Organocatalytic Asymmetric Synthesis of Si-Stereogenic Siloxanols

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.

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

Preliminary screening of nonenzymatic catalysts for silylative desymmetrization (See the SI for full details).

Scheme 1. Bis-Silylation Not Observed during Desymmetrization

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

(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

(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

Preliminary correlation of ee% of siloxanol product to silanediol-catalyst binding affinity (K_a).