Chiral rhodium carboxylate

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). 

Activation of a C-H bond requires a metallocarbenoid of suitable reactivity and electrophilicity.105-115 Most of the early literature on metal-catalyzed carbenoid reactions used copper complexes as the catalysts.46,116 Several chiral complexes with Ce-symmetric ligands have been explored for selective C-H insertion in the last decade.117-127 However, only a few isolated cases have been reported of impressive asymmetric induction in copper-catalyzed C-H insertion reactions.118,124 The scope of carbenoid-induced C-H insertion expanded greatly with the introduction of dirhodium complexes as catalysts. Building on initial findings from achiral catalysts, four types of chiral rhodium(n) complexes have been developed for enantioselective catalysis in C-H activation reactions. They are rhodium(n) carboxylates, rhodium(n) carboxamidates, rhodium(n) phosphates, and < // < -metallated arylphosphine rhodium(n) complexes. 

Hashimoto and co-workers (55) reported that generation of ylide 152 from aryl ester 151 in the presence of a chiral rhodium complex Rh2(S-PTTL)4, a chiral phthalimide substimted carboxylate, followed by cycloaddition with DMAD, led to the formation of adduct 153 in good yield and in 74% enantiomeric excess (ee). 

Intramolecular Cyclopropanation with Chiral Rhodium(II) 2-Pyrroli-done-5-carboxylates. Applications of chiral copper and cobalt catalysts, including... 

Chiral rhodium(II) oxazolidinones 5-7 were not as effective as Rh2(MEPY)4 for enantioseleetive intramolecular cyclopropanation, even though the sterie bulk of their chiral ligand attachments (COOMe versus /-Pr or C Ph) are similar. Significantly lower yields and lower enantiomeric excesses resulted from the decomposition of 11 catalyzed by either Rh2(4S-IPOX)4, Rh2(4S-BNOX)4, or Rh2(4R-BNOX)4 (Table 3). In addition, butenolide 12, the product from carbenium ion addition of the rhodium-stabilized carbenoid to the double bond followed by 1,2-hydrogen migration and dissociation of RI12L4 (Scheme II), was of considerable importance in reactions performed with 5-7 but was only a minor constituent ( 1%) from reactions catalyzed by Rh2(5S-MEPY)4. This difference can be attributed to the ability of the carboxylate substituents to stabilize the earboeation form of the intermediate metal carbene. 

Chiral rhodium(II) carboxamides are exceptional catalysts for highly enantio-selective intermolecular cyclopropenation reactions (50). With ethyl diazoacetate and a series of alkynes, use of dirhodium(II) tetrakis[methyl 2-pyrrolidone-5-(R)-carboxylate], Rh2(5R-MEPY)4, in catalytic amounts ( 1.0 mol %) results in the formation of ethyl eyelopropene-3-earboxylates (eq 4) with enantiomeric excesses... 

This collection begins with a series of three procedures illustrating important new methods for preparation of enantiomerically pure substances via asymmetric catalysis. The preparation of 3-[(1S)-1,2-DIHYDROXYETHYL]-1,5-DIHYDRO-3H-2.4-BENZODIOXEPINE describes, in detail, the use of dihydroquinidine 9-0-(9 -phenanthryl) ether as a chiral ligand in the asymmetric dihydroxylation reaction which is broadly applicable for the preparation of chiral dlols from monosubstituted olefins. The product, an acetal of (S)-glyceralcfehyde, is itself a potentially valuable synthetic intermediate. The assembly of a chiral rhodium catalyst from methyl 2-pyrrolidone 5(R)-carboxylate and its use in the intramolecular asymmetric cyclopropanation of an allyl diazoacetate is illustrated in the preparation of (1R.5S)-()-6,6-DIMETHYL-3-OXABICYCLO[3.1. OJHEXAN-2-ONE. Another important general method for asymmetric synthesis involves the desymmetrization of bifunctional meso compounds as is described for the enantioselective enzymatic hydrolysis of cis-3,5-diacetoxycyclopentene to (1R,4S)-(+)-4-HYDROXY-2-CYCLOPENTENYL ACETATE. This intermediate is especially valuable as a precursor of both antipodes (4R) (+)- and (4S)-(-)-tert-BUTYLDIMETHYLSILOXY-2-CYCLOPENTEN-1-ONE, important intermediates in the synthesis of enantiomerically pure prostanoid derivatives and other classes of natural substances, whose preparation is detailed in accompanying procedures. 

