Carbenoid intermediates

Tlie desulfurization of thiono compounds is another frequently used synthetic approach for the formation of double bonds via carbenoid intermediates. By this methodology, some indigoid 1,3,5,7-tetraazafulvalenes 88 and 90 were synthesized (83BSB781 90JPR949).Tliis dimerization starting from 2,4,5-tris(dimethylamino)imidazolium chloride via the appropriate thione 87 has been realized in the presence of phosphanes or phosphites to... 

Muller et al. have also examined the enantioselectivity and the stereochemical course of copper-catalyzed intramolecular CH insertions of phenyl-iodonium ylides [34]. The decomposition of diazo compounds in the presence of transition metals leads to typical reactions for metal-carbenoid intermediates, such as cyclopropanations, insertions into X - H bonds, and formation of ylides with heteroatoms that have available lone pairs. Since diazo compounds are potentially explosive, toxic, and carcinogenic, the number of industrial applications is limited. Phenyliodonium ylides are potential substitutes for diazo compounds in metal-carbenoid reactions. Their photochemical, thermal, and transition-metal-catalyzed decompositions exhibit some similarities to those of diazo compounds. 

Esters of a-diazoalkylphosphonic acids (95) show considerable thermal stability but react with acids, dienophiles, and triphenylphosphine to give the expected products. With olefinic compounds in the presence of copper they give cyclopropane derivatives (96), but with no such compounds present vinylphosphonic esters are formed by 1,2-hydrogen shift, or, when this route is not available, products such as (97) or (98) are formed, resulting from insertion of a carbenoid intermediate into C—C or C—H bonds. The related phosphonyl (and phosphoryl) azides (99) add to electron-rich alkynes to give 1,2,3-triazoles, from which the phosphoryl group is readily removed by hydrolysis. 

Castro CE, WC Kray (1966) Carbenoid intermediates from polyhalomethanes and chromium (II). The homogeneous reduction of geminal halides by chromous sulfate. J Am Chem Soc 88 4447-4458. 

There are several reactions that are conceptually related to carbene reactions but do not involve carbene, or even carbenoid, intermediates. Usually, these are reactions in which the generation of a carbene is circumvented by a concerted rearrangement process. Important examples of this type are the thermal and photochemical reactions of a-diazo ketones. When a-diazo ketones are decomposed thermally or photochemically, they usually rearrange to ketenes, in a reaction known as the Wolff rearrangement.232... 

Catalysts of the Co(salen) family incorporating chiral centers on the ligand backbone are useful in asymmetric synthesis and the field has been reviewed.1377,1378 In two examples, the hydroxy-lation reaction (Equation (14)) involving (269) proceeds with 38% ee,1379 whereas the cyclo-propanation reaction with (271) (Equation (15)) proceeds with 75% ee and with 95 5 trans cis.1380 A Co(V) salen carbenoid intermediate has been suggested in these reactions. 

Yanez et al. reported the synthesis of miconazole and analogs through a carbenoid intermediate. The process involves the intermolecular insertion of carbe-noid species to imidazole from a-diazoketones with copper acetylacetonate as the key reaction of the synthetic route [11]. 

Aziridines have been synthesized, albeit in low yield, by copper-catalyzed decomposition of ethyl diazoacetate in the presence of an inline 260). It seems that such a carbenoid cyclopropanation reaction has not been realized with other diazo compounds. The recently described preparation of 1,2,3-trisubstituted aziridines by reaction of phenyldiazomethane with N-alkyl aldimines or ketimines in the presence of zinc iodide 261 > most certainly does not proceed through carbenoid intermediates rather, the metal salt serves to activate the imine to nucleophilic attack from the diazo carbon. Replacement of Znl2 by one of the traditional copper catalysts resulted in formation of imidazoline derivatives via an intermediate azomethine ylide261). 

It has been widely accepted that the carbene-transfer reaction using a diazo compound and a transition metal complex proceeds via the corresponding metal carbenoid species. Nishiyama et al. characterized spectroscopically the structure of the carbenoid intermediate that underwent the desired cyclopropanation with high enantio- and diastereoselectivity, derived from (91).254,255 They also isolated a stable dicarbonylcarbene complex and demonstrated by X-ray analysis that the carbene moiety of the complex was almost parallel in the Cl—Ru—Cl plane and perpendicular to the pybox plane (vide infra).255 These results suggest that the rate-determining step of metal-catalyzed cyclopropanation is not carbenoid formation, but the carbene-transfer reaction.254... 

As described in Section 9.4.7.1, some Rh and Ru carbenoid intermediates that undergo cyclopropanation reactions have been spectroscopically identified.294,254 Less reactive metal-carbenoid intermediates (108) and (109) have been isolated and their structures have been determined unequivocally by X-ray analysis.255 258 The isolated carbenoid intermediate (108) undergoes cyclopropanation at high temperature (110°C),255 and another intermediate (109) serves as the catalyst for asymmetric cyclopropanation (Figure 11).258... 

The metal-carbenoid intermediates, especially ones derived from a-diazocarbonyl compounds, are electrophilic, and electron-rich olefins in general react more easily with the carbenoid intermediates than electron-deficient olefins. For the interaction of metal carbenoid and olefin, three different mechanisms have been proposed, based on the stereochemistry of the reactions and the reactivity of the substrates (Figure 12) 21 (i) a nonconcerted, two-step process via a metallacyclobutane 226,264... 

Figure 9 Classification of carbenoid intermediates and common precursors.

