A solution to the stereochemical problems posed by amaryllidaceae constituents using a highly syn-selective arylcuprate conjugate addition to γ-amino and γ-carbamato-α,β-enoates

Various substituted arylcuprates undergo stereocontrolled additions to l-serine-derived γ-amino- and γ-carbamato-α,β-enoates with high syn-selectivities. The stereochemical outcome of these reactions is fully consistent with the reductive elimination-based model proposed previously. This method is well suited for the preparation of a broad range of biologically active amaryllidaceae constituents and their aromatic analogues.

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Methyl (4R)-(E)-5-(tert-butyldiphenylsilanyloxy)-4-dibenzylaminopent-2-enoateC36H41NO3Si[α]D23=-21.4 (c 0.14, CHCl3)Source of chirality: l-serineAbsolute configuration: (R)

Methyl (3R,4R)-5-(tert-butyldiphenylsilanyloxy)-4-dibenzylamino-3-phenylpentanoateC42H47NO3Si[α]D23=-12.6 (c 0.15, CHCl3)Source of chirality: l-serineAbsolute configuration: (3R,4R)

Methyl (3R,4R)-5-(tert-butyldiphenylsilanyloxy)-4-dibenzylamino-3-(4-methoxyphenyl)pentanoateC43H49NO4Si[α]D24=-10.7 (c 0.06, CHCl3)Source of chirality: l-serineAbsolute configuration: (3R,4R)

Methyl (3R,4R)-5-(tert-butyldiphenylsilanyloxy)-4-dibenzylamino-3-(4-fluorophenyl)pentanoateC42H46FNO3Si[α]D24=-22.9 (c 0.02, CHCl3)Source of chirality: l-serineAbsolute configuration: (3R,4R)

Methyl (3R,4R)-5-(tert-butyldiphenylsilanyloxy)-4-dibenzylamino-3-(4-chlorophenyl)pentanoateC42H46ClNO3Si[α]D24=-11.8 (c 0.1, CHCl3)Source of chirality: l-serineAbsolute configuration: (3R,4R)

Methyl (3R,4R)-5-(tert-butyldiphenylsilanyloxy)-4-dibenzylamino-3-(3,4- dimethoxyphenyl)pentanoateC44H51NO5Si[α]D24=-13.6 (c 0.03, CHCl3)Source of chirality: l-serineAbsolute configuration: (3R,4R)

Methyl (3R,4R)-5-(tert-butyldiphenylsilanyloxy)-4-dibenzylamino-3-(benzo[1,3]dioxol-5-yl)pentanoateC43H48NO5Si[α]D24=-9.1 (c 0.01, CHCl3)Source of chirality: l-serineAbsolute configuration: (3R,4R)

(R)-tert-Butyl-4-((R)-2-(methoxycarbonyl)-1-phenylethyl)-2,2-dimethyloxazolidine-3-carboxylateC20H29NO5[α]D21=+35.7 (c 0.02, CHCl3)Source of chirality: l-serineAbsolute configuration: (R,R)

(R)-tert-Butyl-4-((R)-2-(methoxycarbonyl)-1-(4-methoxyphenyl)ethyl)-2,2-dimethyloxazolidine-3-carboxylateC21H31NO6[α]D21=+40.0 (c 0.02, CHCl3)Source of chirality: l-serineAbsolute configuration: (R,R)

(R)-tert-Butyl-4-((R)-2-(methoxycarbonyl)-1-(4-fluorophenyl)ethyl)-2,2-dimethyloxazolidine-3-carboxylateC20H28FNO5[α]D21=+33.6 (c 0.03, CHCl3)Source of chirality: l-serineAbsolute configuration: (R,R)

(R)-tert-Butyl-4-((R)-2-(methoxycarbonyl)-1-(4-chlorophenyl)ethyl)-2,2-dimethyloxazolidine-3-carboxylateC20H28ClNO5[α]D21=+26.0 (c 0.03, CHCl3)Source of chirality: l-serineAbsolute configuration: (R,R)

(R)-tert-Butyl-4-((R)-2-(methoxycarbonyl)-1-(3,4-dimethoxyphenyl)ethyl)-2,2-dimethyloxazolidine-3-carboxylateC22H33NO7[α]D21=+38.2 (c 0.01, CHCl3)Source of chirality: l-serineAbsolute configuration: (R,R)

(R)-tert-Butyl-4-((R)-2-(methoxycarbonyl)-1-(benzo[d][1,3]dioxol-6-yl)ethyl)-2,2-dimethyloxazolidine-3-carboxylateC21H29NO7[α]D21=+29.4 (c 0.02, CHCl3)Source of chirality: l-serineAbsolute configuration: (R,R)

(R)-tert-Butyl-4-((R)-2-(methoxycarbonyl)-1-(4-methoxybenzo[d][1,3]dioxol-6-yl)ethyl)-2,2-dimethyloxazolidine-3-carboxylateC22H31NO8[α]D21=+73.3 (c 0.01, CHCl3)Source of chirality: l-serineAbsolute configuration: (R,R)

(4R,5R)-5-(Hydroxymethyl)-4-phenylpyrrolidin-2-oneC11H13NO2[α]D23=-63.4 (c 0.01, CH3OH)Source of chirality: l-serineAbsolute configuration: (4R,5R)

(4R,5R)-5-(Hydroxymethyl)-4-(4-methoxyphenyl)pyrrolidin-2-oneC12H15NO3[α]D23=-95.7 (c 0.02, CH3OH)Source of chirality: l-serineAbsolute configuration: (4R,5R)

(4R,5R)-4-(4-Fluorophenyl)-5-(hydroxymethyl)pyrrolidin-2-oneC11H12FNO2[α]D23=-105.7 (c 0.03, CH3OH)Source of chirality: l-serineAbsolute configuration: (4R,5R)

(4R,5R)-4-(4-Chlorophenyl)-5-(hydroxymethyl)pyrrolidin-2-oneC11H12ClNO2[α]D23=-113.7 (c 0.01, CH3OH)Source of chirality: l-serineAbsolute configuration: (4R,5R)

(4R,5R)-5-(Hydroxymethyl)-4-(3,4-dimethoxyphenyl)pyrrolidin-2-oneC13H17NO4[α]D21=-110.0 (c 0.01, CH3OH)Source of chirality: l-serineAbsolute configuration: (4R,5R)

(4R,5R)-4-(Benzo[d][1,3]dioxol-6-yl)-5-(hydroxymethyl)pyrrolidin-2-oneC12H13NO4[α]D23=-104.2 (c 0.003, CH3OH)Source of chirality: l-serineAbsolute configuration: (4R,5R)

(4R,5R)-5-(Hydroxymethyl)-4-(4-methoxybenzo[d][1,3]dioxol-6-yl)pyrrolidin-2-oneC13H15NO5[α]D24=-123.4 (c 0.01, CH3OH)Source of chirality: l-serineAbsolute configuration: (4R,5R)