Allylic Silanes Research Articles

N-Trifluoroethoxy Benzotriazolium Triflate: A Readily Available Reagent for Direct Radical Trifluoroethoxylation of Alkenes.

Herein, we describe the development and application of a novel benzotriazole-based reagent toward radical trifluoroethoxylation. Various alkene classes, including styrene derivatives, enol carbonates, and allyl silanes, are viable reaction partners in this transformation, yielding diverse trifluoroethoxylated products. Furthermore, this method is readily applicable for the late-stage modification of natural product and drugs molecules. Mechanistic and computational studies suggest the intermediacy of an OCH2CF3 radical generated under photocatalytic conditions.

Tris(pentafluorophenyl)borane‐Catalyzed Functionalization of Benzylic C−F Bonds

AbstractThe activation of C(sp3)−F bonds by the commercially available catalyst B(C6F5)3 is reported and applied in reactions with arenes, allylic, vinylic and acetylenic silanes, and olefins to achieve a variety of C−C bond formations (45 examples).

Catalyst-Free Trifluoromethoxylation of Silyl Enol Ethers and Allyl Silanes with Bis(trifluoromethyl)peroxide.

Radical trifluoromethoxylation is an attractive approach to prepare compounds featuring the important OCF3 group, however most existing methods have focused on aromatic substrates. Here, we report novel methodologies with alkenyl substrates employing bis(trifluoromethyl)peroxide (BTMP) as a practical and comparatively atom economical trifluoromethoxylating reagent. With silyl enol ether substrates, switching reaction solvent allows for the synthesis of either α-(trifluoromethoxy)ketone products or unprecedented alkenyl-OCF3 species. Furthermore, allyl silanes have been employed as substrates for the first time, affording allyl(trifluoromethyl)ether products in good yields. In each case, the methods operate at room temperature without large excesses of the alkene substrate while, in contrast to previous radical trifluoromethoxylation reactions, no catalyst, light or other activators are required.

Catalyst‐Free Trifluoromethoxylation of Silyl Enol Ethers and Allyl Silanes with Bis(trifluoromethyl)peroxide

AbstractRadical trifluoromethoxylation is an attractive approach to prepare compounds featuring the important OCF3 group, however most existing methods have focused on aromatic substrates. Here, we report novel methodologies with alkenyl substrates employing bis(trifluoromethyl)peroxide (BTMP) as a practical and comparatively atom economical trifluoromethoxylating reagent. With silyl enol ether substrates, switching reaction solvent allows for the synthesis of either α‐(trifluoromethoxy)ketone products or unprecedented alkenyl‐OCF3 species. Furthermore, allyl silanes have been employed as substrates for the first time, affording allyl(trifluoromethyl)ether products in good yields. In each case, the methods operate at room temperature without large excesses of the alkene substrate while, in contrast to previous radical trifluoromethoxylation reactions, no catalyst, light or other activators are required.

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In nature, differences in temperature create completely distinguishable landscapes in winter and spring. Similarly, by controlling the reaction temperature, efficient regioselective control of nickel‐catalyzed hydrosilylation of conjugated dienes with primary silanes can be achieved, facilitating the divergent synthesis of various homoallylic silanes and allylic silanes under mild conditions. More details are discussed in the article by Zhang et al. on page 13—19.image

Nickel‐Catalyzed Regioselective Hydrosilylation of Conjugated Dienes†

Comprehensive SummaryWith the increasing demand for homoallylic silanes and allylic silanes, the highly efficient and regioselective hydrosilylations of conjugated dienes are urgently needed. Herein, we developed a Ni‐catalyzed regiodivergent hydrosilylation of aromatic conjugated dienes by adjusting the temperature and ligands. Under low temperature (–30 °C), an eternal‐ligand‐free system (Ni/t‐BuOK) can efficiently facilitate the 3,4‐anti‐Markovnikov hydrosilylation to provide homoallylic silanes via electrophilic activation process; under room temperature (25 °C), a ligand‐controlled system (Ni/t‐BuOK/PPh3) can eventuate the 3,4‐Markovnikov hydrosilylation to produce allylic silanes via Chalk‐Harrod process. Both systems are compatible with various conjugated dienes and primary silanes in excellent yields and regioselectivities.

