Amination/annulation of chlorobutenones with chiral amine compounds: synthesis of 1,2,4-trisubstituted pyrroles

A series of 1,2,4-trisubstituted pyrroles have been synthesized in 83–96% yields on treatment of chiral primary amines, amino alcohols and esters of α-amino acids with different chlorobutenones in benzene-triethylamine. The conversions proceed without racemization.

Figure optionsDownload as PowerPoint slide

(S)-2-(2,4-Dimethyl-pyrrol-1-yl)-propionic acid methyl esterC10H15NO2Ee = 99%[α]D25=+3.75 (c 0.8, CH2Cl2)Source of chirality: chiral amino acid

(R)-2,4-Dimethyl-1-(1-phenyl-ethyl)-1H-pyrroleC14H17NEe = 99%[α]D25=-4.2 (c 1.1, CHCl3)Source of chirality: chiral amine

(S,R)-2-(2,4-Dimethyl-pyrrole-1-yl)-1-phenyl-propan-1-olC15H19NOEe = 99%[α]D25=-3.8 (c 0.6, CHCl3)Source of chirality: chiral amino alcohol

(S)-2-(2,4-Dimethyl-pyrrol-1-yl)-4-methylsulfanyl-butyric acid ethyl esterC13H21NO2SEe = 99%[α]D25=-3.4 (c 1.3, CHCl3)Source of chirality: chiral amino acid

(S)-2-(2,4-Dimethyl-pyrrol-1-yl)-3-(4-hydroxy-phenyl)-propionic acid ethyl esterC17H21NO3Ee = 99%[α]D25=-4.4 (c 1, CHCl3)Source of chirality: chiral amino acid

(R)-2-Cyclohexyl-4-methyl-1-(1-phenyl-ethyl)-1H-pyrroleC19H25NEe = 99%[α]D25=-2.8 (c 0.9, CHCl3)Source of chirality: chiral amine

(S,R)-2-(2-Cyclohexyl-4-methyl-pyrrol-1-yl)-1-phenyl-propan-1-olC20H27NOEe = 99%[α]D25=+2.5 (c 0.5, CHCl3)Source of chirality: chiral amino alcohol

(S)-2-(4-Methyl-2-phenyl-pyrrol-1-yl)-4-methylsulfanyl-butyric acid ethyl esterC18H23NO2SEe = 99%[α]D25=-9.6 (c 1.3, CHCl3)Source of chirality: chiral amino acid

(S)-2-(4-Methyl-2-phenyl-pyrrol-1-yl)-propionic acid methyl esterC15H17NO2Ee = 99%[α]D25=+4.2 (c 0.5, CHCl3)Source of chirality: chiral amino acid

(S)-2-(2-Isopropyl-4-methyl-pyrrol-1-yl)-4-methylsulfanyl-butyric acid ethyl esterC15H25NO2SEe = 99%[α]D25=-15.6 (c 3, CHCl3)Source of chirality: chiral amino acid

(R)-2-Isopropyl-4-methyl-1-(1-phenylethyl)-1H-pyrroleC16H21NEe = 99%[α]D25=+31.6 (c 3.3, CHCl3)Source of chirality: chiral amine

(S,R)-2-(2-Isopropyl-4-methyl-pyrrol-1-yl)-1-phenyl-propan-1-olC17H23NOEe = 99%[α]D25=-5.1 (c 1.3, CHCl3)Source of chirality: chiral amino alcohol

(S)-2-(2-Isopropyl-4-methyl-pyrrol-1-yl)-propionic acid methyl esterC12H19NO2Ee = 99%[α]D25=+3.6 (c 1.2, CHCl3)Source of chirality: chiral amino acid