Carbene, carbon-hydrogen insertion reactions

One of the most dramatic recent developments in metal carbene chemistry catalyzed by dirhodium(II) has been demonstration of the feasibility and usefulness of intermolecular carbon-hydrogen insertion reactions [38, 91]. These were made possible by recognition of the unusual reactivity and selectivity of aryl- and vinyldiazoacetates [12] and the high level of electronic control that is possible in their reactions. Some of the products that have been formed in these reactions, and their selectivities with catalysis by Rh2(S-DOSP)4, are reported in Scheme 10. 

Stang etal. (94JA93) have developed another alkynyliodonium salt mediated approach for the synthesis of y-lactams including bicyclic systems containing the pyrrole moiety. This method is based on the formation of 2-cyclopentenones 114 via intramolecular 1,5-carbon-hydrogen insertion reactions of [/3-(p-toluenesulfonyl)alkylidene]carbenes 113 derived from Michael addition of sodium p-toluenesulfinate to /3-ketoethynyl(phenyl) iodonium triflates 112 (Scheme 32). Replacing 112 by j8-amidoethynyl (phenyl)iodonium triflates 115-119 provides various y-lactams as outlined in Eqs. (26)-(30). 

Intramolecular carbon-hydrogen insertion reactions have well known to be elTectively promoted by dirhodium(ll) catalysts [19-23]. Insertion into the y-position to form five-membered ring compounds is virtually exclusive, and in competitive experiments the expected reactivity for electrophilic carbene insertion (3°>2° 1°) is observed [49], as is heteroatom activation [50]. A recent theoretical treatment [51] confirmed the mechanistic proposal (Scheme 15.4) that C-C and C-H bond formation with the carbene carbon proceeds in a concerted fashion as the ligated metal dissociates [52]. Chemoselectivity is dependent on the catalyst ligands [53]. 

Metal Carbene TVansformations. The effectiveness of Rh2(55 -MEPY)4 and its 5R-form, Rh2 5R-MEPY)4, is exceptional for highly enantioselective intramolecular cyclopropanation and carbon-hydrogen insertion reactions. Intermolecular cyclopropanation occurs with lower enantiomeric excesses than with alternative chiral copper salicylaldimine or C2-symmetric semicorrin or bis-oxazoline copper catalysts, but intermolecular cyclopropenation exhibits higher enantio-control with Rh2(MEPY)4 catalysts. The methyl carboxylate attachment of Rh2(55-MEPY)4 is far more effective than steri-cally similar benzyl or isopropyl attachments for enantioselective metal carbene transformations. The significant enhancement in enantiocontrol is believed to be due to carboxylate carbonyl stabilization of the intermediate metal carbene and/or to dipolar influences on substrate approach to the carbene center. 

Rhodium(II)-MEPY and rhodium(II)-MACIM (methyl 1-acetylimidazolidin-2-one-4-carboxylate) complexes are efficient chiral catalysts for intramolecular carbon-hydrogen insertion reactions of diazoacetates (224) and metal carbene transformations (225). Dirhodium(II) carboxylates of similar structure (eg, piperidinonate complexes of the Rh2(ligand)4 type) have been found efficient catalysts for asymmetric cyclopropanation of olefins (226). 

Among typical carbon-carbon bond (C-C) formation reactions with carbenes, the cyclopropanation reaction with olefins has been well studied including its application to industrial processes. The second typical reaction of carbenes is the insertion reaction into the carbon-hydrogen bond (C-H) which seems to be a direct and efficient C-C bond forming reaction. However, its use for synthetic purpose has often been limited due to low selectivity of the reactions.3... 

A completely different approach was used to probe the reactivity of tert-butyl-carbene, one of Frey s original examples. Table 7.6 shows the varying products of thermal and photochemical decomposition of the diazo compound. It would appear that carbon-hydrogen insertion and carbon-carbon insertion are about equally facile in the carbene presumed to be formed in photolytic reactions. Even in 1964, this observation should have seemed strange (as it clearly did to... 

The carbon-hydrogen insertion (C,H insertion) is one of the most striking reactions of carbenes and carbenoids. The reaction is interesting and very useful for the construction... 

Most reactions of this category involve the base-induced generation of alkylidene-carbenes (R2C = C ) which undergo an intramolecular 1,5-carbon-hydrogen insertion providing a useful route for the construction of substituted cyclopentenes a competing intramolecular pathway is rearrangement to alkynes. 

In alternative (a), ring-formation takes place electrocyclically and leads to isobenzene (7 1,2,4-cyclohexatriene) as the primary reaction intermediate [10]. This highly strained cy-cloallene subsequently aromatizes to 2 by hydrogen migration. In the second route, pathway (b), reversible generation of a vinylidene carbene (8 see above) constitutes the first step, and is followed by 1,6-carbon hydrogen insertion. Finally, in pathway (c), vinyl radicals of type 9... 

PROBLEM 10.63 A reaction of carbenes not mentioned in the text is called carbon—hydrogen insertion. In this startling reaction, a reactive carbene ultimately places itself between the carbon and hydrogen of a carbon-hydrogen hond. 

Carbenes can rearrange to alkenes in many cases. A 1,2-hydrogen shift leads to an alkene, and this is often competitive with insertion reactions.Benzylchlorocarbene (42) rearranges via a 1,2-hydrogen shift to give the alkene.Similarly, carbene (43) rearranges to alkene (44), and replacement of H on the a-carbon with D showed a... 

A second process that has a central position in the analysis of the chemical properties of carbenes is their reaction with hydrocarbons. As is the case for alcohols, singlet and triplet carbenes react with hydrocarbons in distinctive ways. It has long been held that very electrophilic singlet carbenes can insert directly into carbon-hydrogen bonds (11) (Kirmse, 1971). On the other hand, triplet carbenes are believed to abstract hydrogen atoms to generate radicals that go on to combine and disproportionate in subsequent steps (12)... 

Like carbene insertions into carbon-hydrogen bonds, metal nitrene insertions occur in both intermolecular and intramolecular reactions.For intermole-cular reactions, a manganese(III) meio-tetrakis(pentafluorophenyl)porphyrm complex gives high product yields and turnovers up to 2600 amidations could be effected directly with amides using PhI(OAc)2 (Eq. 51). The most exciting development in intramolecular C—H reactions thus far has been the oxidative cychzation of sulfamate esters (e.g., Eq. 52), as well as carbamates (to oxazolidin-2-ones), ° and one can expect further developments that are of synthetic... 

Products which can be ascribed to the intermediate formation of radicals have long been observed in carbene reactions. In the gas phase these products could arise by homolytic decomposition of excited primary products before collisional deactivation rather than from radicals generated in the course of insertion. This is not so in solution. It is found that, in the thermal decomposition of diphenyldiazomethane (Bethell et al., 1965) or photolysis of diphenylketene (Nozaki et al., 1966) in toluene solution, the product of insertion of diphenylmethylene into the benzylic carbon-hydrogen bonds, 1,1,2-triphenylethane, is accompanied by substantial amounts of 1,1,2,2-tetraphenylethane and bibenzyl. This is a strong indication that discrete diphenylmethyl and benzyl radicals are formed, and, taken in conjunction with EPR (Section IIB) and other evidence (Etter et al., 1959) that diphenylmethylene is a ground-state triplet, would support the view that equation (20) is an adequate representation of triplet insertion. 

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