An efficient synthesis of enantiomerically pure unnatural aryl glycinols and aryl glycines

A quick route to enantiomerically pure unnatural aryl glycinols and aryl glycines has been established based on an asymmetric azidation reaction using a chiral benzosultam auxiliary. The synthesis of aryl glycinols involves three steps starting from arylacetic acids, and the chiral auxiliary can be readily recovered.

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2-[2-(tert-Butyldimethylsilanyloxy)-phenyl]-1-(3(S)-tert-butyl-1,1-dioxo-1,3-dihydro-1λ6-benzo[d]isothiazol-2-yl)ethanoneC25H35NO4SSiEe = 100%[α]D27=-12.1 (c 1.00, CHCl3)Source of chirality: 3-(S)-tert-butyl-1,2-benzisothiazoline 1,1-dioxideAbsolute configuration: (S)

1-(3(S)-tert-Butyl-1,1-dioxo-1,3-dihydro-1λ6-benzo[d]isothiazol-2-yl)-2-(naphthalen-1-yl)ethanoneC23H23NO3SEe = 100%[α]D26=-32.7 (c 1.54, CHCl3)Source of chirality: 3-(S)-tert-butyl-1,2-benzisothiazoline 1,1-dioxideAbsolute configuration: (S)

2(S)-Azido-2-[3-(tert-butyldimethylsilanyloxy)phenyl]-1-(3(S)-tert-butyl-1,1-dioxo-1,3-dihydro-1λ6-benzo[d]isothiazol-2-yl)ethanoneC25H34N4O4SSiEe = >99%[α]D25=+47.7 (c 0.52, CHCl3)Source of chirality: 3-(S)-tert-butyl-1,2-benzisothiazoline 1,1-dioxideAbsolute configuration: (S,S)

2(S)-Azido-1-(3(S)-tert-butyl-1,1-dioxo-1,3-dihydro-1λ6-benzo[d]isothiazol-1-yl)-2-(naphthalen-1-yl)ethanoneC23H22N4O3SEe = >99%[α]D25=-94.4 (c 0.52, CHCl3)Source of chirality: 3-(S)-tert-butyl-1,2-benzisothiazoline 1,1-dioxideAbsolute configuration: (S,S)

2(S)-Amino-2-[3-(tert-butyldimethylsilanyloxy)phenyl]ethanolC14H25NO2SiEe = 91%[α]D23=+21.8 (c 1.00, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

2(S)-Amino-2-(naphthalen-1-yl)ethanolC12H13NOEe = 95%[α]D26=+82.7 (c 0.51, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-Azido[3-(tert-butyldimethylsilanyloxy)phenyl]acetic acidC14H21N3O3SiEe = >99%[α]D22=+122 (c 0.5, acetone)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-Azido(naphthalen-1-yl)acetic acidC12H9N3O2Ee = >99%[α]D22=+142 (c 0.5, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-Amino(3-hydroxyphenyl)acetic acidC8H9NO3Ee = 99%[α]D22=+128 (c 0.2, 1 M HCl)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-Amino(naphthalen-1-yl)acetic acidC12H11NO2Ee = 99%[α]D22=+141 (c 0.2, 1 M HCl)Source of chirality: asymmetric synthesisAbsolute configuration: (S)