Optical activity chiral enantioselective

Optically active polymers are potentially very useful in areas such as asymmetric catalysis, nonlinear optics, polarized photo and electroluminescence, and enantioselective separation and sensing.26 Transition metal coupling polymerization has also been applied to the synthesis of these polymers.27 For example, from the Ni(II)-catalyzed polymerization, a regioregular head-to-tail polymer 32 was obtained (Scheme 9.17).28 This polymer is optically active because of the optically active chiral side chains. 

The dioxirane epoxidation of a prochrral alkene will produce an epoxide with either one new chirality center for terminal alkenes, or two for internal aUcenes. When an optically active dioxirane is nsed as the oxidant, expectedly, prochiral alkenes should be epoxi-dized asymmetrically. This attractive idea for preparative purposes was initially explored by Curci and coworkers in the very beginning of dioxirane chemistry. The optically active chiral ketones 1 and 2 were employed as the dioxirane precursors, but quite disappointing enantioselectivities were obtained. Subsequently, the glucose-derived ketone 3 was used, but unfortunately, this oxidatively labile dioxirane precursor was quickly consumed without any conversion of the aUcene . After a long pause (11 years) of activity in this challenging area, the Curci group reported work on the much more reactive ketone... 

Epoxides that have meso structures can be converted to optically active chiral compounds via enantioselective ring opening (Scheme 125). 

Catalytic enantioselective Mannich reactions provide one of the most versatile approaches for the synthesis of optically active chiral amines. Recently, several organocatalytic protocols have been developed using the parent cinchona alkaloids or their derivatives. 

Unless a resolution step is included, the a-amino acids prepared by the synthetic methods just described are racemic. Optically active amino acids, when desired, may be obtained by resolving a racemic mixture or by enantioselective synthesis. A synthesis is described as enantioselective if it produces one enantiomer of a chiral compound in an amount greater than its mirror image. Recall from Section 7.9 that optically inactive reactants cannot give optically active products. Enantioselective syntheses of amino acids therefore require an enantiomerically enriched chiral reagent or catalyst at some point in... 

Optically active chiral wall porphyrin iodorhodium(III) complexes promote the cyclopropa-nation of several olefins with ethyl diazoacetate with good cis selectivity, but with modest enantioselectivities (10-60% ee)120. 

As expected, the cis/trans diastereoselectivity is influenced by the structure of the catalyst precursor, and is controllable by choosing a proper catalyst and polymerization conditions. The enantioselectivity (the relative stereochemistry between the rings) of PMCP is also affected by the catalyst structure. Complexes la, lb (Figure 19.2), and 2a, which give atactic poly(a-olefin)s, produce atactic PMCP, and the isoselective catalysts 3 and 4a yield isotactic PMCPs. These differences in enantioselectivity versus catalyst type are consistent with those for the polymerization of a-olefins. trans-Isotactic polymers can be optically active (chiral) if homochiral catalysts are used. The Waymouth research group showed that the MAO-activated homochiral ansa-zirconocene BINOL complex 5 (BINOL = l,l -bi-2-naphtholate Figure 19.2) gave optically active trany-polymer. 

Xu KX, He YB, Qin HJ et al (2005) Enantioselective recognition by optically active chiral fluorescence sensors bearing amino acid units. Tetrahedron Asymmetry 16 3042-3048... 

In 2008, Ishihara established a practical procedure for the synthesis of optically active, chiral l,l -binaphthyl-2,2 -disulfonic acid (BINSA) (26) from BINOL, and also showed that in situ-generated 26-2,6-diphenylpyridine (1 2) salts behaved as an efficient enantioselective catalyst in the direct Mannich-type reaction of 1,3-diketones with aromatic aldimines (Scheme 7.45) [70, 71]. 

Two years later, enantioselective variants of this type of cascade reaction were achieved by replacing the enones with relatively more active enals. Zhao et al. reported a cascade Michael/annulation process combining amino and palladium catalysis [49] to furnish cyclic products with improved complexity and diversity (Scheme 9.55). First, a secondary amine catalyst promoted Michael addition of alkyne-tethered active methylene compounds to a, 3-unsaturated aldehydes to produce optically active chiral aldehydes... 

Synthetic utility of stereoselective alkylations in natural product chemistry is exemplified by the preparation of optically active 2-arylglycine esters (38). Chirally specific a-amino acids with methoxyaryl groups attached to the a-carbon were prepared by reaction of the dimethyl ether of a chiral bis-lactam derivative with methoxy arenes. Using SnCl as the Lewis acid, enantioselectivities ranging from 65 to 95% were obtained. 

Enantioselective differences in absorption, metaboHsm, clearance, dmg— macromolecule binding affinity, and other factors, which culminate in the observed enantioselective efficacy of chiral dmgs, are considered herein. More inclusive Hsts of optically active dmgs and theit enantioselective differences are available (93). 

Efficient enantioselective asymmetric hydrogenation of prochiral ketones and olefins has been accompHshed under mild reaction conditions at low (0.01— 0.001 mol %) catalyst concentrations using rhodium catalysts containing chiral ligands (140,141). Practical synthesis of several optically active natural... 

