Keto carbene

Decomposition of the diazoacetic ester (548) to the keto carbene (549) is promoted by copper(II) trifluoromethanesulfonate. In the presence of nitriles, 1,3-dipolar addition to the nitrile occurred giving the oxazole (550) (75JOM(88)ll5) (see also Section 4.03.8.1). 

The intramolecular addition of alkynyl-substituted a-diazoketones is catalyzed by Rh2(OAc)4 to give transient cyclopropenes, which spontaneously rearrange to vinylogous a-keto carbene intermediates for further carbon-skeleton transformations [54]. 

The examples are vinyl carbenes, keto carbenes or ketoimines. 

The product distribution depends upon the substituents on the dipolar system. The details of the complex mechanistic pathway were demonstrated on the most simple first example as early as 1987 (Scheme 36) (87TL2689). In all cases the first step is postulated as a 1,7-electrocyclization. The formation of pyrrole 123 may proceed through the key intermediate 119 (a conjugated keto-carbene) which is formed either directly from 114, or from 116, or possibly from the N/O Cope product 115. 

The insertion of keto carbene to the N—H bond in 361 to form the carbapenem ring system 362 is a commercially established synthesis [119]. 

The ambident nucleophilic character of enaminones is again demonstrated by the reaction with keto carbenes, produced in situ from diazoketones. Acyclic enaminones react via the -position to directly yield pyrroles (equation 11). Cyclic enaminones are shown to react at the nitrogen to give adducts which can be cyclized with KOH to... 

Transition metal carbenes constitute a very important class of molecules that have found a multitude of applications. With reference to manganese, a number of new carbene complexes have been reported recently. The ) -alkyne complex (18) was found to undergo oxidation by dimethyldioxirane to afford the a-keto carbene (19). The fascinating aspect of this reaction is the likely existence of an oxirene intermediate (20). Stable oxirene complexes have never been reported, imdoubtedly because of the extreme instability of the antiaromatic oxirene ring. The possibility of trapping an oxirene by epoxidation of a coordinated alkyne is intriguing. Scheme 10 summarizes the chemistry involved. 

The ester group in II is suggestive—although it is not a proof—of the intermediacy of a ketene, and ketene production in diazocarbonyl chemistry usually implies a Wolff rearrangement. The construction of a three-carbon chain on the other side of the ketone is a confirmation of this prediction. In turn, the Wolff rearrangement requires an a-keto carbene precursor that is the fate of diazo compounds exposed to ultraviolet light (wavelength lower than 3200 A). All this is translated into the mechanism depicted in Scheme 43.1. 

Two procedures have been devised for the synthesis of a novel class of cyclosteroids, the 4a,6a-cyclo-5/8-derivatives (190). Carbenoid decomposition (NaOMe 160 °C) of the tosylhydrazone (187) gave the unsaturated acid (188). Copper-catalysed decomposition of the derived diazo-ketone (189) gave the desired 4a,6a-cyclo-ketone (190) by a keto-carbene addition to the 5,6-double bond. A more satisfactory synthesis proceeded from the 6/3-tosylate (191), which gave the 4a,6a-cyclosteroid in high yield on reaction with base (KO Bu-HO Bu). Several hormone analogues with the 4a,6a-cyclo modification were devoid of biological activity. ... 

Wolff rearrangement The rearrangement of a diazo ketone, RCOCHN2, via the keto carbene, RCOCH, to the ketene, RCHCO, which may then be hydrated to a carboxylic acid, RCH2C02H, as in the Arndt-Eistert synthesis. 

A simple example of the examination of a proposed structure through synthesis is provided in this section. In 2005, Takita12 proposed the structure of the male-produced aggregation pheromone of the stink bug Eysarcoris lewisi as the sesquisabinene alcohol, ( )-2-methyl-6-(4 -methylenebicyclo[3.1.0]hexyl)hept-2-en-l-ol (8) (Scheme 1). Mori13 synthesized (61 )-8 and (6S)-8 from the enantiomers of citronellal (10). The key steps were the intramolecular addition of an ct-keto carbene to the alkene bond (11—>12) and ( )-selective olefination of 13 to give 14. The 1H- and 13C-NMR spectra of 8 around the trisubstituted double bond at C-2 were different from those of the natural pheromone. 

Tliere is no chemistry corresponding to such simple disconnections, but preliminary FGl to ketones (60) or (61) looks promising as we can make Of-keto carbenes (Chapter 30) from diazomethane. Since either (60) or (61) will do, a preliminary carbene disconnection (Chapter 31) to (62) allows an unambiguous common bond disconnection to (63). 

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