Numerous studies aimed at the understanding of the mechanism of these processes rapidly appeared. In this context, Murai examined the behavior of acyclic linear dienyne systems in order to trap any carbenoid intermediate by a pendant olefin (Scheme 82).302 A remarkable tetracyclic assembly took place and gave the unprecedented tetracyclo[6.4.0.0]-undecane derivatives as single diastereomer, such as 321 in Scheme 82. This transformation proved to be relatively general as shown by the variation of the starting materials. The reaction can be catalyzed by different organometallic complexes of the group 8-10 elements (ruthenium, rhodium, iridium, and platinum). Formally, this reaction involves two cyclopropanations as if both carbon atoms of the alkyne moiety have acted as carbenes, which results in the formation of four carbon-carbon bonds. 

Various approaches to epoxide also show promise for the preparation of chiral aziridines. Identification of the Cu(I) complex as the most effective catalyst for this process has raised the possibility that aziridination might share fundamental mechanistic features with olefin cyclopropanation.115 Similar to cyclo-propanation, in which the generally accepted mechanism involves a discrete Cu-carbenoid intermediate, copper-catalyzed aziridation might proceed via a discrete Cu-nitrenoid intermediate as well. 

The use of copper as a catalyst in carbenoid transfer has its roots in the Amdt-Eistert reaction, Eq. 1 (3). Although the original 1935 paper describes the Wolff rearrangement of a-diazo ketones to homologous carboxylic acids using silver, the authors mention that copper may be substituted in this reaction. In 1952, Yates (4) demonstrated that copper bronze induces insertion of diazo compounds into the X-H bond of alcohols, amines, and phenols without rearrangement, Eq. 2. Yates proposal of a distinct metal carbenoid intermediate formed the basis of the currently accepted mechanistic construct for the cyclopropanation reaction using diazo compounds. 

Before turning to specific results we will have a look at the properties of rhodium(II) acetates/carboxamidates as catalysts for reactions with diazocompounds as the substrates via carbenoid intermediates. Rhodium(II) has a d7 electron configuration, forming the lantern type dimers with bridging carboxylates. The single electrons in the respective dz2 orbitals form an electron... 

The geminal dihalogenated cyclopropane derivatives 83a and 83b were lithiated by Vlaar and Klumpp . 7,7-Dichloro- (83a) and 7,7-dibromonorcarane (83b) were reacted with four equivalents of LiDBB in diethyl ether and several reaction conditions were examined by the authors such as reaction temperatures, the influence of different coordinating additives as well as various methods (Scheme 31). The achieved maximum yield for the geminal dilithium compound 84 was 55% (from 83b). Side-products, like the 1,2-dilithioethane derivative 85, the dilithiated dicyclohexylacetylene 86 or 1,3-dilithium compound 87, were observed in different quantities, sensitively depending on the reaction conditions. Also, carbenoid intermediates were formed as verified by trapping reactions (deuteriolysis). 

The most spectacular application of the donor/acceptor-substituted carbenoids has been intermolecular C-H activation by means of carbenoid-induced C-H insertion [17]. Prior to the development of the donor/acceptor carbenoids, the intermolecular C-H insertion was not considered synthetically useful [5]. Since these carbenoid intermediates were not sufficiently selective and they were very prone to carbene dimerization, intramolecular reactions were required in order to control the chemistry effectively [17]. The enhanced chemoselectivity of the donor/acceptor-substituted carbenoids has enabled intermolecular C-H insertion to become a very practical enantioselective method for C-H activation. Since the initial report in 1997 [121], the field of intermolecular enantioselective C-H insertion has undergone explosive growth [14, 15]. Excellent levels of asymmetric induction are obtained when these carbenoids are derived... 

In summary, the chemistry of the donor/acceptor-substituted carbenoids represents a new avenue of research for metal-catalyzed decomposition of diazo compounds. The resulting carbenoids are more chemoselective than the conventional carbenoids, which allows reactions to be achieved that were previously inaccessible. The discovery of pan-tolactone as an effective chiral auxiliary, and rhodium prolinates as exceptional chiral catalysts for this class of rhodium-carbenoid intermediate, broadens the synthetic utility of this chemistry. The successful development of the asymmetric intermolecular C-H activation process underscores the potential of this class of carbenoids for organic synthesis. 

Reaction of diazo compounds with a variety of transition metal compounds leads to evolution of nitrogen and formation of products of the same general type as those formed by thermal and photochemical decomposition of diazoalkanes. These transition metal-catalyzed reactions in general appear to involve carbenoid intermediates in which the carbene becomes bound to the metal.83 The metals which have been used most frequently in synthesis are copper and rhodium. 

Triphenylbismuthonium ylide reacted with terminal alkynes in the presence of a catalytic amount of copper(I) chloride to form furan derivatives (Scheme 11) [27]. Although the yields were low, the products were obtained regioselectively. The reaction was sensitive to steric factors, and internal alkynes did not provide the product. A carbenoid intermediate was probably involved in the reaction. 

Suga et al. (197) reported the first stereocontrolled 1,3-dipolar cycloaddition reactions of carbonyl ylides with electron-deficient alkenes using a Lewis acid catalyst. Carbonyl ylides are highly reactive 1,3-dipoles and cannot be isolated. They are mainly generated through transition metal carbenoid intermediates derived in situ from diazo precursors by treatment with a transition metal catalyst. When methyl o-(diazoacetyl)benzoate is treated with A-methylmaleimide at reflux... 

Oxidative Rearrangements Toste et al. recently developed various oxidative rearrangements of alkynes using sulfoxides as stoichiometric oxidants through carbenoid intermediates. These reactions could provide an entry into products that contain a carbonyl group susceptible to further functionalization [142] (Scheme 8.26). ... 

Although Echavarren et al. reported similar conversions by platinum catalysis, lower selectivity was observed [165-167]. Computational studies then suggested the initial formation of a cyclopropyl carbenoid intermediate 213, as shown in Scheme 8.28. 

---