Asymmetric de novo synthesis of fluorinated d-glucitol and d-mannitol analogues

A highly efficient anti-SE2′ electrophilic fluorination of enantioenriched allylsilanes a subsequent dihydroxylation of the resulting allylic fluorides were used as key steps for the synthesis of three fluorinated carbohydrate analogues, 1,5-di-O-benzyl-2-deoxy-2-fluoro-d-glucitol, 2,6-di-O-benzyl-5-deoxy-5-fluoro-l-glucitol and 1,5-di-O-benzyl-2-deoxy-2-fluoro-d-mannitol. A new catalytic asymmetric route to 1-benzyloxy-4-trimethylsilyl-but-3-yn-2-ol, a common precursor to two advanced allylsilanes, is also described featuring a Noyori asymmetric transfer hydrogenation reaction.

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(2S,3E)-1-(Benzyloxy)-4-(trimethylsilyl)but-3-en-2-yl (benzyloxy)acetateC23H30O4SiEe = 93%[α]D21=+21.3 (c 1.1, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(2R,3R,4E)-2,6-Bis(benzyloxy)-3-(trimethylsilyl)hex-4-enoic acidC23H30O4SiEe = 93%[α]D21=+15.0 (c 1.0, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3R)

(2R,3R,4E)-2,6-Bis(benzyloxy)-3-(trimethylsilyl)hex-4-en-1-olC23H32O3SiEe = 93%[α]D21=-12.6 (c 1.0, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3R)

(2S,3E,5R)-2,6-Bis(benzyloxy)-5-fluorohex-3-en-1-olC20H23FO3Ee = 93%[α]D21=-32.2 (c 1.0, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,5R)

1,5-di-O-Benzyl-2-deoxy-2-fluoro-d-glucitolC20H25FO5Ee = 93%[α]D25=+2.6 (c 0.4, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3S,4S,5R)

2,6-Di-O-benzyl-5-deoxy-5-fluoro-l-glucitolC20H25FO5Ee = 93%[α]D25=-2.0 (c 1.3, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3R,4R,5S)

(2S,3Z)-1-(Benzyloxy)-4-(trimethylsilyl)but-3-en-2-yl (benzyloxy)acetateC23H30O4SiEe = 93%[α]D21=+21.3 (c 1.1, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(2R,3S,4E)-2,6-Bis(benzyloxy)-3-(trimethylsilyl)hex-4-enoic acidC23H30O4SiEe = 93%[α]D21=-11.3 (c 1.0, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3S)

(2R,3S,4E)-2,6-Bis(benzyloxy)-3-(trimethylsilyl)hex-4-en-1-olC23H32O3SiEe = 93%[α]D21=-22.0 (c 1.0, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3S)

(2S,3E,5S)-2,6-Bis(benzyloxy)-5-fluorohex-3-en-1-olC20H23FO3Ee = 93%[α]D21=-38.4 (c 1.1, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,5S)

1,5-di-O-Benzyl-2-deoxy-2-fluoro-d-mannitolC20H25FO5Ee = 93%[α]D21=+20.4 (c 0.5, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3S,4S,5R)

(2S)-1-(Benzyloxy)-4-(trimethylsilyl)but-3-yn-2-yl (2S)-3,3,3-trifluoro-2-methoxy-2-phenylpropanoateC24H27F3O4SiEe = 93%[α]D25=+40.2 (c 1.0, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,2′S)

(2S,3E)-1-(Benzyloxy)-4-(trimethylsilyl)but-3-en-2-yl (2S)-3,3,3-trifluoro-2-methoxy-2-phenylpropanoateC24H29F3O4SiEe = 93%[α]D25=+46.3 (c 1.0, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,2′S)

(2S,3Z)-1-(Benzyloxy)-4-(trimethylsilyl)but-3-en-2-yl (2S)-3,3,3-trifluoro-2-methoxy-2-phenylpropanoateC24H29F3O4SiEe = 93%[α]D25=+45.8 (c 1.1, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,2′S)

(2R,3R,4E)-2,6-Bis(benzyloxy)-3-(trimethylsilyl)hex-4-en-1-yl (2S)-3,3,3-trifluoro-2-methoxy-2-phenylpropanoateC33H39F3O5SiEe = 93%[α]D25=+24.3 (c 1.0, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3R,2′S)

(2R,3S,4E)-2,6-Bis(benzyloxy)-3-(trimethylsilyl)hex-4-en-1-yl (2S)-3,3,3-trifluoro-2-methoxy-2-phenylpropanoateC33H39F3O5SiEe = 93%[α]D25=+11.0 (c 0.7, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3S,2′S)

(2S,3E,5R)-2,6-Bis(benzyloxy)-5-fluorohex-3-en-1-yl (2S)-3,3,3-trifluoro-2-methoxy-2-phenylpropanoateC30H30F4O5Ee = 93%[α]D25=+16.0 (c 0.7, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,5R,2′S)

(2S,3E,5S)-2,6-Bis(benzyloxy)-5-fluorohex-3-en-1-yl (2S)-3,3,3-trifluoro-2-methoxy-2-phenylpropanoateC30H30F4O5Ee = 93%[α]D25=+12.9 (c 0.9, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,5S,2′S)