Radical Cyclization Cascades of Unsaturated Meldrum’s Acid Derivatives

Sautier, Brice; Lyons, Sarah E.; Webb, Michael R.; Procter, David J.

doi:10.1021/ol2029367

Cited by 55 publications

(30 citation statements)

References 36 publications

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“…The desymmetrisation of readily accessible cyclic 1,3-diester derivatives was achieved, affording cis-fused bicyclic hydroxy acids in good yield and with high diastereocontrol. [17,18] The use of substrates bearing different alkene substituents led to single isolated diastereoisomers in moderate to good yields (Scheme 12). [18] Differential activation of the radical acceptors was found to be crucial in order transfer from Sm(ii) to the ester carbonyl forms a pseudoaxial ketyl radicalanion stabilised by an anomeric effect.…”

Section: Cyclisation Cascades Of Meldrum's Acidsmentioning

confidence: 99%

“…[17,18] The use of substrates bearing different alkene substituents led to single isolated diastereoisomers in moderate to good yields (Scheme 12). [18] Differential activation of the radical acceptors was found to be crucial in order transfer from Sm(ii) to the ester carbonyl forms a pseudoaxial ketyl radicalanion stabilised by an anomeric effect. Subsequent reduction of the ketyl radicalanion to the anion, protonation, collapse of the ketal unit and reduction of the resulting aldehyde then affords the hydroxy acid product.…”

Section: Cyclisation Cascades Of Meldrum's Acidsmentioning

confidence: 99%

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Recent Advances in the Chemistry of SmI2–H2O

Sautier¹,

Procter

2012

Chimia

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Recent work from our laboratories has shown SmI(2)-H(2)O to be a versatile, readily-accessible and non-toxic reductant that is more powerful than SmI(2). This review describes the reduction of functional groups that were previously thought to lie beyond the reach of SmI(2) and complexity-generating cyclisations and cyclisation cascades triggered by the reduction of the ester carbonyl group with SmI(2)-H(2)O.

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Section: Cyclisation Cascades Of Meldrum's Acidsmentioning

confidence: 99%

Section: Cyclisation Cascades Of Meldrum's Acidsmentioning

confidence: 99%

Recent Advances in the Chemistry of SmI2–H2O

Sautier¹,

Procter

2012

Chimia

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“…11,12 As a result, SmI 2 can be used to selectively reduce a particular functional group in a multifunctional substrate for follow-up bondforming reactions and is exceptionally effective in reductive couplings, [13][14][15][16][17][18][19][20][21][22] and cascade reactions. [23][24][25][26][27][28][29][30][31][32][33][34][35] Most importantly, its use allows for alternative and selective methods for the synthesis of multifunctional targets. 4,9 While numerous reactions have been developed for SmI 2 , its scope in synthesis certainly has not been exhausted and new applications for this reagent are steadily being discovered.…”

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confidence: 99%

Mechanistic Study and Development of Catalytic Reactions of Sm(II)

Maity

Flowers

2019

J. Am. Chem. Soc.

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Despite the broad utility and application of SmI 2 in synthesis, the reagent is used in stoichiometric amounts and has a high molecular weight, resulting in a large amount of material being used for reactions requiring one or more equivalents of electrons. We report mechanistic studies on catalytic reactions of Sm(II) employing a terminal magnesium reductant and trimethyl silyl chloride in concert with a non-coordinating proton donor source. Reactions using this approach permitted reductions with as little as 1 mol% Sm. The mechanistic approach enabled catalysis employing HMPA as a ligand, facilitating the development of catalytic Sm(II) 5-exo-trig ketyl olefin cyclization reactions. File list (3) download file view on ChemRxiv Sm(II) Catalysis (RAF).pdf (746.24 KiB) download file view on ChemRxiv SI_Sm(II) catalysis.pdf (3.10 MiB) download file view on ChemRxiv Sm(II) Catalysis (RAF).doc (574.50 KiB)

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“…10 (F) Meldrum's acid can act as a carbon-based leaving group. Catalytic hydrogenolysis of Meldrum's acids 2 (R 1 = H) is an excellent route for the synthesis of compounds 13 both with secondary and tertiary benzylic stereocenters in 65-96% yield under mild reaction conditions.…”

Section: Scheme 1 Abstractsmentioning

confidence: 99%

5-Alkyl and 5,5-Dialkyl Meldrum’s Acids

Mieriņa

2013

Synlett

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This feature focuses on a reagent chosen by a postgraduate, highlighting the uses and preparation of the reagent in current research spotlight Introduction 5-Alkyl and 5,5-dialkyl Meldrum's acids (1 and 2, respectively) are used in total synthesis. 1 Monoalkylated derivatives 1 are synthesized from Meldrum's acid 3 by condensation with aldehyde 2 (or by acylation 3 ) followed by hydrogenation. 5-Alkyl and 5,5-Dialkyl Meldrum's Acids5,5-Dialkyl Meldrum's acids 2 can be obtained by alkylation of Meldrum's acid 3 or its monoalkylated derivatives 1 (Scheme 1). 4 Herein, reactions of Meldrum's acids 1 and 2 proceeding with destruction of 1,3-dioxane cycle are reviewed.(A) Hydrolysis of Meldrum's acid 2 leads to malonic or acetic acid derivatives. 5 Radical reduction of compound 2 with SmI 2 and H 2 O forms 3-hydroxypropanoic acids 4 selectively. The first step is activation of Meldrum's acid via coordination of SmI 2 to the carbonyl group, followed by electron transfer. 6 (B) Detz et al. 7 have reported that dimethyl malonate 5 can be obtained from propargylic derivative 2. The authors propose that the first step of the reaction cascade is copper-mediated addition of Meldrum's acid 2 to the triple bond and sequential methanolysis of the dioxane cycle forming lactone 6, which is further cleaved with methoxide leading to compound 5.(C) β-Substituted aldehydes 7 can be synthesized by Lewis base promoted hydrosilylation of Meldrum's acids 1 with phenylsilane, followed by hydrolysis. In situ treatment of aldehyde 7 with an amine and sequential hydrogenation of the formed imine with H 2 in the presence of Pd/C or with NaBH(OAc) 3 gives γ-substituted amines 8. 8 (D) 5-Alkyl Meldrum's acids 1 are used for the rapid synthesis of 2-alkyl acrylates 9 via Mannich-type reactions. The advantage of the method is the clean conversion into products due to the formation of volatile by-products -acetone, carbon dioxide, and dimethylamine. 9

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Radical Cyclization Cascades of Unsaturated Meldrum’s Acid Derivatives

Cited by 55 publications

References 36 publications

Recent Advances in the Chemistry of SmI2–H2O

Recent Advances in the Chemistry of SmI2–H2O

Mechanistic Study and Development of Catalytic Reactions of Sm(II)

5-Alkyl and 5,5-Dialkyl Meldrum’s Acids

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