The chiral diazo ester 29 was cyclized with four commonly used rhodium carboxylate catalysts (Table 2). It was found as before that rhodium pivalate... 

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... 

Early efforts in enantioselective intramolecular cyclopropanation using chiral rhodium catalysts focused on the use of carboxylates as hgands and although these catalysts were highly efficient kinetically in diazo decomposition, the enantiomeric excesses in the products were very hmited. For example, Rh2(S-mande-late)4, (2) in Fig. 3, achieved an ee of 12% in the cychzation in Eq. (18) [40]. 

The most commonly used chiral catalysts are the amino acid based rhodium (II) carboxylates of Hashimoto and Ikegami, and McKervey, and the chiral rhodium (II) carboxamidates of Doyle. The amino acid based catalysts exhibit their highest levels of stereocontrol with non-terminal diazo ketones of structure RCOCN2R1 where Rj H, while the rhodium (II) carboxamidates display high enantiocontrol with diazoacetates. 

Applications of the chiral rhodium (II) carboxylates to the cycHzation of a-di-azo-p-ketosulfones, Eq. (35), have shown that while they are catalytically active at or below room temperature, they provide only low enantiomeric excesses [6]. 

Although the first catalysts were copper-based, the insertion of metal-associated carbenes into carbon-hydrogen bonds has undergone a renaissance with the advent of rhodium(II) carboxylate catalysts [56]. Metal-catalyzed enan-tioselective C-H insertions of carbenes have not been studied in great detail. Most of the efficient enantioselective versions of this reaction involve chiral rhodium complexes and until recently, the use of chiral catalysts derived from metals other than copper and rhodium for the asymmetric C-H insertion of metal-associated carbenes are still unexplored. 

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>. 

Rhodium carboxylates. 13, 266-269 15, 278-280 16, 289-292 17, 298-302 a-Alkoxy esters. Rhodium carbenoids derived from a-diazo esters undergo O-H bond insertion in the reaction with alcohols or phenols. Low to moderate asymmetric induction from chiral esters is observed. ... 

Asymmetric cyclopropanation. The ability to effect ligand exchange between rhodium(II) acetate and various amides has lead to a search for novel, chiral rhodium(II) catalysts for enantioselective cyclopropanation with diazo carbonyl compounds. The most promising to date are prepared from methyl (S)- or (R)-pyroglutamate (1), [dirhodium(ll) tetrakis(methyl 2-pyrrolidone-5-carboxylate)]. Thus these complexes, Rh2[(S)- or (R)-l]4, effect intramolecular cyclopropanation of allylic diazoacetates (2) to give the cyclo-propanated y-lactones 3 in 65 S 94% ee (equation 1). In general, the enantioselectivity is higher in cyclopropanation of (Z)-alkenes. 

Diazo Compounds Decomposition with Chiral Rhodium Catalysts. The first chiral rhodium catalyzed asymmetric cyclopropanation was reported in 1989 (75). Structures of the catalysts were based on the framework of dirhodium(II) tetrakis(carboxylate) 1 with the carboxylate ligands replaced with... 

The Af-[bis(trimethylsilyl)methyl] moiety is also useful in intramolecular C-H insertion reactions catalyzed by chiral rhodium(n) carboxylates and carboxamidates (eq 9). Overall good regio- and chemoselectivity was observed, favoring the formation of y-lactam products. However, these selectivities were also found to be dependent on the type of chiral rhodium(II) catalysts. The degree of asymmetric induction at the newly formed C-4 stereocenter was determined only for y-lactam products. 

The chiral diazo ester 29 was cyclized with four commonly used rhodium carboxylate catalysts (Table 2). It was found as before that rhodium pivalate (17) (entry 4) was most efficient for forming the cyclopentanes and that rhodium trifluoroacetate (entry 1) was best for forming the alkenes (18). For the pivalate, both the yield of the cyclization and the diastereoselectivity improved at lower temperature (entry 5). 

The enantioselective synthesis of axially chiral hydroxy carboxylic acid derivatives 42 was accomplished by the cationic rhodium(I)/BINAP complex-catalyzed [2 + 2 + 2] cycloaddition of a,w-diynes 40 with 2-alkoxynaphthalene-derived alkynyl esters 41 with high yields and ee values (Scheme 9.15) [17],... 

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