Chiral copper complex

The catalytic asymmetric cyclopropanation of an alkene, a reaction which was studied as early as 1966 by Nozaki and Noyori,63 is used in a commercial synthesis of ethyl (+)-(lS)-2,2-dimethylcyclo-propanecarboxylate (18) by the Sumitomo Chemical Company (see Scheme 5).64 In Aratani s Sumitomo Process, ethyl diazoacetate is decomposed in the presence of isobutene (16) and a catalytic amount of the dimeric chiral copper complex 17. Compound 18, produced in 92 % ee, is a key intermediate in Merck s commercial synthesis of cilastatin (19). The latter compound is a reversible... 

The selectivity of the aldol addition can be rationalized in terms of a Zimmer -man-Traxler transition-state model with TS-2-50 having the lowest energy and leading to dr-values of >95 5 for 2-51 and 2-52 [18]. The chiral copper complex, responsible for the enantioselective 1,4-addition of the dialkyl zinc derivative in the first anionic transformation, seems to have no influence on the aldol addition. To facilitate the ee-determination of the domino Michael/aldol products and to show that 2-51 and 2-52 are l -epimers, the mixture of the two compounds was oxidized to the corresponding diketones 2-53. 

Recent Advance of Asymmetric Synthesis of (1R)-tr sms-Chrysanthemic Acid with a New Chiral Copper Complex... 

Asymmetric synthesis of 2,5-dimethyl-2,4-hexadiene (28) and /-menthyl diazoacetate (29) with chiral copper complexes (30) was successfully conducted by Aratani et al. [13] to afford the (1 A)-chrysanthem ic acid /-menthyl ester (31) in high optical and chemical yield. Since this finding, a lot of chiral copper complexes have been reported and applied to the asymmetric synthesis of (IR)-chrysanthemate. However, these copper complexes required more than 1 mol% of the catalyst and the cis/trans ratio still remains unsatisfactory. Moreover, /-menthyl ester was crucial for the high enantioselectivity. Given an industrial production of... 

Cyclopropanation reactions can be promoted using copper or rhodium catalysts or indeed systems based on other metals. As early as 1965 Nozaki showed that chiral copper complexes could promote asymmetric addition of a carbenoid species (derived from a diazoester) to an alkene. This pioneering study was embroidered by Aratani and co-workers who showed a highly enantioselective process could be obtained by modifying the chiral copper... 

The use of chiral copper complexes in asymmetric synthesis was inaugurated in 1966 when the first homogeneous asymmetric metal-catalyzed reaction was reported a copper catalyzed cyclopropanation (2). At the end of 1999, more than 25 distinct reactions were reported wherein the use of a chiral copper complex had induced an enantioselective transformation. The field grew quickly and the best is most likely yet to come. 

This chapter will cover the literature up to December 1999. We have attempted to include all publications involving the use of chiral copper complexes as catalysts... 

Since the first experiments with chiral copper complexes reported by Nozaki [650] and Aratani [1027] many different catalysts have been examined, both for intermolecular and intramolecular cyclopropanations (for a review, see [1369]). Syntheses of natural products [955,1370] and drugs [1371] using asymmetric cyclopropanation with chiral electrophilic carbene complexes have been reported. A selection of useful catalysts is given in Figure 4.20 (see also Experimental Procedure 4.1.1). 

In 1995, Backvall and van Koten reported the first example of a catalytic, enantioselective Sn2 substitution of a primary allylic acetate in the presence of a chiral copper complex [28, 29]. 

In 2004, Kobayashi et al. introduced enecarbamates as nucleophiles to asymmetric catalysis [48], The addition of enecarbamates to imines in the presence of a chiral copper complex provides access to P-amino imines which can be hydrolyzed to the corresponding p-amino carbonyl compounds [49],... 

Much effort this year has been expended on chrysanthemic acid syntheses. Aratani et al. have extended earlier work on asymmetric synthesis (Vol. 6, p. 21) by decomposing various alkyl diazoacetates in 2,5-dimethylhexa-2,4-diene in the presence of chiral copper complexes to yield up to 92% of rrans-chrysanthemic acid in 88% dextrorotatory enantiomeric excess. Mitra has used ozonolysis of (+)-a-pinene to obtain, stereospecifically, the bromo-ketone (104) which undergoes Favorskii rearrangement to yield the anticipated ester (105) from which (+)-trans-chrysanthemic acid is readily obtained a second paper reports another route from (+)-car-3-ene initially to methyl (—)-c/s-chrysanthemate or to (—)-dihydro-chrysanthemolactone (106), both of which are convertible into (+)-rra s-chrysan-... 

Ligand exchange has proved to be very successful in the separation of several enantiomers. Davankov and Rogozhin (41) used chiral copper complexes bonded to silica. The enantiomeric separation is based essentially on the formation of diastereomeric mixed complexes with different thermodynamic stabilities. It is generally accepted that chiral discrimination proceeds via the substitution of one ligand in the coordination sphere of the metal ion. Ligand exchange technique is especially effective for the enantiomeric resolution of aminoacids, aminoacids derivatives, and hydroxy acids (42). 

