Carbon hydrogen insertion

Phenyldiazonium salts react with malonaldioxime to produce a 2-isoxazoline (7 IGEPl 920245), and the diazo ketone (484) when photolyzed gave a mixture of 2-isoxazoline and an isoxazole by a 1,5 carbon-hydrogen insertion. A phenyl migration was apparently not involved (Scheme 124) (66CC689). 

The search for the racemic form of 15, prepared by allylic cyclopropanation of farnesyl diazoacetate 14, prompted the use of Rh2(OAc)4 for this process. But, instead of 15, addition occurred to the terminal double bond exclusively and in high yield (Eq. 6) [65]. This example initiated studies that have demonstrated the generality of the process [66-68] and its suitability for asymmetric cyclopropanation [69]. Since carbon-hydrogen insertion is in competition with addition, only the most reactive carboxamidate-ligated catalysts effect macrocyclic cyclopropanation [70] (Eq. 7), and CuPF6/bis-oxazoline 28 generally produces the highest level of enantiocontrol. 

With nonracemic chiral diazoacetates the insertion process occurs with evident match/mismatch characteristics. This has been demonstrated in reactions of optically pure 2-methylcyclohexyl diazoacetates (Eq. 9) [85] and in carbon-hydrogen insertion reactions of steroidal diazoacetates (Eq. 10) [86], as well as with the synthesis of pyrrolizidines 36 and 37 [84]. The mechanistic preference for formation of a /J-lactone in Eq. 10 over insertion into the 4-position is not clear,but there are other examples of /J-lactone formation [87]. In these and related examples, selectivities in match/mismatch examples are high, and future investigations are anticipated to show even greater applicability. 

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. 

Scheme 6.78 Rhodium(ll)-catalyzed carbon-hydrogen insertion.

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). 

Chiral Dirhodium(ll) Carboxamidates for Asymmetric Cyclopropanation and Carbon-Hydrogen Insertion Reactions... 

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]. 

Scheme 15.4 Mechanism of metal carbene carbon-hydrogen insertion.

Alkylidenecarbenes undergo a carbon-hydrogen-insertion reaction that leads to a mixture of two isomeric products, 2-substituted furo[3,2- ]pyridines, 109, and 2-substituted furo[2,3-. 

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... 

Frey), as there was no known example of an intermolecular carbon-carbon insertion. The ensuing decades have not revealed such a reaction, despite some hard searching. " Why should the intramolecular version of carbon-carbon insertion compete so favorably with carbon-hydrogen insertion It doesn t. Two alternative... 

A similar story attends the chemistry of cyclopropylcarbenes. In the 1960s it was shown that cyclopropyl methyl diazomethane gives almost exclusively the product of apparent carbon-carbon insertion. " Surely we are now suspicious, and rightly so, as neither photolysis of 62 nor deoxygenation of cyclopropyl methyl ketone reproduces these results. Instead, carbon-hydrogen insertion dominates (Scheme 7.25). Once again, a direct reaction of photoexcited diazo compound appears to be the dominant source of the product of ring expansion (carbon-carbon insertion). 

Both cyclopropanation (Eq. 40) and carbon-hydrogen insertion (Eq. 41) are well... 

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... 

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