Asymmetric syntheses, catalyzed

In the second chapter, Hans Wynberg describes one facet—namely asymmetric catalysis—of the currently very active field of asymmetric synthesis. Wynberg and his co-workers have devised efficient asymmetric syntheses catalyzed by cinchona alkaloids. Several of these reactions are reviewed and rationalized by means of mechanistic models. 

Coordination complexes asymmetric syntheses, catalyzed by. 502-5133 bonding, 391-433 conductivity of, 389 electronic spectra of, 433-459 of inner transition metals, 608-613... 

The studies of asymmetric synthesis have a rather long history in which the relation to the asymmetric character of living organisms has been the subject of interest (i). Among these studies, asymmetric syntheses catalyzed by synthetic polypeptide are considered most closely related, in a sense, to the stereospecific enzymatic reaction. 

Asymmetric Synthesis Catalyzed by Chiral Ferrocenylphosphine Complex... 

J. Luis Olivares-Romero was born in Mexico City (1978). He received a B.Sc. degree in pharmaceutical biological chemistry from FES-Zaragoza, UNAM (Mexico, 2003). He is currently working toward the obtention of a Ph.D. under the supervision of Professor Eusebio Juaristi at CINVESTAV (Mexico). His research interests focus on the asymmetric synthesis catalyzed by novel chiral Lewis acids. 

As one of the enzymic reactions, asymmetric synthesis catalyzed by cyclodextrins has been studied in the past, but gave all the products in a low optical yield. We have already found a strong chiral induction for the chlorination of methacrylic acid in the crystalline cyclodextrin complexes. 100 % enantiomeric excess (e.e.) of (-)-2,3-dichloro-2-methyl-propionic acid and 88 % e.e. of its enantiomer were isolated in a- and 3-cyclodextrins, respectively. This paper describes asymmetric addition of gaseous halogens and hydrogen halides in the crystalline complexes comprising trans-cinnamic acid as a reactant and a- or 3-cyclodextrin as chiral matrix. Asymmetric bromination of menthyl cinnamate and of salts from the acid and several chiral amines have been reported, but gave low chiral inductions up to 2 16 % e.e.. 

E. Negishi, Acc. Chem. Res., 1982, 15, 340-348. Palladium- or Nickel-Catalyzed Cross-Coupling. A New Selective Method for Carbon-Carbon Bond Formation. T. Hayashi and M. Kumada, Acc. Chem. Res., 1982, 15, 395-401. Asymmetric Synthesis Catalyzed by Transition-Metal Complexes with Functionalized Chiral Ferro-cenylphosphine Ligands. 

Hayashi T, Hayashizaki K, Kiyoi T, Ito Y. Asymmetric synthesis catalyzed by chiral ferrocenylphosphine-transition-metal complexes. 6. Practical asymmetric synthesis of 1,1 -binaphthyls via asymmetric cross-coupling with a chiral [(alkoxyalkyl)ferrocenyl] monophosphine/nickel catalyst. J. Am. Chem. Soc. 1988 110(24) 8153-8156. 

Hayashi T, Mise T, Fukushima M, Kagotani M, Nagashima N, Hamada Y, Matsumoto A, Kawakami S, Konishi M, Yamamoto K, KumadaM (1980) Asymmetric synthesis catalyzed by chiral ferrocenylphosphine-transition metal complexes. I. Preparation of chiral ferrocenylphosphines. Bull Chem Soc Jpn 53 1138-1151... 

Figure 26 Racemic resolution and asymmetric synthesis catalyzed by a stereospecific amidase from Rhodococcus rhodochrous IFO 15564.

Ru(OCOCH2)2[(3)-BINAP]-(106)-catalyzed reduction of precursor olefin (107). The asymmetric synthesis of analgesic tetrahydroisoquinolines makes use... 

