Catalytic cycloadditions

Scheme 16 Proposed mechanisms for thermal and catalytic cycloaddition reactions...

In contrast to isocyanates, isothiocyanates have hardly been examined as cycloaddition components, because the strong coordination of organosulfur compounds frequently deactivates a catalytic species [21]. Some organoruthe-nium complexes, however, recently proved to be efficient catalysts for the formation of carbon-sulfur bonds [21]. The catalytic cycloaddition of diynes with isothiocyanates was also successfully achieved using Cp RuCl(cod) as a precatalyst [22]. Importantly, the cycloaddition took place at the C=S double bonds of the isothiocyanates to afford thiopyranimines 26 (Eq. 13). This reaction requires 10 mol % of the precatalyst as well as the diynes possessing a quarternary carbon center at the 4-position. When excess amounts of carbon disulfide were also employed in place of the isothiocyanates, a bicyclic dithiopyrone 26 [X is C(C02Me)2, Z is S] was obtained in 50% yield. 

Transition metal-catalyzed higher-order cycloadditions offer a powerful approach for the constmction of medium-sized rings [1]. In this context, Wender and co-work-ers have developed catalytic cycloadditions of vinylcyclopropanes with alkynes,... 

As in Section 1.6.1.2.3.1, the examples that have emerged in processes employing stoichiometric quantities of the metal species will be discussed initially. The majority of this section, however, will be devoted to the applications of catalytic cycloaddition procedures in substrate-controlled stereoselective transformations. 

Catalytic cycloadditions of carbenes to alkenes is a straightforward method for synthesizing cyclopropanes [40]. In fact, cyclopropanes are present in a variety of natural products [41-43]. For example, they occur in some unusual amino acids, in natural phytotoxins such as coronatine, as well as in marine terpenes [44], sesquiterpenes [45], cyclosteroids [46-47] (as part of the A-cycle) or in the side chain of steroids [48]. 

Palladium-catalyzed cycloaddition is one of the most popular and useful reactions for the construction of a variety of cyclic compounds. The first one was the [3 + 2] cycloaddition of 2-[(trimethylsilyl)methyl]aUyl ester with olefins bearing electron-withdrawing groups reported in 1979 (Scheme and later a large number of cycloaddition reactions were studied, where [3 + 2], [3 + 4], [3 + 6], and [1 + 2] cycloaddition reactions were developed (Scheme 2) and applied to natural product synthesis. Most of these catalytic cycloadditions proceed via a trimethylenemethane palladium (TMM-Pd) intermediate or its analogs, oxatrimethylenemethane palladium (OTMM-Pd) and azatrimethylenemelhane palladium (ATMM-Pd) (Scheme 3). 

Scheme 9.6 Retrosynthetic analysis for the synthesis of herbindole, identification of an intramolecular [2+2+2] catalytic cycloaddition of alkynes as a key step [11].

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