Ketocarbenoids

In other cases, oxidation of the rhodium or palladium ketocarbenoid to a 1,2-dicarbonyl compound is well established The Rh2(OAc)4-catalyzed decomposition... 

Special Aspects of Reactions between Functionalized Olefins and Ketocarbenoids... 

With a less reactive olefin such as isopropenyl acetate, diazoketone 86 gives only a low yield of cyclopropane 90 a-acyl enol ether 92, resulting from an intramolecular rearrangement of the ketocarbenoid, becomes the favored reaction product. If 91... 

Ethyl diazopyruvate, under copper catalysis, reacts with alkynes to give furane-2-carboxylates rather than cyclopropenes u3) (Scheme 30). What looks like a [3 + 2] cycloaddition product of a ketocarbenoid, may actually have arisen from a primarily formed cyclopropene by subsequent copper-catalyzed ring enlargement. Such a sequence has been established for the reaction of diazoacetic esters with acetylenes in the presence of certain copper catalysts, but metallic copper, in these cases, was not able to bring about the ring enlargement14). Conversely, no cyclopropene derivative was detected in the diazopyruvate reaction. 

Intramolecular cyclopropanation of 4-aryl-1 -diazo-2-butanones 240 allows construction of the bicyclo[5.3.0]decane framework 12). In a reaction sequence analogous to that described above for the intermolecular ketocarbenoid reaction, bicyclo-[5.3.0]deca-l,3,5-trien-8-ones 241 are formed. They rearrange to the conjugated isomers 242 at the high temperatures needed if the reaction is catalyzed by copper 2311 or CuCl 232), but can be isolated in excellent yield from the Rh2(OAc)4-promoted reaction which occurs at lower temperature 233... 

Reaction of ketocarbenoids with pyrrole and N-alkylpyrroles yields the product of formal insertion into the a-C—H bond (256) in many cases the -insertion product 257 is formed concomitantly, but generally in lower yield 238-241 >. The regioselectivity varies according to the catalyst, the diazo compound and the N-alkyl substituent. Some examples concerning the former two variables are given in Table 18 239 240). 

Table 18. Regioselectivity of ketocarbenoid insertion into C—H bonds of N-methylpyrrole.

In an intramolecular version of ketocarbenoid a-C/H insertion, copper-promoted decomposition of l-diazo-3-(pyrrol-l-yl)-2-propanone (258a) or l-diazo-4-(pyrrol-l-yl)-2-butanone (258b) resulted in quantitative formation of the respective cycli-zation product 259 242 >. The cyclization 260 -> 261, on the other hand, is a low-yield reaction which is accompanied by olefin formation. The product ratio was found to vary with the copper catalyst used, but the total yield never exceeded 35 % 243>. 

Whereas pyrrole was reported not to give N/H insertion by ketocarbenoids, such a reaction mode does occur with imidazole Copper-catalyzed decomposition of ethyl diazoacetate at 80 °C in the presence of imidazole gives ethyl imidazol- 1-ylacetate exclusively (93 %) small amounts of a C-alkylated imidazole were obtained additionally under purely thermal conditions 244). N/H insertion also takes place at benzimidazole 245 a). The reaction is thought to begin with formation of an N3-ylide, followed by N1 - C proton transfer leading to the formal N/H insertion product. Diazomalonic raters behave analogously however, they suffer complete or partial dealkoxycarbonylation under the reaction conditions 244) (Scheme 34). N-alkylation of imidazole and benzimidazole by the carbenoids derived from co-diazoacetophenone and 2-(diazoacetyl)naphthalene has also been reported 245 b>. 