An asymmetric synthesis of estrone begins with an asymmetric Michael addition of lithium enolate (178) to the scalemic sulfoxide (179). Direct treatment of the cmde Michael adduct with y /i7-chloroperbenzoic acid to oxidize the sulfoxide to a sulfone, followed by reductive removal of the bromine affords (180, X = a and PH R = H) in over 90% yield. Similarly to the conversion of (175) to (176), base-catalyzed epimerization of (180) produces an 85% isolated yield of (181, X = /5H R = H). C8 and C14 of (181) have the same relative and absolute stereochemistry as that of the naturally occurring steroids. Methylation of (181) provides (182). A (CH2)2CuLi-induced reductive cleavage of sulfone (182) followed by stereoselective alkylation of the resultant enolate with an allyl bromide yields (183). Ozonolysis of (183) produces (184) (wherein the aldehydric oxygen is by isopropyUdene) in 68% yield. Compound (184) is the optically active form of Ziegler s intermediate (176), and is converted to (+)-estrone in 6.3% overall yield and >95% enantiomeric excess (200). 

The most recent, and probably most elegant, process for the asymmetric synthesis of (+)-estrone appHes a tandem Claisen rearrangement and intramolecular ene-reaction (Eig. 23). StereochemicaHy pure (185) is synthesized from (2R)-l,2-0-isopropyhdene-3-butanone in an overall yield of 86% in four chemical steps. Heating a toluene solution of (185), enol ether (187), and 2,6-dimethylphenol to 180°C in a sealed tube for 60 h produces (190) in 76% yield after purification. Ozonolysis of (190) followed by base-catalyzed epimerization of the C8a-hydrogen to a C8P-hydrogen (again similar to conversion of (175) to (176)) produces (184) in 46% yield from (190). Aldehyde (184) was converted to 9,11-dehydroestrone methyl ether (177) as discussed above. The overall yield of 9,11-dehydroestrone methyl ether (177) was 17% in five steps from 6-methoxy-l-tetralone (186) and (185) (201). 

Enzyme-Catalyzed Asymmetric Synthesis. The extent of kinetic resolution of racemates is determined by differences in the reaction rates for the two enantiomers. At the end of the reaction the faster reacting enantiomer is transformed, leaving the slower reacting enantiomer unchanged. It is apparent that the maximum product yield of any kinetic resolution caimot exceed 50%. 

The variety of enzyme-catalyzed kinetic resolutions of enantiomers reported ia recent years is enormous. Similar to asymmetric synthesis, enantioselective resolutions are carried out ia either hydrolytic or esterification—transesterification modes. Both modes have advantages and disadvantages. Hydrolytic resolutions that are carried out ia a predominantiy aqueous medium are usually faster and, as a consequence, require smaller quantities of enzymes. On the other hand, esterifications ia organic solvents are experimentally simpler procedures, aHowiag easy product isolation and reuse of the enzyme without immobilization. 

Meyers has also reported the use of chiral oxazolines in asymmetric copper-catalyzed Ullmann coupling reactions. For example, treatment of bromooxazoline 50 with activated copper powder in refluxing DMF afforded binaphthyl oxazoline 51 as a 93 7 mixture of atropisomers diastereomerically pure material was obtained in 57% yield after a single recrystallization. Reductive cleavage of the oxazoline groups as described above afforded diol 52 in 88% yield. This methodology has also been applied to the synthesis of biaryl derivatives. 

For his work on chirally catalyzed oxidation reactions, representing a major contribution to the development of catalytic asymmetric synthesis, K. B. Sharpless was awarded the Nobel Prize for chemistry in 2001. ... 

Trost and co-workers have explored asymmetric transidon metal-catalyzed allylic alkyla-dons. Details on this subject have been well reviewed by Trost and others. With the use of asymmetric palladium-catalyzed desymmetrizadon of meso-2-ene-l,4-diols, cii -l,4-dibenzoy-loxy-2-cyclopentene can be converted to the enandometrically pure cii -4-rfirr-butoxycar-bamoyl-l-methoxycarbonyl-2-cyclopentene. The product is a usefid and general building block for synthesis of carbocyclic analogs of nucleosides as presented in Scheme 5.12. 

We now turn to the Takasago Process for the commercial synthesis of (-)-menthol (1),4 one of the most successful industrial applications of catalytic asymmetric synthesis. This exquisite synthesis is based on the BINAP-Rh(i)-catalyzed enantioselecdve isomerization of allylic amines, and has been in operation for the commercial production of (-)-menthol since 1984. 

