Stereospecificity of the Au(I)-catalyzed reaction of 1-alkynyl-bicyclo[4.1.0]-heptan-2-ones with nucleophiles

The stereospecificity of the Au(I)-catalyzed reaction of 1-alkynyl-bicyclo[4.1.0]-heptan-2-ones with nucleophiles was investigated. The substrates were prepared in non-racemic form (up to 88% ee) through parallel kinetic resolution (CBS reduction) and reoxidation of the separated diastereomeric alcohols. The key Au-catalyzed reaction was then found to proceed without significant loss of absolute stereochemical information; this way, an achiral carbocationic intermediate could be excluded. Thus, a bicyclobutonium-type intermediate seems to be attacked in a SN2-type fashion by the nucleophile in accordance with computational predictions.

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(1R,2R,6S)-1-Phenylethynylbicyclo[4.1.0]heptan-2-olC15H16OEe 71%[α]λ (20 °C, CHCl3, c 1): [α]589 = 73.4, [α]546 = 88.4, [α]405 = 200.9, [α]365 = 280.4Source of chirality: parallel kinetic resolution of rac-1-(phenylethynyl)-bicyclo[4.1.0]heptan-2-one using (S)-CBS catalystAbsolute configuration: (1R,2R,6S)

(1S,2R,6R)-1-Phenylethynylbicyclo[4.1.0]heptan-2-olC15H16OEe 88%[α]λ (20 °C, CHCl3, c 1): [α]589 = −90.5, [α]546 = −108.8, [α]405 = −242.9, [α]365 = −338.2, [α]334 = −470.1Source of chirality: parallel kinetic resolution of rac-1-(phenylethynyl)-bicyclo[4.1.0]heptan-2-one using (S)-CBS catalystAbsolute configuration: (1S,2R,6R)

(1S,6R)-1-(Phenylethynyl)-bicyclo[4.1.0]heptan-2-oneC15H14OEe 86%[α]λ (20 °C, CHCl3, c 1): [α]589 = −23.2, [α]546 = −24.3, [α]405 = 16.6, [α]365 = 115.5, [α]334 = 419.3(1S,2R,6R)-1-Phenylethynylbicyclo[4.1.0]heptan-2-olAbsolute configuration: (1S,6R)

(1R,2R,6S)-1-Hex-1-ynylbicyclo[4.1.0]heptan-2-olC13H20OEe could not be determined[α]λ (20 °C, CHCl3, c 1): [α]589 = 46.3, [α]546 = 83.6, [α]405 = 121.1, [α]365 = 163.0Source of chirality: parallel kinetic resolution of rac-1-hex-1-ynyl-bicyclo[4.1.0]heptan-2-one using (S)-CBS catalystAbsolute configuration: (1R,2R,6S)

(1S,2R,6R)-1-Hex-1-ynylbicyclo[4.1.0]heptan-2-olC13H20OEe 81%[α]λ (20 °C, CHCl3, c 1): [α]589 = −38.1, [α]546 = −44.8, [α]405 = −88.3, [α]365 = −113.5Source of chirality: parallel kinetic resolution of rac-1-hex-1-ynyl-bicyclo[4.1.0]heptan-2-one using (S)-CBS catalystAbsolute configuration: (1S,2R,6R)

(1S,6R)-1-Hex-1-ynyl-bicyclo[4.1.0]heptan-2-oneC13H18OEe 79%[α]λ (20 °C, CHCl3, c 1): [α]589 = −13.0, [α]546 = −13.8, [α]405 = −1.9, [α]365 = +29.6Source of chirality: (1S,2R,6R)-1-hex-1-ynylbicyclo[4.1.0]heptan-2-olAbsolute configuration: (1S,6R)

(S)-2-Phenyl-5-methoxy-5,6,7,8-tetrahydro-4H-cyclohepta[b]furanC16H18O2Ee 83%[α]λ (20 °C, CHCl3, c 1): [α]589 = −3.2, [α]546 = −5.0, [α]405 = −27.2, [α]365 = −61.9Source of chirality: (1S,6R)-1-(phenylethynyl)-bicyclo[4.1.0]heptan-2-oneAbsolute configuration: (S)

(S)-5-tert-Butoxy-5,6,7,8-tetrahydro-2-phenyl-4H-cyclohepta[b]furanC19H24O2Ee 83%[α]λ (20 °C, CHCl3, c 1): [α]589 = +7.1, [α]546 = +7.7, [α]405 = +4.6Source of chirality: (1S,6R)-1-(phenylethynyl)-bicyclo[4.1.0]heptan-2-oneAbsolute configuration: (S)

(S)-5,6,7,8-Tetrahydro-2-phenyl-5-(prop-2-ynyloxy)-4H-cyclohepta[b]furanC18H18O2Ee 77%[α]λ (20 °C, CHCl3, c 1): [α]589 = −18.9, [α]546 = −23.5, [α]405 = −103.1Source of chirality: (1S,6R)-1-(phenylethynyl)-bicyclo[4.1.0]heptan-2-oneAbsolute configuration: (S)

(S)-2-Butyl-5,6,7,8-tetrahydro-5-methoxy-4H-cyclohepta[b]furanC14H22O2Ee 79%[α]λ (20 °C, CHCl3, c 1): [α]589 = −2.9, [α]546 = −3.8, [α]405 = −13.8, [α]365 = −23.7Source of chirality: (1S,6R)-1-hex-1-ynyl-bicyclo[4.1.0]heptan-2-oneAbsolute configuration: (S)

(S)-5-tert-Butoxy-2-butyl-5,6,7,8-tetrahydro-4H-cyclohepta[b]furanC17H28O2Ee could not be determined[α]λ (20 °C, CHCl3, c 1): [α]589 = +7.5; [α]546 = +9.2; [α]405 = +16.0Source of chirality: (1S,6R)-1-hex-1-ynyl-bicyclo[4.1.0]heptan-2-oneAbsolute configuration: (S)

(S)-2-Butyl-5,6,7,8-tetrahydro-5-(prop-2-ynyloxy)-4H-cyclohepta[b]furanC16H22O2Ee 80%[α]λ (20 °C, CHCl3, c 1): [α]589 = −2.2, [α]546 = −2.7, [α]405 = −9.6, [α]365 = −17.2, [α]365 = −31.8Source of chirality: (1S,6R)-1-hex-1-ynyl-bicyclo[4.1.0]heptan-2-oneAbsolute configuration: (S)