Diastereoselective synthesis of oxazolo[3,4-b]tetrahydroisoquinolin-3-ones via Lewis acid TMSOTf-mediated Pictet–Spengler reaction

An alternative and efficient method to stereoselectively synthesize oxazolo[3,4-b]tetrahydroisoquinolin-3-ones via a Pictet–Spengler reaction promoted by Lewis acid TMSOTf from readily available (S)-4-benzyl-2-oxazolidinone with various aromatic, aliphatic, and cyclic aldehydes under room temperature is described.

This paper describes an alternative and efficient method to stereoselectively synthesize oxazolo[3,4-b]tetrahydroisoquinolin-3-ones via Pictet–Spengler reaction promoted by Lewis acid TMSOTf from readily available (S)-4-benzyl-2-oxazolidinone with various aromatic, aliphatic, and cyclic aldehydes under room temperature.Figure optionsDownload as PowerPoint slide

(5R,10aS)-5-Phenyl-1,5,10,10a-tetrahydro[1,3]oxazolo[3,4-b]isoquinolin-3-oneC17H15NO2De 98%[α]D23=-261 (c 0.68, CHCl3)Source of chirality: (S)-4-benzyloxazolidin-2-oneAbsolute configuration: (5R,10aS)

(5R,10aS)-5-(p-Tolyl)-1,5,10,10a-tetrahydro[1,3]oxazolo[3,4-b]isoquinolin-3-oneC18H17NO2De >99%[α]D23=-238 (c 0.08, CHCl3)Source of chirality: (S)-4-benzyloxazolidin-2-oneAbsolute configuration: (5R,10aS)

(5R,10aS)-5-(4-Methoxyphenyl)-1,5,10,10a-tetrahydro[1,3]oxazolo[3,4-b]isoquinolin-3-oneC18H17NO3De >99%[α]D23=-214 (c 0.10, CHCl3)Source of chirality: (S)-4-benzyloxazolidin-2-oneAbsolute configuration: (5R,10aS)

(5R,10aS)-5-(4-(Dimethylamino)phenyl)-1,5,10,10a-tetrahydro[1,3]oxazolo[3,4-b]isoquinolin-3-oneC19H20N2O2De >99%[α]D23=-263 (c 0.56, CHCl3)Source of chirality: (S)-4-benzyloxazolidin-2-oneAbsolute configuration: (5R,10aS)

(5R,10aS)-5-(4-Bromophenyl)-1,5,10,10a-tetrahydro[1,3]oxazolo[3,4-b]isoquinolin-3-oneC17H14BrNO2De 93%[α]D23=-178 (c 0.28, CHCl3)Source of chirality: (S)-4-benzyloxazolidin-2-oneAbsolute configuration: (5R,10aS)

(5R,10aS)-5-(4-Fluorophenyl)-1,5,10,10a-tetrahydro[1,3]oxazolo[3,4-b]isoquinolin-3-oneC17H14FNO2De >99%[α]D23=-219 (c 0.15, CHCl3)Source of chirality: (S)-4-benzyloxazolidin-2-oneAbsolute configuration: (5R,10aS)

Methyl 4-((5R,10aS)-3-Oxo-1,5,10,10a-tetrahydro[1,3]oxazolo[3,4-b]isoquinolin-5-yl)benzoateC19H17NO4De 97%[α]D23=-230 (c 0.25, CHCl3)Source of chirality: (S)-4-benzyloxazolidin-2-oneAbsolute configuration: (5R,10aS)

(5R,10aS)-5-(4-Nitrophenyl)-1,5,10,10a-tetrahydro[1,3]oxazolo[3,4-b]isoquinolin-3-oneC17H14N2O4De 98%[α]D23=-240 (c 0.25, CHCl3)Source of chirality: (S)-4-benzyloxazolidin-2-oneAbsolute configuration: (5R,10aS)

(5R,10aS)-5-(2-Bromophenyl)-1,5,10,10a-tetrahydro[1,3]oxazolo[3,4-b]isoquinolin-3-oneC17H14BrNO2De 99%[α]D23=-223 (c 0.66, CHCl3)Source of chirality: (S)-4-benzyloxazolidin-2-oneAbsolute configuration: (5R,10aS)

(5R,10aS)-5-(2-Fluorophenyl)-1,5,10,10a-tetrahydro[1,3]oxazolo[3,4-b]isoquinolin-3-oneC17H14FNO2De >99%[α]D23=-268 (c 0.30, CHCl3)Source of chirality: (S)-4-benzyloxazolidin-2-oneAbsolute configuration: (5R,10aS)

(5R,10aS)-5-(3-Fluorophenyl)-1,5,10,10a-tetrahydro[1,3]oxazolo[3,4-b]isoquinolin-3-oneC17H14FNO2De >99%[α]D23=-250 (c 0.37, CHCl3)Source of chirality: (S)-4-benzyloxazolidin-2-oneAbsolute configuration: (5R,10aS)

(S)-1,5,10,10a-Tetrahydro[1,3]oxazolo[3,4-b]isoquinolin-3-oneC11H11NO2[α]D23=-18 (c 0.04, CHCl3)Source of chirality: (S)-4-benzyloxazolidin-2-oneAbsolute configuration: (S)

(5R,10aS)-5-Phenethyl-1,5,10,10a-tetrahydro[1,3]oxazolo[3,4-b]isoquinolin-3-oneC19H19NO2De >99%[α]D23=-200 (c 0.65, CHCl3)Source of chirality: (S)-4-benzyloxazolidin-2-oneAbsolute configuration: (5R,10aS)

(5R,10aS)-5-(tert-Butyl)-1,5,10,10a-tetrahydro[1,3]oxazolo[3,4-b]isoquinolin-3-oneC15H19NO2De 99%[α]D23=-70 (c 0.30, CHCl3)Source of chirality: (S)-4-benzyloxazolidin-2-oneAbsolute configuration: (5R,10aS)

(5R,10aS)-5-Cyclohexyl-1,5,10,10a-tetrahydro[1,3]oxazolo[3,4-b]isoquinolin-3-oneC17H21NO2De 99%[α]D23=-151 (c 0.24, CHCl3)Source of chirality: (S)-4-benzyloxazolidin-2-oneAbsolute configuration: (5R,10aS)