Metal-catalyzed cyclization

Sequential transition-metal-catalyzed processes are dominated by palladium-17], rhodium- [8], and ruthenium- [9] catalyzed sequences. With respect to Fogg s and de Santos classification, only cyclizing metal-catalyzed one-pot processes [1] in the sense of auto and assisted tandem catalysis will be discussed and highlighted in this overview. 

Transition-Metal Catalyzed Cyclizations. o-Halogenated anilines and anilides can serve as indole precursors in a group of reactions which are typically cataly2ed by transition metals. Several catalysts have been developed which convert o-haloanilines or anilides to indoles by reaction with acetylenes. An early procedure involved coupling to a copper acetyUde with o-iodoaniline. A more versatile procedure involves palladium catalysis of the reaction of an o-bromo- or o-trifluoromethylsulfonyloxyanihde with a triaLkylstaimylalkyne. The reaction is conducted in two stages, first with a Pd(0) and then a Pd(II) catalyst (29). 

The converse situation in which ring closure is initiated by the attack of a carbon-based radical on the heteroatom has been employed only infrequently (Scheme 18c) (66JA4096). The example in Scheme 18d begins with an intramolecular carbene attack on sulfur followed by rearrangement (75BCJ1490). The formation of pyrrolidines by intramolecular attack of an amino radical on a carbon-carbon double bond is exemplified in Scheme 19. In the third example, where cyclization is catalyzed by a metal ion (Ti, Cu, Fe, Co " ), the stereospecificity of the reaction depends upon the choice of metal ion. 

Transition metal-catalyzed cyclizations of heterocycles accompanied by multiple bonds migration 98SL1. 

Transition metal-catalyzed cyclizations accompanied by multiple bond migration with formation of heterocycles 98SL1. 

The diazo function in compound 4 can be regarded as a latent carbene. Transition metal catalyzed decomposition of a diazo keto ester, such as 4, could conceivably lead to the formation of an electron-deficient carbene (see intermediate 3) which could then insert into the proximal N-H bond. If successful, this attractive transition metal induced ring closure would accomplish the formation of the targeted carbapenem bicyclic nucleus. Support for this idea came from a model study12 in which the Merck group found that rhodi-um(n) acetate is particularly well suited as a catalyst for the carbe-noid-mediated cyclization of a diazo azetidinone closely related to 4. Indeed, when a solution of intermediate 4 in either benzene or toluene is heated to 80 °C in the presence of a catalytic amount of rhodium(n) acetate (substrate catalyst, ca. 1000 1), the processes... 

The last method for the preparation of 2-quinolones described in this chapter relies on a intramolecular Heck cyclization starting from heteroaryl-amides (Table 2) [57]. These are synthesized either from commercially available pyrrole- and thiophene-2-carboxylic acids (a, Table 2) or thiophene-and furan-3-carboxylic acids (b, Table 2) in three steps. The Heck cyclization is conventionally performed with W,Ar-dimethylacetamide (DMA) as solvent, KOAc as base and Pd(PPh3)4 as catalyst for 24 h at 120 °C resulting in the coupled products in 56-89% yields. As discussed in Sect. 3.4, transition metal-catalyzed reactions often benefit from microwave irradiation [58-61], and so is the case also for this intramolecular reaction. In fact, derivatives with an aryl iodide were successfully coupled by conventional methods, whereas the heteroarylbromides 18 and 19, shown in Table 2, could only be coupled in satisfying yields by using MAOS (Table 2). 

Scheme 43 Synthesis of enantiopure ring-substituted 1,2-diaminocyclohexanes by transition metal catalyzed and promoted cyclization of 1,7-octadienes...

Organic halides play a fundamental role in organic chemistry. These compounds are important precursors for carbocations, carbanions, radicals, and carbenes and thus serve as an important platform for organic functional group transformations. Many classical reactions involve the reactions of organic halides. Examples of these reactions include the nucleophilic substitution reactions, elimination reactions, Grignard-type reactions, various transition-metal catalyzed coupling reactions, carbene-related cyclopropanations reactions, and radical cyclization reactions. All these reactions can be carried out in aqueous media. 

Keywords Metal-catalyzed Reductive coupling Cyclization... 

The formation of the indole moiety has found immense attention, since it exists in many bioactive compounds such as the indole alkaloids [302]. Whilst the Fischer indole synthesis remains the most important procedure, during the past few years several transition metal-catalyzed syntheses have been developed. Recently, a Cu11-catalyzed cyclization of anilines containing an ortho-alkynyl group was published by Hiroya and coworkers [303], which allows a double cyclization in domino fashion to provide annulated indoles. Thus, reaction of 6/4-92 in the presence of... 

Asymmetric synthesis of tricyclic nitro ergoline synthon (up to 70% ee) is accomplished by intramolecular cyclization of nitro compound Pd(0)-catalyzed complexes with classical C2 symmetry diphosphanes.94 Palladium complexes of 4,5-dihydrooxazoles are better chiral ligands to promote asymmetric allylic alkylation than classical catalysts. For example, allylic substitution with nitromethane gives enantioselectivity exceeding 99% ee (Eq. 5.62).95 Phosphi-noxazolines can induce very high enatioselectivity in other transition metal-catalyzed reactions.96 Diastereo- and enantioselective allylation of substituted nitroalkanes has also been reported.9513... 

