Ketones diazo, reaction with rhodium

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. 

One of the key steps in building the fused ring involves the reaction of the activated acetoacetate methylene group in that compound with toluenesulfonyl azide to give the diazo intemediate (12-1). Treatment of that product with rhodium acetate leads to a loss of nitrogen with the consequent formation of carbene (12-2) this inserts into the adjacent amide N—H bond to form a five-membered ring and thus the carbapenem (12-3) [15]. The first step in the incorporation of the thioenol function consists in the conversion of the ketone to the enol phosphate derivative... 

Although C—H insertion reactions rarely occur in intermolecular reactions with diazoacetates, these are common side reactions with diazomalonates3132 (equation 10) and diazo ketones (with a-allyl vinyl ethers).33 Several mechanistic pathways are available to generate the products of an apparent direct C—H insertion reaction and these include dipolar intermediates, ir-allyl complexes and ring opening of cyclopropanes.1 Oxidative problems due to the presence of oxygen are common with copper catalysts, but these are rarely encountered with rhodium catalysts except in systems where the carbenoid is ineffectively captured.34... 

The total synthesis of the diterpenoid tropone, harringtonolide was accomplished in the laboratory of L.N. Mander. The key step to form the seven-membered ring was the Buchner reaction of a complex polycyclic diazo ketone intermediate. Upon treatment with rhodium mandelate, an unstable adduct was formed and was immediately treated with DBU to afford the less labile cycloheptatriene. 

Insertion of rhodium into the diazo compound gives an intermediate rhodium carbenoid which is trapped intramolecularly to give the ylide. The regiochemistry of the cycloaddition reaction can be explained by invoking a dipole with a more electron-rich carbon atom a- to the ketone, which interacts with the electron-deficient aldehyde carbon atom. Calculations support this, with the prediction that the a- carbon of the dipole has a larger coefficient in the HOMO and therefore interacts best with the carbon atom of the aldehyde, which will bear a larger coefficient in theLUMO. See A. Padwa, G. E. Fryxell and L. Zhi, J. Am. Chem. Soc., 112 (1990), 3100. 

This work was extended to a one-pot multicomponent procedure involving two different ketenes derived from diazo ketones 145 and 149, respectively, and using 4-methoxyphenylazide (ArN3), and rhodium acetate, with in situ conversion of ketene 150 derived from diazo ketone 149 to the imine 147 by reaction with the arylazide, and then subsequent cycloaddition of 147 with ketene 146, also generated in situ, from diazo ketone 145, again forming the P-lactam 148 (Eqn (4.90)). ... 

Diazo compounds, with or without metal catalysis, are well-known sources of carbenes. For synthetic purposes a metal catalyst is used. The diazo compounds employed are usually a- to an electron-withdrawing group, such as an ester or a ketone, for stability. In the early days, copper powder was the catalyst of choice, but now salts of rhodium are favoured. The chemistry that results looks very like the chemistry of free carbenes, involving cyclopropanation of alkenes, cyclopropenation of alkynes, C-H insertion reactions and nucleophilic trapping. As with other reactions in this chapter, free carbenes are not involved. Rhodium-carbene complexes are responsible for the chemistry. This has enormous consequences for the synthetic applications of the carbenes - not only does the metal tame the ferocity of the carbene, but it also allows control of the chemo-, regio- and stereoselectivity of the reaction by the choice of ligands. 

In recent work67, it has been demonstrated that simple a-diazo ketones and esters can, in fact, be induced to undergo 1,5-insertion in preparatively useful yields. It was already known51 that in the rhodium-catalyzed insertion process, methyl C-H is electronically less reactive than methylene C-H or methine C-H. It therefore seemed likely that competing -hydride elimination would be least likely with a diazoethyl ketone. Indeed, on cyclization of 2-diazo-3-tetrade-canone, only a trace of the enone product from /J-hydride elimination is observed. The predominant side reaction competing with 1,5-insertion is dimer formation. 

