Heterocyclization, metal-mediated

Transition metal-mediated transformations of heterocycles 98MI26, 98MI27. 

Metal-mediated iodocarbocyclization and iodoaminocyclizaton reactions leading to heterocycles 99SL1191. 

This chapter has taken the reader through a number of microwave-assisted methodologies to prepare and further functionalize 2-pyridone containing heterocycles. A survey of inter-, intramolecular-, and pericyclic reactions together with electrophilic, nucleophilic and transition metal mediated methodologies has been exemplified. Still, a number of methods remain to be advanced into microwave-assisted organic synthesis and we hope that the smorgasbord of reactions presented in this chapter will inspire to more successful research in this area. 

Abstract A literature overview, up to the end of 2004, of the most important microwave-assisted transition-metal-mediated processes used for the decoration and construction of heterocycles is presented. The emphasis of the chapter lies in the use of palladium-assisted reactions but examples of copper- and nickel-mediated processes are also incorporated. 

W-Heterocyclic Carbene Complexes in other Transition Metal Mediated Reactions... 

Metal-mediated reductive coupling of alkenes and alkynes affords access to complicated organic structures, including carbocyclic and heterocyclic molecules, from readily available starting materials. While most of these coupling reactions were initially developed as stoichiometric processes, many selective, catalytic versions have been developed over the past decade these advancements have made reductive coupling much more attractive to synthetic chemists. 

Transition metal-mediated C-C bond formation through reaction of C02 with acetylenes and dienes can serve as a useful method for the construction of various carbon skeletons, such as linear and cyclic carboxylic acids, and esters and lactams. Enantioselective incorporation of C02 can also be achieved, especially when combined with sterically controlled formation of cyclic carbo- or heterocyclic skeletons. In perspective of the future in this area, development of more efficient and more selective catalytic systems for incorporation or transformation of C02 into useful fine chemicals and polymer materials will continue to be an important and attractive research target. 

Under catalysis of Ag+, 2,3-allenylamines can undergo cycloisomerization to afford N-containing heterocycles [135,136]. Such metal-mediated isomerizations are discussed in detail in Chapter 15. 

Rigby and coworkers305,309 also performed metal mediated [6 + 4] cycloadditions of heterocyclic trienes and tropones with various dienes. In concurrence with the all-carbon trienes, the electronic nature of the diene partners generally had little influence on the cycloaddition efficiency. The only reported exceptions are the reactions of thiepin-1,1-dioxides. Lower yields were observed in the reactions involving electron-deficient dienes in comparison with the reactions with electron-rich dienes. The reaction of complex 514... 

Continuing with the approach of this chapter from previous years metal-mediated reactions, cycloadditions, radical processes and asymmetric applications will be highlighted. Syntheses using traditional approaches will not be covered, unless improvements are reported. Due to the volume of publications concerning pyridines and associated heterocycles many subject areas could not be covered. Combinatorial or solid-phase synthesis will not represented since the area is rather specialized and many of the processes utilize existing methodology. The synthesis and reactions of polyaza-fused systems of the pyridine class will also not be included in this review. 

The great diversity of systems in this chapter makes a comparison of synthetic approaches difficult and most of the best synthetic approaches have counterparts in the syntheses of simpler heterocycles. Since the area was last reviewed <1996CHEC-II(7)841>, established methods have continued to be of synthetic utilit r, in particular, the photocycliza-tion chemistry of l,2-bis(heteroaryl)ethene systems and the chemistry of bis-TTFs have been further explored. The focus, however, of these research efforts has tended to concentrate on the applications of these materials in electronic devices with less emphasis on novel synthetic approaches. A noticeable trend has been the increasing use of metal-mediated chemistry, in particular, chemistry involving transition metals. The diverse range of metals employed and the number of tricyclic systems synthesized admirably demonstrates the importance of this area. 

The last example focuses not on the functionalization of heterocycles by a transition metal mediated carbon-heteroatom bond forming reaction, but the palladium catalyzed conversion of primary amines, including amino-heterocycles, into urea derivatives. A representative example, shown in 8.38., includes the reaction of an amino-carbazole derivative with morpholine, carbon monoxide and oxygen in the presence of catalytic amounts of palladium(II) iodide. The formation of the urea moiety proceeds with great selectivity and in high yield.49 The reaction works equally well for primary aliphatic and aromatic amines. 

To expand the diversity of their libraries Brill et al.16 also modified various heterocycles by alkylation, acylation, or metal-mediated coupling reaction prior to resin capture. A remaining chloro substituent was still available for nucleophilic displacement or a palladium-mediated coupling reaction with anilines, phenols, and boronic acids on solid phase [see Fig. 10 for the preparation of purine derivative (62)]. 

The present account follows the general pattern of earlier surveys in this series. Recently published reviews are mentioned in the appropriate sections with the exception of one that is most conveniently described here. This is a description of transition metal mediated carbonylative ring expansion reactions of heterocyclic compounds (95ACR414) which mentions most of the heterocycles included in this chapter either as starting materials or products. 

Palladium chemistry has been used in the synthesis of tetrahydroisoquinolines. Different combinations of iodoaryl-amine-alkene can be used in these multicomponent reactions. For example, the metal-mediated o-alkylated/alkenyl-ation and intramolecular aza-Michael reaction (Scheme 109) give moderate yields of heterocycle <2004TL6903>, whereas the palladium-catalyzed allene insertion-nucleophilic incorporation-Michael addition cascade (Equation 172) produces good yields of tetrahydroisoquinolines in 15 examples <2003TL7445> with further examples producing tetrahydroquinolines (Scheme 110) <2000TL7125>. 

Transition metal-mediated heterocyclizations and transformations of heterocycles 93JOM(457)167,93JOM(457)273. 

With the application of N-heterocyclic carbene (NHC) ligands, the number of transition metal-catalyzed reactions has grown considerably in the past decade. The replacement of traditional amine or phosphine ligands with electron-rich NHC ligands has led to a substantial enhancement in catalytic activity. This chapter summarizes the recent impact that the use of NHC ligands has had in furthering the field of transition metal-mediated catalysis. 

Several examples of the use of (4a) catalyzed cross metathesis of protected allylic sugars, or vinyl substituted heterocycles or vinylated functional groups have been reported. Vinylphosphonate-linked nucleotide dimers were synthesized by cross metathesis using complex (4a), achieving products with E Z ratios of >20 1 in moderate to good yields (equation 17). A metal-mediated route to acyclic nucleosides developed by Agrofoglio and coworkers produced nucleosides in two steps from parent pyrimidines and purines. ... 

The dipolarophilicity of nitriles can be enhanced by coordination to a metal center, namely toward azides or nitrones, [-0+N(R3)=C(R1)(R2)], to yield, via [2 + 3] cycloadditions, the tetrazolate complexes (1) and (2) (Table 5, the latter derived from the former by sterically promoted linkage isomerization) with a wide variety of metal centers4 and the A4-l,2,4-oxadiazoline complexes (3) with Pt centers,175 respectively. The reactions normally proceed under mild conditions, even for nitriles with electron-donor alkyl groups (R). The tetrazoles177 and the oxadiazolines175 were liberated in some cases and the metal-mediated processes constitute promising routes for the synthesis of such heterocycles as exhibit medicinal and other applications. 

Clavier H, Nolan SP (2007) N-heterocyclic carbenes advances in transition metal-mediated transformations and organocatalysis. Ann Rep Prog Chem Sect B 103 193-222... 

---