Atroposelective Silylation of 1,1'-Biaryl-2,6-diols by a Chiral Counteranion Directed Desymmetrization Enhanced by a Subsequent Kinetic Resolution.

A desymmetrizing silylation of aromatic diols is reported. The previously unknown asymmetric silyl ether formation of phenol derivatives is achieved by applying List's counteranion directed silylation technique. A silylium-ion-like silicon electrophile generated from an allylic silane paired with an imidodiphosphorimidate (IDPi) enables enantioselective discrimination of achiral 1,1'-biaryl-2,6-diols. The enantioselectivity of that desymmetrization is further improved by a downstream kinetic resolution, converting the monosilylated minor enantiomer into the corresponding, again achiral bissilylated diol.

Atropselektive Silylierung von 1,1′‐Biaryl‐2,6‐diolen mittels chiraler gegenaniondirigierter Desymmetrisierung und anschließender Verbesserung durch kinetische Racematspaltung

AbstractEs wird über eine desymmetrisierende Silylierung von aromatischen Diolen berichtet. Die zuvor unbekannte asymmetrische Silyletherbildung von Phenolderivaten wird mit der List'schen gegenaniondirigierten Silylierungsmethode erreicht. Ein silyliumionartiges Siliciumelektrophil, welches aus der Paarung eines Allylsilans und eines Imidodiphosphorimidats (IDPi) hervorgeht, erlaubt eine enantioselektive Unterscheidung von achiralen 1,1′‐Biaryl‐2,6‐diolen. Die Enantioselektivität dieser Desymmetrisierung wird zusätzlich durch eine nachgeschaltete kinetische Racematspaltung verbessert, indem das monosilylierte Mindermengenenantiomer in das entsprechende, abermals achirale bissilylierte Diol überführt wird.

Investigation of a novel approach to the core of stemofoline: enantioselective construction of a bicyclic intermediate with three contiguous chiral centers

<p indent="0mm">The enantioselective synthesis of a bicyclic intermediate containing three contiguous chiral centers for a novel approach to the core of stemofoline is described. A (<italic>S</italic>)-malimide derivative developed in this laboratory was used as the chiral building block. The latter was converted in three steps (<italic>N</italic>-deprotection, a Mitsunobu reaction, and a cross-olefin metathesis) into another malimide with the <italic>N</italic>-substituent bearing a nucleophilic allylic silane moiety. The Grignard reagent addition took place regioselectively at the C-2 carbonyl to yield a hemiaminal. The key intramolecular aza-Sakurai reaction was promoted by trifluoroboron etherate, which led to the desired cyclization in good to excellent combined yields. Four diastereomers were formed from this reaction, whose stereochemistries were determined by NOESY technique. The latter revealed that the major diastereomer (obtained in 35% yield) possessed the correct stereochemistries required for the total synthesis of natural enantiomer of stemofoline. A regioselective Wacker oxidation resulted in the formation of the title compound along with a minor regioisomer (an aldehyde) in a ratio of 18: 1 (combined yield: 50%).

Organocatalytic DYKAT of Si-Stereogenic Silanes.

Chiral organosilanes do not exist in nature and are therefore absent from the "chiral pool". As a consequence, synthetic approaches toward enantiopure silanes, stereogenic at silicon, are rather limited. While catalytic asymmetric desymmetrization reactions of symmetric organosilicon compounds have been developed, the utilization of racemic silanes in a dynamic kinetic asymmetric transformation (DYKAT) or dynamic kinetic resolution (DKR) would significantly expand the breadth of accessible Si-stereogenic compounds. We now report a DYKAT of racemic allyl silanes enabled by strong and confined imidodiphosphorimidate (IDPi) catalysts, providing access to Si-stereogenic silyl ethers. The products of this reaction are easily converted into useful enantiopure monohydrosilanes. We propose a spectroscopically and experimentally supported mechanism involving the epimerization of a catalyst-bound intermediate.

