Rhodium ketoesters

The use of rhodium(II) acetate in carbenoid chemistry has also been extended to promoting intramolecular C/H insertion reactions of ketocarbenoids 277,280,280 ,). From the a-diazo-P-ketoester 305, highly functionalized cyclopentane 306 could thus be constructed in acceptable yields by regiospecific insertion into an unactivated... 

The rhodium-catalyzed conversion of a-diazo-p-hydroxy carbonyl into P-dicarbonyl compounds (Table 23, Entries 6-8) in general seems to be preferable to the acid-catalyzed reaction because of higher yields and absence of side-reactions 37S,377). From a screening of 20 metal salts and complexes, Rh2(OAc)4, RhCl(PPh3)3, PdCl2 and CoCl2 emerged as the most efficient catalysts for the transformation of a-diazo-P-hydroxy esters into P-ketoesters 376). This reaction has become part of... 

Some neutral rhodium catalysts with chiral ligands, such as MCCPM 9 (see Scheme 33.3) [20c], Cy,Cy-oxoProNOP 15, and Cp,Cp-IndoNOP 18, demonstrate excellent enantioselectivities and reactivities in the hydrogenation of a-ketoesters and ketoamides indeed, they compare well with ruthenium-based catalysts (Table 33.2). Togni et al. have successfully used the Josiphos 47 ligand for the hydrogenation of ethyl acetoacetate [27], while the use of MannOPs has led to somewhat high enantioselectivities [18]. 

In recent years, much effort has been devoted to the enantioselective hydrogenation of yS-ketoesters, essentially using ruthenium-based catalysts. The aim of these reactions is to produce selectively enantiopure syn diols which are the key building blocks for the synthesis of inhibitors of HMG-coenzyme A reductase. Due to the availability of the AMPP ligands, and the reactivity of the rhodium catalysts based on them (notably the alkyl-substituted ones) towards ketonic sub-... 

Another approach to substituted 2,3-dihydro-l,4-dioxins 239 involves the reaction between 1,2-diols 238 and rhodium carbenoids generated from a-diazo-/ -ketoester 237 (Scheme 23) <1999H(51)1073>. This method complements the intramolecular reactions described earlier <1997JOC3902>. 

Dauben s group utilized the same retrosynthetic disconnections, but chose to add more functionality to the cycloaddition precursor. From a simple frawi-disubstituted cyclopentane, Dauben used an aldol reaction of a cyclopropylvinyl aldehyde to prepare the cycloaddition precursor. The diazo-substituted (3-ketoester was completed using a Roskamp-Padwa coupling followed by diazo-transfer. Addition of rhodium acetate to the diazo substituted p-ketoester 179 led to an excellent 86% yield of the correct diastereomer (Scheme 4.42). 

Examples are known where intermolecular carbenoid transformations between diazomalonates or certain diazoketones and appropriate olefins result in competition between formation of cyclopropane and products derived from allylic C—H insertion2-4. For example, catalytic decomposition of ethyl diazopyruvate in the presence of cyclohexene gave the 7-ejco-substituted norcarane 93 together with a small amount of the allylic C—H insertion product 94 (equation 95)142 143. In some cases, e.g. rhodium(II) decomposition of a-diazo-j8-ketoester 95, the major pathway afforded C—H insertion products 96 and 97 with only a small amount of the cyclopropane derivative 98. In contrast, however, when a copper catalyst was employed for this carbenoid transformation, cyclopropane 98 was the dominant product (equation 96)144. The choice of the rhodium(II) catalyst s ligand can also markedly influence the chemoselectivity between cyclopropanation and C—H... 

An efficient construction of the 1 / -methylcarbapenam nucleus (87) was established by Kume and co-workers utilizing acid- or rhodium (II)-catalyzed cyclization of the iodonium ylide derivatives (174), which were easily prepared from the corresponding jS-ketoester derivatives (173) with PIDA [133] (Scheme 41). 

Intramolecular Carbon-Hydrogen Insertion. The advantages of rhodium(II) catalysts for carbenoid transformations are nowhere more evident than with carbon-hydrogen insertion reactions. Exceptional regio- and diastereocontrol has been observed for Rh2(OAc)4 catalyzed transformations of a broad selection of diazoketones, a-diazo-p-ketoesters, a-diazo-P-keto-sulfones and -phosphonates which yield cyclopentanone derivatives in moderate to good yields (57-54). In contrast, poor yields and low regioselectivities characterize the corresponding copper catalyzed reactions. Applications of dirhodium(II) catalysts for C-H insertion reactions have even been extended to the synthesis of y-lactones (55), 3(2//)-furanones (56,57), P-laetones (58), and P-lactams (59,60). 

A considerable number of pyrroles 30 with alkyl, alkenyl, or aryl substituents were synthesized by spontaneous cyclization of the enyne precursors 31 (when R = H, Ph, CH2OTHP), or upon treatment of 31 with the catalytic system PdCV KCl (when = H), or alternatively, by treatment of 31 with CuCb (when R H) <03JOC7853>. Treatment of y-ketoalkynes with amines in the presence of catalytic amounts of platinum dichloride constitutes a new route to 1,2,3,5-substituted pyrroles <03AG(E)2681>. An intramolecular rhodium(lI)-catalyzed N-H insertion reaction of 5-amino-7,Y-difluoro-a-diazo-P-ketoesters has been used for the synthesis of a series of 3-fluoropyrroles <03OL745>. 

An approach to imidazolones started from polymer-bound a-diazo-p-ketoester 33, which was transformed to intermediate 35 by treatment with urea 34 in the presence of a rhodium carboxylate catalyst (Scheme 10) [76]. Treatment of the resin-bound insertion product 35 with 10% TFA at room temperature afforded the resin-bound imidazolone 36 within 1 h. The polymer-bound imidazolone could then be cleaved by transesterification to give esters 37 or by a diversity building amidation reaction to provide amides 38. After preparative TLC, the products were obtained in yields of 19-84% (14 examples). 

Optimization of the phosphine ligands has led to high enantioselectivity in the hydrogenation of a-acetami-doacrylic esters with rhodium catalysts and of /3-ketoesters... 

The diphosphine on the left was used with a rhodium catalyst and hydrogen to reduce the dehydroamino acid derivatives. The same reduction could also be carried out with sugar-derived phosphinites, the product being obtained in 97-99% ee.84 The diphosphine on the right, or better its counterpart, in which isopropyl has replaced methyl, was used with a ruthenium catalyst and hydrogen or 2-propanol in the reductions of /3-ketoesters. 1-Acetyl-naphthalene was reduced with a ruthenium catalyst using the ligand on the left with 2-propanol (10.38) in more 99% yield and 97% ee. 

An annelation reaction of pyrroles leading to fused pyrroles 68 involved a rhodium-catalyzed decomposition of a-diazo-p-ketoesters <04T1505>. 

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