Asymmetric synthesis of di- and trisubstituted pyrrolidinones via zirconium-mediated intramolecular coupling of N-3-alkenyl carbamates

N-3-Alkenyl carbamates, which are readily available in enantiomerically pure form, undergo a stereoselective intramolecular coupling under the effect of a Cp2ZrCl2/2n-BuLi reagent. The influence of the carbamate structure on the stereoselectivity was tested. The reaction gives an easy access to various di- and trisubstituted enantiopure pyrrolidinones.

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(R)-2-[(1-Methyl-1H-pyrrol-2-yl)methyleneamino]-2-phenylethanolC14H16N2O[α]D = −28 (c 0.3, CH2Cl2)Source of chirality: (R)-phenylglycinol

(R)-2-[(R) (1-Methyl-1H-pyrrol-2-yl)but-3-enylamino]-2-phenylethanolC17H22N2O[α]D = −44.5 (c 0.9, CH2Cl2)Source of chirality: (R)-phenylglycinol

(R)-3-[(R)-1-Phenylbut-3-enyl]-4-phenyloxozolidin-2-oneC19H19N2O[α]D = −11 (c 1.2, CH2Cl2)Source of chirality: (R)-phenylglycinol

(R)-3-[(R)-(1-Furan-2-yl)but-3-enyl]-4-phenyloxozolidin-2-oneC17H17NO3[α]D = −8.5 (c 1, CH2Cl2)Source of chirality: (R)-phenylglycinol

(R)-3-[(R)-1-(1-Methyl-1H-pyrrol-2-yl)but-3-enyl]-4-phenyloxozolidin-2-oneC18H20N2O2[α]D = −15.5 (c 1, CH2Cl2)Source of chirality: (R)-phenylglycinol

(R)-3-[(R)-1-(2-Methoxyphenyl)but-3-enyl]-4-phenyloxozolidin-2-oneC20H21NO3[α]D = −19 (c 0.8, CH2Cl2)Source of chirality: (R)-phenylglycinol

(R)-3-[(R)-1-(2-Methylhex-5-en-3-yl)]-4-phenyloxozolidin-2-oneC16H21NO2[α]D = −14(c 0.8, CH2Cl2)Source of chirality: (R)-phenylglycinol

(3R,5S)-1-[(R)-2-Hydroxy-1-phenylethyl]-3-methyl-5-phenylpyrrolidin-2-oneC19H21NO2[α]D = −22.5 (c 1.1, CH2Cl2)Source of chirality: (R)-phenylglycinol

(3R,5S)-3-Methyl-5-phenylpyrrolidin-2-oneC11H13NO[α]D = +39 (c 0.5, CH2Cl2)

(3R,5S)-1-[(R)-2-Hydroxy-1-phenylethyl]-3-methyl-5-(2-methoxyphenyl)pyrrolidin-2-oneC20H23NO3[α]D = +93 (c 0.2, CH2Cl2)Source of chirality: (R)-phenylglycinol

(3R,5S)-1-[(R)-2-Hydroxy-1-phenylethyl]-5-isopropyl-3-methylpyrrolidin-2-oneC16H23NO2[α]D = +24.5 (c 0.3, CH2Cl2)Source of chirality: (R)-phenylglycinol

(S)-tert-Butyl benzyl(non-1-en-4-yl)carbamateC21H33NO2[α]D = −11.9 (c 1, CH2Cl2)Source of chirality: (R)-phenylglycinol

(3R,5S)-1-Benzyl-3-methyl-5-pentylpyrrolidin-2-oneC17H25NO[α]D = −22.5 (c 0.5, CH2Cl2)

(R)-2-[(1R,2S)-2-Methyl-1-phenylbut-3-enylamino]-2-phenylethanolC19H23NO[α]D = −23(c 1, CH2Cl2)Source of chirality: (R)-phenylglycinol

(R)-2-[(3S,4R)-2-Methyl-4-phenylhex-5-en-3-ylamino]-2-phenylethanolC21H27NO[α]D = −123 (c 0.5, CH2Cl2)Source of chirality: (R)-phenylglycinol

(R)-2-[(1R,2R)-1-(Furan-2-yl)-2-phenylbut-3-enylamino]-2-phenylethanolC22H23NO2[α]D = −15 (c 0.45, CH2Cl2)Source of chirality: (R)-phenylglycinol

(R)-2-[(1R,2S)-1-Methyl-2-phenylbut-3-enyl]-4-phenyloxazolidin-2-oneC20H21NO2[α]D = −5.5 (c 1.4, CH2Cl2)Source of chirality: (R)-phenylglycinol

(R)-3-[(2R,3R)-1-Benzyloxy-3-phenylpent-4-en-2-yl]-4-phenyloxazolidin-2-oneC27H27NO3[α]D = −102 (c 1.3, CH2Cl2)Source of chirality: (R)-phenylglycinol

(R)-3-[(2R,3R)-1-Benzyloxy-3-phenylpent-4-en-2-yl]-4-phenyloxazolidin-2-oneC27H27NO3[α]D25=-219 (c 1, CH2Cl2)Source of chirality: (R)-phenylglycinol

(3S,4R,5S)-1-[(R)-2-Hydroxy-1-phenylethyl]-3,4-dimethyl-5-phenylpyrrolidin-2-oneC26H29NO3[α]D = +62 (c 1.1, CH2Cl2)

(3S,4S,5R)-1-[(R)-2-Hydroxy-1-phenylethyl]-3,4-dimethyl-5-phenyloxazolidin-2-oneC20H23NO2[α]D = −38(c 1, CH2Cl2)

(3S,4R,5R)-5-Benzyloxymethyl-1-[(R)-2-hydroxy-1-phenylethyl]-3-methyl-4-phenylpyrrolidin-2-oneC27H29NO3[α]D = −60 (c 0.6, CH2Cl2)Source of chirality: (R)-phenylglycinol

(3S,4R,5S)-1-[(R)-2-Hydroxy-1-phenylethyl]-5-isopropyl-3-methyl-4-phenylpyrrolidin-2-oneC22H27NO2[α]D = −75 (c 0.4, CH2Cl2)Source of chirality: (R)-phenylglycinol