Resolving the Mechanistic Complexity in Triarylborane-Induced Conjugate Additions

Previous studies have shown that the catalytically active species in the Lewis acid-catalyzed addition reactions of allyl silanes or silyl enol ethers to carbonyl compounds or Michael acceptors are often silylium-carbonyl adducts rather than the adducts of the carbonyl group with the Lewis acid used for the induction of the reaction. Indirect evidence for such catalyst variations has so far been derived from double-label crossover experiments and comparisons of absolute reaction rates. We have now performed a detailed investigation on the kinetics and mechanism of the triarylborane-initiated conjugate addition reactions of allylsilanes and silyl enol ethers to α,β-unsaturated carbonyl compounds. NMR spectroscopic monitoring of such reactions gave rise to sigmoidal kinetic profiles, allowing us to directly follow the change of the catalytically active Lewis acid from triarylboranes in the induction period to silylium ions during the main part of the reaction. Crossover experiments and the isolation of four- and five-membered cyclic intramolecular trapping products provided further insight into the mechanism. DFT calculations of various mechanistic variants and kinetic modeling elucidated the operation of a complex reaction network, which rationalizes the experimental observations.

One-Pot Synthesis of Styrene Derivatives from Allyl Silanes via B(C6F5)3-Catalyzed Isomerization-Hiyama Coupling.

Herein, we report a one-pot synthesis of styrene derivatives via a novel B(C6F5)3-catalyzed E-selective isomerization of readily accessible allyl silanes and subsequent Hiyama coupling of the versatile alkenyl silane intermediates. This one-pot, two-step approach enables access to a broad range of styrene derivatives, including those containing Lewis basic functional groups, that cannot be accessed via the previously developed B(C6F5)3-catalyzed isomerization of allyl benzenes.

A General Strategy for the Asymmetric Preparation of α‐Stereogenic Allyl Silanes, Germanes, and Boronate Esters via Dual Copper Hydride‐ and Palladium‐Catalysis

Abstractα‐Stereogenic allyl metalloids are versatile synthetic intermediates which can undergo various stereocontrolled transformations. Most existing methods to prepare α‐stereogenic allyl metalloids involve multi‐step sequences that curtail the number of compatible substrates and are limited to the synthesis of boronates. Here, we report a general method for the enantioselective preparation of α‐stereogenic allyl metalloids utilizing dual CuH‐ and Pd‐catalysis. This approach leverages a stereoretentive Cu‐to‐Pd transmetalation of an in situ generated alkyl copper species to allow access to enantioenriched allyl silanes, germanes, and boronate esters with broad functional group compatibility.

A General Strategy for the Asymmetric Preparation of α-Stereogenic Allyl Silanes, Germanes, and Boronate Esters via Dual Copper Hydride- and Palladium-Catalysis.

α-Stereogenic allyl metalloids are versatile synthetic intermediates which can undergo various stereocontrolled transformations. Most existing methods to prepare α-stereogenic allyl metalloids involve multi-step sequences that curtail the number of compatible substrates and are limited to the synthesis of boronates. Here, we report a general method for the enantioselective preparation of α-stereogenic allyl metalloids utilizing dual CuH- and Pd-catalysis. This approach leverages a stereoretentive Cu-to-Pd transmetalation of an in situ generated alkyl copper species to allow access to enantioenriched allyl silanes, germanes, and boronate esters with broad functional group compatibility.

Electrochemical Synthesis of gem-Difluoro- and γ-Fluoro-Allyl Boronates and Silanes.

