Biphenyl chiral synthesis

An enantioselective synthesis of both (R)- and (5)-a-alkylcysteines 144 and 147 is based on the phase-transfer catalytic alkylation of fert-butyl esters of 2-phenyl-2-thiazoline-4-carboxylic acid and 2-ort/ro-biphenyl-2-thiazoline-4-carboxylic acid, 142 and 145 <06JOC8276>. Treatment of 142 and 145 with alkyl halides and potassium hydroxide in the presence of chiral catalysts 140 and 141 gives the alkylated products, which are hydrolyzed to (R)- and (S)-a-alkylcysteines 144 and 147, respectively, in high enantioselectivity. This method may have potential for the practical synthesis of chiral a-alkylcysteines. 

Preparation of the chiral biphenyls and binaphthyls with high enantiose-lectivity can be achieved via substitution of an aromatic methoxyl group with an aryl Grignard reagent using oxazoline as the chiral auxiliary.38 Schemes 8-10 and 8 11 outline the asymmetric synthesis of such chiral biaryl compounds. 

A 2 1 (- )-90-LAH reagent was employed in the asymmetric synthesis of a cij-diol (91) by reduction of c/j-2-acetoxy-6-phenylcyclohexanone (99,100). Diol 91 is of interest as the tetrahydro derivative of a metabolite obtained from the microbial oxidation of biphenyl. Diol 91 was obtained in 46% e.e. as determined by NMR in the presence of a chiral shift reagent. It was shown to have the absolute stereochemistry (lS,2/ )-dihydroxy-3(S)-phenylcyclohexane by oxidation to ( + )-2-(S)-phenyladipic acid of known absolute stereochemistry. 

However, a more exciting application of this reaction is the oxazoline-directed synthesis of axially chiral biaryls. The oxazoline system not only activates the ortho-methoxy group for nucleophilic displacement but also determines the stereochemical outcome of the reaction. This provides a convenient method for the introduction of axial-chirality. Meyers group continues their earlier lead on this subject with reports of the stereoselective synthesis of tetrasubstituted biphenyls 391,392 examples are shown in Table 8.29 (Scheme 8.154). The best... 

In view of this background, we developed a new chiral auxiliary to allow for the first time the efficient asymmetric a-alkylation of sulfonamides [90]. After testing some amine auxiliaries mainly based on proline, which did not show high diastereoselectivities, we synthesized the 4-biphenyl-substituted 2,2-dimethyl-l,3-dioxan-5-amine 108 as a new auxiliary. The racemate obtained according to Erlenmeyer s phenylserine synthesis was resolved with tartaric acid to give both enantiomers. 

The synthesis of acrylic acid or its ester (228) from ethylene has been investigated in AcOH from the standpoint of its practical production 12]. The carbonylation of styrene is a promising commercial process for cinnamate (229) production[207,213,214]. Asymmetric carbonylation of styrene with Pd(acac)2 and benzoquinone in the presence of TsOH using 2,2 -dimethoxy-6, 6 -bis(diphenylphosphino)biphenyl (231) as a chiral ligand gave dimethyl phenylsuccinate 230 in 93% ee, although the yield was not satisfactory, showing that phosphine coordination influences the stereochemical course of the oxidative carbonylation with Pd(II) salt[215]. 

The catalytic asymmetric epoxidation of a,/i-unsaturated carbonyl compounds is one of the synthetically useful reactions in organic synthesis.The resulting chiral epoxides are easily converted to various useful chiral compounds. We developed a new yttrium-(5)-6,6 -[oxybis(ethylene)dioxy]biphenyl-2,2 -diol (1) (Figure 6.10)... 

The enantiomerically pure bridged biphenyl, (—)-(R)-3,9-bis[4-(dodecyloxy)benzoyloxy]-5,7-dihydro-l,ll-dimethyl-dibenzo[c,( ]thiepine 80, was prepared from enantiomerically pure diiodide 197 (Scheme 25) <1998JOC3895>. The synthesis of the precursor 197 was based on Ullmann coupling reaction of the chiral oxazoline (-)-(S)-195. 

Binaphthyl- and Biphenyl-Modified Chiral Phase-Transfer Catalysts for Asymmetric Synthesis... 

This unique phenomenon provides a powerful strategy in the molecular design of chiral catalysts that is, the requisite chirality can be served by the simple binaphthyl moiety, while an additional structural requirement for fine-tuning of reactivity and selectivity can be fulfilled by an easily modifiable achiral biphenyl structure. This certainly obviates the use of two chiral units, and should be appreciated in the synthesis of a variety of chiral catalysts with different steric and/or electronic properties. Actually, quaternary ammonium bromide possessing a sterically demanding substituent such as (S)-12b can be easily prepared, and benzylation with (S)-12b as catalyst gave 9 in 95% yield with 92% ee. Further, theenantioselectivity was enhanced to 95% ee with (S)-12c as a catalyst [12]. 

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