A-Diazo-p-keto esters

McKervey and Ye have developed chiral sulfur-containing dirhodium car-boxylates that have been subsequently employed as catalysts for asymmetric intramolecular C-H insertion reactions of y-alkoxy-ot-diazo-p-keto esters. These reactions produced the corresponding ci -2,5-disubstituted-3(2H)-furanones with diastereoselectivities of up to 47% de. Moreover, when a chiral y-alkoxy-a-diazo-p-keto ester containing the menthyl group as a chiral auxiliary was combined with rhodium(II) benzenesulfoneprolinate catalyst, a considerable diastereoselectivity enhancement was achieved with the de value being more than 60% (Scheme 10.74). 

Scheme 10.74 Rh-catalysed intramolecular C-H insertions of y-alkoxy-a-diazo-P-keto esters with sulfonamide ligands.

The above transformation takes place via the catalytic effect of copper (I), which generated the corresponding carbenoid from a-diazo-p-keto esters. These Cu-carbenoides react with the thiocarbonyl group of thioamides, after cyclocondensation to afford 2-aryl-l,3-thiazole-5-carboxylates (Scheme 18).40... 

Functionalised 2,3-dihydro-l,4-dioxins can be synthesised in a three step-sequence from P-keto esters. The key step is the insertion of a Rh-carbenoid derived from an a-diazo-p-keto ester into an 0-H bond of a 13-diol <99H(51)1073>. The reaction of 2-(l,4-dioxenyl)alkanols with silyl enol ethers yields 23-disubstituted 1,4-dioxanes. When 13-bis(trimethylsilyloxy)-cyclobut-l-ene is used, the expected cyclobutanone products are accompanied by a spirocyclopropane derivative <99TL863>. 1,4-Dioxane-monochloroborane 57 is a highly reactive hydroborating reagent <990L315>. 

Carbacephalosporins The ketene-imine cyclization described above has been extended to a synthesis of a chiral carbacepham (4). This synthesis uses a dihy-droanisole group as the equivalent of a p-keto ester. Thus the azetidinone 1, obtained in 80% yield by the above route, was reduced and acylated in situ to provide 2. Ozonization followed by a rhodium-catalyzed cyclization of an a-diazo-P-keto ester provides 3, which is a useful intermediate to various substituted car-bacephams such as 4. 

Chiral 3,3-disubstituted cyclopentanones. Taber et al have extended a synthesis of cyclopentanones by a rhodium catalyzed intramolecular C—H insertion (11,459) to a synthesis of (+ )-a-cuparenone (3), which contains a chiral quaternary center. Thus the chiral a-diazo-p-keto ester 1, prepared by alkylation of a chiral oxazolidone (11, 379-381) on treatment with Rh2(OAc)4 is converted into 2 in 67% yield. This product is converted in several steps into (+ )-3. 

Intramolecular C—H insertion. The key step in a recent synthesis of pen-talenolactone E methyl ester (3) is the reaction of the a-diazo-p-keto ester (1), prepared in several steps from 4,4-dimethylcyclohexanone, with Rh2(OAc)4. A single product (2) is obtained in high yield even though insertion involves bond formation with a nonfunctionalized carbon atom.4... 

Chiral cyclopentanones.2 The regioselective cyclization of a-diazo-p-keto esters to cyclopentanones (11, 459) is also enantioselective with substrates derived from chiral alcohols. Preliminary studies show that steric factors affect the diastereoselectivity the highest diastereoselectivity is obtained with esters of the alcohol 1, which is available from camphor,3 and in which both the bomane and the naphthalene rings can exert steric effects on the diastereoselectivity. 

P-keto ester a-diazo-P-keto ester Regitz diazo transfer... 

We observed (1,2) that an a-diazo P-keto ester 5 (Scheme 2) would, on exposure to a catalytic amount of Rh2(OAc)4, undergo smooth cyclization to the cyclopentane derivative 6. Since the a-diazo P-keto ester 5 was readily prepared by diazo transfer (3) to the corresponding P-keto ester 4, this established a general route to highly substituted cyclopentanes. The subsequent observation (4) that use of Rh2(02CR)4 catalysts derived from more electron-donating carboxylic acids al-... 

Using this approach, we have successfully predicted the major product from the cyclization of more than 30 a-diazo esters and a-diazo p-keto esters (6), including the cyclization (12) of 1 to 2 (Scheme 1). Not all Rh-mediated intramolecular C-H insertion reactions will proceed to give a single dominant dia-stereomer. Our interest in this initial investigation has been to develop a model... 

Some synthetic approaches to pyrazines relied on metal-assisted reactions. A synthesis of 6-substituted 5H-pyrrolol2,3-bJpyrazines via Pd-catalyzed heteroannulation from W-(3-chloropyrazin-2-yl)methanesulfonamide and alkynes was developed <04TL8087>, and 3- and 5-substituted 2(l//)-pyrazinones were prepared by Suzuki and Heck reactions using 3,5-dichloro-2(l//)-pyrazinones <04TL1885>. An improved synthesis of 6-substituted-5//-pyrrolo 2,3-iiJ-pyrazines via microwave-assisted Pd-catalyzed heteroannulation was developed <04TL8631>, and the reaction of a-diazo-P-keto esters with Boc amino acid amides in the presence of a Rh catalyst gave, after air oxidation, pyrazin-6-ones 111, which were then converted into tetrasubstituted pyrazines 112 <04OL4627>. 

To a magnetically stirred refluxing suspension of Rh2(OAc)4 (3 mg) in dry CH2CI2 (4 mL) was added a solution of the a-diazo-P-keto ester 230 (60 mg, 0.18 mmol) in dry CH2CI2 (14 mL) over a period of 30 min and refluxed for 2 h. Evaporation of the solvent and purification of the residue on a silica gel column using ethyl acetate-hexane (1 19) as eluent furnished an epimeric mixture of the triquinane ester 231 (48 mg, 87%) along with its enol form as an oil. 

The absolute configuration of 1 was set by the Rh-mediated cyclopropanation of 4 with the diazo ester 5. Though closely related to the a-diazo P-keto ester 6, the alkene of 5 donates election density to the intermediate Rh carbene, making it more susceptible to the influence of the chiral ligands. The alkene of the enol ether then participated in the Cope rearrangement, dehvering 8. Routine functional group transformation then converted 8 to 1, that cyclized smoothly to 2. 

SCHEME 5.44 Rh-catalyzed four-component reaction of two a-diazo-P-keto esters and two 1,4-dioxanes. 

Experimental data have provided evidence for the involvment of quantum mechanical tunnelling in the coupled cobalt-carbon bond homolysis-substrate radical generation reaction catalysed by methylmalonyl-CoA mutase. ortho-Metallated dirhodium(II) complexes have been used as catalysts in the dia-stereoselective cyclopropanation of menthyl-a-diazo-P-keto ester and C-H insertion of ot-diazo ester. The iridium complexes [Ir(Me)2(L)(r -C5Me5)] (L = PMes, PPhs) have been found to catalyse the dehydrogenative coupling of dimethylphenylsilane in the presence of one-electron oxidants to yield Me2PhSiSiPhMe2. ... 

Enantioselective tandem carbonyl ylide formation-cycloaddition of a-diazo-p-keto esters is achieved in hexane with [Rh2(S-DOSP)4] (1 mol %) at room temperature to give the corresponding cycloadducts with moderate enantioselectivity [73] (Eq. 8A.49). 

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