Chiral Silanes Research Articles

Vinylogous Aldol Products from Chiral Crotylsilanes Obtained by Enantioselective Rh(II) and Cu(I) Carbenoid Si−H Insertion

Enantioenriched homoallylic ethers containing a alpha,beta-unsaturated ester (syn-vinylogous aldol products) were directly accessed by Lewis acid catalyzed crotylation utilizing chiral silane 2. The reagents were prepared by enantioselective Si-H insertion to an alpha-diazovinylacetates using Davies' Rh(2)(DOSP)(4) catalyst or chiral Cu(I) Schiff base complex.

Preparation of “Si‐Centered” Chiral Silanes by Direct α‐Lithiation of Methylsilanes

The direct alpha-lithiation of methyl-substituted silanes as an efficient method for the preparation and elaboration of Si-chiral compounds is reported. Deprotonation of chiral oligosilanes occurs selectively and with high yields at the methyl group of the stereogenic silicon center, even in the presence of multiple methylsilyl or methylgermyl substituents. Computational studies have confirmed this preference as a consequence of pre-coordination of the lithiating agent by the amino side-arm and repulsion effects in the corresponding transition state. This complexation is also obvious from X-ray structure analyses of the alpha-lithiated silanes, which exhibit intriguing structure formation patterns differing in the type of aggregation and the amount of alkyllithium used. An alternative route to Si-chiral compounds is also presented, which involves desymmetrization of dimethylsilanes mediated by a chiral side-arm. Structure analyses and computational studies have shown that the diastereoselectivity of this alpha-lithiation is influenced by the selectivity of the formation of the stereogenic nitrogen upon complexation of the alkyllithium.

Asymmetric Si–O coupling of alcohols

Stereoselective Si-O couplings are auspicious processes for the synthesis of both chiral alcohols and chiral silanes. Attractive facets of this theme are currently enjoying a renaissance, and the several significant contributions are summarised in this Emerging Area.

B(C6F5)3‐Catalyzed Reduction of Ketones and Imines Using Silicon‐Stereogenic Silanes: Stereoinduction by Single‐Point Binding

AbstractWe recently employed a silicon‐stereogenic silane as astereochemical probe to clarify the mechanism of the B(C6F5)3‐catalyzed hydrosilylation of ketones. When using a prochiral ketone, reasonable stereoinduction was seen, originating from the stereogenicity at the silicon atom, a chirality transfer from silicon to carbon through single‐point binding of the chiral silane to the carbonyl oxygen atom. In the present investigation, we further elaborated on this remarkable observation by systematic variation of the ketone substitution pattern. We then included prochiral imines as well to test for diastereocontrol. Unexpectedly, these substance classes, ketones and imines, yielded diametrically opposed results in the reduction with a silicon‐stereogenic silane. While the level of diastereoselection was decent in the C=O reduction (dr ≈ 80:20), no asymmetric induction was detected in the C=NR reduction. On the basis of these experimental data and our previous mechanistic insight, we propose different reaction pathways for the reduction step of these related B(C6F5)3 catalyses. Aside from these mechanistic implications, we also report an unusual 1,6‐ rather than conventional 1,2‐reduction of a sterically encumbered diaryl‐substituted ketone.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Tandem Asymmetric Aza-Darzens/Ring-Opening Reactions: Dual Functionality from the Silane Lewis Acid

The addition of a stabilized sulfur ylide (generated by the rhodium-catalyzed reaction of Ph(2)S with ethyl diazoacetate) to N-acylhydrazones promoted by a chiral silane Lewis acid leads to the highly diastereo- and enantioselective synthesis of beta-chloro-alpha-hydrazido esters. The addition of electron-rich arenes and ZnCl(2) to the reaction mixture leads to the highly diastereo- and enantioselective one-pot synthesis of diarylalanine derivatives. In both cases, the silane Lewis acid responsible for the first reaction performs the second function of activating the aziridine intermediate toward nucleophilic attack.

