Direct chlorination of alcohols with chlorodimethylsilane catalyzed by a gallium trichloride/tartrate system under neutral conditions

The reaction of secondary alcohols 1 with chlorodimethylsilane (HSiMe(2)Cl) proceeded in the presence of a catalytic amount of GaCl(3)/diethyl tartrate to give the corresponding organic chlorides 3. In the catalytic cycle, the reaction of diethyl tartrate 4a with HSiMe(2)Cl 2 gives the chlorosilyl ether 5 with generation of H(2). Alcohol-exchange between the formed chlorosilyl ether 5 and the substrate alcohol 1 affords alkoxychlorosilane 6, which reacts with catalytic GaCl(3) to give the chlorinated product 3. The moderate Lewis acidity of GaCl(3) facilitates chlorination. Strong Lewis acids did not give product due to excessive affinity for the oxy-functionalities. Although tertiary alcohols were chlorinated by this system even in the absence of diethyl tartrate, certain alcohols that are less likely to give carbocationic species were effectively chlorinated using the GaCl(3)/diethyl tartrate system.     

Palladium-catalyzed asymmetric diene cyclization/hydrosilylation employing functionalized silanes and disiloxanes.

Pentasubstituted disiloxanes and silanes of the form HSiMe(2)CH(x)Ph(3-x)(x = 1 or 2) reacted with dimethyl diallylmalonate (1) and other functionalized 1,6-dienes in the presence of a catalytic 1:1 mixture of (N-N)Pd(Me)Cl [N-N = (R)-(+)-4-isopropyl-2-(2-pyridinyl)-2-oxazoline] [(R)-2] and NaBAr(4) [Ar = 3,5-C(6)H(3)(CF(3))(2)] to form the corresponding silylated cyclopentanes in good yield with high diastereoselectivity. The enantioselectivity of cyclization/hydrosilylation of 1 with disiloxanes and functionalized silanes at -20 degrees C increased in the following order: HSiMe(2)OSiMe(3) (75% ee) < HSiMe(2)OSiMe(2)-t-Bu (80% ee) < HSi(i-Pr)(2)OSiMe(3) (86% ee) = HSiMe(2)Bn (86% ee) < HSiMe(2)OSi(i-Pr)(3) (89% ee) < HSiMe(2)OSiPh(2)-t-Bu (91% ee) < HSiMe(2)CHPh(2) (93% ee). Silylated cyclopentanes derived from HSiMe(2)OSiMe(3) were oxidized with excess KF and peracetic acid at room temperature for 48 h to form the corresponding hydroxymethylcyclopentanes in good yield (82-95%). Silylated cyclopentanes derived from HSiMe(2)OSiPh(2)t-Bu were oxidized with a mixture of tetrabutylammonium fluoride and either H(2)O(2) or peracetic acid to form the corresponding alcohols in 48-76% yield. Silylated carbocycles generated from benzhydryldimethylsilane were oxidized with a mixture of TBAF/KHCO(3)/H(2)O(2) in 71-98% yield. Asymmetric cyclization/hydrosilylation/oxidation employing benzhydryldimethylsilane tolerated allylic and terminal olefinic substitution and a range of functional groups.     

Kinetic Resolution of Tertiary 2‐Alkoxycarboxamido‐Substituted Allylic Alcohols by Chiral Phosphoric Acid Catalyzed Intramolecular Transesterification

A highly enantioselective kinetic resolution of tertiary 2‐alkoxycarboxamido allylic alcohols has been achieved through a chiral phosphoric acid catalyzed intramolecular transesterification reaction. Both alkyl,aryl‐ and dialkyl‐substituted tertiary allylic alcohols were resolved with excellent efficiencies, affording both the recovered tertiary alcohols and the carbamate products with high enantioselectivities (with s factors up to 164.6). A gram‐scale reaction with 1 mol % catalyst loading and the facile conversion of the enantioenriched products into useful chiral building blocks, such as chiral oxazolidinones and β‐amino alcohols, demonstrate the value of this reaction.     

Highly efficient and chemoselective trimethylsilylation of alcohols and phenols with hexamethyldisilazane (HMDS) catalyzed by reusable electron-deficient [Ti(salophen)(OTf)2]

In the present work, highly efficient trimethylsilylation of alcohols and phenols with hexamethyldisilazane (HMDS) catalyzed by high-valent [Ti^IV(salophen)(OTf)₂] is reported. Under these conditions, primary, secondary and tertiary alcohols as well as phenols were silylated in short reaction times and high yields. It is noteworthy that this method can be used for chemoselective silylation of primary alcohols in the presence of secondary and tertiary alcohols and phenols. The catalyst was reused several times without loss of its catalytic activity.     

