Direct synthesis of methyl 2-diazo-4-aryl-3-butenoates and their application to the enantioselective synthesis of 4-aryl-4-(1-naphthyl)-2-butenoates

An improved one-flask synthesis of various methyl 2-diazo-4-aryl and 4-heteroaryl-3-butenoates, precursors to donor/acceptor substituted carbenoids, is described. Their Rh2(S-DOSP)4 catalyzed reaction with 1-acetoxy-3,4-dihydronaphthalene, via a combined C–H activation/Cope rearrangement pathway followed by elimination of acetic acid affords a highly enantioselective (98–99% ee) entry to methyl 4-aryl- and 4-heteroaryl-4-(1-naphthyl)-2-butenoates.

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(S,E)-Methyl 4-(3,4-dimethoxyphenyl)-4-(naphthalen-5-yl)but-2-enoateC23H22O4Ee = 99.5% (by HPLC)[α]D25=+33.6 (c 1.80, CHCl3)Source of chirality: chiral catalyst [Rh2(S-DOSP)4]Absolute configuration: S

(S,E)-Methyl 4-(4-bromophenyl)-4-(naphthalen-5-yl)but-2-enoateC21H17BrO2Ee = 99.4% (by HPLC)[α]D25=+24.5 (c 0.80, CHCl3)Source of chirality: chiral catalyst [Rh2(S-DOSP)4]Absolute configuration: S

(S,E)-Methyl 4-(4-methoxyphenyl)-4-(naphthalen-5-yl)but-2-enoateC22H20O3Ee = 99.1% (by HPLC)[α]D25=+35.1 (c 1.51, CHCl3)Source of chirality: chiral catalyst [Rh2(S-DOSP)4]Absolute configuration: S

(S,E)-Methyl 4-(3,4-dichlorophenyl)-4-(naphthalen-5-yl)but-2-enoateC21H16Cl2O2Ee >98% (by HPLC)[α]D25=+37.7 (c 4.88, CHCl3)Source of chirality: chiral catalyst [Rh2(S-DOSP)4]Absolute configuration: S

(S,E)-Methyl 4-(4-biphenyl)-4-(naphthalen-5-yl)but-2-enoateC27H22O2Ee = 98.5% (by HPLC)[α]D25=+2.4 (c 3.02, CHCl3)Source of chirality: chiral catalyst [Rh2(S-DOSP)4]Absolute configuration: S

(S,E)-Methyl 4-(naphthalen-3-yl)-4-(naphthalen-5-yl)but-2-enoateC25H20O2Ee >98%(by HPLC)[α]D25=+6.9 (c 0.64, CHCl3)Source of chirality:chiral catalyst [Rh2(S-DOSP)4]Absolute configuration:S

tert-Butyl 3-((R,E)-3-(methoxycarbonyl)-1-(naphthalen-5-yl)allyl)-1H-indole-1-carboxylateC28H27NO4Ee >98% (by HPLC)[α]D25=+2.3 (c 3.02, CHCl3)Source of chirality:chiral catalyst [Rh2(S-DOSP)4]Absolute configuration:S

tert-Butyl 3-((R,E)-3-(methoxycarbonyl)-1-(naphthalen-5-yl)allyl)-5-bromo-1H-indole-1-carboxylateC28H27BrNO4Ee >98% (by HPLC)[α]D25=+27.9 (c 4.14, CHCl3)Source of chirality:chiral catalyst [Rh2(S-DOSP)4]Absolute configuration:R

(R,E)-Methyl 4-(5-chlorofuran-2-yl)-4-(naphthalen-5-yl)but-2-enoateC19H15ClO3Ee = 99.6% (by HPLC)[α]D25=+26.9 (c 0.87, CHCl3)Source of chirality:chiral catalyst [Rh2(S-DOSP)4]Absolute configuration:R

(R,E)-Methyl 4-(5-chlorothiophen-2-yl)-4-(naphthalen-5-yl)but-2-enoateC19H15ClO2SEe = 99.5% (by HPLC)[α]D25=+69.8 (c 1.25, CHCl3)Source of chirality:chiral catalyst [Rh2(S-DOSP)4]Absolute configuration:R

(R,E)-Methyl 4-(naphthalen-5-yl)-4-(5-phenylthiophen-2-yl)but-2-enoateC25H20O2SEe = 99.3% (by HPLC)[α]D25=+18.9 (c 1.32, CHCl3)Source of chirality:chiral catalyst [Rh2(S-DOSP)4]Absolute configuration:R

(R,E)-Methyl 4-(benzofuran-2-yl)-4-(naphthalen-5-yl)but-2-enoateC23H18O3Ee = 99.1% (by HPLC)[α]D25=-33.5 (c 0.936, CHCl3)Source of chirality: chiral catalyst [Rh2(S-DOSP)4]Absolute configuration: R