First asymmetric intermolecular bromoesterification catalyzed by chiral Brønsted acid

The first successful enantioselective intermolecular bromoesterification was realized by using a chiral phosphoric acid as a catalyst. The reaction was optimized after screening 2-aminopyridine based basic catalysts, cinchona alkaloid based basic catalysts, and binol backbone based Brønsted acid catalysts. Up to 70% ee and a moderate yield were achieved under the optimized condition. An ion-pair mechanism has been suggested in order to explain the reaction results.

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(1S,2S)-2-Bromocyclohexyl benzoateC13H15BrO2[α]D25=+12.6 (c 0.1, CH2Cl2) ee: 55%Source of chirality: the precursorAbsolute configuration: (1S,2S)

(1S,2S)-2-Bromocyclohexyl 4-methoxybenzoateC14H17BrO3[α]D25=+2.5 (c 0.07, CH2Cl2) ee 40%Source of chirality: the precursorAbsolute configuration: (1S,2S)

(1S,2S)-2-Bromocyclohexyl 4-nitrobenzoateC13H14BrNO4[α]D25=+1.6 (c 0.07, CH2Cl2) ee 41%Source of chirality: the precursorAbsolute configuration: (1S,2S)

(1S,2S)-2-Bromocyclohexyl 4-cyanobenzoateC14H14BrNO2[α]D25=+4.8 (c 0.07, CH2Cl2) ee: 35%Source of chirality: the precursorAbsolute configuration: (1S,2S)

(1S,2S)-2-Bromocyclohexyl 2-hydroxybenzoateC13H15BrO3[α]D25=+3.5 (c 0.1, CH2Cl2) ee 34%Source of chirality: the precursorAbsolute configuration: (1S,2S)

(1S,2S)-2-Bromocyclohexyl 2-oxo-2-phenylacetateC14H15BrO3[α]D25=+7.1 (c 0.10, CH2Cl2) ee 30%Source of chirality: the precursorAbsolute configuration: (1S,2S)

(1S,2S)-2-Bromocyclohexyl 2-(furan-2-yl)-2-oxoacetateC12H13BrO4[α]D25=+2.2 (c 0.10, CH2Cl2) ee: 44%Source of chirality: the precursorAbsolute configuration: (1S,2S)

(1S,2S)-2-Bromocyclohexyl 2-oxo-2-(thiophen-2-yl)acetateC12H13BrO3S[α]D25=+7.7 (c 0.1, CH2Cl2) ee 39%Source of chirality: the precursorAbsolute configuration: (1S,2S)

(1S,2S)-2-Bromocyclohexyl 2-phenylacetateC14H17BrO3[α]D25=+11 (c 0.15, CH2Cl2) ee 57%Source of chirality: the precursorAbsolute configuration: (1S,2S)

(1S,2S)-2-Bromocyclohexyl 2-(2-methoxyphenyl)acetateC15H19BrO3[α]D25=+6.2 (c 0.10, CH2Cl2) ee: 70%Source of chirality: the precursorAbsolute configuration: (1S,2S)

(1S,2S)-2-Bromocyclohexyl 2-(3-methoxyphenyl)acetateC15H19BrO3[α]D25=+10.2 (c 0.7, CH2Cl2) ee 67%Source of chirality: the precursorAbsolute configuration: (1S,2S)

(1S,2S)-2-Bromocyclohexyl 2-(4-methoxyphenyl)acetateC15H19BrO3[α]D25=+14.2 (c 0.1, CH2Cl2) ee 69%Source of chirality: the precursorAbsolute configuration: (1S,2S)

(1S,2S)-2-Bromocyclohexyl 2-(4-fluorophenyl)acetateC14H16BrFO2[α]D25=+10.2 (c 0.20, CH2Cl2) ee: 53%Source of chirality: the precursorAbsolute configuration: (1S,2S)

(1S,2S)-2-Bromocyclohexyl 2-(2-nitrophenyl)acetateC14H16BrNO4[α]D25=+2.2 (c 0.07, CH2Cl2) ee 63%Source of chirality: the precursorAbsolute configuration: (1S,2S)

(1S,2S)-2-Bromocyclohexyl 2-(naphthalen-1-yl)acetateC18H19BrO2[α]D25=+5.0 (c 0.1, CH2Cl2) ee 53%Source of chirality: the precursorAbsolute configuration: (1S,2S)

(1S,2S)-2-Bromocyclohexyl 1-naphthoateC17H17BrO2[α]D25=+4.8 (c 0.10, CH2Cl2) ee: 28%Source of chirality: the precursorAbsolute configuration: (1S,2S)

(1S,2S)-2-Bromocyclohexyl 3-phenylpropanoateC15H19BrO2[α]D25=+8.5 (c 0.1, CH2Cl2) ee 33%Source of chirality: the precursorAbsolute configuration: (1S,2S)

(1S,2S)-2-Bromocyclopentyl benzoateC12H13BrO2[α]D25=+3.7 (c 0.1, CH2Cl2) ee 20%Source of chirality: the precursorAbsolute configuration: (1S,2S)

(1S,2S)-2-Bromocyclooctyl benzoateC17H17BrO2[α]D25=+5.8 (c 0.10, CH2Cl2) ee: 10%Source of chirality: the precursorAbsolute configuration: (1S,2S)

(2R,3S)-3-Bromotetrahydro-2H-pyran-2-yl benzoateC12H13BrO3[α]D25=+2.8 (c 0.1, CH2Cl2) ee 7.5%Source of chirality: the precursorAbsolute configuration: (1S,2S)