Aratani catalyst

This report initiated activities that resulted in the discovery of 183, the Aratani catalyst. It is now applied in the enantioselective synthesis of ethyl-2,3-dimethoxycyclopropanecarboxylate, the key intermediate in the preparation of cilastatin (Scheme 5-57).94... 

Dauben et al. (15) applied the Aratani catalyst to intramolecular cyclopropanation reactions. Diazoketoesters were poor substrates for this catalyst, conferring little asymmetric induction to the product, Eq. 10. Better results were found using diazo ketones (34). The product cyclopropane was formed in selectivities as high as 77% ee (35a, n = 1). A reversal in the absolute sense of induction was noted upon cyclopropanation of the homologous substrate 34b (n = 2) using this catalyst, Eq. 11. Dauben notes that the reaction does not proceed at low temperature, as expected for a Cu(II) precatalyst, but that thermal activation of the catalyst results in lower selectivities (44% ee, 80°C, PhH, 35a, n = 1). Complex ent-11 may be activated at ambient temperature by reduction with 0.25 equiv (to catalyst) DIBAL-H, affording the optimized selectivities in this reaction. The active species in these reactions is presumably the aluminum alkoxide (33). Dauben cautions that this catalyst slowly decomposes under these conditions. 

In intramolecular cyclopropanation, Doyle s catalysts (159) show outstanding capabilities for enantiocontrol in the cyclization of allyl and homoallyl diazoesters to bicyclic y-and <5-lactones, respectively (equations 137 and 138)198 205. The data also reveal that intramolecular cyclopropanation of Z-alkenes is generally more enantioselective than that of E-alkenes in bicyclic y-lactone formation198. Both Rh(II)-MEPY enantiomers are available and, through their use, enantiomeric products are accessible. In a few selected cases, the Pfaltz catalyst 156 also results in high-level enandoselectivity in intramolecular cyclopropanation (equation 139)194. On the other hand, the Aratani catalyst is less effective than the Doyle catalyst (159) or Pfaltz catalyst (156) in asymmetric intramolecular cyclo-propanations201. In addition, the bis-oxazoline-derived copper catalyst 157b shows lower enantioselectivity in the intramolecular cyclopropanation of allyl diazomalonate (equation 140)206. 

When the carbinol substituents (R) were the bulky 5-ler -butyl-2-(n-octyloxy)phenyl group, optimum enantioselectivities were achieved with the catalytic use of the corresponding Cu(II) complex (2) in both enantiomeric forms. Specific applications of the Aratani catalysts have included the synthesis of chrysanthemic acid esters (Eq. 5.6) and a precursor to permethrinic acid, both potent units of pyrethroid insecticides, and for the commercial preparation of ethyl (S)-2,2-dimethylcyclopropanecarboxylate (Eq. 5.2), which is used for constructing cilastatin. Several other uses of these catalysts and their derivatives for cyclopropanation reactions have been reported albeit, in most cases, with only moderate enantioselectivities [26-29],... 

TABLE 5.2. Diastereoselective Cyclopropanation of Alkenes with /-menthyl Diazoacetate (/-MDA) Catalyzed by the Aratani Catalyst 2 (A = CH3) [5] ... 

With modified Aratani catalysts (2, R = Ph and A = CH2Ph), Reissig observed moderate enantioselectivities (30-40% ee for the trans cyclopropane isomer) for reactions between trimethylsilyl vinyl ethers and methyl diazoacetate [26], but vinyl ethers are the most reactive olefins towards cyclopropanation and also the least selective [30,31]. Other chiral Schiff bases have been examined for enantio-selection by using the in situ method for catalyst preparation that was pioneered by Brunner, but enantioselectivities were generally low [32]. 

