Steric Tuning of Reactivity and Enantioselectivity in Addition of Thiophenol to Enoates Catalyzed by an External Chiral Ligand

Nishimura, Katsumi; Ono, Masashi; Nagaoka, Yasuo; Tomioka, Kiyoshi

doi:10.1021/ja9729950

Cited by 126 publications

(31 citation statements)

References 19 publications

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“…ENANTIOSELECTIVITY 44) The enantioselectivity of the addition of thiophenol to methyl crotonate was at most 71％. To improve the enantioselectivity as well as reactivity, we examined steric eŠect of substituents on a phenyl ring of thiophenol.…”

Section: Steric Tuning Of Reactivity Andmentioning

confidence: 99%

Asymmetric Conjugate Addition of Arylthiols to Enoates and Its Application to Organic Synthesis of Biologically Potent Compounds

Nishimura

Tomioka

2003

YAKUGAKU ZASSHI

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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 a,b-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 eŠectively controls a stereochemistry of the reaction. One signiˆcant 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-diŠerentiating 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 v-oxo-a,b-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. Total synthesis of (-)-neplanocin A was achieved by using the tandem cyclization as a key tool for the direct construction of aˆve-membered carbocycle where every carbon is functionalized.

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Section: Steric Tuning Of Reactivity Andmentioning

confidence: 99%

Asymmetric Conjugate Addition of Arylthiols to Enoates and Its Application to Organic Synthesis of Biologically Potent Compounds

Nishimura

Tomioka

2003

YAKUGAKU ZASSHI

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“…Tomioka et al reported the asymmetric Michael addition of an aromatic thiol to α,β-unsaturated esters in the presence of 8 mol% of 53 to provide 54 in up to 97% ee in 99% yield (Eq. 7.40)[47].…”

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confidence: 99%

Sulfur (and Related Elements)–X Activation

Kuniyasu

2001

Catalytic Heterofunctionalization

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“…The enantioselective conjugate addition of thiol nucleophiles to electron-deficient olefins constitutes one of the most direct and versatile methods. [5] However, the substrate scope was usually restricted to a,b-unsaturated aldehydes, [6] ketones [7] and imides. [8] Additionally, the dearylation process of aryl sulfides to yield the eventually desired free thiol was not always straightforward when aromatic thiols were used as nucleophiles.…”

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confidence: 99%

Organocatalytic Asymmetric CS Bond Formation: Synthesis of α‐Methylene‐β‐mercapto Esters with Simple Alkyl Thiols

et al. 2011

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Steric Tuning of Reactivity and Enantioselectivity in Addition of Thiophenol to Enoates Catalyzed by an External Chiral Ligand

Cited by 126 publications

References 19 publications

Asymmetric Conjugate Addition of Arylthiols to Enoates and Its Application to Organic Synthesis of Biologically Potent Compounds

Asymmetric Conjugate Addition of Arylthiols to Enoates and Its Application to Organic Synthesis of Biologically Potent Compounds

Sulfur (and Related Elements)–X Activation

Organocatalytic Asymmetric CS Bond Formation: Synthesis of α‐Methylene‐β‐mercapto Esters with Simple Alkyl Thiols

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