Carbocyclizations 4+2+2 carbocyclization reaction

The formation of a metallacyclopentene, which is presumed to be the key intermediate in the preceding examples, prompted the question of whether a Ci unit, such as CO or an isocyanide, could be inserted into this intermediate and thereby allow for an [m-i- -i-l] carbocyclization reaction (Scheme 11.2). These types of reactions wiU be discussed in detail in this chapter. 

Transition metal-catalyzed carbocycUzation reactions of tethered diene, enyne, diyne, and vinylallene derivatives represent an important class of transformations in synthetic organic chemistry. This may be attributed to the abihty to significantly increase molecular complexity through the highly selective combination of acyclic components, thereby facilitating the synthesis of complex polycychc products. Recently, rhodium-catalyzed carbocyclization reactions have attracted significant attention due to their immense synthetic versatility and the unique selectivities observed over a range of different transformations. This chapter provides an account of recent developments in rhodium-catalyzed [4-1-2] and [4-i-2-t2] carbocyclization reactions. 

Gilbertson and co-workers were also able to facilitate the rhodium-catalyzed [4-i-2-1-2] carbocyclization reaction with a substrate having an all-carbon tether (Eq. 13). This methodology has been extended to the asymmetric rhodium-catalyzed [4-t 2-1-2] reaction (Eq. 14). Although the exact origin of asymmetric induction was not discussed, the ability to accomplish the asymmetric rhodium-catalyzed [4-i-2-1-2] reaction provides a novel approach to eight-membered ring systems. 

Scheme 12.10 Proposed catalytic cycle of the [4 + 2 + 2] carbocyclization reaction.

Tab. 12.9 Scope of the intermolecular rhodium-catalyzed [4-I-2-I-2] carbocyclization reaction.

This cataiyst system was also applied to the [5 + 2] carbocyclization reactions, discussed at length in Chapter 13 of this book. 

Equivalently, the enthalpy of reaction 47 is equated to that of the analogous (unsubstituted, saturated, carbocyclic) reaction 48. The difference is 29 kJmol , taken as the strain energy of cyclopentane. 

In this chapter, we focus on catalytic carbocyclization involving ruthenium vinylidene as a reaction intermediate. The carbocyclization reactions involving allenylidene intermediates are described in Chapter 7. The reactions are categorized according to the types of substrates. Several stoichiometric carbocyclizations are also included in this chapter because of their mechanistic significance. 

Ruthenium vinylidene species can be transformed into small carbocyclic rings via carbocyclization reactions. Ruthenium vinylidene complex 2, generated from the electrophilic reaction of alkyne complex 1 with haloalkanes, was deprotonated with "BU4NOH to give the unprecedented neutral cyclopropenyl complex 3 (Scheme 6.2) [5]. Gimeno and Bassetti prepared ruthenium vinylidene species 4a and 4b bearing a pendent vinyl group when these complexes were heated in chloroform for a brief period, cyclobutylidene products 5a and Sb formed via a [2 + 2] cycloaddition between the vinylidene Ca=Cp bond and olefin (Scheme 6.3) [6]. 

Oxidative Hetero- and Carbocyclization Reactions of Alkenes Bearing Tethered Nucleophiles... 

The intramolecular addition of carbon nucleophiles to alkenes has received comparatively little attention relative to heterocyclization reactions. The first examples of Pd-catalyzed oxidative carbocyclization reactions were described by Backvall and coworkers [164-166]. Conjugaled dienes with appended al-lyl silane and stabilized carbanion nucleophiles undergo 1,4-carbochlorination (Eq. 36) and carboacetoxylation (Eq. 37), respectively. The former reaction employs BQ as the stoichiometric oxidant, whereas the latter uses O2. The authors do not describe efforts to use molecular oxygen in the reaction with allyl silanes however, BQ was cited as being imsuccessful in the reaction with stabihzed car-banions. Benzoquinone is known to activate Ti-allyl-Pd intermediates toward nucleophilic attack (see below. Sect. 4.4). In the absence of BQ, -hydride eUm-ination occurs to form diene 43 in competition with attack of acetate on the intermediate jr-allyl-Pd" species to form the 1,4-addition product 44. 

We note, however, that this is not the case for the corresponding carbocyclic reaction 19. 

The zinc-enolate carbocyclization reaction was applied to the synthesis of diverse 3-substituted proline chimeras. To this end, the stable cyclic organozinc intermediate... 

The zinc-enolate cyclizations are not restricted to a-aminoesters as /3-aminoesters have also been successfully involved in such reactions275. The preformed lithium enolate generated by treatment of the /J-arninoester 423 with LDA had to be added dropwise to an ethereal solution of ZnBr2 in order to avoid a competing /3-elimination reaction induced by the zinc enolate. this reverse addition protocol was respected, a smooth carbocyclization reaction occurred and provided, after hydrolysis, the substituted 3-carbomethoxypyrrolidine 424 as a 87/13 mixture of diastereomers (equation 183). 

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