Synthesis and application of bulky phosphoramidites: highly effective monophosphorus ligands for asymmetric hydrosilylation of styrenes

A series of bulky monodentate phosphoramidite ligands were synthesized from chiral 3,3'-diaryl substituted BINOL derivatives and achiral or dendritic amines in good yields. Asymmetric hydrosilylation of styrenes with trichlorosilane in the presence of palladium complexes of these bulky ligands gave chiral silanes in high yields with excellent activity and productivity. Oxidation of these chiral silanes with hydrogen peroxide gave the corresponding chiral secondary alcohols in up to 96% ee.

Facile preparation of CF3-substituted carbinols with an azine donor and subsequent kinetic resolution through stereoselective Si–O coupling

A number of CF(3)-substituted carbinols decorated with an azine donor are efficiently prepared from fluoral and kinetically resolved in a reagent-controlled, Cu-H-catalysed Si-O coupling with a chiral silane. Selectivity factors are high, indicating a larger steric effect than CH(3) or C(6)H(5) groups.

Enantioselective Carbene Insertion into Si-H Bonds

Carbene insertion into silicone-­hydrogen bonds is a well-established process ­pioneered by M. P. Doyle, C. J. Moody and co-workers (Tetrahedron Lett. 1996, 38, 7631). The majority of the developments in this area, how­ever, have been dominated by rhodium catalysis. The authors report a copper-catalyzed protocol where, by utilizing a new spiro-diimine ligand, chiral silanes are formed in high yield and enantio­selectivities.

A New Silicon Lewis Acid for Highly Enantioselective Mannich Reactions of Aliphatic Ketone-Derived Hydrazones

The first general method for the highly enantioselective Mannich reaction of aliphatic ketimines is reported. A new, second generation chiral silane Lewis acid has been developed that promotes the reaction between ketone-derived hydrazones and silyl ketene acetals, providing the beta,beta-disubstituted beta-amino esters with good enantioselectivity even for the hydrazone derived from 2-butanone (methyl vs ethyl, 91% ee). Several examples are provided, including a reaction with a substituted (propanoate-derived) silyl ketene acetal.

Asymmetric Hydrosilylation of Styrenes by Use of New Chiral ­Phosphoramidites

New chiral phosphoramidites were synthesized from chiral unsymmetrical amines and BINOL in good yields. Enantioselective hydrosilylation of styrenes with trichlorosilane in the presence of palladium complexes of these ligands provided chiral silanes in medium to high yields. Oxidation of these chiral silanes with hydrogen peroxide gave the corresponding chiral secondary alcohols in up to 97% ee.

パラジウム錯体触媒による置換アレン類の立体選択的合成法の開発とその応用

A novel Pd-catalyzed reaction of a 2-halo- or 2-trifloxy-l, 3-butadiene derivative with a soft nucleophile is developed. The reaction proceeds via an exo-alkylidene-π-allylpalladium intermedi-ate in a formal SN2' fashion to give an allenic compound exclusively. A variety of soft nucleophiles, such as malonates, phenoxides, and imides, are applicable to the reaction, and thus a wide range of functionality can be introduced to the products. The reaction is extended into an asymmetric counterpart and axially chiral allenes are prepared with up to 93% ee by the use of chiral palladium catalysts. A formal total synthesis of an insect pheromone is achieved using the Pd-catalyzed asymmetric reaction as a key step. The Pd-catalyzed reaction also enables to prepare axially chiral (allenylmethyl) silanes and allenylsilanes in optically active forms. Reactions of these silylallenes with appropriate electrophiles proceed via SE', pathways and the allenic axial chirality is efficiently transferred to stereogenic carbon centers in the SE', products.

Brønsted Acid-Catalyzed Desymmetrization of meso-Aziridines

The enantioselective ring-opening of meso-aziridines with azide nucleophiles proceeded in the presence of a catalytic amount of a chiral phosphoric acid catalyst. The reaction affords the formation of the products in excellent yield and enantioselectivity. Preliminary mechanistic studies indicate that the active catalytic species is a chiral silane that is generated in situ.

