Reductive-cyclization

The allylstannane 474 is prepared by the reaction of allylic acetates or phosphates with tributyltin chloride and Sml2[286,308] or electroreduction[309]. Bu-iSnAlEt2 prepared in situ is used for the preparation of the allylstannane 475. These reactions correspond to inversion of an allyl cation to an allyl anion[3l0. 311], The reaction has been applied to the reductive cyclization of the alkenyl bromide in 476 with the allylic acetate to yield 477[312]. Intramolecular coupling of the allylic acetate in 478 with aryl bromide proceeds using BuiSnAlEti (479) by in situ formation of the allylstannane 480 and its reaction with the aryl bromide via transmetallation. (Another mechanistic possibility is the formation of an arylstannane and its coupling with allylic... 

As another example of nitrene formation, the reaction of o-nitrostilbene (96) with CO in the presence of SnCU affords 2-phenylindole (97). The reaction is explained by nitrene formation by deoxygenation of the nitro group with CO, followed by the addition of the nitrene to alkene. Similarly, the 2//-indazole derivative 99 was prepared by reductive cyclization of the A-(2-nitrobenzyli-dene)amine 98[89]. 

A two-step synthesis of indoles from o-nitrobenzaldehydes proceeds by condensation with nitromcthanc followed by reductive cyclization. Like the Leim-gruber Batcho method, the principal application of the reaction is to indoles with only carbocyclic substituents. The forniation of the o,p-dinitrostyrenes is usually done under classical Henry condensation conditions but KF/18-crown-6 in propanol was found to be an advantageous reaction medium for acetoxy-substituted compounds[1]. The o,p-dinitrostyrenes can also be obtained by nitration of p-nitrostyrenes[2]. 

Acylation of the Leimgruber Batcho enamines with phosgene followed by methanolysis and reductive cyclization generates methyl indole-3-carb-oxylates[8]... 

Several procedures have been explored for the reductive cyclization of o-nitrostyrenes. Triethyl phosphite accomplishes this transformation by deoxy-... 

A reversal of the position of the substituents on the pyrimidine ring is involved in the reductive cyclization of 4-ketoalkyl-5-phenylazopyrimidines to give, e.g. 6-alkylpyrido[3,2- f]pyrimidines (76JHC439). 

An oxidative cyclization, (151) -> (152), with azodicarboxylate (78CC764) is balanced by the synthesis of 5-deazaalloxazines from aryl bis(6-aminouracilyl)methanes, which involves azodicarboxylate in an intermediate electrophilic capacity (153 -> 154) (79CPB2507). Other methods involve reductive cyclizations (72AP751). 

The main reaction of this type has been the reductive cyclization of nitropyridine derivatives carrying an o-amino ester or o-aminocarbonyl substituent. These cyclize in situ via the o-diamino derivative to give pyridopyrazines of known constitution, either for establishment of structure of products obtained in the ambiguous Isay synthesis (see Section 2.15.15.6.1), or in the synthesis of aza analogues of biologically active molecules. 

Illustrative examples of oxidative and reductive cyclizations of (CCCNO) synthons are shown in equations (33)-(39). 

An Index to types of reactions, e.g. alkylations, stereoselective reductions, cyclizations etc. and... 

The alkylation of enamines with nitroolefins, which gives intermediates for reductive cyclization (6S2), also provided an example of a stable cycliza-tion product derived from attack of the intermediate imonium function by the nitro anion (683). A previously claimed tetrasubstituted enamine, which was obtained from addition of a vinylsulfone to morpholinocyclohexene (314), was shown to be the corresponding cyclobutane (684). Perfluoro-olefins also gave alkylation products with enamines (685). Reactions of enamines with diazodicarboxylate (683,686) have been used diagnostically for 6-substituted cyclohexenamines. In a reaction of 2-penten-4-one with a substituted vinylogous amide, stereochemical direction was seen to depend on solvent polarity (687). 

Garcia et al. has extended the Batcho-Leimgruber procedure to the synthesis of 2-substituted indoles. Treatment of 36 with o-fluorobenzoyl chloride 37, followed by in situ hydrolysis and deformylation gave ketone 38. Reduction of nitroarylketone 38 with sodium hydrosulfite then furnished indole 39. Similarly, bromoacetylation of 36 gave an acylenamine which was converted into the phthalimido derivative 40. Hydrolysis and deformylation gave phthalimidoketone 41 which underwent reductive cyclization to furnish indole 42. 

The Reissert procedure involves base-catalyzed condensation of an o-nitrotoluene derivative 1 with an ethyl oxalate (2) which is followed by reductive cyclization to an indole-2-carboxylic acid derivative 4, as illustrated below . ... 

Dihydroquinazolines are stable and a large number have been prepared. They have been synthesized by reductive cyclization of acyl derivatives of o-nitrobenzylamines, and by acylation of o-amino-benzylamines followed by ring closure. The ring closure can be effected by heating with anhydrous zinc chloride ° or by distillation. ... 

An old and satisfactory method is the Riedel synthesis in which o-nitrobenzaldehyde is converted to its bisformaraido derivative followed by reductive cyclization with zinc and acetic acid, or with iron and hydrochloric acid. This synthesis has been used to make... 

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