Iridium‐Catalyzed Regioselective Silylation of Aromatic and Benzylic CH Bonds Directed by a Secondary Amine

Li, Qian; Drieß, Matthias; Hartwig, John F.

doi:10.1002/anie.201404620

Cited by 77 publications

(49 citation statements)

References 59 publications

(17 reference statements)

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“…To address this concern, we demonstrated the strategy for traceless, formal acetate directing group-assisted ortho -silylation of phenols (Table 1). Gratifyingly, the single-pot, two-step strategy involving Ir-catalyzed ester hydrosilylation (0.1 mol % of [Ir(coe)Cl] 2 ]), Rh-catalyzed C–H bond silylation using [Rh(nbd)Cl] 2 (0.4 mol %), and monodentate phosphine P(4-MeOPh) 3 ) 17e (2.4 mol %) directly produced benzodioxasiline 12a in excellent yield (95%). A distinctive feature of this mixed O,O- acetal-directed Rh-catalyzed C–H silylation was essentially complete reaction within 15 min despite the fact that a putative cyclometalated rhodacycloheptane intermediate might be involved.…”

Section: Resultsmentioning

confidence: 99%

“…Although diverse catalytic arene dehydrogenative silylations have been developed to prepare valuable organosilanes, 17 surprisingly, only one example of catalytic ortho- C–H silylation of phenol derivatives has been developed (Hou group, 2011) 17h as depicted in Scheme 1a1. Although Hou’s pioneering work associated with scandium metallocene-catalyzed directed ortho -silylation of anisoles exhibits excellent site-selectivity despite requiring highly strained, four-membered metallacycle 2 , it requires excess anisole substrates (10-fold) and has a somewhat limited substrate scope (inaccessible to 1,2,3-trisubstituted arenes 3 to 4 ).…”

Section: Introductionmentioning

confidence: 99%

“…Herein, we report a single-pot sequential metal-catalyzed reductive ortho -C–H silylation of phenols with traceless mixed acetal directing groups, utilizing inexpensive and an easily installable acetyl formal directing group and readily available catalyst and silane. This strategy involves the relay of Ir-catalyzed hydrosilylation of phenyl acetates 8 22 exploiting disubstituted silyl synthons 7 to afford silyl acetals 10 and Rh-catalyzed C–H silylation 17b,c,e,n,q,r to provide dioxasilines 12 . A subsequent nucleophilic addition to silicon removes the acetal directing groups and provides unmasked phenol products 9 in a single vessel.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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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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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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“…[25] We began our investigation of the enantioselective silylation of cyclopropanes by examining the reactions of (1-phenylcyclopropyl)methanol (1a). The dehydrogenative coupling of 1a with diethylsilane catalyzed by [Ir(cod)Cl] 2 or [Ir(cod)OMe] 2 under conditions we reported previously for the dehydrogenative silylation of alcohols and amines [24,[26][27][28] formed a a mixture of hydrosilyl ether 2a and dialkoxysilane 4. In contrast, the reaction catalyzed by 0.2 mol % Ru(PPh 3 ) 3 Cl 2 at 50 °C (eq 1) formed 2a exclusively.…”

mentioning

confidence: 94%

“…This process is a rare example of the silylation of secondary C-H bonds, [20][21][22][23][24] and the product undergoes oxidation with full conservation of the enantiomeric excess of the silylation product to form a diol containing a secondary carbinol stereocenter that would be difficult to set by more classical hydrogenation of the corresponding ketone. [25] We began our investigation of the enantioselective silylation of cyclopropanes by examining the reactions of (1-phenylcyclopropyl)methanol (1a [24,[26][27][28] formed a a mixture of hydrosilyl ether 2a and dialkoxysilane 4. In contrast, the reaction catalyzed by 0.2 mol % Ru(PPh 3 ) 3 Cl 2 at 50 °C (eq 1) formed 2a exclusively.…”

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confidence: 99%

Rhodium‐Catalyzed Enantioselective Silylation of Cyclopropyl C−H Bonds

Lee

Hartwig

2016

Angewandte Chemie

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We describe an enantioseleclive silylation of cyclopropanes catalyzed by a rhodium precursor and the bisphosphine (S)-DTBM-SEGPHOS. (Hydrido)silyl ethers, generated in situ by the dehydrogenative silylation of cyclopropylmethanols with diethylsilane, undergo asymmetric, intramolecular silylation of cyclopropyl C-H bonds in high yields with high enantiomeric excesses in the presence of the rhodium catalyst. The resulting enantioenriched oxasilolanes are suitable substrates for Tamao-Fleming oxidation to form cyclopropanols with conservation of the ee from the C-H bond silylation. Preliminary mechanistic data suggest that C-H cleavage is likely to be the turnover-limiting and enantioselectivity-determining step. Graphical Abstract(Hydrido)silyl ethers, generated in situ by the dehydrogenative silylation of cyclopropylmethanols with diethylsilane, undergo asymmetric, intramolecular silylation of cyclopropyl C-H bonds in high yields with high enantiomeric excesses in the presence of a rhodium catalyst. The silylation products are suitable substrates for Tamao-Fleming oxidation to form cyclopropanols with conservation of the ee from the C-H bond silylation.Keywords asymmetric catalysis; C-H activation; cyclopropane; rhodium; silylation The functionalization of C-H bonds with boranes and silanes has been studied intensively, due to the high regioselectivity of these processes for sterically accessible C-H bonds and widespread utility of the products. [1,2] However, the development of enantioselective variants of these reactions, particularly enantioselective functionalization of alkyl C-H bonds, has been limited (Scheme 1). [3][4][5] Kuninobu, Murai and Takai reported the Correspondence to: John F. Hartwig, jhartwig@berkeley.edu. Supporting information for this article is given via a link at the end of the document. HHS Public Access Author ManuscriptAuthor Manuscript Author ManuscriptAuthor Manuscript asymmetric silylation of a C-H bond to generate a stereogenic silicon center with up-to 88% enantiomeric excess (ee) (Scheme 1A). [6,7] Shibata, He, Murai and Takai independently reported the synthesis of planar chiral compounds with moderate to high enantioselectivities by asymmetric C-H silylation of ferrocenes. [8][9][10] Recently, we reported an enantioselective silylation of aryl C-H bonds to form enantioenriched benzoxasilole products with up-to 99% ee. [11] Although these reactions can occur with high enantioselectivity, they are limited to the functionalization of aryl C-H bonds. The only published set of enantioselective silylations of alkyl C-H bonds occurs with low ee (37-40% ee) and with limited scope (Scheme 1B). [12] To create the first silylations of alkyl C-H bonds that occur with high enantioselectivity, we investigated systems for the reactions of cyclopropanes. C-H bonds of cyclopropanes are more reactive than sp 3 C-H bonds of unstrained rings or alkyl chains, [13] and the rigid conformation of a cyclopropane could allow for high stereoselectivity. Yu and co-workers reported enantioselective...

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Ir‐Catalyzed Heterocycles Synthesis

Obora

2016

Transition Metal‐Catalyzed Heterocycle Synthesis via CH Activation

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Iridium‐Catalyzed Regioselective Silylation of Aromatic and Benzylic CH Bonds Directed by a Secondary Amine

Cited by 77 publications

References 59 publications

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

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

Rhodium‐Catalyzed Enantioselective Silylation of Cyclopropyl C−H Bonds

Ir‐Catalyzed Heterocycles Synthesis

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