Furans and some of its derivatives have been cyclopropanated with the ketocarbenoids derived from ethyl diazoacetate and copper catalysts. The 2-oxabicyclo[3.1.0]hex-3-enes thus formed are easily ring-opened to 1,4-diacylbutadienes thermally, thermo-catalytically or by proton catalysis 14,136). The method has been put to good use by Rh2(OAc)4-catalyzed cyclopropanation of furan with diazoketones 275 to bicyclic products 276. Even at room temperature, they undergo electrocyclic ring-opening and cis, trans-dienes 277a are obtained with fair selectivity 257,258). These compounds served as starting materials in the total syntheses 257 259) of some HETE s (mono-... 

The use of rhodium(II) acetate in carbenoid chemistry has also been extended to promoting intramolecular C/H insertion reactions of ketocarbenoids 277,280,280 ,). From the a-diazo-P-ketoester 305, highly functionalized cyclopentane 306 could thus be constructed in acceptable yields by regiospecific insertion into an unactivated... 

C—H bond 174-280,28i por comparison, only trace amounts of cyclopentane resulted from the CuS04-catalyzed decomposition of 1 -diazo-2-octanone or l-diazo-4,4-dimethyl-2-pentanone 277). It is obvious that the use of Rh2(OAc)4 considerably extends the scope of transition-metal catalyzed intramolecular C/H insertion, as it allows for the first time, efficient cyelization of ketocarbenoids derived from freely rotating, acyclic diazoketones. This cyelization reaction can also be highly diastereo-selective, as the exclusive formation of a m is-2,3-disubstituted cyclopentane carboxylate from 307 shows281 a). The stereoselection has been rationalized by... 

Copper-catalyzed ketocarbenoid C/H insertion has been shown to occur with retention of configuration 282 and the same is true for the Rh2(OAc)4-promoted reaction. Advantage has been taken of this fact for a synthesis of (+)-a-cuparenone,... 

Failure to obtain the desired azacarbacephem 331 had to be accepted with the diazetidinone 330. Instead of the hoped-for N/H insertion, the ketocarbenoid derived from 330 attacked the more nucleophilic N-l atom to give an intermediate ammonium ylide which then went on to the products 332 and 334 as suggested... 

Dihydrofurans.m Dihydrofurans can be obtained by reaction of ot,a-dibro-modeoxybenzoin (1) with Sml2 and an alkene. The reaction evidently involves a 1,3-dipolar addition of a ketocarbenoid to an alkene. 

The use of ketocarbenoids with chiral auxiliaries has not been terribly effective at chiral induction. Menthol and bomeol esters of diazoacetates resulted in very low enantioselectivity.38 Some improvements were obtained by using the chiral amide (29 equation 13), but low overall yields were obtained due to competing intramolecular side reactions.39 Related studies with other types of carbenoids, however, have resulted in high enantioselectivity.60... 

The reaction of ketocarbenoids with alkynes is a direct method for the synthesis of functionalized cyclopropenes.1 122 123 Until quite recently copper catalysis was generally used and the reactions proceeded in fairly moderate yields, except with terminal alkynes, which failed to generate cyclopropenes due to competing C—H insertions.1 This limitation could be circumvented, however, by using trimethylsilyl derivatives. This approach is illustrated in the synthesis of (131), the unsaturated analog of 1-aminocy-clopropanecarboxylic acid, the biosynthetic precursor to ethylene in plants (Scheme 27).124 The initial... 

The reaction of ketocarbenoids with pyrroles leads to either substitution or cyclopropanation products, depending on the functionality on nitrogen. With N-acylated pyrrole (209) reaction of ethyl diazoacetate in the presence of copper(I) bromide generated the 2-azabicyclo[3.1.0]hex-3-ene system (210) and some of the diadduct (211 Scheme 44).162163 On attempted distillation of (210) in the presence of copper(I) bromide rearrangement to the 2-pyrrolylacetate (212) occurred, which was considered to proceed through the dipolar intermediate (213). In contrast, on flash vacuum pyrolysis (210) was transformed to the dihydropyridine (214). A plausible mechanism for the formation of (214) involved rearrangement of (210) to the acyclic imine (215), which then underwent a 6ir-electrocyclization. 

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