Enantiopure hydroxymethylated cycloalkenols as privileged small molecular multifunctional scaffolds for the asymmetric synthesis of carbocycles

Enantiopure hydroxymethylated cycloalkenols bearing a quaternary stereocenter have been synthesized by a Pybox mediated enantioselective desymmetrization method. The synthesized cycloalkenols serve as starting precursors for the construction of several chiral small ring carbocyclic frameworks by a distinct functional group transformation.

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(R)-2-(Hydroxymethyl)-2-methylpent-4-enyl benzoateC14H18O3[α]D28 = +5.2 (c 1.0, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (2R)

(R)-2-((4-Methoxybenzyloxy)methyl)-2-methylpent-4-enyl benzoateC22H26O4[α]D28 = +6.8 (c 0.8, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (2R)

(S)-2-((4-Methoxybenzyloxy)methyl)-2-methylpent-4-en-1-olC15H22O3[α]D28 = −4.2 (c 1.0, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (2S)

(1S,5R)-5-((4-Methoxybenzyloxy)methyl)-5-methylcyclopent-2-enolC15H20O3[α]D28 = +24.6 (c 0.5, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (1S,5R)

(1S,5R)-5-(Hydroxymethyl)-5-methylcyclopent-2-enolC7H12O2[α]D28 = +48.8 (c 0.6, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (1S,5R)

(1R,5R)-5-((4-Methoxybenzyloxy)methyl)-5-methylcyclopent-2-enolC15H20O3[α]D28 = +73.2 (c 1.2, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (1R,5R)

(1R,5R)-5-(Hydroxymethyl)-5-methylcyclopent-2-enolC7H12O2[α]D28 = +42.2 (c 0.8, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (1R,5R)

(S)-2-((tert-Butyldiphenylsilyloxy)methyl)-2-methylpent-4-enyl benzoateC30H36O3Si[α]D28 = +10.2 (c 0.5, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (2S)

(S)-2-((tert-Butyldiphenylsilyloxy)methyl)-2-methylpent-4-en-1-olC23H32O2Si[α]D28 = +6.8 (c 0.3, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (2S)

(R)-2-((4-Methoxybenzyloxy)methyl)-2-methylpent-4-en-1-olC15H22O3[α]D28 = +4.6 (c 1.0, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (2R)

(1S,6R)-6-((4-Methoxybenzyloxy)methyl)-6-methylcyclohex-3-enolC16H22O3[α]D28 = +22.8 (c 0.8, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (1S,6R)

(1R,6R)-6-((4-Methoxybenzyloxy)methyl)-6-methylcyclohex-3-enolC16H22O3[α]D28 = +58.8 (c 1.1, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (1R,6R)

(1R,2R,3R,4R)-4-((4-Methoxybenzyloxy)methyl)-4-methylcyclopentane-1,2,3-triolC15H22O5[α]D28 = +33.8 (c 1.2, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (1R,2R,3R,4R)

(1S,2S,3R,4R)-4-((4-Methoxybenzyloxy)methyl)-4-methylcyclopentane-1,2,3-triolC15H22O5[α]D28 = −12.8 (c 0.5, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (1S,2S,3R,4R)

(1R,2R,3R,5S)-3-((4-Methoxybenzyloxy)methyl)-3-methyl-6-oxabicyclo[3.1.0]hexan-2-olC15H20O4[α]D28 = −23.9 (c 0.5, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (1R,2R,3R,5S)

(1S,2R,3R,4R)-4-((4-Methoxybenzyloxy)methyl)-4-methylcyclopentane-1,2,3-triolC15H22O5[α]D28 = +16.8 (c 1.0, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (1S,2R,3R,4R)

tert-Butyl((1S,5R)-5-((4-methoxybenzyloxy)methyl)-5-methylcyclopent-2-enyloxy)dimethylsilaneC21H34O3Si[α]D28 = +55.4 (c 0.8, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (1S,5R)

