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. 2016 Jun 29;138(25):7982-91.
doi: 10.1021/jacs.6b04018. Epub 2016 Jun 16.

Catalytic Reductive ortho-C-H Silylation of Phenols with Traceless, Versatile Acetal Directing Groups and Synthetic Applications of Dioxasilines

Yuanda Hua  1 , Parham Asgari  1 , Thirupataiah Avullala  1 , Junha Jeon  1
Affiliations

Catalytic Reductive ortho-C-H Silylation of Phenols with Traceless, Versatile Acetal Directing Groups and Synthetic Applications of Dioxasilines

Yuanda Hua et al. J Am Chem Soc. .

Abstract

A new, highly selective, bond functionalization strategy, achieved via relay of two transition metal catalysts and the use of traceless acetal directing groups, has been employed to provide facile formation of C-Si bonds and concomitant functionalization of a silicon group in a single vessel. Specifically, this approach involves the relay of Ir-catalyzed hydrosilylation of inexpensive and readily available phenyl acetates, exploiting disubstituted silyl synthons to afford silyl acetals and Rh-catalyzed ortho-C-H silylation to provide dioxasilines. A subsequent nucleophilic addition to silicon removes the acetal directing groups and directly provides unmasked phenol products and, thus, useful functional groups at silicon achieved in a single vessel. This traceless acetal directing group strategy for catalytic ortho-C-H silylation of phenols was also successfully applied to preparation of multisubstituted arenes. Remarkably, a new formal α-chloroacetyl directing group has been developed that allows catalytic reductive C-H silylation of sterically hindered phenols. In particular, this new method permits access to highly versatile and nicely differentiated 1,2,3-trisubstituted arenes that are difficult to access by other catalytic routes. In addition, the resulting dioxasilines can serve as chromatographically stable halosilane equivalents, which allow not only removal of acetal directing groups but also introduce useful functional groups leading to silicon-bridged biaryls. We demonstrated that this catalytic C-H bond silylation strategy has powerful synthetic potential by creating direct applications of dioxasilines to other important transformations, examples of which include aryne chemistry, Au-catalyzed direct arylation, sequential orthogonal cross-couplings, and late-stage silylation of phenolic bioactive molecules and BINOL scaffolds.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1
Catalytic Site-Selective C–H Silylation of Phenols and Phenol Derivatives
Scheme 2
Scheme 2
Synthesis of Multi-Substituted Arenes via Dual Catalytic Reductive ortho-C–H Silylation of Aromatic Acetates with Traceless Acetal Directing Groupsa aConditions: (a) [Ir(coe)Cl]2 (0.5 mol %), H2SiEt2 (4 equiv), THF (2 M), 60 °C, 10 h; (b) [Rh(nbd)Cl]2 (1 mol %), P(4-OMePh)3 (6 mol %), nbe (4 equiv), THF (1 M), 120 °C, 30 min; (c) MeLi (6 equiv), THF, −78 °C; (d) [Ir(coe)Cl]2 (0.5 mol %), H2SiEt2 (2 equiv), THF (2 M), rt, 10 h; (e) MeLi (3 equiv), THF, −78 °C; (f) PivCl (1.5 equiv), Et3N (2 equiv), CH2Cl2, rt.
Scheme 3
Scheme 3
Dioxasilines as Halosilane Equivalents for the Synthesis of Functionalized Silanesa aIsolation yield from 12.
Scheme 4
Scheme 4
Synthesis of 1,2,3-Trisubstituted Arenes via Catalytic Reductive C–H Silylation of Sterically Hindered Phenyl Acetates: Dual Activation of Iridium Silyl Hydride by an α-Chloroacetyl Directing Groupa aDetermined by 1H NMR spectroscopy utilizing an internal standard (CH2Br2). bIsolated yield (two steps from the corresponding phenyl acetate).
Scheme 5
Scheme 5
Synthetic Applications of Benzodioxasilines
Scheme 6
Scheme 6
Au-Catalyzed Oxidative Direct Cross-Coupling of ortho-Silyl Phenols with Arenes
Scheme 7
Scheme 7
Sequential Orthogonal Cross-Couplings of Benzodioxasilines
Scheme 8
Scheme 8
Selective C–H Silylation and Ring-Opening Reactions of Estrone and Estradiol
Scheme 9
Scheme 9
3,3′-Bis-Silylation of BINOL
See this image and copyright information in PMC

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