Cyclization reactions transition-metal-catalyzed

Acridines have continued to be of interest but the Bemthsen reaction has generally been replaced by a stepwise cyclization using transition metal catalyzed amination of aryl ketones or acids followed by acid catalyzed cyclization to form the acridine ring system. ... 

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 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). 

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. 

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... 

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)). 

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... 

During cyclization with acetylene, the chiral center is maintained. This reaction has recently been extended to the synthesis of bipyridyl compounds having optically active substituents (75PC1) and provides access to chiral ligands of potential interest in transition-metal-catalyzed asymmetric catalysis. 

With respect to the large number of unsaturated diazo and diazocarbonyl compounds that have recently been used for intramolecular transition metal catalyzed cyclopropanation reactions (6-8), it is remarkable that 1,3-dipolar cycloadditions with retention of the azo moiety have only been occasionally observed. This finding is probably due to the fact that these [3+2]-cycloaddition reactions require thermal activation while the catalytic reactions are carried out at ambient temperature. A7-AUyl carboxamides appear to be rather amenable to intramolecular cycloaddition. Compounds 254—256 (Scheme 8.61) cyclize intra-molecularly even at room temperature. The faster reaction of 254c (310) and diethoxyphosphoryl-substituted diazoamides 255 (311) as compared with diazoacetamides 254a (312) (xy2 25 h at 22 °C) and 254b (310), points to a LUMO (dipole) — HOMO(dipolarophile) controlled process. The A -pyrazolines expected... 

Dienes are less reactive toward transition metals than enynes and diynes, and perhaps for this reason, the development of effective catalyst systems for the cyclization/hydrosilylation of dienes lagged behind development of the corresponding procedures for enynes and diynes. The transition metal-catalyzed cyclization/hydrosilylation of dienes was first demonstrated by Tanaka and co-workers in 1994. Reaction of 1,5-hexadiene with phenyl-silane catalyzed by the highly electrophilic neodymium metallocene complex Cp 2NdCH(SiMe2)3 (1 mol%) in benzene at room temperature for 3 h led to 5- ///76 -cyclization and isolation of (cyclopentylmethyl)phenylsilane in 84% yield (Equation (15)). In comparison, neodymium-catalyzed reaction of 1,6-heptadiene with phenylsilane led to 5- X(9-cyclization to form (2-methylcyclopentylmethyl)phenylsilane in 54% yield as an 85 15 mixture of trans. cis isomers (Equation (16)). 

During the present decade, a wide variety of polycyclic carbacephem derivatives have been reported starting from readily available monocyclic /3-lactams, which after transformation in more functionalized compounds and further cyclization yielded different fused carbacephems. Several approaches for the preparation of fused carbacephem derivatives including cycloaddition reactions such as the [2+2], 1,3-dipolar, and Diels-Alder reactions, as well as transition metal-catalyzed reactions such as the Pauson-Khand and ring-closing metathesis (RCM) reactions have been reported in the literature. 

The transition metal catalyzed or mediated cyclizations of alkynes are also classified into this category. The Ni complex catalyzed reaction of alkynes with... 

Transition metals catalyze a very wide variety of hydrocarbon reactions ranging from hydrogenation of olefins and exchange of paraffins with deuterium at lower temperatures to skeletal rearrangement, cyclization, hydrogenolysis, cracking, and carbiding under more severe conditions. Because of this flexibility in... 

Me3SiCN is a convenient, reactive cyanide donor in transition metal-catalyzed processes. The Pd-catalyzed reaction of aryl iodides with Me3SiCN is useful for the synthesis of aryl cyanides.257 Me3SiCN works also as an effective co-catalyst for the Pd-catalyzed cyanation of aryl iodides with KCN.258 Allylic acetates, carbonates, and the related compounds undergo the Pd-catalyzed cyanation with Me3SiCN.259-261 The tandem cyclization-cyanation reaction of 2-bromo-l,6-heptadienes with Me3SiCN proceeds under catalysis by an Ni complex (Equation (68)).262... 

The classical routes to 2//-pyran-2-ones (-pyrones) are illustrated in Scheme 124 . Additional examples include various transition metal-catalyzed cyclizations , e.g., the palladium-catalyzed reaction of -chloroacrylates with internal alkynes (Scheme 125) <2001NJC179> and the coupling of tributyl-stannyl allenes with (Z)—iodoacrylic acid (Scheme 126) <2005JOC6669>. 

The intramolecular Heck reaction and similar transition metal-catalyzed cyclizations are commonly used in organic synthesis as illustrated by the preparation of 3-cyanoindole 63 (Scheme 38) <2004BMC2867>. Similar Heck cyclizations have also been employed in the syntheses of tryptophan derivatives <1996T14975>. Solid phase protocols based... 

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