Stereoselective synthesis of optically active cyclopenta[c]pyrans and cyclopenta[c]furans by the intramolecular Pauson–Khand reaction

An intramolecular Pauson–Khand reaction of enynes derived from homoallyl, homopropargyl, and allyl alcohols is described. 2-Heteroaryl-substituted homoallyl, homopropargyl, and allyl alcohols are easily and efficiently resolved through enzymatic resolution in high ee (91–99%) and with a known stereochemistry. Each enantiomerically enriched enyne derived from homoallyl and homopropargyl alcohols affords the conformationally most stable diastereomeric cyclopenta[c]pyran ring system as the sole product, whereas enantiomerically enriched enynes derived from allyl alcohols give a diastereomeric cis:trans mixture of the cyclopenta[c]furan ring system.

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(S)-(−)-2-(1-(Prop-2-ynyloxy)but-3-enyl)thiopheneC11H12OSEe = 99%[α]D28=-97.6 (c 1.3, CH2Cl2)Source of chirality: enzymatic resolutionAbsolute configuration: (1S)

(S)-(−)-2-(1-(Prop-2-ynyloxy)but-3-enyl)pyridineC12H13NOEe = 98%[α]D26=-136.9 (c 3.0, CH2Cl2)Source of chirality: enzymatic resolutionAbsolute configuration: (1S)

(S)-(−)-2-(1-(Allyloxy)but-3-ynyl)thiopheneC11H12OSEe = 99%[α]D29=-33.1 (c 1.3, CH2Cl2)Source of chirality: enzymatic resolutionAbsolute configuration: (1S)

(S)-(−)-2-(1-(Allyloxy)but-3-ynyl)pyridineC12H13NOEe = 98%[α]D18=-63.6 (c 0.9, CH2Cl2)Source of chirality: enzymatic resolutionAbsolute configuration: (1S)

(S)-(−)-2-(1-(Prop-2-ynyloxy)allyl)furanC10H10O2Ee = 99%[α]D20=-7.1 (c 1.0, CH2Cl2)Source of chirality: enzymatic resolutionAbsolute configuration: (1S)

(S)-(−)-2-(1-(Prop-2-ynyloxy)allyl)thiopheneC10H10OSEe = 97%[α]D22=-13.4 (c 1.0, CH2Cl2)Source of chirality: enzymatic resolutionAbsolute configuration: (1S)

(S)-(−)-2-(1-(Prop-2-ynyloxy)allyl)pyridineC11H11NOEe = 91%[α]D15=-7.0 (c 1.0, CH2Cl2)Source of chirality: enzymatic resolutionAbsolute configuration: (1S)

(3S,4aR)-(+)-3-(Thiophen-2-yl)-3,4,4a,5-tetrahydrocyclopenta[c]pyran-6(1H)-oneC12H12O2SEe = 99%[α]D18=+53.4 (c 1.6, CH2Cl2)Source of chirality: enzymatic resolutionAbsolute configuration: (3S,4aR)

(3S,4aR)-(+)-3-(Pyridin-2-yl)-3,4,4a,5-tetrahydrocyclopenta[c]pyran-6(1H)-oneC13H13NO2Ee = 98%[α]D18=+33.6 (c 1.0, CH2Cl2)Source of chirality: enzymatic resolutionAbsolute configuration: (3S,4aR)

(3S,7aR)-(+)-3-(Thiophen-2-yl)-3,4,7,7a-tetrahydrocyclopenta[c]pyran-6(1H)-oneC12H12O2SEe = 99%[α]D18=+250.0 (c 0.45, MeOH)Source of chirality: enzymatic resolutionAbsolute configuration: (3S,7aR)

(3S,7aR)-(+)-3-(Pyridin-2-yl)-3,4,7,7a-tetrahydrocyclopenta[c]pyran-6(1H)-oneC13H13NO2Ee = 98%[α]D18=+126.1 (c 1.0, MeOH)Source of chirality: enzymatic resolutionAbsolute configuration: (3S,7aR)

(3S,3aR)-(−)-3-(Furan-2-yl)-3a,4-dihydro-1H-cyclopenta[c]furan-5(3H)-oneC11H10O3Ee = 99%[α]D18=-30.1 (c 1.0, CH2Cl2)Source of chirality: enzymatic resolutionAbsolute configuration: (3S,3aR)

(3S,3aS)-(+)-3-(Furan-2-yl)-3a,4-dihydro-1H-cyclopenta[c]furan-5(3H)-oneC11H10O3Ee = 99%[α]D20=+39.8 (c 0.83, CH2Cl2)Source of chirality: enzymatic resolutionAbsolute configuration: (3S,3aS)

(3S,3aR)-(−)-3-(Thiophen-2-yl)-3a,4-dihydro-1H-cyclopenta[c]furan-5(3H)-oneC11H10O2SEe = 97%[α]D22=-32.0 (c 1.0, CH2Cl2)Source of chirality: enzymatic resolutionAbsolute configuration: (3S,3aR)

(3S,3aS)-(+)-3-(Thiophen-2-yl)-3a,4-dihydro-1H-cyclopenta[c]furan-5(3H)-oneC11H10O2SEe = 97%[α]D22=+128.2 (c 1.0, CH2Cl2)Source of chirality: enzymatic resolutionAbsolute configuration: (3S,3aS)

(3S,3aS)-(+)-3-(Pyridin-2-yl)-3a,4-dihydro-1H-cyclopenta[c]furan-5(3H)-oneC12H11NO2Ee = 91%[α]D24=+85.5 (c 1.0, CH2Cl2)Source of chirality: enzymatic resolutionAbsolute configuration: (3S,3aS)

(3S,3aR)-(−)-3-(Pyridin-2-yl)-3a,4-dihydro-1H-cyclopenta[c]furan-5(3H)-oneC12H11NO2Ee = 91%[α]D18=-27.6 (c 0.5, CH2Cl2)Source of chirality: enzymatic resolutionAbsolute configuration: (3S,3aR)