Tandem reactions heterocycles

A more recent development in quinone chemistry has been the tandem reaction sequence. In seeking elegant syntheses of complex molecules, careful orchestration of transformations has become essential. The use of the Thiele-Winter reaction in tandem with arylation gives good yields of pharmacologically interesting heterocycles, such as (62), from 2,5-dihydroxy-l,4-ben2oquinone [615-94-1] and pyridines, where R = H or CH (60). 

Tandem reactions of heterocycles combining Diels-Alder reactions with sig-matropic rearrangements 98S227. 

Tandem reactions combining Diels-Alder reactions with sigmatropic rearrangements in syntheses of heterocycles 98S227. 

Meerwein type arylations involving radical additions to carbon-heteroatom multiple bonds such as in isothiocyanates have been further extended to tandem reactions leading to heterocycles [117, 118]. 

Pyrrolidines are an important class of five-membered heterocycles with noteworthy biological properties [46]. In addition to pharmaceutical applications, the pyrrolidine moiety has also been widely used as a chiral auxiliary for asymmetric synthesis [47]. Although many elegant syntheses of chiral nonracemic pyrrolidines have been reported within the past decade or so [48-50], an alternative approach based on the intramolecular reaction of an azide and organoborane has been developed very recently [51-53], This approach utilizes the hydroboration-azide alkylation tandem reaction as a key sequence, taking advantage of the efficient stereocon-trolled steps. Scheme 20 shows an application of the synthesis of 3-substituted 5-(2-pyrrolidinyl)isoxazole which has been found to have nanomolar activity, comparable to (5)-nicotine, against whole rat brain [54]. 

The cyclic carbopalladation-cross-coupling tandem reaction has been extensively developed over the past several years. Despite earlier favorable findings with A1 and Zr [84], these metals are still scarcely used. On the other hand, organometals containing Sn and B have been widely used, and favorable results have been obtained for the formation of ffve-membered car-bocycles and heterocycles containing N and O from halodienes [88] (Eqs. 1 and 2 in Scheme 29), haloenynes [89-92] (Eqs. 3-5 in Scheme 29), haloaryl-alkynes [94,95] (Eqs. 6 and 7 in Scheme 29), and allenene derivatives [93,96] (Eqs. 8 and 9 in Scheme 29). 

Keywords Cyclization Heterocycles Michael addition Tandem reactions ... 

Recently the same group reported new free radical-mediated tandem reactions of oxime ethers for the synthesis of heterocycles via two C-C bond-forming... 

Tandem reactions involving organolithium reagents (reactions with formation and participation of heterocycles) 03OPP445. 

Stereochemical control in the double conjugate addition Tandem Reactions as Polymerisation Terminated by Cyclisation The MIMIRC sequence with vinylphosphonium salts Tuning the MIMIRC sequence with different Michael acceptors Heterocycles by Tandem Conjugate Additions Tandem conjugate addition and Mannich reaction Tandem Conjugate Addition and Aldol Reaction... 

Part IV - Other Tandem Reactions Leading to Heterocycles... 

The Mannich reaction is a very common process that occurs in many tandem reaction sequences. For example, the Overman Aza-Cope cascade sequence is terminated by a Mannich reaction (cf. Scheme 35). Several groups have used variants of the Mannich reaction to initiate cascades that lead to the formation of heterocyclic molecules. For example, the Lewis acid-catalyzed intermolecular vinylogous Mannich reaction (01T3221) of silyloxy furan 281 with nitrone 282 produced a diastereomeric mixture (49 3 42 6) of azabicycles 284a-d in 97% combined yield (Scheme 52) (96TA1059). These products arose from an intramolecular Michael addition of the initially formed oxonium ion 283. 

The synthesis of chromenes, chromanes, coumarins, and related heterocycles via tandem reactions of salicylic aldehydes or salicylic imines with a,p-unsaturated compounds 07OBC1499. 

Enantioselective multicatalyzed tandem reactions (2010—2012) 13T7171. Heterocyclization of 1- and 2-alkynyl-9,10-anthraquinones (2005— 2012) 13KGS153. 

Recent developments in solvent-free multicomponent reactions A perfect synergy for eco-compatible organic synthesis 12RCA4547. Synthesis of fimctional heterocycles via tandem reaction 13YZ879. Synthetic applications of Passerini reaction 12COC418. 

Multicomponent reactions (MCRs) or tandem reactions have developed as a powerful tool for delivering the molecular diversity needed for the synthesis of interesting heterocyclic scaffolds, to efficiently constmct a variety of intermediates possessing an indolyl or indolizyl subunit and are particularly attractive especially if they start from simple molecules [11]. 

Liu, Y. Y. and Wan, J.-R 2011. Tandem reactions initiated by copper-catalyzed crosscoupling A new strategy towards heterocycle synthesis. Org. Biomol. Chem. 9(20) 6873-6894. 

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