Asymmetric Conjugate Addition of Arylthiols to Enoates and Its Application to Organic Synthesis of Biologically Potent Compounds.
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Accession number;03A0037841
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| Title;Asymmetric Conjugate Addition of Arylthiols to Enoates and Its Application to Organic Synthesis of Biologically Potent Compounds. |
| Author;
NISHIMURA K
(Kyoto Univ., Kyoto, Jpn)
TOMIOKA K
(Kyoto Univ., Kyoto, Jpn)
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Journal Title;Journal of the Pharmaceutical Society of Japan
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Journal Code:F0508A
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ISSN:0031-6903
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VOL.123;NO.1;PAGE.9-18(2003)
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| Figure&Table&Reference;FIG.13, TBL.2, REF.89 |
| Pub. Country;Japan |
| Language;English |
| Abstract;As a part of our studies aimed at asymmetric catalytic reactions by using an external chiral ligand, we have developed a catalytic asymmetric addition reaction of an arylthiol to .ALPHA.,.BETA.-unsaturated esters under the control of an external chiral ligand. The characteristic of our technology is a double activation of a thiol by lithiation and chelate formation with a chiral tridentate amino diether ligand, which simultaneously and effectively controls a stereochemistry of the reaction. One significant feature of an arylthiol is a bulky 2-substitution on aryl group, which enables the formation of a really reactive monomeric thiolate species. s-Cis conformation and capability of electron lone pair-differentiating coordination of a carbonyl oxygen to lithium are structural requirements of the substrates for high enantioselectivity. The enantioselectivity came up to 97% under the cited conditions. Asymmetric protonation of a transient enolate, generated by conjugate addition of a lithium thiolate to an enoate, was also realized. The stereochemistry of the protonation was controlled by the conformation of initially formed transient enolate in a 1,2-asymmetric induction manner. This technology enabled the asymmetric synthesis of (S)-naproxene. Stereoselective tandem C-S and C-C bond-forming reaction was developed as a logical extension by trapping the transient enolate intermediate with an aldehyde as a carbo-electrophile in the presence of phenylthiotrimethylsilane as an equilibrium-shift reagent. This tandem reaction was extended to a stereoselective cyclization of .OMEGA.-oxo-.ALPHA.,.BETA.-unsaturated esters initiated by a lithium thiolate. Stereoselectivity of both tandem inter- and intramolecular reaction is predictable by an allylic strain-controlled conformation model of the enolate, in which an approach of aldehyde takes place anti to C-S bond through coordination of an aldehyde oxygen to lithium.... (author abst.) |
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