C enantioselective synthesis

Busca, P., Paradisi, E., Moynihan, E., Maguire, A.R. and Engel, P.C., Enantioselective synthesis of non-natural amino acids using phenylalanine dehydrogenases modified by site-directed mutagenesis. Org. Biomol. Chem., 2004, 2, 2684. 

C. Enantioselective synthesis allows for the synthesis of one enantiomer of a compound, rather than a racemic mixture. 

Scheme 15 (a) Au(I) catalysed intermolecular hydroalkoxylation reaction, (b) attempted isolation of geminal-digold complexes from Au(I) bimetallic complexes during the hydroalkoxylation of alkynols, and (c) enantioselective synthesis of O-heterocycles using the chiral bimetallic Au(I) complex (36)... 

Enders D, Schubert H, Niibling C. Enantioselective synthesis of a-substituted primary amines by nucleophilic addition to aldehyde-SAMP hydrazones. Angew. Chem. Int. Ed. Engl. 1986 25 1109-1110. 

Donnoli MI, Scafato P, Nardiello M, Casarini D, Giorgio E, Rosini C. Enantioselective synthesis and absolute stereochemistry of both the enantiomers of trans-magnolione, a fragrance structurally related to trans-methyl jasmonate. Tetrahedron 2004 60(23) 4975-4981. 

Blechert S, Stapper C. Enantioselective synthesis of (—)-ana-ferine dihydrochloride by a ruthenium-catalysed tandem ring rearrangement metathesis. Eur. J. Org. Chem. 2002 16 2855-2858. 

The target molecule above contains a chiral center. An enantioselective synthesis can therefore be developed We use this opportunity to summarize our knowledge of enantioselective reactions. They are either alkylations of carbanions or addition reactions to C = C or C = 0 double bonds ... 

Silyl ethers serve as preeursors of nucleophiles and liberate a nucleophilic alkoxide by desilylation with a chloride anion generated from CCI4 under the reaction conditions described before[124]. Rapid intramolecular stereoselective reaction of an alcohol with a vinyloxirane has been observed in dichloro-methane when an alkoxide is generated by desilylation of the silyl ether 340 with TBAF. The cis- and tru/u-pyranopyran systems 341 and 342 can be prepared selectively from the trans- and c/.y-epoxides 340, respectively. The reaction is applicable to the preparation of 1,2-diol systems[209]. The method is useful for the enantioselective synthesis of the AB ring fragment of gambier-toxin[210]. Similarly, tributyltin alkoxides as nucleophiles are used for the preparation of allyl alkyl ethers[211]. 

Depending on the stereoselectivity of the reaction, either the or the 5 configuration can generated at C-2 in the product. This corresponds to enantioselective synthesis of the d md L enantiomers of a-amino acids. Hydrogenation using chiral catalysts has been carefully investigated. The most effective catalysts for the reaction are ihodiiun... 

The potential of Fischer carbene complexes in the construction of complex structures from simple starting materials is nicely reflected in the next example. Thus, the reaction of alkenylcarbene complexes of chromium and tungsten with cyclopentanone and cyclohexanone enamines allows the di-astereo- and enantioselective synthesis of functionalised bicyclo[3.2.1]octane and bicyclo[3.3.1]nonane derivatives [12] (Scheme 44). The mechanism of this transformation is initiated by a 1,4-addition of the C -enamine to the alkenylcarbene complex. Further 1,2-addition of the of the newly formed enamine to the carbene carbon leads to a metalate intermediate which can... 

An (E)-selective CM reaction with an acrylate (Scheme 61) was applied by Smith and O Doherty in the enantioselective synthesis of three natural products with cyclooxygenase inhibitory activity (cryptocarya triacetate (312), cryptocaryolone (313), and cryptocaryolone diacetate (314)) [142]. CM reaction of homoallylic alcohol 309 with ethyl acrylate mediated by catalyst C led (E)-selectively to d-hydroxy enoate 310 in near quantitative yield. Subsequent Evans acetal-forming reaction of 310, which required the trans double bond in 310 to prevent lactonization, led to key intermediate 311 that was converted to 312-314. 

Because of the nature of the transition state in the pericyclic mechanism, optically active substrates with a chiral carbon at C-3 or C-4 transfer the chirality to the product, making this an enantioselective synthesis (see p. 1451 for an example in the mechanistically similar Claisen rearrangement). ... 

T. C. Boge, G. I. Georg, The medicinal chemistry of / -amino acids paclitaxel as an illustrative example in Enantioselective Synthesis of /3-amino acids, E. Juaristi (Ed.), Wiley-VCH, New York, 1997. 

Mermerian AH, Fu GC (2003) Catalytic enantioselective synthesis of quaternary stereocenters via intermolecular C-acylation of silyl ketene acetals dual activation of the electrophile and the nucleophile. J Am Chem Soc 125 4050-4051... 

Szantay, C., Kardos-Balogh, Z., Moldvai, I., Szantay, C. Jr., Temesvari-Major, E., Blasko, G. (1996) A Practical Enantioselective Synthesis of Epibatidine. Tetrahedron, 52, 11053-11062. 