The resolution of optically active compounds by gas chromatography with chiral phases is a well-established procedure, and the separation of Al-perfluoto-acetylated ammo acid ester enantiomers m 1967 was the first successful application of enantioselective gas-liquid chromatography [39] Ammo acids have been resolved as their A -trifluoroacetyl esters on chiral diamide phases such as N-lauroyl-L-valineferf-butylamideorAl-docosanoyl-L-valme /ez-r-butylamide [40,41,... 

The catalytic enantioselective cycloaddition reaction of carbonyl compounds with conjugated dienes has been in intensive development in recent years with the main focus on synthetic aspects the number of mechanistic studies has been limited. This chapter will focus on the development and understanding of cycloaddition reactions of carbonyl compounds with chiral Lewis acid catalysts for the preparation of optically active six-membered ring systems. 

The second system studied was the separation of the chiral epoxide enantiomers (la,2,7,7a-tetrahydro-3-methoxynaphth-(2,3b)-oxirane Sandoz Pharma) used as an intermediate in the enantioselective synthesis of optically active drugs. The SMB has been used to carry out this chiral separation [27, 34, 35]. The separation can be performed using microcrystalline cellulose triacetate as stationary phase with an average particle diameter greater than 45 )tm. The eluent used was pure methanol. A... 

The disclosure, in 1982, that cationic, enantiopure BINAP-Rh(i) complexes can induce highly enantioselective isomerizations of allylic amines in THF or acetone, at or below room temperature, to afford optically active enamines in >95 % yield and >95 % ee, thus constituted a major breakthrough.67-68 This important discovery emerged from an impressive collaborative effort between chemists representing Osaka University, the Takasago Corporation, the Institute for Molecular Science at Okazaki, Japan, and Nagoya University. BINAP, 2,2 -bis(diphenylphosphino)-l,l -binaphthyl (Scheme 7), is a fully arylated, chiral diphosphine which was introduced in... 

Since the addition of dialkylzinc reagents to aldehydes can be performed enantioselectively in the presence of a chiral amino alcohol catalyst, such as (-)-(1S,2/ )-Ar,A -dibutylnorephedrine (see Section 1.3.1.7.1.), this reaction is suitable for the kinetic resolution of racemic aldehydes127 and/or the enantioselective synthesis of optically active alcohols with two stereogenic centers starting from racemic aldehydes128 129. Thus, addition of diethylzinc to racemic 2-phenylpropanal in the presence of (-)-(lS,2/ )-Ar,W-dibutylnorephedrine gave a 75 25 mixture of the diastereomeric alcohols syn-4 and anti-4 with 65% ee and 93% ee, respectively, and 60% total yield. In the case of the syn-diastereomer, the (2.S, 3S)-enantiomer predominated, whereas with the twtf-diastereomer, the (2f ,3S)-enantiomer was formed preferentially. 

Chiral, nonracemic allylboron reagents 1-7 with stereocenters at Cl of the allyl or 2-butenyl unit have been described. Although these optically active a-substituted allylboron reagents are generally less convenient to synthesize than those with conventional auxiliaries (Section 1.3.3.3.3.1.4.), this disadvantage is compensated for by the fact that their reactions with aldehydes often occur with almost 100% asymmetric induction. Thus, the enantiomeric purity as well as the ease of preparation of these chiral a-substituted allylboron reagents are important variables that determine their utility in enantioselective allylboration reactions with achiral aldehydes, and in double asymmetric reactions with chiral aldehydes (Section 1.3.3.3.3.2.4.). 

Combination of nickel bromide (or nickel acetylacetonate) and A. A -dibutylnorephcdrinc catalyzed the enantioselective conjugate addition of dialkylzincs to a./Tunsaturated ketones to afford optically active //-substituted ketones in up to ca. 50% ee53. Use of the nickel(II) bipyridyl-chiral ligand complex in acetonitrile/toluenc as an in situ prepared catalyst system afforded the //-substituted ketones 2, from aryl-substituted enones 1, in up to 90% ee54. 

An excellent synthetic method for asymmetric C—C-bond formation which gives consistently high enantioselectivity has been developed using azaenolates based on chiral hydrazones. (S)-or (/ )-2-(methoxymethyl)-1 -pyrrolidinamine (SAMP or RAMP) are chiral hydrazines, easily prepared from proline, which on reaction with various aldehydes and ketones yield optically active hydrazones. After the asymmetric 1,4-addition to a Michael acceptor, the chiral auxiliary is removed by ozonolysis to restore the ketone or aldehyde functionality. The enolates are normally prepared by deprotonation with lithium diisopropylamide. 

The highest enantioselectivities in the base-catalyzed Michael additions have so far been obtained using achiral bases complexed to chiral crown ethers. The addition of methyl 2,3-dihydro-l-oxo-1//-indene-2-carboxylate (1) to 3-buten-2-one using 4 mol% of a [l,T-binaphthalcnc]-2,2 -diol derived optically active crown ether 3 in combination with potassium AY/-butoxide as the base illustrates this successful method 259 260 It is assumed that the actual Michael donor is the potassium enolate complex of 1 and crown ether 3. 

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