Asymmetric synthesis of aryl cyclitols based on 1,2,3,4-tetrahydronaphthalene scaffolds

A series of aryl cyclitols based on a 1,2,3,4-tetrahydronaphthalene scaffold have been synthesized in a stereocontrolled manner. These cyclitols possess four contiguous stereocenters amongst which one is a quaternary stereocenter, which has been constructed by applying enzymatic kinetic resolution reaction. The remaining stereocenters have been created by substrate directed asymmetric dihydroxylation reaction and stereoselective keto-reduction process.

Figure optionsDownload as PowerPoint slide

Acetic acid (R)-2-(tert-Butyl-phenyl-silanyloxymethyl)-1-oxo-1,2-dihydronaphthalen-2-ylmethyl esterC30H32O4SiSource of chirality: asymmetric synthesisAbsolute configuration: (R)[α]D29=+8.3 (c 1.0, CHCl3)

Acetic acid (2S,3S,4R)-2-(tert-butyl-diphenyl-silanyloxymethyl)-3,4-dihydroxy-1-oxo-1,2,3,4-tetrahydronaphthalen-2-ylmethyl esterC30H34O6SiSource of chirality: asymmetric synthesisAbsolute configuration: (2S,3S,4R)[α]D29=+20.1 (c 0.2, CHCl3)

(2R,3R,4S)-2-(tert-Butyl-diphenyl-silanyloxymethyl)-3,4-dihydroxy-2-hydroxymethyl-3,4-dihydro-2H-naphthalen-1-oneC28H32O5SiSource of chirality: asymmetric synthesisAbsolute configuration: (2R,3R,4S)[α]D29=-23.3 (c 0.25, CHCl3)

(1S,2R,3S,4S)-3-(tert-Butyl-diphenyl-silanyloxymethyl)-3-hydroxymethyl-1,2,3,4-tetrahydronaphthalene-1,2,4-triolC28H34O5SiSource of chirality: asymmetric synthesisAbsolute configuration: (1S,2R,3S,4S)[α]D29=-33.5 (c 0.2, CHCl3)

Acetic acid (S)-2-(tert-butyl-phenyl-silanyloxymethyl)-6-methoxy-1-oxo-1,2-dihydronaphthalen-2-ylmethyl esterC31H34O5SiSource of chirality: asymmetric synthesisAbsolute configuration: (S)[α]D29=+16.5 (c 1.0, CHCl3)

Acetic acid (2S,3S,4R)-2-(tert-butyl-diphenyl-silanyloxymethyl)-3,4-dihydroxy-6-methoxy-1-oxo-1,2,3,4-tetrahydronaphthalen-2-ylmethyl esterC31H36O7SiSource of chirality: asymmetric synthesisAbsolute configuration: (2S,3S,4R)[α]D29=+11.3 (c 0.5, CHCl3)

(2R,3R,4S)-2-(tert-Butyl-diphenyl-silanyloxymethyl)-3,4-dihydroxy-2-hydroxymethyl-6-methoxy-3,4-dihydro-2H-naphthalen-1-oneC29H34O6SiSource of chirality: asymmetric synthesisAbsolute configuration: (2R,3R,4S)[α]D29=+22.65 (c 1.1, CHCl3)

(1S,2R,3S,4S)-3-(tert-Butyl-diphenyl-silanyloxymethyl)-3-hydroxymethyl-7-methoxy-1,2,3,4-tetrahydronaphthalene-1,2,4-triolC29H36O6SiSource of chirality: asymmetric synthesisAbsolute configuration: (1S,2R,3S,4S)[α]D29=-19.8 (c 0.8, CHCl3)

Acetic acid (R)-2-(tert-butyl-phenyl-silanyloxymethyl)-7-methoxy-1-oxo-1,2-dihydronaphthalen-2-ylmethyl esterC31H34O5SiSource of chirality: asymmetric synthesisAbsolute configuration: (R)[α]D29=-22.0 (c 1.1, CHCl3)

Acetic acid (2R,3R,4S)-2-(tert-butyl-diphenyl-silanyloxymethyl)-3,4-dihydroxy-7-methoxy-1-oxo-1,2,3,4-tetrahydronaphthalen-2-ylmethyl esterC31H36O7SiSource of chirality: asymmetric synthesisAbsolute configuration: (2R,3R,4S)[α]D29=-19.25 (c 0.6, CHCl3)

(2R,3R,4S)-2-(tert-Butyl-diphenyl-silanyloxymethyl)-3,4-dihydroxy-2-hydroxymethyl-7-methoxy-3,4-dihydro-2H-naphthalen-1-oneC29H34O6SiSource of chirality: asymmetric synthesisAbsolute configuration: (2R,3R,4S)[α]D29=-12.3 (c 0.5, CHCl3)

(1R,2S,3R,4R)-3-(tert-Butyl-diphenyl-silanyloxymethyl)-3-hydroxymethyl-6-methoxy-1,2,3,4-tetrahydronaphthalene-1,2,4-triolC29H36O6SiSource of chirality: asymmetric synthesisAbsolute configuration: (1R,2S,3R,4R)[α]D29=+44.1 (c 1.2, CHCl3)

Acetic acid (S)-2-(tert-butyl-phenyl-silanyloxymethyl)-4-methyl-1-oxo-1,2-dihydronaphthalen-2-ylmethyl esterC31H34O4SiSource of chirality: asymmetric synthesisAbsolute configuration: (S)[α]D29=+6.9 (c 1.0, CHCl3)

Acetic acid (2S,3S,4R)-2-(tert-butyl-diphenyl-silanyloxymethyl)-3,4-dihydroxy-4-methyl-1-oxo-1,2,3,4-tetrahydronaphthalen-2-ylmethyl esterC31H36O6SiSource of chirality: asymmetric synthesisAbsolute configuration: (2S,3S,4R)[α]D29=+12.65 (c 0.2, CHCl3)

(2S,3S,4R)-2-(tert-Butyl-diphenyl-silanyloxymethyl)-3,4-dihydroxy-2-hydroxymethyl-4-methyl-3,4-dihydro-2H-naphthalen-1-oneC29H34O5SiSource of chirality: asymmetric synthesisAbsolute configuration: (2S,3S,4R)[α]D29=+22.3 (c 0.5, CHCl3)

(1S,2R,3S,4S)-3-(tert-Butyl-diphenyl-silanyloxymethyl)-3-hydroxymethyl-1-methyl-1,2,3,4-tetrahydronaphthalene-1,2,4-triolC29H36O5SiSource of chirality: asymmetric synthesisAbsolute configuration: (1S,2R,3S,4S)[α]D29=-7.05 (c 0.4, CHCl3)