More than a Protective Group: Synthesis and Applications of a New Chiral Silane

Enantiomerically pure (-)-(R)- and (+)-(S)-(1-methoxy-2,2,2-triphenylethyl)dimethylsilanes (MOTES-H) were synthesized from triphenylacetaldehyde in five synthetic steps and with 60% overall yield. MOTES-protected alpha- and beta-hydroxycarbonyl compounds were used in Grignard and Diels-Alder reactions in the presence of MgBr2 to afford addition products with 87-98% yield and selectivities of up to >120:1 dr. With this method, the pine beetle pheromone (-)-frontalin (67%, 98.5% ee) and naturally occurring (-)-(R)-octane-1,3-diol (90%, >99% ee) were synthesized.

Synthesis of Chiral Allenyl Silanes and Homopropargylic Amines from Aldimines

Synthesis of Chiral Allenyl Silanes and Homopropargylic Amines from Aldimines

Intermolecular Chirality Transfer from Silicon to Carbon: Interrogation of the Two-Silicon Cycle for Pd-Catalyzed Hydrosilylation by Stereoisotopochemical Crossover

A “two-silicon cycle” for the highly efficient intermolecular chirality transfer from silicon to carbon (98−99% ct) in the palladium-catalyzed hydrosilylation of norbornenes emerges from an investigation involving catalytic crossover experiments with isotopically labeled silicon-stereogenic silanes. A key outcome of these experiments, which are supported by product-distribution modeling, is the conclusion that the chirality transfer arises from thermodynamically controlled reversible silapalladation of the alkene rather than from kinetic control during irreversible σ-bond metathesis of the resulting β-silyl σ-alkyl palladium complex with chiral silane.

A Simple, Efficient, and Highly Enantioselective Synthesis of MS‐153 Employing a Chiral Silane Lewis Acid‐Promoted Acylhydrazone‐Enol Ether [3+2] Cycloaddition

AbstractOur previously reported chiral silane‐promoted enol ether‐acylhydrazone [3+2] cycloaddition reaction has been applied to a brief and efficient synthesis of the neuroprotective agent MS‐153. Unsatisfactory and variable levels of efficiency and enantioselectivity with the requisite acetaldehyde‐derived acylhydrazone occasioned a modification to the chiral silane Lewis acid, which led to the key cycloaddition step proceeding with excellent efficiency (85 % yield) and enantioselectivity (≥98 % ee).

Hydrosilylation of ketones catalyzed by C2-symmetric proline-derived complexes

Extracoordinate chiral hydrosilanes were generated in situ from triethoxysilane and a C2-symmetric ligand derived from bisproline 7. In the presence of a catalytic amount of ligand 7, prochiral ketones were reduced in moderate yield with moderate enantioselectivity (up to 64% ee). Alternatively, TiF4 complexes of 7 were used to provide higher enantioselectivity and with improved yields. The copper complex of ligand 7 and 29Si NMR data provide some guidance as to the key factors responsible for the observed reactivity at the silicon and at the ligand centre.Key words: extracoordinate chiral silane, C2-symmetry, enantioselectivity, Lewis acid titanium catalysis.

Chiral Silanes via Asymmetric Hydrosilylation with Catalytic CuH.

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Enantioselective α-Silylation of Enones

In the presence of a chiral, proline-based Rh(II) catalyst, easily synthesized α-diazo­enones can be hydrosilylated enantioselectively to the corresponding α-silylenone in moderate to good yield and with good to very good enantioselectivity. Interestingly, when the opposite-antipode catalyst was used, lower enantioselectivities were observed. The chiral silane was also shown to be synthetically useful for the construction of vicinal and remote chiral centers upon reaction with organometallic reagents.

Enantiodifferentiation of a silane and the analogous hydrocarbon by the dirhodium method—silane⋯dirhodium complex interaction

Chiral silane 1 was enantiodifferentiated by recording NMR spectra in the presence of the chiral dirhodium complex Rh 2 ( II ) [ ( R ) - ( + ) - MTPA 4 ] ( Rh ∗). This is the first report of direct chiral recognition by spectroscopic methods with this class of compounds. A comparison with the carba-analogue 2 shows that 1 is a soft Lewis-base ligand and that the Si–H hydrogen is the binding site, presumably by forming an adduct with a (3c-2e) silicon–hydrogen–rhodium contact (end-on), which exists in equilibrium with the free ligands.