As with the Aratani catalysts, enantioselectivities for cyclopropane formation with 4 and 5 are responsive to the steric bulk of the diazo ester, are higher for the trans isomer than for the cis form, and are influenced by the absolute configuration of a chiral diazo ester (d- and 1-menthyl diazoacetate), although not to the same degree as reported for 2 in Tables 5.1 and 5.2. 1,3-Butadiene and 4-methyl- 1,3-pentadiene, whose higher reactivities for metal carbene addition result in higher product yields than do terminal alkenes, form cyclopropane products with 97% ee in reactions with d-men thy 1 diazoacetate (Eq. 5.8). Regiocontrol is complete, but diastereocontrol (trans cis selectivity) is only moderate. 

Cu catalysts for metal carbene transformations are active as Cu(I) complexes and not as Cu(II). Although in the distant past there was some disagreement with this proposition, bis-oxazoline, semicorrin, and even the Aratani catalysts are active only when Cu is in its +1 oxidation state [6,34,39,40], The chiral Cu(I) catalysts have been produced from the correspond-... 

Intramolecular cyclopropanation reactions of alkenyl diazo carbonyl compounds are among the most useful catalytic metal carbene transformations, and the diversity of their applications for organic syntheses is substantial [7,10,24,84]. Their catalytic asymmetric reactions, however, have only recently been reported. An early application of the Aratani catalyst 2 (A = PhCH2) to... 

Figure 2. Representative Applications of the Aratani Catalysts for Intermoleeu-lar Cyelopropanation...

Enantioselection can be controlled much more effectively with the appropriate chiral copper, rhodium, and cobalt catalyst.The first major breakthrough in this area was achieved by copper complexes with chiral salicylaldimine ligands that were obtained from salicylaldehyde and amino alcohols derived from a-amino acids (Aratani catalysts ). With bulky diazo esters, both the diastereoselectivity (transicis ratio) and the enantioselectivity can be increased. These facts have been used, inter alia, for the diastereo- and enantioselective synthesis of chrysan-themic and permethrinic acids which are components of pyrethroid insecticides (Table 10). 0-Trimethylsilyl enols can also be cyclopropanated enantioselectively with alkyl diazoacetates in the presence of Aratani catalysts. In detailed studies,the influence of various parameters, such as metal ligands in the catalyst, catalyst concentration, solvent, and alkene structure, on the enantioselectivity has been recorded. Enantiomeric excesses of up to 88% were obtained with catalyst 7 (R = Bz = 2-MeOCgH4). 

Table 10. Enantioselective Cyclopropanation with Aratani Catalysts...

In rhodium(II)-catalyzed intermolecular cyclopropanation reactions, chiral dirhodium(II) carb-oximidates provide only limited enantiocontrol. " Tetrakis(5-methoxycarbonyl-2-pyrrolidonato)dirhodium [18, Rh2(MEPY)J, in both enantiomeric forms of the carboxamide ligands, produces the highest enantioselectivities. As can be seen for the cyclopropanation of styrene with diazoacetates, a high level of double diastereoselectivity results from the combination of this chiral catalyst with /- or d-menthyl diazoacetate, but not with diazoacetates bearing other chiral residues.In terms of trans/cis selectivity and enantioselectivity for styrene giving 19 this catalyst is comparable to the Aratani catalysts, but they cannot match the high enantiocontrol of the chiral copper catalysts developed by Pfaltz, Masamune, and Evans vide supra). 

Bicyclo[3.1.0]hexan-2-one and bicyclo[4.1.0]heptan-2-one were obtained from the corresponding unsaturated diazo ketones with 75 and 95% ee, respectively, when the chiral bis(semicorrinato)copper(II) catalyst developed by Pfaltz (see Section 1.2.1.2.4.2.6.3.2.) was used, ° whereas Aratani catalysts, in general, provided low to moderate enantioselectivities for these transformations. " Modest ee-values (35-40%) were also observed when the Pfaltz catalyst was applied to unsaturated /1-keto-a-diazo esters such as methyl 2-diazo-3-oxohept-6-enoate and -oct-7-enoate. ° ... 

TABLE 5.1. Cyclopropanatioii of 2.5-Dimethyl-2,4-hexadiene with Diazo Esters (Eq. 5.6) Catalyzed by the Aratani Catalysts [4]"... 

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