-62 in 48% yield. Nevertheless, a small structural modification, namely the placement of a chlorine atom at the allyl moiety as in 3-63, induced a 5-exo-/G-endo- instead of the 5-exo-/5-... 

In the area of [3 + 2]-cycloadditions (1,3-dipolar cycloadditions), chiral silver catalysts have been utilized extensively for the enantioselective formation of five-membered rings from prochiral substrates. For example, Zhang and co-workers360 have reported the highly enantioselective Ag(i)-catalyzed [3 + 2]-cycloaddition of azomethine ylides to electron-deficient alkenes. Thus, reaction of ct-imino esters 442 with dimethyl maleate in the presence of catalytic amounts of silver(i) acetate and the chiral bisferrocenyl amide phosphine 443 provided the chiral pyrrolidines 444 with high stereoselectivities and chemical yields (Scheme 131). Only the endo-products were isolated in all cases. 

Only a few cyclopropanes have been synthesized by C-N bond cleavage accompanied by C-H bond formation. When 1,1 -(bicyclo[4.1.0]hept-7-ylidene)dipyrrolidine and exo-7-(pyrrolidin-l -yl)bicyclo[4.1.0]heptan-enr/o-7-ol were treated with sodium borohydride a pyrrolidinyl group was expelled and replaced with hydrogen. In both cases the leaving group occupied the endo position, giving W-(bicyclo[4.1.0]hept-endo-7-yl)pyrrolidine and bicyclo[4.1.0]heptan-endo-7-ol, respectively, as the products. The former product appears to have been obtained in almost quantitative yield. ... 

Normally, 5-endo-trig-cyclisations are disfavoured geometrically (Baldwin s rules), however formation of pyrrolidines does take place with tosylamide anion as nucleophile in a situation where 5-ejco-fef-attack at a trihalomethyl group is inhibited electrostatically. ... 

Iminium ion-alkene cyclizations accomplished under standard Eschweiler-Clarke methylation conditions have been employed to prepare five-, six- and seven-membered azacycles (Scheme 25).57,58 It is important to note that under identical conditions amines (62) and (63) did not cyclize but afforded the corresponding IVjV-dimethylamines. With regard to the alkene participant these results are in full accord with Baldwin s rules for ring formation.2 However, the formation of pyrrolidine (61) demonstrates that 5-endo-trig cyclizations2 can take place with respect to the iminium ion n-participant. The observed regioselectivity and the failure of (63) to cyclize are in accord with obligatory formation of an intermediate with tertiary carbocation character. 

The stereoselectivity of pyrrolidine formation by an overall 5-endo-trig process is greatly affected by a base. ... 

Interestingly, pyrrolidine provided access to the cyclohexanone products in good yield (70%) and moderate exo.endo selectivities (6 1). The exo product was conjectured to form preferentially due to more favourable iminium ion solvation and hydrophobic interactions in the transition state, compared to the standard secondary orbital interactions contributing to endo selectivity. Other ketones could undergo self-Diels-Alder formation ... 

---