Indoles can be formed by metal-catalyzed cyclizations of azobenzenes on disubstituted alkynes (Equation (106)). 

Among early and group III transition metals, the yttrocene catalysts have been studied in greatest detail. However, related metallocenes show great promise as catalysts for reductive cyclization. Neodymocene-catalyzed cyclization of 1,5- and 1,6-dienes 14a and 15a proceeds readily in the presence of silane to afford cyclopentanes 14b and 15b.37 Lutetocenes and samarocenes also catalyze silane-mediated cyclization of 1,5-diene 14a to cyclopentane 14b.38 39 In the case of the samarium-based metallocenes, the feasibility of borane-mediated cyclization has been established, as demonstrated by the highly diastereoselective conversion of phenyl-substituted diene 16a to cyclopentane 16b (Scheme ll).40... 

While the transition metal-catalyzed Alder-ene reaction has been developed to offer excellent regio- and chemos-electivity, stereoselective variants have only recently begun to appear in the literature.58 The scope and limitations of many of these protocols have yet to be established. Nonetheless, several groups have published exciting examples of asymmetric Alder-ene cyclizations. 

Trost et al.59 were the first to report enantioselectivity in the transition metal-catalyzed Alder-ene reaction. Several different acids were surveyed for the degree of efficacy in oxidizing the Pd(0) precursor to the active Pd(n) species and for compatibility with the catalyst, substrate, and product. Among acids surveyed were several chiral carboxylic acids products of reactions using these optically active acids were formed with modest enantioselectivity. (A)-binaphthoic acid gave the most promising result, with the cyclized product 83 obtained with 33% ee (Equation (52)). 

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)). 

While the notion that the alkoxides derived from aliphatic alcohols are poor nucleophiles toward 7r-allylmetal complexes has prevailed over the years, much progress made in the recent past has rendered the transition metal-catalyzed allylic alkylation a powerful method for the O-allylation of aliphatic alcohols. In particular, owing to the facility of five- and six-membered ring formation, this process has found extensive utility in the synthesis of tetrahydrofurans (THFs) (Equation (29))150-156 and tetrahydropyrans (THPs).157-159 Of note was the simultaneous formation of two THP rings with high diastereoselectivity via a Pd-catalyzed double allylic etherification using 35 in a bidirectional synthetic approach to halichondrin B (Equation (30)).157 The related ligand 36 was used in the enantioselective cyclization of a Baylis-Hillman adduct with a primary alcohol (Equation (31)).159... 

Enantiomerically pure 84 has been obtained in only seven synthetic operations in 40% overall yield starting from simple and commercially available precursors (Scheme 25). All C-C bond formations are metal-assisted or metal-catalyzed, with the RCM-based cyclization of the 12-membered ring (82->83) being particularly efficient [33]. 

The transition metal-catalyzed domino reactions will undoubtedly have a splendid future which is underlined by the increasing number of publications in this area Steglich et al. presented an approach to arcyriacyanin A via a domino Heck reaction between a bromo(indolyl)maleiimide and 4-bromoindole.1811 The synthesis of 33 -bifurans by Ling et al. was achieved using a novel palladium-catalyzed domino dimerization and subsequent cyclization of acetylenic ketones.1821 Other applications of a combination of Heck reactions for domino processes are the syntheses of aza-heterocydes developed by our group.1831... 

Beyond the numerous applications of palladium in transition metal-catalyzed domino reactions there are a lot of other metals inducing domino processes. Ihara et al. found a strategy for the enan-tioselective synthesis of (+)-equilenin catalyzed by mangan and palladium complexes,1841 Whitby et al.1851 initiated domino cyclizations on a zirconocene template and furthermore Scherf et al. generated phenantrones by a nickel-mediated one-pot domino reaction.1861... 

Dehydrocyclization, 30 35-43, 31 23 see also Cyclization acyclic alkanes, 30 3 7C-adsorbed olefins, 30 35-36, 38-39 of alkylaromatics, see specific compounds alkyl-substituted benzenes, 30 65 carbene-alkyl insertion mechanism, 30 37 carbon complexes, 32 179-182 catalytic, 26 384 C—C bond formation, 30 210 Q mechanism, 29 279-283 comparison of rates, 28 300-306 dehydrogenation, 30 35-36 of hexanes over platintim films, 23 43-46 hydrogenolysis and, 23 103 -hydrogenolysis mechanism, 25 150-158 iridium supported catalyst, 30 42 mechanisms, 30 38-39, 42-43 metal-catalyzed, 28 293-319 n-hexane, 29 284, 286 palladium, 30 36 pathways, 30 40 platinum, 30 40 rate, 30 36-37, 39... 

This article will deal with metal-catalyzed cyclization reactions, with reference to oxide and dual-function catalysts. Product cycles may contain five or six carbon atoms. The respective prefixes C5 and will point to the resulting structure (5). The term dehydrocyclization will be applied to reactions that end up with aromatic products the formation of saturated (cycloalkane) rings will henceforth be called cyclization. ... 

Direct ( hydrogenative ) Cj cyclization of alkanes to give saturated C5 cyclic products. This is a typical metal-catalyzed reaction occurring in a hydrogen-rich atmosphere over a narrow group of metals (25). 

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