Gold-catalyzed synthesis of enantioenriched furfurylamines from amino acids

A convenient gold-catalyzed asymmetric synthesis of polysubstituted furfurylamines starting from amino acids has been achieved. The cyclization proceeded under mild conditions and generally provided the furan or iodofuran derivatives in good to excellent yields and with high enantiomeric excess. Iodofurans were validated as good intermediates for classical organometallic coupling reactions.

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tert-Butyl (S)-(2-(benzyloxy)-1-(5-ethylfuran-2-yl)ethyl)carbamateC20H27NO4[α]D22 = −35.1 (c 1.00, CH2Cl2)Source of chirality: N-Boc-l-serineAbsolute configuration: (S)

tert-Butyl (R)-(2-(phenyl)-1-(5-propylfuran-2-yl)ethyl)carbamateC20H27NO3[α]D22 = +43.4 (c 1.07, CH2Cl2)Source of chirality: N-Boc-d-phenylalanineAbsolute configuration: (R)

tert-Butyl (S)-(2-(benzyloxy)-1-(5-ethyl-4-iodofuran-2-yl)ethyl)carbamateC20H26INO4[α]D22 = −36.5 (c 1.02, CH2Cl2)Source of chirality: N-Boc-l-serineAbsolute configuration: (S)

tert-Butyl (R)-(1-(4-iodo-5-propylfuran-2-yl)-2-phenylethyl)carbamateC20H26INO3[α]D22 = +38.3 (c 1.08, CH2Cl2)Source of chirality: N-Boc-d-phenylalanineAbsolute configuration: (R)

(S)-2-(4-Iodo-5-phenylfuran-2-yl)pyrrolidine-1-carboxylic acid tert-butyl esterC19H22INO3[α]D22 = −101.0 (c 1.04, CH2Cl2)Source of chirality: N-Boc-l-prolineAbsolute configuration: (S)

tert-Butyl (S)-(2-(benzyloxy)-1-(5-ethyl-4-(4-fluorophenyl)furan-2-yl)ethyl)carbamateC26H30FNO4[α]D22 = −36.4 (c 0.99, CH2Cl2)Source of chirality: N-Boc-l-serineAbsolute configuration: (S)

tert-Butyl (R)-(1-(4-(4-fluorophenyl)-5-propylfuran-2-yl)-2-phenylethyl)carbamateC26H30FNO3[α]D22 = +36.6 (c 1.00, CH2Cl2)Source of chirality: N-Boc-d-phenylalanineAbsolute configuration: (R)

(S)-2-(4-(4-((tert-Butoxycarbonyl)amino)phenyl)-5-phenylfuran-2-yl)pyrrolidine-1-carboxylic acid tert-butyl esterC30H36N2O5[α]D22 = −86.3 (c 0.91, CH2Cl2)Source of chirality: N-Boc-l-prolineAbsolute configuration: (S)

(R,E)-3-(5-(1-((tert-Butoxycarbonyl)amino)-2-phenylethyl)-2-propylfuran-3-yl)acrylic acid methyl esterC24H31NO5[α]D22 = +31.7 (c 0.94, CH2Cl2)Source of chirality: N-Boc-d-phenylalanineAbsolute configuration: (R)

(R)-(2-Phenyl-1-(4-(phenylethynyl)-5-propylfuran-2-yl)ethyl)carbamic acid tert-butyl esterC28H31NO3[α]D22 = +34.2 (c 1.04, CH2Cl2)Source of chirality: N-Boc-d-phenylalanineAbsolute configuration: (R)

(S)-2-(4((tert-Butoxycarbonyl)amino)-5-phenylfuran-2-yl)pyrrolidine-1-carboxylic acid tert-butyl esterC24H32N2O5[α]D22 = −89.0 (c 1.23, CH2Cl2)Source of chirality: N-Boc-l-prolineAbsolute configuration: (S)

(S)-(1-(5-Ethylfuran-2-yl)-2-hydroxyethyl)carbamic acid tert-butyl esterC13H21NO4[α]D22 = −51.1 (c 1.00, CH2Cl2)Source of chirality: N-Boc-l-serineAbsolute configuration: (S)

(S)-(1-(5-Ethyl-4-(4-fluorophenyl)furan-2-yl)-2-hydroxyethyl)carbamic acid tert-butyl esterC19H24FNO4[α]D22 = −49.4 (c 0.50, CH2Cl2)Source of chirality: N-Boc-l-serineAbsolute configuration: (S)

(S)-2-Amino-2-(5-ethylfuran-2-yl)ethan-1-ol, hydrochlorideC8H14ClNO2[α]D22 = −16.2 (c 0.50, CH3OH)Source of chirality: N-Boc-l-serineAbsolute configuration: (S)