Desymmetrization of meso-methylenecyclopropanes by a palladium-catalyzed asymmetric ring-opening bis(alkoxycarbonylation) reaction

Desymmetrization of various meso-methylenecyclopropanes was accomplished by a palladium-catalyzed asymmetric ring-opening bis(alkoxycarbonylation) reaction employing a chiral bioxazoline ligand. The reaction proceeded smoothly in the presence of copper(I) triflate under carbon monoxide and oxygen at ambient pressure to give the corresponding optically active α-methyleneglutarates with up to 60% ee. Desymmetrization of protected meso-(3-methylenecyclopropane-1,2-diyl)dimethanols was also carried out to give enantioenriched highly oxygen-functionalized α-methyleneglutarates.

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(S,S)-4,4′-Bis(1-naphthalenylmethyl)-4,4′,5,5′-tetrahydro-2,2′-bioxazoleC28H24N2O2Ee = 100%[α]D25 = −5 (c 0.9, CHCl3)Source of chirality: (S)-2-amino-3-(1-naphthalenyl)-1-propanolAbsolute configuration: (S,S)

(R,R)-4,4′-Bis(2-naphthalenylmethyl)-4,4′,5,5′-tetrahydro-2,2′-bioxazoleC28H24N2O2Ee = 100%[α]D25 = −26 (c 0.3, CHCl3)Source of chirality: (R)-2-amino-3-(2-naphthaleny)-1-propanolAbsolute configuration: (R,R)

(1R,2S)-Methyl 2-(3-methoxy-3-oxo-1-propen-2-yl)cyclohexanecarboxylateC12H18O4Ee = 60%[α]D25 = −49 (c 0.6, EtOH)Source of chirality: asymmetric ring-opening bis(alkoxycarbonylation) reactionAbsolute configuration: (1R,2S)

(1R,2S)-Methyl 2-(3-methoxy-3-oxo-1-propen-2-yl)cyclooctanecarboxylateC14H22O4Ee = 45%[α]D25 = −11 (c 0.1, EtOH)Source of chirality: asymmetric ring-opening bis(alkoxycarbonylation) reactionAbsolute configuration: (1R,2S)

(2S,3S)-Dimethyl 2,3-bis((benzyloxy)methyl)-4-methylenepentanedioateC24H28O6Ee = 28%[α]D25 = +6 (c 1.3, EtOH)Source of chirality: asymmetric ring-opening bis(alkoxycarbonylation) reactionAbsolute configuration: (2S,3S)

(3S,4S)-Dimethyl 2-methylene-3,4-bis((trityloxy)methyl)pentanedioateC48H44O6Ee = 42%[α]D25 = +5 (c 0.5, EtOH)Source of chirality: asymmetric ring-opening bis(alkoxycarbonylation) reactionAbsolute configuration: (3S,4S)

(3S,4S)-Dimethyl 2-methylene-3,4-bis((triphenylsilyloxy)methyl)pentanedioateC46H44O6Si2Ee = 48%[α]D25 = +6 (c 1.5, CHCl3)Source of chirality: asymmetric ring-opening bis(alkoxycarbonylation) reactionAbsolute configuration: (3S,4S)

(2S,3S)-Dimethyl 2,3-bis((tert-butyldiphenylsilyloxy)methyl)-4-methylenepentanedioateC42H52O6Si2Ee = 51%[α]D25 = +3 (c 1.9, EtOH)Source of chirality: asymmetric ring-opening bis(alkoxycarbonylation) reactionAbsolute configuration: (2S,3S)

(1S,4R)-2-((1S,2R)-2-((((1S,4R)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carbonyl)oxy)methyl)cyclohexyl)allyl 4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carboxylateC30H42O8Ee = 100%[α]D25 = −11 (c 0.1, EtOH)Source of chirality: asymmetric ring-opening bis(alkoxycarbonylation) reactionAbsolute configuration: (1S,4R),(1S,2R),(1S,4R)