Stereoselective Michael/aldol tandem reaction triggered by thiolate anion or analogues

Kamimura, Akio; Mitsudera, Hiromasa; Asano, Shigeru; Noguchi, Michihiko; Kakehi, Akikazu

doi:10.1039/a800870a

Cited by 32 publications

(3 citation statements)

References 13 publications

(3 reference statements)

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“…When the present investigation was launched, the chemistry of the thio-tandem process with α,β-unsaturated esters, despite the few reports of the reaction with α,β-unsaturated ketones, had remained unestablished: neither had the reaction conditions been opitimized nor had the stereochemical course of the reaction been known . Recently, we have demonstrated that the tandem strategy successfully works for acrylates with the aldehydes in CH 2 Cl 2 and that a high syn-aldol selectivity is achieved with tert -butyl acrylate. , This research reports in full detail our latest results on the tandem process, discussing a plausible pathway of the reaction and its stereochemical course. We will also demonstrate a stereoselective preparation of trisubstituted tetrahydrofuran derivatives from the tandem adduct as an extension of the methodology.…”

Section: Introductionmentioning

confidence: 89%

Stereoselective Thio-Michael/Aldol Tandem Reaction to α,β-Unsaturated Esters

et al. 1999

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A mixture of lithium thiophenolate, R, -unsaturated ester, and aldehyde in CH 2 Cl 2 afforded Michael/ aldol tandem adducts, -hydroxy-R-(1-phenylthioalkyl) esters, in moderate to good yields with a high syn-aldol selectivity. The reaction proceeded effectively when CH 2 Cl 2 or ether was used as a solvent. The countercation of thiolate proved important; lithium cation provided the best results. The stereoselectivity and yield of the adducts greatly depended on the steric size of the ester group. Lithium selenolate, generated in situ by treatment of diphenyldiselenide with methyllithium, brought similar results, whereas alkoxide was too inert for the reaction. Application of the reaction to methacrylate provided a useful method to form a quaternary carbon center on a similar stereoselective level. In the reaction with crotonates, on the other hand, the anti-Michael selectivity dominated over the syn-aldol selectivity. The tandem adduct was useful for the stereoselective preparation of trisubstituted tetrahydrofuran via radical cyclization, whose configuration was found to be 2,3-trans-3,5-trans.

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Section: Introductionmentioning

confidence: 89%

Stereoselective Thio-Michael/Aldol Tandem Reaction to α,β-Unsaturated Esters

et al. 1999

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“…A Baylis-Hillman-like three-component reaction gives 3hydroxy-2-(phenylthio)methyl esters in good yield and with moderate diastereocontrol. 111 Thus, reaction of acrylates with lithium thiophenolate in the presence of a range of aldehydes gave primarily syn-hydroxy esters. The process was also found to be productive when selenolates were employed rather than thiolates (Scheme 129 and Table 87).…”

Section: Scheme 118 Reagentsmentioning

confidence: 99%

Alcohols, ethers and phenols

George

Mabon

Sweeney

et al. 2000

J. Chem. Soc., Perkin Trans. 1

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“…The conformation of the enolate isˆxed by an allylic strain, and the approach of aldehyde takes place anti to C S bond with a coordination of aldehyde oxygen to lithium as shown in A. Coincidently to us, Kamimura's group reported similar stereoselectivity in thiolate-initiated Michael aldol tandem reaction of acrylates with aldehydes. [73][74] MICHAEL ALDOL TANDEM CYCLIZATION REACTION 75) Stereoselective Michael aldol tandem cyclization reaction was developed by an extension of the intermolecular reaction to an intramolecular reaction of v-oxo-a,b-enoate which has enoate and aldehyde moieties in a molecule. Tandem cyclization reactions, especially Michael Michael reactions, have been reported with the re‰ection of an importance of ring skeleton construction.…”

Section: Tandem Michael Aldol Carbon Carbon Bond-forming Reactionmentioning

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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Stereoselective Michael/aldol tandem reaction triggered by thiolate anion or analogues

Cited by 32 publications

References 13 publications

Stereoselective Thio-Michael/Aldol Tandem Reaction to α,β-Unsaturated Esters

Stereoselective Thio-Michael/Aldol Tandem Reaction to α,β-Unsaturated Esters

Alcohols, ethers and phenols

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

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