Asymmetric Silyl Research Articles

Brønsted Acid Catalyzed Asymmetric Silylation of Biaryl Diols

AbstractWe report a Brønsted acid catalyzed enantioselective silylation of biaryl diols with an allylsilane as a silicon source. This process enables facile access to enantioenriched biaryl silyl ethers with an axial stereogenicity. A control experiment supports a mechanism proceeding by desymmetrization followed by kinetic resolution.

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.

Mechanistic investigations of alcohol silylation with isothiourea catalysts.

The mechanism of the asymmetric silylation of alcohols with isothiourea catalysts was studied by employing reaction progress kinetic analysis. These reactions were developed by the Wiskur group, and use triphenyl silyl chloride and chiral isothiourea catalysts to silylate the alcohols. While the order of most reaction components was as expected (catalyst, amine base, alcohol), the silyl chloride was determined to be a higher order. This suggested a multistep mechanism between the catalyst and silyl chloride, with the second equivalent of silyl chloride assisting in the formation of the reactive intermediate leading to the rate-determining step. Through the addition of additives and investigating changes in the silyl chloride, an understanding of the catalyst equilibrium emerged for this reaction and provided pathways for further reaction development.

Polymer compositions on kinetic resolution of secondary alcohols using polymer-supported silyl chlorides

Modulating the polarity of the polymer backbone affects the selectivity of asymmetric silylation.

Copper-catalyzed asymmetric silyl addition to alkenyl-substituted N-heteroarenes.

Asymmetric conjugate addition of PhMe2SiBPin to a wide range of N-heteroaryl alkenes proceeded in the presence of a copper catalyst coordinated with an easily accessible chiral phosphoramidite ligand to afford useful β-silyl N-heteroarenes in high yields (up to 96%) and excellent enantioselectivities (up to 97% ee).

Silylative Kinetic Resolution of Racemic 1-Indanol Derivatives Catalyzed by Chiral Guanidine.

Efficient kinetic resolution of racemic 1-indanol derivatives was achieved using triphenylchlorosilane by asymmetric silylation in the presence of chiral guanidine catalysts. The chiral guanidine catalyst (R,R)-N-(1-(β-naphthyl)ethyl)benzoguanidine was found to be highly efficient as only 0.5 mol % catalyst loading was sufficient to catalyze the reaction of various substrates with appropriate conversion and high s-values (up to 89). This catalyst system was successfully applied to the gram-scale silylative kinetic resolution of racemic 1-indanol with high selectivity.

The search for an easily-prepared sparteine surrogate

Abstract (−)-Sparteine has proven itself to be a highly efficient and versatile ligand. However, in recent years it has become difficult to source. In addition the (+)-enantiomer is also not readily available. Here we report a suite of chiral diamines as potential sparteine surrogates. Chiral trans -1,2-diaminocyclohexane is commercially available in both enantiomeric forms and the parent structure can be easily modified. New (and known) chiral diamines have been tested in the asymmetric silylation of N -Boc pyrrolidine, N -Boc piperidine, the α-alkylation of dimethylhydrazones and in the rearrangement of meso -epoxides. While none match the selectivity of the highly evolved natural product, there is certainly potential for this class of diamine ligands to perform in a diverse set of asymmetric transformations.

ChemInform Abstract: An Insoluble Copper(II) Acetylacetonate—Chiral Bipyridine Complex that Catalyzes Asymmetric Silyl Conjugate Addition in Water.

Acicular purplish crystals were obtained from Cu(acac)2 and a chiral bipyridine ligand. Although the crystals were not soluble, they nevertheless catalyzed asymmetric silyl conjugate addition of lipophilic substrates in water. Indeed, the reactions proceeded efficiently only in water; they did not proceed well either in organic solvents or in mixed water/organic solvents in which the catalyst/substrates were soluble. This is in pronounced contrast to conventional organic reactions wherein the catalyst/substrates tend to be in solution. Several advantages of the chiral Cu(II) catalysis in water over previously reported catalyst systems have been demonstrated. Water is expected to play a prominent role in constructing and stabilizing sterically confined transition states and accelerating subsequent protonation to achieve high yields and enantioselectivities.

2.2]Paracyclophane-based N-heterocyclic carbene as efficient catalyst or as ligand for copper catalyst for asymmetric α-silylation of N-tosylaldimines

A carbene precursor plays a dual role as both an organocatalyst and as a ligand for the copper catalyst in asymmetric silylation.

An Insoluble Copper(II) Acetylacetonate-Chiral Bipyridine Complex that Catalyzes Asymmetric Silyl Conjugate Addition in Water.

Acicular purplish crystals were obtained from Cu(acac)2 and a chiral bipyridine ligand. Although the crystals were not soluble, they nevertheless catalyzed asymmetric silyl conjugate addition of lipophilic substrates in water. Indeed, the reactions proceeded efficiently only in water; they did not proceed well either in organic solvents or in mixed water/organic solvents in which the catalyst/substrates were soluble. This is in pronounced contrast to conventional organic reactions wherein the catalyst/substrates tend to be in solution. Several advantages of the chiral Cu(II) catalysis in water over previously reported catalyst systems have been demonstrated. Water is expected to play a prominent role in constructing and stabilizing sterically confined transition states and accelerating subsequent protonation to achieve high yields and enantioselectivities.

