Cascade reactions nitrogen nucleophiles

The successful utilization of nitrogen-based nucleophiles in the previously described cascade reactions has allowed for the synthesis of complex polycyclic structures from simple and readily available starting materials. The fact that carbamates can participate as nucleophiles has provided the opportunity for development of diastereoselective ring closures onto the halocyclopropane-derived allyl cation. 

Termination by external nitrogen nucleophiles has been investigated for various systems (cf. Ref. [53]). AUenes, which are excellent relays for cascade reactions, give rise to the formation of Tr-aUylpaUadium complexes. The latter can be reacted in a straightforward manner with amines to yield highly functionalized allylamines (Scheme 30, Eqs. 1 and... 

There are hardly any examples for the use of sulfur nucleophiles in terminating cascade carbopalladation sequences, in contrast to oxygen and especially nitrogen nucleophiles. One reason for this might be found in the problems associated with the high degree of coordination of the palladium with the less oxidized sulfur nucleophiles such as thiols. However, arylsulfinates are excellent nucleophiles for cascade termination reactions, as has been shown by Grigg et al. (Scheme 34). ... 

Synthesis of chiral heterocycles by domino organocatalytic processes has also been intensively studied. In particular, various benzo-fused heterocycles, such as chiral chromans, " thiochromanes, hydro-quinolines, dihydropyranes, or thiopyranes were investigated. These organocatalytic sequence were typically initiated by a hetero-Michael addition of a sulfur, oiqrgen or nitrogen nucleophile, which triggers the formation of an enolate/enamine that adds to the ortho electrophile terminating the cascade reaction. An elimination step or an additional cyclisation step follows (Scheme 8.25). 

More recently, Enders et al. disclosed a facile access to tetracyclic double annulated indole derivatives 175, which basically relies on the chemistry of the acidic 2-substituted indole and its nitrogen nucleophilicity. Indeed, the employed quadruple cascade is initiated by the asymmetric aza-Michael-type A-alkylation of indole-2-methylene malono-nitrile derivative 174 to o,p-unsaturated aldehydes 95 under iminium activation (Scheme 2.57). The next weU-known enamine-iminium-enamine sequence, which practically is realized with an intramolecular Michael addition followed by a further intermolecular Michael and aldol reactions, gives access to the titled tetracyclic indole scaffold 175 with A-fused 5-membered rings annulated to cyclohexanes in both diastereo- and enantioselectivity [83]. 

Ketones can be converted to a-imidoketones by a one-pot cascade reaction, whereby A-bromosuccinimide provides both electrophilic bromine (for a-bromination of enolate) and nucleophilic nitrogen in conjugation with diazabicyclo[5.4.1]undec-7-ene (DBU) as activator. ... 

Jia et al. reported a novel Michael/aza-Henry reaction of well-designed chalcones 217 and nitromethane 218 catalyzed by thiourea 130c (Scheme 2.60). Initiated by the Michael addition of nitromethane to an electron-deficient double bond, the resulting intermediate subsequently underwent an aza-Henry reaction to furnish multisubsti-tuted tetrahydroquinolines 219a with up to 20 1 dr and >99% ee [86a], Later, the same group presented an alternative way to construct the same skeletons with different diastereoselectivities [86b], which employed nitrogen as the nucleophilic site to trigger the cascade process (Scheme 2.60). Very recently, a multifunctional... 

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