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. 2024 Jan 5;14(2):1005-1012.
doi: 10.1021/acscatal.3c03932. eCollection 2024 Jan 19.

Organocatalytic Asymmetric Synthesis of Si-Stereogenic Siloxanols

Jacob J Dalton  1 , Adilene Bernal Sánchez  1 , Austin T Kelly  1 , James C Fettinger  1 , Annaliese K Franz  1
Affiliations

Organocatalytic Asymmetric Synthesis of Si-Stereogenic Siloxanols

Jacob J Dalton et al. ACS Catal. .

Abstract

We report the organocatalytic synthesis of Si-stereogenic compounds via desymmetrization of a prochiral silanediol with a chiral imidazole-containing catalyst. This metal-free silylation method affords high yields with enantioselectivity up to 98:2 for various silanediol and silyl chloride substrate combinations (including secondary alkyl, vinyl, and H groups), accessing products with potential for further elaboration. NMR and X-ray studies reveal insight into the H-bonding interactions between the imidazole organocatalyst and the silanediol and the dual activating role of the Lewis basic imidazole to account for the high enantioselectivity.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
(a) Desymmetrization of prochiral silanediols via Cu-catalyzed SiO-H insertion; (b) desymmetrization of prochiral silanediols via Bronstead acid catalysis; (c) desymmetrization of meso-diols via Lewis base-catalyzed silylation; and (d) desymmetrization of prochiral silanediols via Lewis base-catalyzed silylation.
Figure 2
Figure 2
Preliminary screening of nonenzymatic catalysts for silylative desymmetrization (See the SI for full details).
Scheme 1
Scheme 1. Bis-Silylation Not Observed during Desymmetrization
Figure 3
Figure 3
29Si NMR spectra for (a) 2b, (b) 2b with 1 equiv of 4a, and (c) 2b with 1 equiv of NMI. All NMR spectra were taken in C6D6 (0.075 M) at 23 °C.
Figure 4
Figure 4
(a) Replacing the imidazole ring of organocatalyst 4a with a phenyl or pyridyl group results in loss of catalyst activity. (b) Adding NMI as a cocatalyst; adding 6 as a cocatalyst.
Figure 5
Figure 5
(a) X-ray crystal structure of 1a bound with 4a (R = t-Bu). Hydrogen atoms and one t-butyl group have been omitted for clarity. Hydrogen bond lengths are shown for N(imidazole)-HOSi 1.74 Å and N–H(amide)-OSi 2.14 Å. (b) 1H NMR binding data of silanediol 1b with catalyst 4a. I = 0 equiv 1b, II = 1 equiv 1b, III = 3 equiv 1b, and IV = 5 equiv 1b. V = 7 equiv 1b. VI = 10 equiv 1b. All 1H NMR spectra were collected at 0.02 M 4a in C6D6 at room temperature.
Figure 6
Figure 6
Preliminary correlation of ee% of siloxanol product to silanediol-catalyst binding affinity (Ka).
See this image and copyright information in PMC

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