N-endo-trig cyclization

Palladium The Pd(0)-BINAP complex has been shown to catalyse the aza-Michael 6 N) -endo-trig cyclization of dienamides (487), activated by both A-/ -toluenesulfonyl group and the R substituents the reaction affords 2-piperidinones (488) with <81%... 

Intramolecular cyclization can also be initiated from the radical-cation of a styrene residue [57], Oxidative cyclization of 31, n = 1 and 31, n = 2 give five and seven membered ring products respectively but in contrast 32 failed to yield a five membered ring product, giving only intractable mixtures. This difference in reactivities can be explained in terms of Baldwin s rules where the 5-endo-trig cyclization of the radical-cation from 32 is disfavoured [58]. 

Retrosynthetic path a corresponds to Pd-catalysed exo-trig cyclization of o-halo-/V-allylan ilines. Path b involves the endo-trig cyclization of o-halo-N-vinyl anilines. Path c is a structurally similar cyclization which can be effected photochemically in the absence of an o-substituent. Retrosynthetic path d involves intramolecular Friedel-Crafts oxyalkylation followed by aromatiz-ation. 

The uncyclized enamine 183 was treated in boiling toluene for 5 h. prior to radical cyclization, and then further treated with tri-n-butyltin hydride in boiling toluene. A successful tandem double S-exo-trig, 6-endo-trig cyclization of the aryl radical generated from 184 afforded the tetrahydrolysergate 185 which was obtained as die only isolable product in 75% yield as a 3 1 mixture of two epimers at the 10-position (Scheme 39). 

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 indole alkaloid arena, the general rules of radical cyclizations apply. For example, radical cyclization via the 5-endo-trig mode is usually disfavored unless the substrate possesses a structural setup (e.g. N,N-disubstituted amides, but not N-phenyl or N-allyl [17d]) that conformationally favors the 5-endo-trig mode. Radical cyclizations via the 5-endo-trig mode do occur for some substrates, such as 1,3, and 7. 

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. 

Castedo, Dominguez and coworkers [67] carried out the cyclization of the N-formyl enamines 264. The 1-endo trig radical cyclization of the enamines 264 with Bu3SnH and AIBN using slow addition technique proceeded with excellent stereoselectivity to generate only the trans isomer of the tetracyclic system 265. 

The mechanism of the cyclization reactions in Scheme 15 is yet unclearl °n i either an unusual 5-endo-trig carbopalladation takes place as key step or a cyclopalladationi i followed by reductive elimination. More typical examples of the latter type of process are discussed in Sect. D. Whatever the mechanism, the yields achieved are good to excellent in every case. Moreover, this type of starting material is easy to build up, even in situ from aniline derivatives and suitable carbonyl compounds (Scheme... 

An intramolecular redox C-H activation process of alkenyl sulfoximines has been reported. The process is proposed to proceed through a 6-endo-trig hydride transfer to produce a zwitterionic intermediate (Scheme 47). This intermediate can cyclize to novel heterocycles, produce N-H alkyl sulfoximines, or form novel and chiral A-dienyl sulfoximines." ... 

The intramolecular reaction of N-aryl imine 210 under phase-transfer conditions in the presence of cinchonidinium chloride 211 furnishes the chiral indoline 212 in quantitative yield with high enantiomeric excess (Scheme 28.27). An intramolecular Marmich reaction under kinetic control formally constitutes a 5- etwlexo)-endo trig reaction, which is stereo-electronicaUy demanding as delineated by the Baldwin rules therefore, this transformation includes a cation-directed 6k electro-cyclization as depicted in the reaction model 213 [106]. 

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