Ruthenium-catalyzed tertiary amine formation from nitroarenes and alcohols

A highly selective ruthenium-catalyzed C-N bond formation was developed by using the hydrogen-borrowing strategy. Various tertiary amines were obtained efficiently from nitroarenes and primary alcohols. The reaction tolerates a wide range of functionalities. A tentative mechanism was proposed for this direct amination reaction of alcohols with nitroarenes.     

Selectivity of tetrahydrofuran formation from inactivated aliphatic alcohols by the bromine-silver-salt reaction

Studies of the bromine-silver carbonate reaction with aliphatic alcohols in which intramoleular δ-H competition is possible are generally quite specific. Loss of tertiary δ- hydrogen occurs preferentially from both tertiary and secondary alfphatic alcohols to yield the most highly substituted cyclic ether. For example, 2,5-dimethyl-2-octanol yields only 2,2,5-trimethyl-5-propyletrahydrofuran as the cyclic ether product; 2-methyl-2-isopentyltetrahydrofuran is not detected.     

Novel palladium(II) complex containing a chelating anionic N-O ligand: efficient carbonylation catalyst

[reaction: see text] A novel palladium(II) complex containing chelating anionic pyridine-2-carboxylato and labile tosylato ligands is a highly efficient catalyst for the carbonylation of organic alcohols and olefins to carboxylic acids/esters. Carbonylation of primary, secondary, and tertiary alcohols as well as linear and functionalized terminal olefins was studied. In all cases remarkable activity and selectivity were observed. The catalyst is stable under reaction conditions even in the absence of excess phosphine ligands.     

Rapid,highly efficient and chemoselective trimethylsilylation of alcohols and phenols with hexamethyldisilazane (HMDS) catalyzed by reusable electron‐deficient tin(IV)porphyrin

In this paper, rapid and highly efficient trimethylsilylation of alcohols and phenols with hexamethyldisilazane (HMDS) in the presence of catalytic amounts of high‐valent [Sn^IV(TPP)(OTf)₂] is reported. This catalytic system catalyzes trimethylsilylation of primary, secondary and tertiary alcohols as well as phenols, and the corresponding TMS‐ethers were obtained in high yields and short reaction times at room temperature. It is noteworthy that this method can be used for chemoselective silylation of primary alcohols in the presence of secondary and tertiary alcohols and phenols. The catalyst was reused several times without loss of its catalytic activity. Copyright © 2009 John Wiley & Sons, Ltd.     

Cp*(iPr3P)Ru(Cl)(eta2-HSiClMe2): the first complex with simultaneous Si-H and RuCl...SiCl inter-ligand interactions

The addition of HSiMe2Cl to the unsaturated compound Cp*(iPr3P)RuCl gives an unstable adduct which, according to NMR (J(H-Si)= 33.5 Hz), X-ray crystal structure and DFT evidence, is a silane sigma-complex Cp*(iPr3P)Ru(Cl)(eta2-HSiMe2Cl) supported by an unprecedented, simultaneous inter-ligand RuCl...SiCl hypervalent interaction between the chloride ligand on ruthenium and the SiMe2Cl group.     

Isothiourea-Catalyzed Acylative Kinetic Resolution of Tertiary α-Hydroxy Esters

A highly enantioselective isothiourea-catalyzed acylative kinetic resolution (KR) of acyclic tertiary alcohols has been developed. Selectivity factors of up to 200 were achieved for the KR of tertiary alcohols bearing an adjacent ester substituent, with both reaction conversion and enantioselectivity found to be sensitive to the steric and electronic environment at the stereogenic tertiary carbinol centre. For more sterically congested alcohols, the use of a recently-developed isoselenourea catalyst was optimal, with equivalent enantioselectivity but higher conversion achieved in comparison to the isothiourea HyperBTM. Diastereomeric acylation transition state models are proposed to rationalize the origins of enantiodiscrimination in this process. This KR procedure was also translated to a continuous-flow process using a polymer-supported variant of the catalyst.     

Dioxomolybdenum(VI) complexes as catalysts for the hydrosilylation of aldehydes and ketones

The dioxomolybdenum(VI) complexes [MoO2Cl2] (1), [MoO2(acac)2] (2), [MoO2(S2CNEt2)2] (3), [CpMoO2Cl] (4), [MoO2(mes)2] (5) and the polymeric organotin-oxomolybdates [(R3Sn)2MoO4] [R = n-Bu (6), t-Bu (7), Me (8)] were examined as catalysts for the hydrosilylation of aldehydes and ketones with dimethylphenylsilane. Of these, [MoO2Cl2] (1) was the most efficient catalyst, affording quantitative yields of the corresponding silylated ethers at room temperature in acetonitrile. Complexes 2, 4-8 also catalyzed the same reaction but required heating at 80 degrees C and longer reaction times compared with 1. Compound 3 is inactive. The wide scope of molybdenum oxide-mediated hydrosilylation was established with a variety of aldehydes and ketones. Counter intuitively, the activity of is 1 highest in NCMe. In the absence of a carbonyl substrate, [MoO2Cl2(NCBu(t))] (10) reacts with HSiMe2Ph affording [MoO(OSiMe2Ph)Cl2]2 (11) which has been fully characterized by NMR and IR spectroscopy, elemental analyses and mass spectrometry. Addition of radical scavengers strongly slows down the [MoO2Cl2]-based hydrosilylation suggesting the intermediacy of oxygen-centered radicals.     

