Catalytic and highly enantioselective Friedel–Crafts type reactions of heteroaromatic compounds with trifluoropyruvate and glyoxylate by a dicationic palladium complex

The highly enantioselective Friedel–Crafts alkylation of furan and thiophene derivatives with trifluoropyruvate, which have never provided the high level of asymmetric induction and yield until now, was achieved by using dicationic palladium complexes as Lewis acid catalysts. Moreover, glyoxylate instead of trifluoropyruvate as an electrophile led to complete change of regioselectivity with 2-trimethylsilylated furan, thiophene, and pyrrole derivatives to give the corresponding heteroarylated products in high yields and enantioselectivities. The respective products with trifluoropyruvate and glyoxylate could also be obtained via sequential catalytic reaction; intramolecular cyclization of alkynyldiols using cationic Au catalyst followed by Friedel–Crafts type reactions using dicationic Pd catalyst.

Figure optionsDownload as PowerPoint slide

(R)-Ethyl 3,3,3-trifluoro-2-hydroxy-2-(5-(trimethylsilyl)furan-2-yl)propanoateC12H17F3O4Si[α]D25 = −15.2 (c 1.3, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (R)

(R)-Ethyl 3,3,3-trifluoro-2-(furan-2-yl)-2-hydroxypropanoateC9H9F3O4[α]D25 = −20.3 (c 0.80, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (R)

(R)-Ethyl 3,3,3-trifluoro-2-hydroxy-2-(5-methylfuran-2-yl)propanoateC10H11F3O4[α]D25 = −10.7 (c 0.70, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (R)

(R)-Ethyl 3,3,3-trifluoro-2-hydroxy-2-(5-phenylfuran-2-yl)propanoateC15H13F3O4[α]D25 = −35.2 (c 1.2, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (R)

(R)-Ethyl 2-(5-(((tert-butyldiphenylsilyl)oxy)methyl)furan-2-yl)-3,3,3-trifluoro-2-hydroxypropanoateC26H29F3O5Si[α]D25 = −19.0 (c 0.7, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (R)

(R)-Ethyl 2-(3,5-diphenylfuran-2-yl)-3,3,3-trifluoro-2-hydroxypropanoateC21H17F3O4[α]D25 = −23.3 (c 1.3, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (R)

(R)-Ethyl 3,3,3-trifluoro-2-hydroxy-2-(thiophen-2-yl)propanoateC9H9F3O3S[α]D25 = −14.5 (c 1.4, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (R)

(R)-Ethyl 3,3,3-trifluoro-2-hydroxy-2-(5-methylthiophen-2-yl)propanoateC10H11F3O3S[α]D25 = −10.6 (c 0.8, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (R)

(R)-Ethyl 3,3,3-trifluoro-2-hydroxy-2-(1H-pyrrol-2-yl)propanoateC9H10F3NO3[α]D25 = −8.6 (c 0.8, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (R)

(E,R)-2-Hydroxy-4-phenyl-2-trifluoromethyl-but-3-enoic acid ethyl esterC13H13F3O3[α]D25 = −68.6 (c 1.6, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (R)

(R,3E,5E)-Ethyl 2-hydroxy-6-phenyl-2-(trifluoromethyl)hexa-3,5-dienoateC15H15F3O3[α]D25 = −33.7 (c 2.16, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (R)

(R)-Ethyl 2-(furan-2-yl)-2-hydroxyacetateC8H10O4[α]D25 = −108.3 (c 0.80, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (R)

(R)-Ethyl 2-hydroxy-2-(5-methylfuran-2-yl)acetateC9H12O4[α]D25 = −42.3 (c 1.1, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (R)

(R)-Ethyl 2-hydroxy-2-(5-phenylfuran-2-yl)acetateC14H14O4[α]D25 = −44.4 (c 0.86, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (R)

(R)-Ethyl 2-(5-(((tert-butyldiphenylsilyl)oxy)methyl)furan-2-yl)-2-hydroxyacetateC25H30O5Si[α]D25 = −35.6 (c 1.1, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (R)

(R)-Ethyl 2-(3,5-diphenylfuran-2-yl)-2-hydroxyacetateC20H18O4[α]D25 = −19.5 (c 1.05, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (R)

(R)-Ethyl 2-(4,5-diphenylfuran-2-yl)-2-hydroxyacetateC20H18O4[α]D25 = −36.1 (c 0.88, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (R)

(R)-Ethyl 2-hydroxy-2-(thiophen-2-yl)acetateC8H10O3S[α]D25 = −73.8 (c 0.55, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (R)

(R)-Ethyl 2-hydroxy-2-(5-methylthiophen-2-yl)acetateC9H12O3S[α]D25 = −59.7 (c 1.16, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (R)

(R)-Ethyl 2-hydroxy-2-(5-phenylthiophen-2-yl)acetateC14H14O3S[α]D25 = −13.6 (c 1.0, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (R)

(R)-Ethyl 2-(5-(((tert-butyldiphenylsilyl)oxy)methyl)thiophen-2-yl)-2-hydroxyacetateC25H30O4SSi[α]D25 = −24.5 (c 1.12, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (R)

(R)-tert-Butyl 2-(2-ethoxy-1-hydroxy-2-oxoethyl)-1H-pyrrole-1-carboxylateC13H19NO5[α]D25 = −50.7 (c 0.96, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (R)

(R)-tert-Butyl 2-(2-ethoxy-1-hydroxy-2-oxoethyl)-5-methyl-1H-pyrrole-1-carboxylateC14H21NO5[α]D25 = −40.3 (c 0.86, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (R)

(R)-tert-Butyl 2-(2-ethoxy-1-hydroxy-2-oxoethyl)-5-phenyl-1H-pyrrole-1-carboxylateC19H23NO5[α]D25 = −15.2 (c 0.64, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (R)

(R)-tert-Butyl 2-(((tert-butyldiphenylsilyl)oxy)methyl)-5(2-ethoxy-1-hydroxy-2-oxoethyl)-1H-pyrrole-1-carboxylateC30H39NO6Si[α]D25 = −25.6 (c 1.03, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (R)

Ethyl (R)-2-(5-((R)-2-ethoxy-1-hydroxy-2-oxoethyl)furan-2-yl)-3,3,3-trifluoro-2-hydroxypropanoateC13H15F3O7[α]D25 = −52.3 (c 0.72, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (R,R)