Indium-Promoted Reformatsky Reaction: A Straightforward Access to β-Amino and β-Hydroxy α,α-Difluoro Carbonyl Compounds

Poisson, Thomas; Belhomme, Marie‐Charlotte; Pannecoucke, Xavier

doi:10.1021/jo301873y

Cited by 56 publications

(30 citation statements)

References 59 publications

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“…Finally, indium beads were tested but no conversion was obtained. 27 Scheme 6. Attempts to synthesize enantiopure sulfoxide 7a by performing Reformatsky-type reactions on enantiopure (-)-menthyl (S)-p-toluenesulfinate 19…”

Section: Scheme 4 Preparation Of a Less Electron-deficient Sulfide Amentioning

confidence: 99%

Efficient asymmetric synthesis of aryl difluoromethyl sulfoxides and their use to access enantiopure α-difluoromethyl alcohols

et al. 2019

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The-CHF2 moiety has shown a growing interest in pharmaceutical and agrochemical applications over the last few years. Its introduction is therefore a current research topic for organic chemists. Several groups have reported the synthesis of difluoromethylated compounds. However, the more challenging enantioselective introduction of the difluoromethyl group has been scarcely described yet. We recently developed a new strategy, based on the use of an enantiopure difluoromethyl sulfoxide used as chiral and traceless auxiliary, for the synthesis of highly enantioenriched αdifluoromethyl alcohols. 8 The first method developed in our laboratory aims to access highly stereoenriched α,α-difluoro-β-hydroxysulfoxides through the condensation of the enantiopure difluoromethyl sulfoxide on carbonyl derivatives. It is noteworthy that highly diastereo-and enantioenriched α,α-difluoro-β-hydroxysulfoxides can also be accessed after the diastereoselective reduction of highly enantioenriched α,α-difluoro-β-ketosulfoxides. Finally, the expected difluoromethyl-substituted alcohols can be obtained after removal of the chiral auxiliary with complete retention of stereoenrichment at carbon.

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Section: Scheme 4 Preparation Of a Less Electron-deficient Sulfide Amentioning

confidence: 99%

Efficient asymmetric synthesis of aryl difluoromethyl sulfoxides and their use to access enantiopure α-difluoromethyl alcohols

et al. 2019

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“…The Reformatsky reaction was first investigated by a short optimization effort using sulfiminine 8S, which was predicted to proceed with matched double diastereoselection. 30 Promotion by indium 34 4 , DCM Next, the Reformatsky reaction was investigated on a range of sulfinylimines (Table 3).…”

Section: N S T-bumentioning

confidence: 99%

Stereoselectivity of the Honda–Reformatsky Reaction in Reactions with Ethyl Bromodifluoroacetate with α-Oxygenated Sulfinylimines

et al. 2014

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Abstract-The Reformatsky reaction of ethyl bromodifluoroacetate to α-oxygenated sulfinylimines is described. Using Honda-Reformatsky conditions, the reaction proceeds with double diastereodifferentiation, with the configuration of the sulfinyl group determining the stereochemical course of the reaction. Excellent diastereoselectivities (>94:6) are obtained for the matched cases. In contrast, reaction with sulfinylimines derived from unsubstituted alkanals proceeded with virtually no diastereoselectivity.

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“…Recent progress in difluoromethylene chemistry successfully led to the finding of bioactive compounds such as pantoprazole, a proton pump in-hibitor [5], and AFP-07, a prostaglandin I2 receptor-selective agonist [6][7][8], which suggests the importance of the difluoromethylene unit in drug discovery (Figure 1). There have been many reports for the construction of the difluoromethylene unit, such as the deoxygenating conversion of a carbonyl group to the difluoromethylene unit using N,N-diethylaminosulfur trifluoride (DAST) [9][10][11][12][13][14], the Reformatsky reaction of ethyl bromodifluoroacetate [15][16][17][18][19][20][21][22][23], and transformations of tetrafluoroethylene using suitable metal catalysts [24][25][26][27][28][29][30][31]. Additionally, recent advances in difluoromethylene chemistry have demon- strated the synthesis of aryl fluoroalkyl ethers as shown in Scheme 1 [32][33][34].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of aryl 2-bromo-2-chloro-1,1-difluoroethyl ethers through the base-mediated reaction between phenols and halothane

Karuo¹,

Kametani²,

Tarui³

et al. 2021

Beilstein J. Org. Chem.

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An efficient and convenient method for the synthesis of structurally unique and highly functionalized aryl 2-bromo-2-chloro-1,1-difluoroethyl ethers has been developed. This approach exhibits a broad reaction scope, a simple operation and without the need of any expensive transition-metal catalyst, highly toxic or corrosive reagents. Notably, we demonstrate the potential utility of halothane for the synthesis of aryl gem-difluoroalkyl ethers containing the bromochloromethyl group.

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Indium-Promoted Reformatsky Reaction: A Straightforward Access to β-Amino and β-Hydroxy α,α-Difluoro Carbonyl Compounds

Cited by 56 publications

References 59 publications

Efficient asymmetric synthesis of aryl difluoromethyl sulfoxides and their use to access enantiopure α-difluoromethyl alcohols

Efficient asymmetric synthesis of aryl difluoromethyl sulfoxides and their use to access enantiopure α-difluoromethyl alcohols

Stereoselectivity of the Honda–Reformatsky Reaction in Reactions with Ethyl Bromodifluoroacetate with α-Oxygenated Sulfinylimines

Synthesis of aryl 2-bromo-2-chloro-1,1-difluoroethyl ethers through the base-mediated reaction between phenols and halothane

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