Optically enriched

The rhodium-catalyzed isomerization can also be carried out with the chiral catalyst, Ru2Cl4(diop)3 (H2, 20-80°, 1-6 h, 47-90% yield). In this case, optically enriched enol ethers are obtained. ... 

Azirines can be prepared in optically enriched form by the asymmetric Neber reaction mediated by Cinchona alkaloids. Thus, ketoxime tosylates 173, derived from 3-oxocarhoxylic esters, are converted to the azirine carboxylic esters 174 in the presence of a large excess of potassium carbonate and a catalytic amount of quinidine. The asymmetric bias is believed to be conferred on the substrate by strong hydrogen bonding via the catalyst hydroxyl group <96JA8491>. 

Based on these preliminary findings, related couplings to pyruvates and iminoacetates were explored as a means of accessing a-hydroxy acids and a-amino acids, respectively. It was found that hydrogenation of 1,3-enynes in the presence of pyruvates using chirally modified cationic rhodium catalysts delivers optically enriched a-hydroxy esters [102]. However, chemical yields were found to improve upon aging of the solvent 1,2-dichloroethane (DCE), which led to the hypothesis that adventitious HC1 may promote re-... 

Chiral Bronsted acid co-catalysts do not promote formation of optically enriched products in analogous couplings to pyruvates, although increased rate and conversion in response to the Bronsted acid co-catalyst is unmistakably apparent. For pyruvates, protonation likely occurs subsequent to the C-C... 

Wang et al.36 have used the chiral catalyst (DHQ)2 PHAL (see Chapter 4 for the structure) for the asymmetric synthesis of the taxol side chain. Optically enriched diol was obtained at 99% ee via asymmetric dihydroxylation. Sub-... 

Scheme 6.18. Three-component Zr-catalyzed asymmetric alkylation of imines by alkylzincs leads to the formation of optically enriched amines not accessible by alternative methods such as catalytic hydrogenation.

As is also illustrated in Scheme 6.23, the optically enriched amino nitriles can be converted to the corresponding a-amino esters through a four-step sequence (74—> 75). Unlike the aforementioned imine alkylations with alkylzinc reagents, methylation of the phenolic OH is required, since the corresponding o-methoxy aniline is less reactive and affords significantly lower enantioselectivities similar observations are made when aniline is used. 

Pd-catalyzed Heck reactions are among the most effective methods for the formation of quaternary carbon centers. Considering the significance and the strategic difficulties associated with the synthesis of quaternaiy carbons, particularly in the optically enriched or pure form, it is not a surprise that the development of catalytic asymmetric Heck reactions has held center stage for the past few years. One of the leading labs in this area is that of Shibasaki, who in 1993 reported a concise total synthesis of eptazodne 23 (Scheme 4).141 Thus, treatment of silyl ether 18 with 10 mol% Pd(OAc>2 and 25 mol% (S)-19 leads to the formation of 20 in 90 % yield and 90% ee As illustrated in Scheme 4, once the quaternary carbon center is synthesized efficiently and selectively, the target molecule is accessed in a few steps. 

A series of thiazolo[2,3- ]isoquinolines 426, 3-one derivatives 427, and J-oxide derivatives 428 have been studied in detail as regard to their spectroscopic properties <2001T3499, 2002TA2329, 2003T1173>. These compounds have been prepared using previously reported chemistry. One of the 3-one derivatives 427 was prepared in enantiomeri-cally pure form and therefore gave access to optically enriched 428. Isolated diastereoisomers of this A-oxide were however found to be unstable and to epimerize to give a thermodynamic mixture of syn- and //-diastereoisomers. This epimerization was accompanied by a racemization (Scheme 110). 

Another report by Rychnovsky et al. explored the potential of chirality transfer in the transannular cyclization of cyclodecene 45 [42], They proposed a radical deoxygenation of 45, which produces an intermediate cyclodecenyl radical that can cyclize in a 5-exo fashion to yield 5,7-fused bicycle 48 (Scheme 13). The potential for the optically enriched radical precursor 45 to undergo enantioselective cyclization is dependent on the rate of transannular cyclization. That is, if the radical generated from optically pure... 