Without question, the most significant advance in the use of sulfur-centered nucleophiles was made by Shibasaki, who discovered that 10 mol% of a novel gallium-lithium-bis(binaphthoxide) complex 5 could catalyze the addition of tert-butylthiol to various cyclic and acyclic meso-epoxides with excellent enantioselectiv-ities and in good yields (Scheme 7.11) [21], This work builds on Shibasaki s broader studies of heterobimetallic complexes, in which dual activation of both the electrophile and the nucleophile is invoked [22]. This method has been applied to an efficient asymmetric synthesis of the prostaglandin core through an oxidation/ elimination sequence (Scheme 7.12). 

The hydrosilation of conjugated dienes is catalyzed by transition metal complexes34, and has been developed into a useful asymmetric synthesis of allylsilanes35,36. 

Many other known pyruvate lyases are unsuited to application in asymmetric synthesis since they catalyze C-C bond formation with random stereochemistry30. 

Hiroi K. Transition Metal or Lewis Acid-Catalyzed Asymmetric Reactions With Chiral Organosulfur Eunctionahty Rev. Heteroat. Chem. 1996 14 21-57 Keywords hefero-Diels-Alder reactions, asymmetric synthesis, chiral organosulfur functionality... 

Oxazol-4-ones 132 have been prepared by Trost and co-workers via a microwave-assisted cyclocondensation of bromo imides in the presence of NaF [86]. These products where then employed for a Mo-catalyzed asymmetric synthesis of Q -hydroxycarboxylic acid derivatives 134 (Scheme 47). 

Chiral epoxides and their corresponding vicinal diols are very important intermediates in asymmetric synthesis [163]. Chiral nonracemic epoxides can be obtained through asymmetric epoxidation using either chemical catalysts [164] or enzymes [165-167]. Biocatalytic epoxidations require sophisticated techniques and have thus far found limited application. An alternative approach is the asymmetric hydrolysis of racemic or meso-epoxides using transition-metal catalysts [168] or biocatalysts [169-174]. Epoxide hydrolases (EHs) (EC 3.3.2.3) catalyze the conversion of epoxides to their corresponding vicinal diols. EHs are cofactor-independent enzymes that are almost ubiquitous in nature. They are usually employed as whole cells or crude... 

Figure 10.21 Aldolase-catalyzed asymmetric synthesis of uncommon L-configured sugars (a), and selected examples of carbohydrate-related product structures that are accessible by enzymatic aldolization (b).

Figure 10.36 Enzyme-catalyzed asymmetric synthesis of a pancratistatin analog using a naphthalene dioxygenase and RhuA-catalyzed aldolization for the creation of four contiguous stereocenters.

Of course, new variants of the (N + C=C) approach continue to be reported. Muller and coworkers, who recently reviewed the field of rhodium(II)-catalyzed aziridinations with [N-(p-nitrobenzenesulfonyl)imino]phenyliodinane <96JP0341>, have explored the application of this technology to asymmetric synthesis. Thus, treatment of c/s-p-methylstyrene (141) with PhI=NNs and Pirrung s catalyst [Rh2 (-)(R)-bnp 4] in methylene chloride medium afforded the corresponding aziridine (142) in 75% yield and 73% ee <96TET1543>. 

Only a few other cobalt complexes of the type covered in this review (and therefore excluding, for example, the cobalt carbonyls) have been reported to act as catalysts for homogeneous hydrogenation. The complex Co(DMG)2 will catalyze the hydrogenation of benzil (PhCOCOPh) to benzoin (PhCHOHCOPh). When this reaction is carried out in the presence of quinine, the product shows optical activity. The degree of optical purity varies with the nature of the solvent and reaches a maximum of 61.5% in benzene. It was concluded that asymmetric synthesis occurred via the formation of an organocobalt complex in which quinine was coordinated in the trans position (133). Both Co(DMG)2 and cobalamin-cobalt(II) in methanol will catalyze the following reductive methylations ... 

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