(1R,2R,3R,4R)-3-(tert-Butyldimethylsilyloxy)-4-((4-methoxybenzyloxy)methyl)-4-methylcyclopentane-1,2-diolC21H36O5Si[α]D28 = +10.8 (c 1.1, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (1R,2R,3R,4R)

(1S,2S,3R,4R)-3-(tert-Butyldimethylsilyloxy)-4-((4-methoxybenzyloxy)methyl)-4-methylcyclopentane-1,2-diolC21H36O5Si[α]D28 = +38.8 (c 1.2, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (1S,2S,3R,4R)

tert-Butyl((3aR,4R,5R,6aR)-5-((4-methoxybenzyloxy)methyl)-2,2,5-trimethyltetrahydro-3aH-openta[d][1,3]dioxol-4-yloxy)dimethylsilaneC24H40O5Si[α]D28 = +22.6 (c 0.8, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (3aR,4R,5R,6aR)

((3aR,4R,5R,6aR)-4-(tert-Butyldimethylsilyloxy)-2,2,5-trimethyltetrahydro-3aH-clopenta[d][1,3]dioxol-5-yl)methanolC16H32O4Si[α]D28 = +44.2 (c 0.8, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (3aR,4R,5R,6aR)

tert-Butyldimethyl((3aR,4R,5R,6aR)-2,2,5-trimethyl-5-vinyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yloxy)silaneC17H32O3Si[α]D28 = +8.7 (c 0.4, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (3aR,4R,5R,6aR)

(3aR,4R,5R,6aR)-4-(Allyloxy)-2,2,5-trimethyl-5-vinyltetrahydro-3aH-cyclopenta[d][1,3]dioxoleC14H22O3[α]D28 = −12.6 (c 1.1, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (3aR,4R,5R,6aR)

((3R,4S,4aS,6R,7R,7aR)-4a-Methyloctahydrocyclopenta[b]pyran-3,4,6,7-tetrayl tetraacetatelC17H24O9[α]D28 = +78.2 (c 1.2, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (3R,4S,4aS,6R,7R,7aR)

(1S,2S,3R,5S)-3-((4-Methoxybenzyloxy)methyl)-3-methylbicyclo[3.1.0]hexan-2-olC16H22O3[α]D28 = −23.8 (c 0.4, MeOH)source of chirality: Asymmetric synthesisAbsolute configuration: (1S,2S,3R,5S)

tert-Butyl((1S,2S,3R,5S)-3-((4-methoxybenzyloxy)methyl)-3-methylbicyclo[3.1.0]hexan-2-yloxy)dimethylsilaneC22H36O3Si[α]D28 = −32.6 (c 1.0, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (1S,2S,3R,5S)

((1S,2S,3R,5S)-2-(tert-Butyldimethylsilyloxy)-3-methylbicyclo[3.1.0]hexan-3-yl)methanolC14H28O2Si[α]D28 = −22.8 (c 0.5, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (1S,2S,3R,5S)

tert-Butyldimethyl((1S,2S,3R,5S)-3-methyl-3-vinylbicyclo[3.1.0]hexan-2-yloxy)silaneC15H28OSi[α]D28 = −17.8 (c 1.2, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (1S,2S,3R,5S)

(1S,2S,3R,5S)-3-Methyl-3-vinylbicyclo[3.1.0]hexan-2-olC9H14O[α]D28 = −12.2 (c 1.0, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (1S,2S,3R,5S)

(1S,2S,3R,5S)-2-(Allyloxy)-3-methyl-3-vinylbicyclo[3.1.0]hexaneC12H18O[α]D28 = −29.8 (c 1.0, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (1S,2S,3R,5S)

(1S,3S,4R,6R)-4-((4-Methoxybenzyloxy)methyl)-4-methyl-7-oxabicyclo[4.1.0]heptan-3-olC16H22O4[α]D28 = +13.8 (c 0.3, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (1S,3S,4R,6R)

