Cyclization reactions nitrogen heterocycles

Negishi reaction 157 Nitriles, reduction/hydrolysis 25 Nitrogen heterocycles, on-resin cyclization, minopropenones 108 C-Nucleoside analogues 274... 

The majority of sequential radical reactions deal with cyclizations as the key steps. The constructions of carbocycles, oxygen, and nitrogen heterocycles using (TMSlsSiH as a mediator are many and represents the expansion and importance of these synthetic approaches. For example, Nicolaou and coworkers found that (TMSlsSiH serves as a superior reagent in the radical-based approach toward the synthesis of azadirachtin, an antifeedant agent currently used as an insecticide, and in other related systems. ° ° Here below we collected a number of reactions mostly from the recent work in the area of intramolecular reactions. 

In contrast to the palladium-catalyzed reactions, little attention has been paid to other transition-metal catalysts. Recently some efficient reactions using copper(i or 11), gold(m), platinum(n), and tungsten(O) have been developed for the synthesis of nitrogen-heterocycles. The copper-catalyzed cyclizations of 2-alkynylaniline derivatives into... 

Some heterocyclic nucleophiles may also be successfully employed in these cyclization reactions (Schemes 25 and 26) [131]. In contrast, no cyclization was observed in an aniline-based system (Scheme 27), which reflects the reduced nucleophilicity of the aniline nitrogen [142],... 

Another oxidative cyclization to afford a nitrogen heterocycle is illustrated in Scheme 12 [33]. This reaction was accomplished using a platinum gauze electrode at a controlled potential of -t-1.8 V versus Ag/AgCl. The reaction proceeded through the initial oxidation of the amide. Evidence... 

The recent impact of solid-phase synthesis on medicinally relevant benzoaime-lated nitrogen heterocycles has been recently reviewed [16], therefore in this section only recent publications are included. Benzoannelated heterocycles can be prepared efficiently through cyclization on solid supports employing classical heterocycle forming reactions such as the Fischer [425], the Bischler-Napieralski [426], Tsuge [427], Nenitzescu [428], and Richter [140] reactions. In addition, the... 

Reductive cyclization of the 2-halogenophenyl group onto an adjacent phenyl substituent is a useful reaction for the preparation of condensed ring nitrogen heterocycles. Examples of the process include the formation of aromatic and conjugated 7t-systems [168, 169]. It has been applied to the synthesis of an aporphine... 

Yttrium-catalyzed diene cyclization/hydrosilylation was applied to the synthesis of aliphatic nitrogen heterocycles such as the indolizidine alkaloid ( )-epilupinine. l-Allyl-2-vinylpiperidine 30 was synthesized in four steps in 59% overall yield from commercially available ( )-2-piperidinemethanol (Scheme 10). Treatment of 30 with phenylsilane and a catalytic amount of Gp 2YGH3(THF) gave silylated quinolizidine derivative 31 in 84% yield, resulting from selective hydrometallation of the A-allyl G=G bond in preference to the exocyclic vinylic G=G bond. Oxidation of the crude reaction mixture with tert-huVf hydrogen peroxide and potassium hydride gave (i)-epilupinine in 51-62% yield from 30 (Scheme 10). 

Mori has independently developed a procedure for the cyclization/stannylsilylation of enynes similar to that developed by Lautens. As an example of Mori s procedure, reaction of dimethyl allylpropargylmalonate with trimethylsilyltributylstannane catalyzed by Pearlman s catalyst [Pd(OH)2/C] in THF at room temperature for 20 h formed cyclopentane 94 [X = C(C02Me)2] in 90% yield (Equation (61)). The transformation was compatible with a number of functional groups, tolerated limited substitution of the G=C bond, and was applicable to the synthesis of nitrogen heterocycles. In a notable example, reaction of the benzhydryl-protected allylpropargylamine 95 with MesSiSnBus catalyzed by Pd(OH)2/C formed the bis(functionalized) octahydroindole 96 in 66% yield as a single diastereomer (Equation (62)). 

Cyclization of haloamines (cyclic amines) dealkylation of quaternary salts of nitrogen heterocycles 0-45 Reaction between dihalides and cy-anamide (cyclic amines)... 

In reactions of primary alkylamines with internal perfluoroolefins, intramolecular nucleophilic cyclization gives a heterocyclic compound with a perfluoroalkyl group. As mentioned above, primary alkylamines can be binucleophilic reagents with nucleophilic centers on the nitrogen atom. Such compounds having an NH2 group form four-membered heterocycles and many polycyclic heterocycles with one nitrogen atom. 

Many of the chiral selenium electrophiles have also been employed in cyclization reactions. Various internal nucleophiles can be used and access to different heterocycles is possible. Not only oxygen nucleophiles can be used for the synthesis of heterocyclic compounds, but also nitrogen nucleophiles are widely employed and even carbon nucleophiles can be used for the synthesis of carbacycles with new stereogenic centers. Oxygen nucleophiles have been widely used and some selected examples of selenolactonizations of unsaturated acids 50 and 52 and seleno-etherifications of unsaturated alcohols 54 and 56 are shown in Scheme 10. 

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