Rhodium mandelate

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. 

The choice of transition-metal catalysts can play an important role in determining reaction pathways as shown in the model studies toward the synthesis of harringtonolide. The epimeric C-H insertion products 80 are obtained in 75% and 40-50% yield, respectively, with Rh2(tpa)4 and rhodium mandelate. In contrast, bis(A -t-butylsalicyl-aldiminato) copper(II) generates the very labile cycloheptatriene 82 (50% yield), which is converted to the more stable isomer 83 upon treatment with l,8-diazabicyclo[5.4.0]undec-7-ene (DBU). ... 

A solution of 76 g (S)-( + )-mandelic acid in 400 ml methanol and 5 ml acetic acid was reduced over 5% rhodium-on-alumina under 100 psig for 10 h. The catalyst was removed by filtration through Celite, and the methanol was removed in a rotary evaporator. The white, solid residue was dissolved in I 1 of hot diethyl ether and filtered while hot. After reduction of the volume to 400 ml, 250 ml cyclohexane was added. The remainder of the ether was removed, and the cyclohexane solution was stored for several hours in a refrigerator. The white crystals were filtered and dried in vacuo at 40 C the yield of (S)-( + )-hexahydromandelic acid was 71%. 

The intramolecular reaction between diazo ketones and benzenes is an effective way to generate a range of bicyclic systems.7 The earlier copper-based catalysts have largely been superseded by rho-dium(ll) salts. Unlike the case in the intermolecular reactions, rhodium(ll) acetate is the catalyst that has been most commonly used. Studies by McKervey,133 136 however, indicated that rhodium(II) mandelate, which would be expected to generate a slightly more electrophilic carbenoid than rhodium(ll) acetate, often gave improved yields. 

In contrast to benzyl alcohol, a-substituted benzyl alcohols, benzyl ethers, and aryl ketones may be successfully hydrogenated over rhodium and rhodium-platinum catalysts to give the corresponding saturated products in high yields, as shown in eqs. 11.38-11.41. In the hydrogenations shown in eqs. 11.38 and 11.39, no racemization took place D-mandelic acid afforded D-hexahydromandelic acid in 94% yield and meso- and dl-2,3-dicyclohexyl-2,3-butanediol were obtained in 93 and 94% yields, respectively, by hydrogenation of the corresponding diphenyl compounds. 

Rhodium(II) mandelate-catalyzed decomposition of diazoester 257 involves intermolecular addition of the intermediate carbenoid to the triple bond to afford the carbenoid intermediate 258. The latter again reacts... 

In 1990, Brunner [5], McKervey [6], and Ikegami [7] and their respective coworkers independently introduced chiral rhodium(II) carboxylates for asymmetric diazocarbonyl transformations. At that time the only chiral rhodium(II) carboxylates known were those derived from (R) and (S)-mandelic acid which had been prepared by Cotton and co-workers [8] for structural and chiroptical studies. Enantiopure carboxylates (1) on a dirhodium core (substituents varied from H, Me, and Ph to OH, NHAc, and CFj) were assessed by Brunner [5] for enantioselective cyclopropanation of alkenes with ethyl diazoacetate. McKervey... 

In another example, rhodium carboxylates, chirally modified with mandelate or proline-derived compounds, were used in intramolecular cyclopropanation of unsaturated diazo ketones (e.g., 4) to give bicyclo[3.1.0]hexanonc products in 97% yield with 12% ee7f>. 

A similar strategy starts with an intramolecular alkyne insertion of an a-diazo ketone. Thus, rhodium(II)-catalyzed reaction of 2-(6,8-nonadien-1-ynyl)-or-diazoacetophenones 112 at 0°C in dichloromethanc affords cyclopen%]azulenones 115 in 50-58% yield879. Due to the enhanced solubility, rhodium(II) mandelate has proved to be superior to the acetate. 

O-Methylation of mandelic acid leads to the enantiomers of a-methoxy-M-phcnylacetic acid (10), which are also commercially available. This methylation without noticeable racemiza-tion was achieved with diazomethane, using aluminum tris(tert-butanoate) as catalyst8. Alternatively, dimethyl sulfate/ sodium hydroxide has been used15, as described in detail for the racemic compound10. The acids have been used for the construction of quite sophisticated chiral auxiliaries, e.g., a rhodium cyclopentadienyl complex (Section 7.2.2.), and for chiral dienes applied in both normal and inverse Diels-Alder reactions (Section D.1.6.1.1.1.). Chiral dienes, e.g., 1, for normal Diels -Alder reactions were prepared by pyrolysis (460 C) of a tricyclic precursor cstcrified with (S)-O-methylmandeloyl chloride or with the free acid and dicyclohexylcarbodiimide/4-dimethylaminopyridine11 -13. 

Reduction of benzene derivatives carrying oxygen or nitrogen functions in ben-zylic positions is complicated by the easy hydrogenolysis of such groups, particularly over palladium catalysts. Preferential reduction of the benzene ring in these compounds is best achieved with ruthenium or rhodium catalysts, which can be used under mild conditions. For example, mandelic acid is readily converted into the cyclohexyl derivative 29 over rhodium-alumina, whereas with palladium, hydrogenolysis to phenylacetic acid is the main reaction (7.18)... 

The [3+4] annulation approach to the hydroazulenes is achieved with high asymmetric induction (greater than 90% de) by using (/ )-pantolactone as a chiral auxiliary (Table 7). The nature of the catalyst has a considerable effect on the level of asymmetric induction. A sterically crowded catalyst, such as rhodium pivalate, results in much lower diastereoselectivity than rhodium(II) acetate or rho-dium(II) hexanoate. Consequently, even though the enantiomers of rhodium(II) mandelate exhibit double stereodifferentiation with the (/ )-pantolactone auxiliary (entries 5,6), both catalysts are bulky and result iinferior asynunetric induction compared to that obtained with an uncrowded achiral catalyst (entries 1-3). 

More highly substituted aromatics have also been studied in the course of natural product synthesis. For example, rhodium(II) mandelate-catalyzed cyclization of diazoketone 41 produces the ring expanded product 42, which on hydrogenations furnishes the tricyclic lactone 43. ... 

Hydroxy-acids.—A full report has been published on the preparation of chiral a-hydroxy-acids in optical yields of up to 98% from a, -unsaturated acid chlorides by sequential N-acylation of an optically pure a-amino-acid, bromo-lactonization, dehydrobromination, and hydrolysis " (2, 23). Enolates of /-menthyl mandelate can be alkylated in ca. 50% yield with typical enantiomeric excesses of less than 40%, An elegant use of the prophos ligands in rhodium(i)-catalysed asymmetric hydrogenation (see 3,322) is in the preparation of all twelve isomers of chiral methyl chiral lactic acid the method is illustrated for one isomer in Scheme 5. The other isomers are obtained by changing the order of introduction of H, D, and T and the chirality (i.e. R or S) of the prophos ligand. 

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