The electrochemical synthesis of fluorinated allyl silanes and boronates was disclosed. The addition of electrogenerated boryl or silyl radicals onto many α-trifluoromethyl or α-difluoromethylstyrenes in an undivided cell allowed the formation of a large panel of synthetically useful gem-difluoro and γ-fluoroallyl boronates and silanes (64 examples, from 31 % to 95 % yield). In addition, a scale up of the reactions under continuous flow was showcased using an electrochemical reactor with promising volumetric productivity (688 g.L-1 .h-1 and 496 g.L-1 .h-1 ). Moreover, the synthetic utility of these building blocks was highlighted through versatile transformations. Finally, plausible reaction mechanisms were suggested to explain the formation of the products.

Catalytic Enantioselective Synthesis of Functionalized Cyclopropanes from α-Substituted Allyl Sulfones with Donor-Acceptor or Diacceptor Diazo Reagents.

The catalytic asymmetric synthesis of highly functionalized cyclopropanes from α-substituted allyl sulfones and silanes is reported. The reaction, using α-aryl diazoacetates or diacceptor diazo reagents, catalyzed by a chiral rhodium complex (Rh2 ((S)-BTPCP)4 ), furnished the corresponding cyclopropanes in moderate to high yields (27-97 %), high diastereoselectivities (68 : 32 to 20 : 1 d.r.) and moderate to excellent ee (40-99 %). This methodology offers a privileged access to an underexplored class of enantioenriched cyclopropanes with a high level of functionality, an asset for further post-functionalization and their incorporation into more complex structure.

Photochemical Organocatalytic Regio- and Enantioselective Conjugate Addition of Allyl Groups to Enals.

We report the first catalytic enantioselective conjugate addition of allyl groups to α,β‐unsaturated aldehydes. The chemistry exploits the visible‐light‐excitation of chiral iminium ions to activate allyl silanes towards the formation of allylic radicals, which are then intercepted stereoselectively. The underlying radical mechanism of this process overcomes the poor regio‐ and chemoselectivity that traditionally affects the conjugate allylation of enals proceeding via polar pathways. We also demonstrate how this organocatalytic strategy could selectively install a valuable prenyl fragment at the β‐carbon of enals.

Photochemical Organocatalytic Regio‐ and Enantioselective Conjugate Addition of Allyl Groups to Enals

AbstractWe report the first catalytic enantioselective conjugate addition of allyl groups to α,β‐unsaturated aldehydes. The chemistry exploits the visible‐light‐excitation of chiral iminium ions to activate allyl silanes towards the formation of allylic radicals, which are then intercepted stereoselectively. The underlying radical mechanism of this process overcomes the poor regio‐ and chemoselectivity that traditionally affects the conjugate allylation of enals proceeding via polar pathways. We also demonstrate how this organocatalytic strategy could selectively install a valuable prenyl fragment at the β‐carbon of enals.

Boron Chelates Derived from N-Acylhydrazones as Radical Acceptors: Photocatalyzed Coupling of Hydrazones with Carboxylic Acids.

Difluoroboryl complexes obtained from N-acyl hydrazones upon brief treatment with boron trifluoride and allylic silane serve as efficient acceptors of alkyl radicals. The reaction of the boryl chelates with carboxylic acids in the presence of an acridine-type photocatalyst leading to N-acyl hydrazides is described. The efficiency of addition at the C═N bond of the chelates is determined by the formation of a nitrogen-centered radical stabilized by the boron-containing heterocyclic ring.

The Silicon–Hydrogen Exchange Reaction: Catalytic Kinetic Resolution of 2-Substituted Cyclic Ketones

AbstractWe have recently reported the strong and confined, chiral acid-catalyzed asymmetric ‘silicon−hydrogen exchange reaction’. One aspect of this transformation is that it enables access to enantiopure enol silanes in a tautomerizing σ-bond metathesis, via deprotosilylation of ketones with allyl silanes as the silicon source. However, until today, this reaction has not been applied to racemic, 2-substituted, cyclic ketones. We show here that these important substrates readily undergo a highly enantioselective kinetic resolution furnishing the corresponding kinetically preferred enol silanes. Mechanistic studies suggest the fascinating possibility of advancing the process to a dynamic kinetic resolution.