Ylide compounds carbene/carbenoid additions

As with any modern review of the chemical Hterature, the subject discussed in this chapter touches upon topics that are the focus of related books and articles. For example, there is a well recognized tome on the 1,3-dipolar cycloaddition reaction that is an excellent introduction to the many varieties of this transformation [1]. More specific reviews involving the use of rhodium(II) in carbonyl ylide cycloadditions [2] and intramolecular 1,3-dipolar cycloaddition reactions have also appeared [3, 4]. The use of rhodium for the creation and reaction of carbenes as electrophilic species [5, 6], their use in intramolecular carbenoid reactions [7], and the formation of ylides via the reaction with heteroatoms have also been described [8]. Reviews of rhodium(II) ligand-based chemoselectivity [9], rhodium(11)-mediated macrocyclizations [10], and asymmetric rho-dium(II)-carbene transformations [11, 12] detail the multiple aspects of control and applications that make this such a powerful chemical transformation. In addition to these reviews, several books have appeared since around 1998 describing the catalytic reactions of diazo compounds [13], cycloaddition reactions in organic synthesis [14], and synthetic applications of the 1,3-dipolar cycloaddition [15]. 

Carbonyl ylides can be viewed as an adduct between a carbonyl group and a carbene and, in fact, some ylides have been prepared this way (see above). The application of carbonyl ylides to the synthesis of complex natural products has been greatly advanced by the finding that stabilized carbenoids can be generated by the decomposition of ot-diazocarbonyl compounds with copper and rhodium complexes. The metallocarbenoids formed by this method are highly electrophilic on carbon and readily add nucleophiles such as the oxygen of many carbonyl derivatives to form carbonyl ylides. This type of reaction is in fact quite old with the first report being the addition of diazomalonate and benzaldehyde (33,34). 

Cyclopropanation reactions are one set in an array of C-C bond-forming transformations attributable to metal carbenes (Scheme 5.1) and are often mistakenly referred to by the nonspecific term carbenoid. Both cyclopropanation and cyclopropenation reactions, as well as the related aromatic cycloaddition process, occur by addition. Ylide formation is an association transformation, and insertion requires no further definition. All of these reactions occur with diazo compounds, preferably those with at least one attached carbonyl group. Several general reviews of diazo compounds and their reactions have been published recently and serve as valuable references to this rapidly expanding field [7-10]. The book by Doyle, McKervey, and Ye [7] provides an intensive and thorough overview of the field through 19% and part of 1997. 

Heimgartner and co-workers treated a-diazoketones and a-diazoamides 64 with thiones, with and without a catalyst such as Rh(OAc)2 present (1998HCA285). The products were substituted thiiranes 65 and/or substituted 1,3-oxathioles. In all cases, a thiocarbonyl ylide intermediate, which could undergo either a 1,3- or a 1,5-electro-cyclization, was held responsible. The ylide could arise either from addition of a carbene or a carbenoid to S of the thiocarbonyl compound or by loss of N2 from a primary cycloadduct between the diazo and the thiocarbonyl compounds. In one case, such a primary adduct was isolated. The thiirane carboxamides could be desulfurized with (Me2N)3P in tetrahydrofuran (THF) at 60 °C to afford acrylamides 66 (Scheme 11). 

In analogy with the carbenoid 1,1-cyloadditions of nitrile ylides (Section II,B), nitrilimines can undergo intramolecular cyclizations to give 1,2-diazepines or cyclopropa[c]cinnolines (Eq. 41).197 The latter compounds are formed stereospecifically, thus supporting a concerted carbene-like 1,1-addition of the nitrilimine to the olefinic double bond.197a... 

The generation of a carbene (or when using a metal catalyst, a carbenoid) from an a-diazocarbonyl compound, in the presence of a nitrile results in overall cycloaddition and the formation of an oxazole. Both a-diazoketones and a-diazoesters have been used, the examples in the sequence below showing that the result in the latter situation is the formation of a 5-oxygenated oxazole.The exact sequence of events is not certain but may involve a nitrile ylide, the result of electrophilic addition of the carbene to the nitrile nitrogen. 

The addition of a diazocarbonyl compound to an alkene with metal catalysis is an effective method for the formation of cyclopropanes, as discussed above. However, direct addition to aldehydes, ketones or imines is normally poor. Epoxide or aziridine formation can be promoted by trapping the carbene with a sulfide to give an intermediate sulfur ylide, which then adds to the aldehyde or imine. For example, addition of tetrahydrothiophene to the rhodium carbenoid generated from phenyldiazomethane gave the ylide 131, which adds to benzaldehyde to give the trans epoxide 132 in high yield (4.104). On formation of the epoxide, the sulfide is released and hence the sulfide (and the rhodium complex) can be used in substoichiometric amounts. 

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