The use of expensive and unstable ZnPli2 in the preparation of chiral di-arylmethanol derivatives, with electronically and sterically similar aryl rings, made this approach less attractive for the enantioselective synthesis. In order to avoid this inconvenience, other alternative preparations of arylzinc reagents were evaluated.As a first choice, Yus et al. proposed the use of arylboronic adds as a viable source of phenyl (Scheme 4.19). Thus, the reaction of various boronic acids with an excess of ZnEt2 at 70 °C gave the corresponding arylzinc intermediates (probably aryl(ethyl)zincs), which were trapped by reaction with dif-... 

Another enantioselective synthesis, shown in Scheme 13.18, involves a early kinetic resolution of the alcohol intermediate in Step B-2 by lipase PS. The stereochemistry at the C(7) methyl group is controlled by the exo selectivity in the conjugate addition (Step D-l). 

The syntheses in Schemes 13.45 and 13.46 illustrate the use of oxazolidinone chiral auxiliaries in enantioselective synthesis. Step A in Scheme 13.45 established the configuration at the carbon that becomes C(4) in the product. This is an enolate alkylation in which the steric effect of the oxazolidinone chiral auxiliary directs the approach of the alkylating group. Step C also used the oxazolidinone structure. In this case, the enol borinate is formed and condensed with an aldehyde intermediate. This stereoselective aldol addition established the configuration at C(2) and C(3). The configuration at the final stereocenter at C(6) was established by the hydroboration in Step D. The selectivity for the desired stereoisomer was 85 15. Stereoselectivity in the same sense has been observed for a number of other 2-methylalkenes in which the remainder of the alkene constitutes a relatively bulky group.28 A TS such as 45-A can rationalize this result. 

An enantioselective synthesis of (—)-lupinine 6 was based on a similar reductive amination process. In this case, (k)-phcnylglycinol was used to obtain a chiral nonracemic oxazololactam which was cyclized after reduction of N-C and O-C bonds and subsequent hydrolysis of the masked aldehyde <2004T5433>. 

Hoveyda, A. H. Diversity-Based Identification of Efficient Homochiral Organometallic Catalysts for Enantioselective Synthesis. In Handbook of Combinatorial Chemistry, Nicolaou, K. C., Hanko, R., Hartwig, W., Eds. Wiley-VCH Weinheim, Germany, 2002, Vol. 2, pp 991-1016. 

The enantioenriched sulfoxide intermediate 72 (R = CH2OH), obtained by asymmetric 5-oxidation with a chiral oxaziridine (89 11 enantiomeric ratio), has provided a highly enantioselective synthesis of the benzothiepin derivative 71 (4R, 5R). The aldehyde intermediate 72 (R = CHO) was cyclized asymmetrically to 71 (4R, 5R) with >98 2 enantiomeric ratio. Base treatment (f-BuOK, -10°C, THF) of the racemic benzothiepin 73... 

Kovacik, I., Wicht, D.K., Grewal, N.S., Glueck, D.S., Incarvito, C.D., Guzei, I.A., and Rheingold, A.L., Pt(Me-Duphos)-catalyzed asymmetric hydrophosphination of activated olefins enantioselective synthesis of chiral phosphines,... 

Diastereoselective intermolecular nitrile oxide—olefin cycloaddition has been used in an enantioselective synthesis of the C(7)-C(24) segment 433 of the 24-membered natural lactone, macrolactin A 434 (471, 472). Two (carbonyl)iron moieties are instrumental for the stereoselective preparation of the C(8)-C(ii) E,Z-diene and the C(i5) and C(24) sp3 stereocenters. Also it is important to note that the (carbonyl)iron complexation serves to protect the C(8)-C(ii) and C(i6)-C(i9) diene groups during the reductive hydrolysis of an isoxazoline ring. 

Transformation of chiral nitrones into enantiomer enriched a-chiral N -hydroxylamines and their derivatives, has been successfully employed in the enantioselective synthesis of (+ )-(R)- and (—)-(S)-zileuton (216). An expeditious synthesis of thymine polyoxin C (347), based on the stereocontrolled addition of 2-lithiofuran (a masked carboxylate group) to the A-benzyl nitrone derived from methyl 2,3-O-isopropylidene-dialdo-D-ribofuranoside, is described (Scheme 2.151) (194). 

The benzylic C-H activation has been effectively applied to the enantioselective synthesis of (+)-imperanene (Equation (16)).80 The key step was the Rh2(i -DOSP)4-catalyzed functionalization of the benzylic methyl C-H bond in arene 2. An impressive feature of this transformation was that both the carbenoid and substrate contained very electron-rich aromatic rings, which were compatible with the highly electrophilic carbenoids because they were still sterically protected. 

A wide variety of iridium-based hydrogenation catalysts are currently under development, notably for organic syntheses including enantioselective synthesis. Hydrogenation by hydrogen transfer is well known [15], and the reduction of C=0 and C=N double bonds is also possible [16, 17]. 

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