Cycloisomerization metal-catalyzed

Figure 2 Ligands for effecting asymmetric transition metal-catalyzed Alder-ene cycloisomerization.

Allenes, while arguably underused in synthesis as a whole, have become popular functionalities in cycloisomerization chemistry and provide access to a wide variety of products. Ruthenium, cobalt, platinum, palladium, rhodium, and iridium catalysts are efficient in the transition metal-catalyzed Alder-ene reactions of allenes. 

Malacria and co-workers76 were the first to report the transition metal-catalyzed intramolecular cycloisomerization of allenynes in 1996. The cobalt-mediated process was presumed to proceed via a 7r-allyl intermediate (111, Scheme 22) following C-H activation. Alkyne insertion and reductive elimination give cross-conjugated triene 112 cobalt-catalyzed olefin isomerization of the Alder-ene product is presumed to be the mechanism by which 113 is formed. While exploring the cobalt(i)-catalyzed synthesis of steroidal skeletons, Malacria and co-workers77 observed the formation of Alder-ene product 115 from cis-114 (Equation (74)) in contrast, trans-114 underwent [2 + 2 + 2]-cyclization under identical conditions to form 116 (Equation (75)). 

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. 

Enamines (cf. 63JCE194, 82T1975,88MI1,08H(75)1849) play an important role in the syntheses under review, both as target substances (see Schemes 16 and 17) and as precursors (see Scheme 9 and following Schemes 19-21). Thus, noble-metal-catalyzed enyne and diene cyclizations have been described (Scheme 19) palladium-catalyzed cycloisomerization of... 

The intramolecular Alder-ene reaction (enyne cydoisomerization reaction) with alkynes as the enophiles has found wide application compared with diene systems. The reason may be the ready chemo-differentiation between alkene and alkyne functionality and the more reactive alkyne moiety. Furthermore, the diene nature of the products will promote further applications such as Diels-Alder reactions in organic synthesis. Over the past two decades the transition metal-catalyzed Alder-ene cycloisomerization of l,n-enynes (typically n= 6, 7) has emerged as a very powerful method for constructing complicated carbo- or heterocydic frameworks. The transition metals for this transformation indude Pd, Pt, Co, Ru, Ni-Cr, and Rh. Lewis acid-promoted cydoisomerization of activated enynes has also been reported [11],... 

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. 

Abstract This review gives an insight into the growing field of transition metal-catalyzed cascades. More particularly, we have focused on the construction of complex molecules from acyclic precursors. Several approaches have been devised. We have not covered palladium-mediated cyclizations, multiple Heck reactions, or ruthenium-catalyzed metathesis reactions because they are discussed in others chapters of this book. This manuscript is composed of two main parts. In the first part, we emphasize cascade sequences involving cycloaddition, cycloisomerization, or ene-type reactions. Most of these reaction sequences involve a transition metal-catalyzed step that is either followed by another reaction promoted by the same catalyst or by a purely thermal reaction. A simple change in the temperature of the reaction mixture is often the only technical requirement to go from one step to another. The second part covers the cascades relying on transition metalo carbenoid intermediates, which have recently undergone tremendous... 

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>. 

In the following scheme, the benzo[Z>]furan core of antibiotic erypoegin H was built up by a PtCL-catalyzed cycloisomerization of or// o-alkynylphenyl-0,(9-acetals <07AGE4760>. A similar type of reaction was applied to the syntheses of 2,3-disubstituted bcnzo b furans <07T8670>. A metal-catalyzed cyclization was also used in the syntheses of 5,6-disubstituted furo 2,3-c/]pyrimidines from alkynyl-pyrimidinols and aryl iodides <07T1931>. 

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