Esters, 3-keto diazo transfer

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

The process from the FMC company involves as the pivotal step an intramolecular stereoselective [2 + 1 [-cycloaddition. In a Prins reaction [94] of chloral and isobutene, followed by an isomerisation, a racemic, trichloromethyl-substituted aUyl alcohol is obtained. Reaction with the isocyanate from (R)-naphthylethyl-amine enables separation ofthe diastereomers by crystallisation. The carbamate is cleaved by trichlorosilane/triethylamine, thus permitting the recycling of the chiral auxiliary. The optically pure (R)-aUyl alcohol is reacted with diketene, to produce the / -keto-ester. After diazo transfer and basic cleavage, the diazoacetate is obtained catalysed by a copper salt, this is converted in a [2 + 1 ]-cyclo-addition into a bicyclic lactone. The Boord reaction (discovered by Cecil E. Boord in 1930) [95] finally gives (IR)-cis-permethric acid. [96]... 

A second route was devised using chiral /3-keto ester 14, which was identified as our precursor for 2 [7]. This idea was in analogy with the carbapenem chemistry [8], as depicted in Scheme 2.4, where Masamune reaction [9] for carbon elongation, diazo-transfer, and transition metal-mediated carbene insertion reaction [10] were employed as key steps sequentially. 

We initially observed [4, 5] that an a-diazo / -keto ester 5 would, on exposure to a catalytic amount of Rh2(OAc)4, undergo smooth cyclization to the cyclopentane derivative 6 (Scheme 16.2). The a-diazo / -keto ester 5 is readily prepared by diazo transfer [6] from... 

The transformation of an active CH compound into the corresponding diazo derivative with -toluenesulfonyl azide has been designated a diazo transfer reaction and possesses a variety of preparative uses. The method has been useful for the syntheses of diazo derivatives of cyclopentadiene, 1,3-dicar-bonyl compounds, 1,3-disulfonyl compounds,1,3-keto-sulfonyl compounds, ketones, " carboxylic acid esters, and /3-keto imines. Further reaction of these diazo intermediates can lead to azo compounds,"- " 1,2,3-triazoles, and pyrazolinones. ... 

The original Regitz procedure for diazo transfer to a -keto ester (131) used p-toluenesulfonyl azide (132 equation 54). This reagent works well, and is easy to prepare from the corresponding sulfonyl chloride. A disadvantage of this reagent is that the p-toluenesulfonylamide coproduct (134), as well as any excess p-toluenesulfonyl azide, have to be removed from the product diazo ketone (133) before it can be used. 

Malonate esters and vinylogous malonates, as well as 1,3-diketones, readily undergo diazo transfer. In addition, the less acidic -keto phosphonates (138 equation 55) ° and p-keto sulfones (140 equation 56) have been shown to participate in this reaction. 

The possible mechanism for diazo transfer from p-toluenesulfonyl azide to active methylene compound 3 (flanked by carbonyl groups) is depicted below.1,3 Deprotonation of a-keto ester 3 with NEt3 leads to enolate 4 which attacks at the electrophilic N of the sulfonyl azide 5 to give intermediate tosyl derivative 6. Proton transfer occurs within intermediate 6 followed by elimination of p-toluenesulfonamide, leading to diazo compound 7 and the by-product -toluene sulfonamide 8.1,3... 

The diazo keto ester 154 is prepared from the p-keto ester 153 using tosyl azide or p-NBSA.69,70 The diazo ester (156) could not be prepared by diazo transfer with TsN3/NEt3, since elimination usually occurs to yield acrylate.71 A diazo transfer agent, l-ethyl-2-azidopyridinium tetrafluoroborate, successfully converted isoindole keto ester (155) to diazo keto ester (156).71... 

In another penem building block synthesis, a functionalised azetidinone is reacted with benzyl 2-bromopropionate in the presence of diethylaluminium chloride in hexane/THF. A mixture of epimers is obtained, which has to be separated chromatographically. Afterwards, the lactam nitrogen is protected, and the benzyl residue reductively cleaved. The next steps bear a close resemblance to those of the thienamycin synthesis construction of a jS-ketoester, diazo transfer and rhodium-catalysed insertion of a carbenoid into the lactam N-H bond. Finally, the jS-keto-ester is activated with diphenyl chlorophos-phonate. [60]... 

A study of reactions of benzocyclic jS-keto esters with sulfonyl azides has provided further indication, from results for a benzosuberone, that the electronic features of the azide can profoundly influence the distribution of azidation, diazo transfer, and ring contraction products. 

Bis-acceptor-substituted diazomethanes are most conveniently prepared by diazo group transfer to CH acidic compounds either with sulfonyl azides under basic conditions [949,950] or with l-alkyl-2-azidopyridinium salts [951] under neutral or acidic conditions [952-954]. Diazo group transfer with both types of reagents usually proceeds in high yield with malonic acid derivatives, 3-keto esters and amides, 1,3-diketones, or p, y-unsaturated carbonyl compounds [955,956]. Cyano-, sulfonyl, or nitrodiazomethanes, which can be unstable or sensitive to bases, can often only be prepared with 2-azidopyridinium salts, which accomplish diazo group transfer under neutral or slightly acidic reaction conditions. Other problematic substrates include amides of the type Z-CHj-CONHR and P-imino esters or the tautomeric 3-amino-2-propenoic esters, which upon diazo group transfer cyclize to 1,2,3-triazoles [957-959]. 

Diazocarbonyl compounds can be prepared on insoluble supports by diazo group transfer with sulfonyl azides or by diazotization of primary amines. Diazo group transfer from sulfonyl azides to 1,3-dicarbonyl compounds proceeds on cross-linked polystyrene as smoothly as in solution (Table 10.19). When 3-keto esters or amides are... 

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