(1R,3S,4R,6S)-4-((4-Methoxybenzyloxy)methyl)-4-methyl-7-oxabicyclo[4.1.0]heptan-3-olC16H22O4[α]D28 = −18.2 (c 1.1, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (1R,3S,4R,6S)

(1S,2S,4S,5R)-5-(Hydroxymethyl)-5-methylcyclohexane-1,2,4-triolC8H16O4[α]D28 = +33.5 (c 1.1, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (1S,2S,4S,5R)

(1S,4R,6S)-4-((4-Methoxybenzyloxy)methyl)-4-methylbicyclo[4.1.0]heptan-3-olC17H24O3[α]D28 = −28.0 (c 1.1, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (1R,3S,4R,6S)

tert-Butyl((1S,6R)-6-((4-Methoxybenzyloxy)methyl)-6-methylcyclohex-3-enyloxy)dimethylsilaneC22H36O3Si[α]D28 = +38.8 (c 0.9, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: 1S,6R

(1S,2R,4R,5S)-5-(tert-Butyldimethylsilyloxy)-4-((4-methoxybenzyloxy)methyl)-4-methylcyclohexane-1,2-diolC22H38O5Si[α]D28 = +44.2 (c 1.0, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: 1S,2R,4R,5S

(1S,2R,4R,5S)-5-(tert-Butyldimethylsilyloxy)-4-((4-methoxybenzyloxy)methyl)-4-methylcyclohexane-1,2-diolC22H38O5Si[α]D28 = +32.8 (c 0.6, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (1R,2S,4R,5S)

tert-Butyl((3aS,5S,6R,7aR)-6-((4-methoxybenzyloxy)methyl)-2,2,6-trimethylhexahydrobenzo[d][1,3]dioxol-5-methylsilaneC25H42O5Si[α]D28 = +23.8 (c 1.0, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (3aS,5S,6R,7aR)

((3aR,5R,6S,7aS)-6-(tert-Butyldimethylsilyloxy)-2,2,5-trimethylhexahydrobenzo[d][1,3]dioxol-5-yl)methanolC17H34O4Si[α]D28 = +22.8 (c 1.0, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (3aR,5R,6S,7aS)

tert-Butyldimethyl((3aS,5S,6R,7aR)-2,2,6-trimethyl-6-vinylhexahydrobenzo[d][1,3]dioxol-5-yloxy)silaneC18H34O3Si[α]D28 = +12.4 (c 0.8, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (3aS,5S,6R,7aR)

(3aS,5S,6R,7aR)-2,2,6-Trimethyl-6-vinylhexahydrobenzo[d][1,3]dioxol-5-olC12H20O3[α]D28 = +8.6 (c 0.6, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (3aS,5S,6R,7aR)

(3aR,5R,6S,7aS)-6-(Allyloxy)-2,2,5-trimethyl-5-vinylhexahydrobenzo[d][1,3]dioxoleC15H24O3[α]D28 = +25.4 (c 1.0, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (3aR,5R,6S,7aS)

(3aS,4aS,8aR,9aR)-2,2,8a-Trimethyl-4,4a,6,8a,9,9a-hexahydro-3aH-[1,3]dioxolo[4,5-g]chromeneC13H20O3[α]D28 = +38.2 (c 1.0, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (3aS,4aS,8aR,9aR)

(3aS,4aS,7R,8S,8aR,9aR)-2,2,8a-Trimethyloctahydro-3aH-[1,3]dioxolo[4,5-g]chromene-7,8-diolC13H22O5[α]D28 = +44.2 (c 0.8, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (3aS,4aS,7R,8S,8aR,9aR)

(3R,4S,4aR,6R,7S,8aS)-4a-Methyloctahydro-2H-chromene-3,4,6,7-tetraolC10H18O5[α]D28 = +69.2 (c 1.0, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (3R,4S,4aR,6R,7S,8aS)