Reactions of a-Diazo Ketones

Rhodium carboxylates have been found to be effective catalysts for intramolecular C—H insertion reactions of a-diazo ketones and esters.215 In flexible systems, five-membered rings are formed in preference to six-membered ones. Insertion into methine hydrogen is preferred to a methylene hydrogen. Intramolecular insertion can be competitive with intramolecular addition. Product ratios can to some extent be controlled by the specific rhodium catalyst that is used.216 In the example shown, insertion is the exclusive reaction with Rh2(02CC4F9)4, whereas only addition occurs with Rh2(caprolactamate)4, which indicates that the more electrophilic carbenoids favor insertion. 

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... 

The 1,3-dipolar cycloaddition of a-keto carbenoids to the polar double bond of heterocumulenes provides a direct access to five-membered heterocycles. The reaction of a-diazo ketones 132 with phenyl isocyanate in the presence of a Rh2(OAc)4 catalyst affords the 1,3-cycloadduct, 3-phenyl-2(3//)-oxazolones 133 (Fig. 5.32). ... 

Cyclopropanation of furanyl diazo ketones. The reaction of a-diazo ketones of furanylpropionic acids with Rh2(OAc)4 involves formation of an unstable cyclo-... 

Aldehydes are efficiently converted to /3-diketo esters in 50-90 % yield by addition of ethyl diazoacetate in the presence of SnCl2 (Eq. 5). Although the reaction can be effected by a variety of Lewis acids, SnCl2, BF3, and GeCl2 are the most effective [14]. 1,3-Diketones can be prepared in 42-90 % yield by SnCl2-catalyzed reaction of a-diazo ketones with aldehydes (Eq. 6) [15]. 

The synthesis of substituted chromanones 369 via a C—H insertion reaction of a-diazo ketones 370 has demonstrated that high levels of enantiose-lectivity are attainable through the use of chiral rhodium carboxylates (92CC823). Treating diazo ketone 370 (R = CH=CH2, R = H) with Rh2[(S)(-l-)BINAP]4 leads enantioselectively to the cis isomer of chroma-none 369 (92TL5983). 

Bestmann and co-workers developed a synthesis of o-ketoaldehydes which involves in the first step reaction of a diazo ketone with triphenylphosphine to form a phosphorazane (3). This can be converted into the a-ketoaldehyde (6) by hydrolysis o o... 

Figure 6.5 High-dilution trident for Rh-catalyzed reaction of a diazo ketone ...

Reaction of a-diazo ketones with alkynes. Reaction of the acetylenic a-diazo ketone 1 with an alkyne in the presence of Rhj(OAc)4 at 25° results in an intermediate a, formed by an intramolecular alkyne insertion, that reacts wilh the external alkyne lo form a cyclopropene (2). Rearrangement of the cyclopropene group by Rh2(OAc)44... 

D.iii. Cyclization Reactions of a-Diazo Ketones. An attractive application of cyclopropanation is intramolecular trapping of carbenes to form bicyclic compounds with a three-membered ring appended to another ring. When diazoalkanes are treated with transition metals in the presence of an alkene, particularly... 

Muthusamy S, Gunanathan C et al (2004) Regioselective synthesis of mono- and bis-decahy-drobenzocarbazoles via tandem reactions of a-diazo ketones. Tetrahedron 60 7885-7897 Nambu H, Hikime M et al (2009) Asymmetric approach to the pentacyclic skeleton of aspidosperma alkaloids via enantioselective intramolecular 1,3-dipolar cycloaddition of carbonyl ylides catalyzed by chiral dirhodium(II) carboxylates. Tetrahedron Lett 50 3675-3678... 

Reaction of a-diazo ketones ketone 1 with an alkyne in the prevcoct a, formed by an intramolecular alkvrte to form a cyclopropene (2). Rearraneci... 

Reaction of a-diazo ketones with DDO leads to a-keto aldehyde hydrates (eq 24). Oximes are converted to the free ketones by DD0.3 ... 

Fig. 3.4 Comparison of peroxy acid oxidation of an alkyne with the analogous reaction of a diazo ketone. The relative yields of products from alkyne and from diazo ketone (italics) are shown. The similarities and difference between such reactions has been ascribed to various possibilities (see text)...

Muthusamy and co-workers have reported the indium(III) triflate-catalyzed OH inserhon reaction of a-diazo ketones. In the presence of 10 mol % of catalyst, a range of alcohols and thiols decomposed a variety of aromatic and aliphatic diazo compounds affording the respective a-alkoxy ketones under mild conditions (eq 20). 

The E boron enolates of acyclic ketones can be obtained by reaction of a-diazo ketones with trialkylboranes." They can be isomerized to the Z-isomer by a catalytic amount of a weak base such as phenoxide ion. 

Lithium enolates were also generated by rhodium-catalyzed double-bond shifts in allyl lithium alkoxides [177], the cleavage of cyclopropyl ketones with lithium in ammonia [137b, 178] and various other methods [2c,d,e]. The first preparation of boron enolates, achieved by Hooz and coworkers [179], is based on a reaction of a-diazo ketones 188 with tributylborane. The primary adduct 189 releases nitrogen, andthetautomerism ofthe intermediate 190 finally leads to the boron enolate 191 (Scheme 2.55). 

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