Feringa reported an enantioselective allylic oxidation of cyclohexene to optically active 2-cyclohexenyl propionate 25 by using a chiral copper complex prepared from Cu(OAc)2 and (S)-proline, as chiral catalyst (Scheme 9.14) [32], In the absence of additives, a negative NLE was observed, whereas in the presence of a catalytic amount of anthraquinone, a positive NLE (asymmetric amplification) was observed. Moreover, higher enantioselectiv-ity was attained when enantiopure (S)-proline was used. However, the role of the additive remains elusive. 

The asymmetric synthesis of the spiroazepinone skeleton present in certain marine toxins was reported by Murai et al. A Diels-Alder reaction was key to the synthetic approach. For example, 70 was accessed in 82% yield (96% ee 99 1 exolendo ratio) from 68 and the diene 69 with X = AsF6 in the chiral copper complex (Equation 9) <2002SL403>. 

Attempts to aziridinate alkenes with iron catalysts in an asymmetric manner have met with only limited success to date [101], In an early report on the use of various chiral metal salen complexes, it was found that only the Mn complex catalyzed the reaction whereas all other metals investigated (Cr, Fe, Co, Ni etc.) gave only unwanted hydrolysis of the iminoiodinane to the corresponding sulfonamide and iodoben-zene [102], Later, Jacobsen and coworkers and Evans et al. achieved good results with chiral copper complexes [103]. 

Drury III, L. Ryzhkov, A. E. Taggi, T. Lectka, J. Am. Chem. Soc. 2002, 124, 67 for an example using chiral copper complexes derived either from xylyl-BINAP or chiral diamines, see i) S. Kobayashi,... 

Details of the preparation of methyl (-)-cis-chrysanthemate from (+)-car-3-ene have appeared (Vol. 5, p. 15 is misleading).159 Both ( )-cis- and (+)-trans-chrysanthemic acids are again reported from (+)-car-3-ene via ozonolysis 160 this work is very similar to that reported (Vol. 5, p. 15) by Sukh Dev and illustrates the lamentable delay from receipt to publication in some journals. The decomposition of ethyl diazoacetate in 2,5-dimethylhexa-2,4-diene in the presence of the chiral copper complex (72) leads to cis- and frvms-chrysanthemic acids in 60—70% optical yield the degree of asymmetric induction is dependent upon the steric bulk of R1 and R2 in (72).161 cis-Chrysanthemic acid has also been prepared from 3,3-dimethylcyclopropene, isoprene, and 2-methylpropenylmagnesium bromide followed by treatment with carbon dioxide.162... 

Asymmetric allylic oxidation of alkenes using peresters is possible when the ligand L of the Cu(III) intermediate is chiral. Copper complexes of chiral bis(pyri-dine)- and bis(oxazoline)-type ligands have been used with fert-butyl perbenzoate to obtain optically active allylic benzoates. 

Another Mukaiyama-type dienolate addition was used in the synthesis of the C o-C]6 fragment 125. This time, enantioselective addition to benzyloxyacetalde-hyde, catalyzed by the chiral copper complex 126, gave 127 with >99% ee (Scheme 9-40). Subsequent manipulations, including an rmh-selective reduction, provided the C o-C 6 fragment 125. 

Bolm and coworkers developed a chiral copper complex from an oxazoline and salicylic acid for the Baeyer-Villiger oxidation employing oxygen and an aldehyde for the oxidant, and high ee was obtained with a 4-nitro-6-(f-butyl)salicylic acid derivative (equation Salicylaldehyde itself can be used as a catalyst ligand for the... 

The oldest syntheses of chrysanthemates are those starting from 2,5-dimethyl-2,4-hexadiene (238). There have been more papers on the use of rhodium or antimony to catalyze the addition of diazoacetate and chiral copper complexes to create asymmetry during the addition (see Vol. 4, p. 482, Refs. 219-222). The problem with this route is to avoid the use of diazo compounds. An old synthesis of Corey and Jautelat used the ylide addition of a sulfurane to a suitable precursor (in this case a C3 unit was added to methyl 5-methyl-2,4-hexadienoate, 239), and a recent paper gives details about the addition of ethyl dimethylsulfuranylideneacetate to 2,5-dimethyl-4-hexen-3-one (240). This led exclusively to the tran -isomer 241, from which ethyl trans-chrysanthemate (185, R = Et) was made. Other ylide additions are mentioned below. 

Kobayashi and coworkers pioneered the use of enamides or enecarbamates as nucleophiles in enantioselective reactions with either glyoxylates or glyoxylate derived imines catalyzed by chiral copper complexes [65]. The reaction using enamides or enecarbamates as nucleophilic components, namely, the aza ene reaction, with imines provides P amino imines that can be readily transformed into... 

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