A similar transformation was observed with the rhodium trifluoroacetate catalyzed decomposition of diazo ketones in the presence of benzene (Scheme 32).130 The cycloheptatrienes (147) formed in this case were acid labile and could be readily rearranged to benzyl ketones (148) on treatment with TFA. The reaction was effective even when the side chain contained reactive halogen and cyclopropyl functionality, but competing intramolecular reactions occurred with benzyl diazomethyl ketone. A more exotic example of this reaction is the rhodium(ll) trifluoroacetate catalyzed decomposition of the diazopenicillinate (149) in the presence of anisole, which resulted in the formation of two cycloheptatriene derivatives (150) and (151) (equation 35).m... 

There has been great interest in recent years in methods for the generation of azomethine ylides and in exploitation of these reactive species in tandem/cascade processes for the rapid assembly of polyaza, polycyclic, multifunctional systems. a-Diazo ketones have featured greatly in such studies, treatment with a catalytic amount of rhodium(II) acetate generating transient rhodium carbenoids. A very common feature of many investigations of this type is the occurrence of quite unexpected reactions. For example, treatment of the diazo ketone 1 with a catalytic amount of... 

This report covers two topics (1) The generation of 2-thioxo-2,4-dihydro-3fT-imidazol-l-ium-l-imides as intermediates in the course of [3+2] cycloaddition reactions of azoalkenes and thiocyanic acid resulting in the formation of l-aminoimidazole-2-thione derivatives some further reactions of these heterocycles are presented as well. (2) The rhodium-catalyzed intramolecular interaction of co-diazenyl a -diazo ketones giving rise to the formation of mostly two cyclic azomethine imine isomers with an exocyclic terminal nitrogen atom and with all three... 

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). 

Indeed, triethyl phosphonoglyoxylate was easily prepared by this approach using propylene oxide as the oxygen donor (100 % by NMR, 84 % isolated), with refluxing benzene (16 hr) as the solvent [79]. The course of the reaction was conveniently monitored by 31P-NMR (diazo ester resonance, 610.8 ppm, ketone ester resonance <5 -2 ppm). Workup is simple both side products (dinitrogen and propylene) are gases at room temperature, and excess propylene oxide and solvent is removed in vacuo. On reuse, recovered rhodium catalyst was found to retain its activity. When 0.02 eq. (tenfold more) catalyst was used, the reaction was complete in approximately 2 h. 

Allyldiethylamine behaves similarly, but the yields are low since neither the starting amine nor the products are stable to the reaction conditions. For the efficiency of the cyclopropanation of the allylic systems under discussion, a comparison can be made between the triplet-sensitized photochemical reaction and the process carried out in the presence of copper or rhodium catalysts whereas with allyl halides and allyl ethers, the transition metal catalyzed reaction often produces higher yields (especially if tetraacetatodirhodium is used), the photochemical variant is the method of choice for allyl sulfides. The catalysts react with allyl sulfides (and with allyl selenides and allylamines, for that matter) exclusively via the ylide pathway (see Section 1.2.1.2.4.2.6.3.3. and Houben-Weyl, Vol. E19b, pll30). It should also be noted that the purely thermal decomposition of dimethyl diazomalonate in allyl sulfides produces no cyclopropane, but only the ylide-derived product in high yield.Very few cyclopropanes have been synthesized by photolysis of other diazocarbonyl compounds than a-diazo esters and a-diazo ketones, although this should not be impossible in several cases (e.g. a-diazo aldehydes, a-diazocarboxamides). Irradiation of a-diazo-a-(4-nitrophenyl)acetic acid in a mixture of 2-methylbut-2-ene and methanol gave mainly l-(4-nitrophenyl)-2,2,3-trimethylcyclo-propane-1-carboxylic acid (19, 71%) in addition to some O-H insertion product (10%). ... 

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