ChemInform Abstract: Catalytic Enantioselective Silylation of N‐Sulfonylimines: Asymmetric Synthesis of α‐Amino Acids from CO2 via Stereospecific Carboxylation of α‐Amino Silanes.

AbstractAn asymmetric silylation of N‐tert‐butylsulfonylimines by using a Cu‐secondary diamine complex as the catalyst is developed.

McQuade’s Six-Membered NHC–Copper(I) Complexes for Catalytic Asymmetric­ Silyl Transfer

A full account of our work on enantioselective silylation of typical prochiral acceptors employing chiral six-membered NHC–copper(I) complexes introduced by McQuade and co-workers is presented. With these precatalysts, asymmetric branched-selective substitution of allylic phosphates and 1,2-addition to imines had become possible for the first time. The successful application of these catalysts in two fundamentally different reactions raised the question whether these are a privileged ligand motif for catalytic asymmetric silyl transfer. To assess their generality, these were utilized in the related 1,2-addition to aldehydes and in conjugate addition to representative α,β-unsaturated acceptors, but with limited success in both cases. This study also includes an optimization of the allylic silylation, now overcoming the limited scope of the previous protocol. The scope of the imine addition is extended to heteroaryl­-substituted aldimines.

Enantioselective Syntheses of α‐Silyl Amines via a Copper‐N‐Heterocyclic Carbene Catalyzed Nucleophilic Silicon Transfer to Imines

AbstractWe developed an efficient and enantioselective method for the synthesis of chiral α‐silyl amines. In the presence of a copper(I)‐chiral monodentate N‐heterocyclic carbene complex (5 mol %), smooth nucleophilic silicon transfer from Me2PhSiBpin (pin=pinacolato) to tosyl‐protected aldimines affords the corresponding α‐silyl amines in 77–93 % yields over 15 examples and satisfactory ee of 79–99 %. The asymmetric silylation of ketimines was also explored.

Cu(I)–NHC Catalyzed Asymmetric Silyl Transfer to Unsaturated Lactams and Amides

The first asymmetric silylation of unsaturated lactams and amides using Cu(I)-NHC catalysts and PhMe2SiBpin has been accomplished. The method has been exploited in an expedient asymmetric synthesis of the (R)-enantiomer of the nootropic drug oxiracetam.

Resolution of Terminal 1,2-Diols via Silyl Transfer

Through kinetic analysis and optimization, we report an improved resolution of terminal 1,2-diols via asymmetric silyl transfer. Because the reaction is a regiodivergent resolution, the monoprotected product could be isolated in excess of 95:5 er and 40% yield. The described method offers a means of chemically differentiating a terminal 1,2-diol with concomitant resolution of the enantiomers.

ChemInform Abstract: NHC—Cu(I) Catalyzed Asymmetric Conjugate Silyl Transfer to Unsaturated Lactones: Application in Kinetic Resolution.

AbstractA convenient procedure is elaborated for the asymmetric silyl transfer to unsaturated lactones.

NHC–Cu(i) catalysed asymmetric conjugate silyl transfer to unsaturated lactones: application in kinetic resolution

The scope of the asymmetric silyl transfer to unsaturated lactones utilising a C2-symmetric NHC-Cu(I) catalyst has been established and kinetic resolutions mediated by silyl transfer have been used to prepare enantiomerically enriched anti-4,5-disubstituted 5-membered lactones. The method has been exploited in an expedient synthesis of (+)-blastmycinone.

Catalytic enantioselective dehydrogenative Si–O coupling of oxime ether-functionalized alcohols

Asymmetric silylation of alcohols is an unusual but effective approach to their kinetic resolution, and the Cu–H-catalyzed dehydrogenative Si–O coupling is particularly noteworthy as dihydrogen is formed as the sole by-product. Our laboratory had previously reported on diastereoselective (with silicon-stereogenic silanes) and enantioselective (with achiral silanes) Si–O couplings of azine donor-functionalized alcohols. The limitation, that is, the requirement of a nitrogen donor atom, prompted us to seek equally useful donor groups. Oxime ethers were identified as a suitable alternative, and we describe herein the preparation of a series of oxime ether-functionalized alcohols. To assess different substitution patterns in their kinetic resolution, these were tested in the reagent-controlled Si–O coupling using a silicon-stereogenic silane. The optimal substituents at the oxime carbon atom (dr=85:15 in the diastereoselective coupling) were then chosen for the related catalyst-controlled Si–O coupling but selectivity factors were only moderate.

Asymmetric Silyl Transfer by Transition-Metal-Free NHC Catalysis

Asymmetric Silyl Transfer by Transition-Metal-Free NHC Catalysis