Pyrrolines and pyrroles can be readily prepared from the rearrangement of a-aminoallenes. Optically enriched a-aminoallene 137 is rearranged to pyrroline 138 by catalytic silver nitrate (Eq. 13.45) [53], The yield of the reaction is high and the cyclization occurs with high levels of asymmetry transfer. Annulated 3-pyrroline 140 is the product of rearrangement of allenyl pyrrolidine 139 (Eq. 13.46) [53]. 

In order to elucidate the nature of this mechanism further, Gibson (nee Thomas) studied134,136 the conversion of an optically pure sample of vinylke-tone 121.fi to the corresponding vinylketene (221.e). The vinylketone was resolved by carbonyl ligand substitution with (+)-neomenthyldiphenyl-phosphine, followed by subsequent separation of the resultant diastereo-mers to yield an optically enriched product.136,137 When 222.e, of known e.e., was treated with methyllithium under an atmosphere of carbon monoxide, the expected vinylketene complex 221.e was isolated and was found... 

As seen in the conversion of an optically enriched vinylketone complex to the corresponding vinylketene complex (vide supra), the availability of enantiomerically pure samples of the vinylketene complexes 221 allowed the subsequent reactions of these complexes to be screened for the presence of symmetrical intermediates along the reaction coordinate. Their... 

An analogous study was carried out38 to investigate the alkyne insertion mechanism. Reacting optically enriched samples of vinylketene complexes 221.c and 221.e with three different alkynes, the expected adducts (247.b, 247.d, 247.k, and 247.n) were isolated, and their e.e. measured by HPLC or NMR methods. It was shown that there had been no loss of stereochemical information, and comparison of CD spectra (along with X-ray... 

Hill, C.L., Verma, C.S. and Grogan, G., Des3mimetrisations of l-alkylbicyclo[3.3.0]octane-2,8-diones by enzymatic retro-Claisen reaction yield optically enriched 2,3-substituted cyclopenta-nones. Adv. Synth. Catal. 2007, 349, 916. 

H-NMR two dimensions, NOE (very high ionic strength), no optical enrichment, for low binding levels no Z to B transformation - With d(CGCGATCGCG)2, both A and A bind into minor groove of the 60,61... 

Gagne and coworkers utilized this combination to discover enantioselec-tive receptors for (-)-adenosine [12]. A racemic dipeptide hydrazone [( )-pro-aib] generated a stereochemically diverse DCL of n-mer. The dimers were composed of two chiral (DD/LL) and one achiral isomer (DL), the four trimers (DDD, LLL, DDL, and LLD), the tetramers of four chiral and two achiral isomers, etc. Two techniques were used to measure the enan-tio-imbalance that was caused by the enantioselective binding of the chiral analyte to the enantiomeric receptors (Fig. 5.11). Since the unperturbed library is optically inactive, the optical enrichment of each library component could be measured by a combined HPLC optical rotation detection scheme (laser polarimeter, LP). LP detection differentiated unselective binding (amplification but not optical enrichment) from enantioselective recognition of the analyte (amplification and optical enrichment). In this manner the LL dimer (SS) of the dipeptide was amplified and identified as the enantioselective match for (-)-adenosine. 

Tricyclic amine 259 forms by allylation and ring-closing metathesis from optically enriched precursor 258 that itself is the product of asymmetric RCM (03OL4899). 

Figure 5. NMR spectra of 2.2,2-trifluoro-l-phenylethanol (optically enriched) in 0 racemic and optically active l-(l-naphthyl)ethanaminc83.

Jeong and co-workers utilized a cobalt-alkyne complex to enhance enantioselectivity of the addition of bis (homoallyl)zinc to propargyl aldehydes 68 by the exaggeration of steric environment. The reaction provided optically enriched propargyl alcohol 69 in the presence of a chiral ligand and titanium tetra(isopropoxide) in excess. Adduct 69 was subjected to PKR to yield optically enriched bicyclic compounds 70 (Equation (39)). ... 

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