Metal-catalyzed cycloisomerizations

For an excellent review covering enantio-selective metal-catalyzed cycloisomerization of 1,6- and 1,7-enynes, see I.J.S. Fairlamb, Angew. Chem. Int. Ed. 2004,... 

Chapter 15 contains more of the transition metal-catalyzed cycloisomerizations of allenes. 

Considering the mechanistic rationales of the transition metal-catalyzed enyne cycloisomerization, different catalytic pathways have been proposed, depending on the reaction conditions and the choice of metal catalyst [3-5, 45], Complexation of the transition metal to alkene or alkyne moieties can activate one or both of them. Depending on the manner of formation of the intermediates, three major mechanisms have been proposed. The simultaneous coordination of both unsaturated bonds to the transition metal led to the formation of metallacydes, which is the most common pathway in transition metal-catalyzed cycloisomerization reactions. Hydrometalation of the alkyne led to the corresponding vinylmetal species, which reacts in turn with olefins via carbometalation. The last possible pathway involves the formation of a Jt-allyl complex which could further react with the alkyne moiety. The Jt-allyl complex could be formed either with a functional group at the allylic position or via direct C-H activation. Here the three major pathways will be discussed in a generalized form to illustrate the mechanisms (Scheme 8). 

JV-Tosyl-l,2,3,4-tetrahydropyridines 208, which have at the 4-position a tethered electron-deficient alkyne, undergo metal-catalyzed cycloisomerization to give 2-azahydrindans 209, which can undergo Diels-Alder reactions with acroleins to give highly functionalized 1-azadecalins 210 (Scheme 55) <20040L5023>. 

Porco et al.74 accessed pyrroloisoquinoline heterocycles 46 by employing a domino process. Initially, a metal-catalyzed cycloisomerization of alkynyl iV-benzylidene glycinates 45 gave azomethine ylide CC (Scheme 5.21), which underwent... 

Hashmi, A. S. K. Transition Metal-catalyzed Cycloisomerizations of Allenes. In Modem Allene Chemistry Krause, N., Hashmi, A. S. K., Eds. Wiley-VCH Weinheim, 2004 pp 877-923. 

Two different research groups independently reported metal-catalyzed cycloisomerizations of alkynyl-substituted pyridines leading to indolizines. Specifically, treatment of pyridine 7 with silver tetrafluoroborate gave indolizine 8 in excellent yield <07OL3433>. This reaction could also be mediated by copper(I) iodide <07JOC7783>. 

Metal-catalyzed cycloisomerization reactions of w-alkynols (4-pentyn-l-ol derivatives) provide a rapid and efficient access to tetrahydrofurans. In general, these reactions may proceed through two different reaction pathways, formally leading to endo- or r-vo-cycloisomerization products. The formation of the rwn-tetrahydrofuran product can be achieved with catalytic amounts of tungsten pentacarbonyl (Equation 85) <2005CEJ5735>. 

Enyne metathesis Transition metal catalyzed cycloisomerization of [1,n]-enynes to the corresponding 1,3-dienes. 152... 

Trost, B. M. Transition metal-catalyzed cycloisomerizations of enynes. Janssen Chimica Acta 1991, 9, 3-9. 

Scheme 27. Metal-catalyzed cycloisomerization of ortho-alkynylated biphenyl derivatives feature...

Shortly after the discovery of enyne metathesis, Trost began developing cycloisomerization reactions of enynes using Pd(ll) and Pt(ll) metallacyclic catalysts (429-433), which are mechanistically divergent from the metal-carbene reactions. The first of these metal catalyzed cycloisomerization reactions of 1,6-enynes appeared in 1985 (434). The reaction mechanism is proposed to involve initial enyne n complexation of the metal catalyst, which in this case is a cyclometalated Pd(II) cyclopentadiene, followed by oxidative cyclometala-tion of the enyne to form a tetradentate, putative Pd(IV) intermediate [Scheme 42(a)]. Subsequent reductive elimination of the cyclometalated catalyst releases a cyclobutene that rings opens to the 1,3-diene product. Although this scheme represents the fundamental mechanism for enyne metathesis and is useful in the synthesis of complex 1,3-cyclic dienes [Scheme 42(fe)], variations in the reaction pathway due to selective n complexation or alternative cyclobutene reactivity (e.g., isomerization, p-hydride elimination, path 2, Scheme 40) leads to variability in the reaction products. Strong evidence for intermediacy of cyclobutene species derives from the stereospecificity of the reaction. Alkene... 

A regioselective transition metal-catalyzed cycloisomerization reaction of boron-containing alkynyl epoxides toward C-2- and C-3-borylated furans was developed. It was found that the copper catalyst as well as the gold catalyst with a relatively more basic triflate counterion favored boryl migration toward C-3-borylated furans, whereas employment of the cationic gold hexafluoroantimonate afforded C-2-borylated furans via a formal 1,2-hydrogen shift (14JA13146). 

Enantioselective synthesis of alcohols and amines by iridium-catalyzed hydrogenation, transfer hydrogenation, and related processes 13CEJ7274. Enantioselective, transition metal-catalyzed cycloisomerizations 12CSR 4884. 

Transition metal-catalyzed cycloisomerizations of a,w-dienes providing atom-economical routes to various carbo- and heterocyclic compounds 12CRV4736. 

Seregin, I., Schammel, A. and Gevorgyan, V. 2008. Multisubstituted N-fused heterocycles via transtion metal-catalyzed cycloisomerization protocols. Tetrahedron 64 6876-6883. 

Recently, a novel approach for the synthesis of highly substituted furans vas developed by Larock and covrorkers (Scheme 8.37). It vas reported that 2-alkynyle-nones [151-153] 93 undervrent a facile transition metal-catalyzed cycloisomerization affording highly substituted furans 94 in the presence of the external O- or electron... 

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