Transition metal catalyzed construction

Transition Metal Catalyzed Construction of Carbocyclic Rings (-)-Hamigeran B... 

The previous sections have described methods to obtain 2-pyridone scaffolds. Both in the construction of new materials and especially in drug design and development, there is a desire to be able to derivatize and optimize the lead structures. In the following sections, some recent developments using MAOS to effectively substitute and derivatize 2-pyridone heterocycles are described. The reaction types described range from electrophilic-, and nucleophilic reactions to transition metal-catalyzed transformations (Fig. 7). To get an overview of how these systems behave, their characteristics imder conventional heating is first described in brevity. 

Transition metal-catalyzed carbenoid transfer reactions, such as alkene cyclopro-panation, C-H insertion, X-H insertion (X = heteroatom), ylide formation, and cycloaddition, are powerful methods for the construction of C-C and C-heteroatom bonds [1-6]. In contrast to a free carbene, metallocarbene-mediated reactions often proceed stereo- and regioselectively under mild conditions with tolerance to a wide range of functionalities. The reactivity and selectivity of metallocarbenes can be... 

Late transition-metal hydroamination is the method of choice for the atom economical and functional group-tolerant construction of C—N bonds, and in this context Ir plays a central role (indeed, homogenous transition-metal-catalyzed OHA was discovered with Rh and Ir). However, there is a strong need for the development of better OHA catalyst systems that are applicable to a wider range of substrates and conditions. The characteristics of current Ir based catalyst systems to function via N—H bond activation, though, is a potential handicap to achieve this goal, since it implies highly reactive Ir intermediates that are prone... 

Carbon-carbon bond-forming reactions are one of the most basic, but important, transformations in organic chemistry. In addition to conventional organic reactions, the use of transition metal-catalyzed reactions to construct new carbon-carbon bonds has also been a topic of great interest. Such transformations to create chiral molecules enantioselectively is therefore very valuable. While various carbon-carbon bond-forming asymmetric catalyses have been described in the literature, this chapter focuses mainly on the asymmetric 1,4-addition reactions under copper or rhodium catalysis and on the asymmetric cross-coupling reactions catalyzed by nickel or palladium complexes. 

Transition-metal-catalyzed cross-coupling reactions also represent a powerful approach for the construction of carbon-carbon bonds. As a result, these processes have been widely studied in the past few decades. Among the transition metals... 

The transition metal-catalyzed allylic amination is particularly pertinent, because of the synthetic utihty of aUyhc amines in the construction of biologically important natural and urmatural products [34]. The allylic amination of cyclic and acycHc substrates. 

Transition metal-catalyzed allylic substitution with phenols and alcohols represents a fundamentally important cross-coupling reaction for the construction of allylic ethers, which are ubiquitous in a variety of biologically important molecules [44, 45]. While phenols have proven efficient nucleophiles for a variety of intermolecular allylic etherification reactions, alcohols have proven much more challenging nucleophiles, primarily due to their hard, more basic character. This is exemphfied with secondary and tertiary alcohols, and has undoubtedly limited the synthetic utihty of this transformation. 

CEJ1358> and the ruthenium mediated isomerization of double bonds (cf. Scheme 89, Section 8.11.7) <2007TL137> are recent examples of transition metal catalyzed manipulations at the side chain carbon atoms of 1,3-heterocycles. A novel side-chain addition reaction of aldehydes to 6-alkylidene-l,3-dioxin-4-ones was used for the construction of intermediates of lophotoxin <2006CJC1226>. An acid-catalyzed intramolecular cycloaddition of a hydroxy group to an alkene has been effected by the presence of an adjacent 1,3-dithiane moiety <2006TL4549>. 

Many of the limitations of C—C bond formation by C —H insertion outlined for intermolecular reactions (Section 1.2.1.) can be overcome by making the reaction intramolecular. Thus, hydrogen atom abstraction followed by intramolecular radical-radical coupling or radical addition to an alkene are increasingly popular processes. Two-electron carbene insertions, either thermal or transition metal catalyzed, have also been used extensively. In either case, ring construction involves net C—C bond formation at a previously unactivated C-H site. 

The transition metal catalyzed synthesis of five membered heterocycles, particularly of condensed ring systems, has attracted considerable attention. The ease of the formation of five membered rings has been utilised both in intramolecular ring closure processes, and in the combination of two (three) fragments through the formation of a carbon-carbon and a carbon-heteroatom bond. This chapter is dedicated to examples, where the construction of the five membered heterocycle is achieved in a transition metal catalysed step. 

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],... 

Recently, the transition-metal-catalyzed addition of active methylene C-H bonds to electron-deficient olefins having a carbonyl, a nitrile, or a sulfonyl group has been extensively studied by several research groups. In particular, the asymmetric version of this type of catalytic reaction provides a new route to the enantioselective construction of quaternary carbon centers [88]. Another topic of recent interest is the catalytic addition of active methylene C-H bonds to acetylenes, allenes, conjugate ene-ynes, and nitrile C-N triple bonds. In this section, the ruthenium-catalyzed addition of C-H bonds in active methylene compounds to carbonyl groups and C-C multiple bonds is described. 

Transition-metal-catalyzed cycloaddition reactions provide a new synthetic method for the construction of a numerous types of ring systems, which are... 

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