Enantioselective enzymatic desymmetrization of prochiral 1,3-diols and enzymatic resolution of monoprotected 1,3-diols based on α-tetralone and related multifunctional scaffolds

Novel multifunctional chemotypes based on α-tetralone, α-indanone, and chromanone have been synthesized by a chemo-enzymatic approach by applying an enzymatic irreversible transesterification strategy. The scaffolds synthesized can be further elaborated with subsequent enzymatic as well as chemical transformations for the generation of new sets of structurally related organic molecules.

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Acetic acid 2-(tert-butyl-diphenyl-silanyloxymethyl)-1-oxo-1,2,3,4-tetrahydro-naphthalen-2-ylmethyl esterC30H34O4SiEe = 98%[α]D28=+6.7 (c 0.2, MeOH)Source of chirality: enzymatic transesterificationAbsolute configuration: (2S)

Acetic acid 2-(tert-butyl-diphenyl-silanyloxymethyl)-1-oxo-indan-2-ylmethyl esterC29H32O4SiEe = 98%[α]D28=+15.8 (c 0.24, MeOH)Source of chirality: enzymatic transesterificationAbsolute configuration: (2S)

Acetic acid 2-(tert-butyl-diphenyl-silanyloxymethyl)-6-methoxy-1-oxo-1,2,3,4-tetrahydro-naphthalen-2-ylmethyl esterC31H36O5SiEe = 96%[α]D28=+11.1 (c 0.2, MeOH)Source of chirality: enzymatic transesterificationAbsolute configuration: (2S)

Acetic acid 2-(tert-butyl-diphenyl-silanyloxymethyl)-7-methoxy-1-oxo-1,2,3,4-tetrahydro-naphthalen-2-ylmethyl esterC31H36O5SiEe = 96%[α]D28=+23.8 (c 0.2, MeOH)Source of chirality: enzymatic transesterificationAbsolute configuration: (2S)

Acetic acid 2-(tert-butyl-diphenyl-silanyloxymethyl)-5,8-dimethoxy-1-oxo-1,2,3,4-tetrahydro-naphthalen-2-ylmethyl esterC32H38O6SiEe = 93%[α]D28=+13.3 (c 0.4, MeOH)Source of chirality: enzymatic transesterificationAbsolute configuration: (2S)

Acetic acid 2-(tert-butyl-diphenyl-silanyloxymethyl)-5-chloro-1-oxo-indan-2-ylmethyl esterC29H31O4SiClEe = 96%[α]D28=+13.1 (c 0.2, MeOH)Source of chirality: enzymatic transesterificationAbsolute configuration: (2S)

Acetic acid 2-(tert-butyl-diphenyl-silanyloxymethyl)-5-methoxy-1-oxo-indan-2-ylmethyl esterC30H34O5SiEe = 93%[α]D28=+18.3 (c 0.4, MeOH)Source of chirality: enzymatic transesterificationAbsolute configuration: (2S)

Acetic acid 2-(tert-butyl-diphenyl-silanyloxymethyl)-6-methyl-1-oxo-indan-2-ylmethyl esterC30H34O4SiEe = 98%[α]D28=+10.6 (c 0.4, MeOH)Source of chirality: enzymatic transesterificationAbsolute configuration: (2S)

Acetic acid 3-(tert-butyl-diphenyl-silanyloxymethyl)-4-oxo-chroman-3-ylmethyl esterC29H32O5SiEe = 98%[α]D28=+11.0 (c 0.2, MeOH)Source of chirality: enzymatic transesterificationAbsolute configuration: (3S)

Acetic acid 3-(tert-butyl-diphenyl-silanyloxymethyl)-7-chloro-4-oxo-chroman-3-ylmethyl esterC29H32O5SiClEe = 88%[α]D28=+12.8 (c 1.0, MeOH)Source of chirality: enzymatic transesterificationAbsolute configuration: (3S)

Acetic acid 3-(tert-butyl-diphenyl-silanyloxymethyl)-7-methoxy-4-oxo-chroman-3-ylmethyl esterC30H32O6SiEe = 93%[α]D28=+14.2 (c 0.1 MeOH)Source of chirality: enzymatic transesterificationAbsolute configuration: (3S)

Acetic acid 3-(tert-butyl-diphenyl-silanyloxymethyl)-6,7-dimethoxy-4-oxo-chroman-3-ylmethyl esterC31H36O7SiEe = 94%[α]D28=+3.6 (c 0.18 MeOH)Source of chirality: enzymatic transesterificationAbsolute configuration: (3S)

Acetic acid 7-(tert-butyl-diphenyl-silanyloxymethyl)-8-oxo-7,8-dihydro-6H-[1,3]dioxolo[4,5-g]chromen-7-ylmethyl esterC31H36O7SiEe = 95%[α]D28=+3.9 (c 0.36, MeOH)Source of chirality: enzymatic transesterificationAbsolute configuration: (3S)

Toluene-4-sulfonic acid (R)-2-(tert-butyl-diphenyl-silanyloxymethyl)-1-oxo-1,2,3,4-tetrahydro-naphthalen-2-ylmethyl esterC35H38O5SSiEe = 98%[α]D28=+33.9 (c 0.9, MeOH)Source of chirality: enzymatic transesterificationAbsolute configuration: (2R)

(R)-2-(tert-Butyl-diphenyl-silanyloxymethyl)-2-methyl-3,4-dihydro-2H-naphthalen-1-oneC28H32O2SiEe = 98%[α]D28=+21.2 (c 0.9, MeOH)Source of chirality: enzymatic transesterificationAbsolute configuration: (2R)