Cycloadditions multi-component

Design and Development of Multi-component [5+2+1] Cycloadditions of VCPs, Alkynes, and CO... 

Wright DL, Robotham CV, Aboud K (2002) Studies on the sequential multi-component coupling/Diels-Alder cycloaddition reaction. Tetrahedron Lett 43 943-946... 

The covalent assembly of functional Jt-systems is a general synthetic principle and in some cases they can even be achieved in a multi-component fashion. One of the most impressive examples is the very elegant access to covalently linked donor-fullerene arrangements by 1,3-dipolar cycloadditions with in situ-generated azomethine ylids [59]. However, here only the multi-component de novo synthesis of the chromophore structures will be considered. The major developments have been achieved in condensation-based and cross-coupling strategies. 

In an exploration of multi-component reactions for the synthesis of a diverse array of heterocyclic scaffolds Martin et al. demonstrated a cascade reaction involving the imine, formed from the condensation of 2-azidobenzaldehyde 97 with propargylamine, acetyl chloride and ketene acetal 98 to furnish the triazolo-fused benzodiazepine 99 via an intramolecular [3+2] cycloaddition <07OL4223>. 

Multi-component couplings open up an economic and straightforward route to very different compound libraries. For example, 1,3-dipolar cycloaddition reactions of nitrones with alkenes furnish isoxazolines, which can be transformed reductively to hydroxyketones or )8-amino alcohols. In 1997, two groups reported on the synthesis of isoxazolines by rare earth metal-catalyzed [3 + 2] cycloadditions (Scheme 4) [13,14]. 

SPS of isoxazolidines through 1,3-dipolar cycloaddition and their transformations have been reviewed <2005CSR507>. Isoxazolidines were also prepared by nitrone 1,3-dipolar cycloaddition on silica gel in solvent-free conditions under microwave irradiation <2001J(P1)452>. Fused polycyclic isoxazolidines were prepared via a multi-component palladium-catalyzed allene insertion-intramolecular 1,3-dipolar cycloaddition cascade <2002CC1754, 2005AGE7570>. 

Solution-phase multicomponent methodology for the synthesis of heterocyclic compounds, (non-catalytic syntheses, catalysis with acids and metals, multi-component reactions including cycloaddition are reviewed) 03S1471. 

A straightforward synthesis of fused dihydrotriazolo[l,5-Q ]pyrazinones and triazolobenzodiazepines by sequential Ugi/alkyne-azide cycloaddition reactions was recently demonstrated by Djuric et al. [55]. The couphng of the Ugi multi-component reaction with the intramolecular alkyne-azide cycloaddition provides access to highly functionaUzed heterocyclic ring systems in just two steps. 

Parsons and co-workers reported a multi-component reaction (74 -i- 75 + 76 -i- 77) involving sequential [ l-i-3] and [2-i-3] cycloadditions for the synthesis... 

B. Groenendaal, E. Ruijter, R. V. A. Orru, Chem. Commun. 2008, 5474-5489. 1-Azadienes in cycloaddition and multi-component reactions towards A -heterocycles. 

For representative reviews on metal-catalyzed MCRs, see (a) D. M. D Souza, T. J. J. Muller, Chem. Soc. Rev. 2007, 36, 1095-1108. Multi-component syntheses of heterocycles by transition-metal catalysis, (b) J. A. Varela, C. Saa, Synlett 2008, 2571-2578. Recent advances in the synthesis of pyri-dines by transition-metal-catalyzed [2+2+2] cycloaddition, (c) H. Clavier, H. PeUissier, Adv. Synth. Catal. 2012, 354, 3347-3403. Recent developments in enantioselective metal-catalyzed domino reactions. 

Z. N. Tisseh, M. Dabiri, M. Nobahar, H. R. Khavasi, A. Bazgir, Tetrahedron 2012, 68,1769-1773. Catalyst-free, aqueous and highly diastereoselective synthesis of new 5-substituted H-tetrazoles via a multi-component domino Knoevenagel condensation/l,3-dipolar cycloaddition reaction. 

Moreover, MCPs have been used as three-carbon components participating in [3+2+2] or [4+3] cycloadditions to build seven-membered rings. Early in the 1980s, Binger reported some examples of [3+2+2] and [4+3] cycloadditions a multi-component [3+2+2] cycloaddition of MCP and two units of aUenes catalyzed by Pd(0) [99], a mono-component [3+2+2] cycloaddition of three units of MCPs catalyzed by Ni(0) [100], and a [4+3] cycloaddition of MCPs and dienes catalyzed by Pd(0) [78] (Scheme 13). Saito and co-workers have made some impressive contributions in this area. They developed a series of Ni(0)-catalyzed [3+2+2] and... 

A transannular 4 + 2-cycloaddition initiates the tandem 4 + 2/3+2-cycloaddion cascade of 1,3,4-oxadiazoles (1) to yield cycloadduct intermediates (2) used for the synthesis of analogues of vinblastine (Scheme 1)." The multi-component 4+ 2/3+2-domino cycloaddition reactions of 3-nitroindole derivatives with vinyl ethers and acrylates were studied computationally and experimentally. The 4+2-reaction follows a classical concerted asynchronous process while the 3 + 2-addition involves an electron donation by an electron-deficient reaction partner. ... 

For this multi-component reaction (MCR [28]) proceeding without the need for a further catalyst, a mechanism is suggested which involves primary attack of the isocyanide to the triple bond of DMAD followed by 1,3-dipolar cycloaddition of the resulting dipole 87 to the aldehyde C=0 group (87 88) subsequent (l,5)-H-shift in 88 complements formation of the aminofuran system 86. 

S.M. Rajesh, B.D. Bala, S. Perumal, Multi-component, 1,3-dipolar cycloaddition reactions for the chemo-, regio- and stereoselective synthesis of novel hybrid spiroheterocycles in ionic liquid. Tetrahedron Lett. 53 (2012) 5367-5371. 

Jia F-C, Xu C, Zhou Z-W, Cai Q, Li D-K, Wu A-X (2015) Consecutive cycloaddition/SNAr/reduction/cyclization/oxidation sequences a copper-catalyzed multi-component s5mthesis of fused N-heterocycles. Org Lett 17(ll) 2820-2823... 

Perreault S, Rovis T. Multi-component cycloaddition approaches in the catal) tic asymmetric synthesis of alkaloid target. Chem. Soc. Rev. 2009 38 3149-3159. 

Bora and co-workers44 have developed a microwave-assisted three-component synthesis of indolizines. The reaction involves a 1,3-dipolar cycloaddition reaction between the in situ generated dipole (from the bromoacetophenone and pyridine) and acetylene, Scheme 5.26. The developed method provides fast access to cycloadducts, which otherwise are accessible only through multi-step synthesis. 

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