Direct, catalytic enantioselective nitroaldol (Henry) reaction of trifluoromethyl ketones: an asymmetric entry to alpha-trifluoromethyl-substituted quaternary carbons

Herein we describe the first direct, catalytic enantioselective nitroaldol (Henry) reaction of simple alpha-trifluoromethyl ketones with nitromethane using a chiral monometallic lanthanum(III) triflate salt complex, namely [(Delta,S,S,S)-Binolam]3.La(OTf)3, as enantioselective catalyst. The resulting alpha-trifluoromethyl tertiary nitroaldols were obtained in moderate to high yields (up to 93%) and enantioselectivities (up to 98% ee). These adducts are versatile chiral building blocks and may be reduced (NiCl2/NaBH4) to their beta-amino-alpha-trifluoromethyl tertiary alcohols without loss of enantiomeric purity.     

Rhodium(I)-catalyzed carbonyl allenylation versus propargylation via redox transmetalation across tetragonal tin(II) oxide

[reaction: see text] A reagent combination of beta-SnO and catalytic [Rh(COD)Cl](2) in THF-H(2)O promotes the reaction of propargyl bromides and aldehydes and directs the regioselectivity toward the formation of either allenic alcohols or homopropargylic alcohols. This highly regioselective either/or transformation proceeds via a transmetalation from rhodium to tin, in which metallotropic rearrangement between a propargylmetal and allenylmetal is arrested.     

Electron-deficient [Ti(salophen)(OTf)2]: A new and highly efficient catalyst for the acetylation of alcohols and phenols with acetic anhydride

In the present work, a highly efficient method for acetylation of alcohols and phenols with acetic anhydride catalyzed by high-valent [Ti^IV(salophen)(OTf)₂] is reported. Under these conditions, primary, secondary and tertiary alcohols as well as phenols were acetylated with short reaction times and high yields. The catalyst was reused several times without loss of its catalytic activity.     

Selective Aerobic Oxygenation of Tertiary Allylic Alcohols with Molecular Oxygen

Aerobic epoxidation of tertiary allylic alcohols remains a significant challenge. Reported here is an efficient and highly chemoselective copper‐catalyzed epoxidation and semipinacol rearrangement reaction of tertiary allylic alcohols with molecular oxygen. The solvent 1,4‐dioxane activates dioxygen, thereby precluding the addition of a sacrificial reductant.     

Isothiourea‐Catalyzed Acylative Kinetic Resolution of Tertiary α‐Hydroxy Esters

A highly enantioselective isothiourea‐catalyzed acylative kinetic resolution (KR) of acyclic tertiary alcohols has been developed. Selectivity factors of up to 200 were achieved for the KR of tertiary alcohols bearing an adjacent ester substituent, with both reaction conversion and enantioselectivity found to be sensitive to the steric and electronic environment at the stereogenic tertiary carbinol centre. For more sterically congested alcohols, the use of a recently‐developed isoselenourea catalyst was optimal, with equivalent enantioselectivity but higher conversion achieved in comparison to the isothiourea HyperBTM. Diastereomeric acylation transition state models are proposed to rationalize the origins of enantiodiscrimination in this process. This KR procedure was also translated to a continuous‐flow process using a polymer‐supported variant of the catalyst.     

Yttrium triflate-catalyzed efficient chemoselective S-benzylation of indoline-2-thiones using benzyl alcohols

A highly efficient yttrium triflate-catalyzed chemoselective S-benzylation of indolin-2-thiones using variously substituted benzyl alcohols has been developed for the synthesis of indole-based sulfides. This procedure presents a greener approach for the synthesis of S-alkylated indoles. The reaction condition is amenable to primary, secondary, and tertiary benzylic alcohols as the benzyl group donors.     

Enantiocontrolled synthesis of trialkyl-substituted stereogenic carbons. A general route to cis-3,5-dialkyl gamma-lactones

[reaction: see text] Lewis acid treatment of tertiary Co2(CO)6-propargylic alcohols having a stereochemically defined benzyloxy group at the gamma-benzyl position yielded after cobalt demetalation sec-dialkyl bishomopropargylic alcohols in good yields. The reaction is highly stereoselective and predictable, providing pure stereoisomers. The use of benzyl-alpha,alpha'-d2 ethers permitted the stereoselective d-labeling of methines and methylenes. Very simple chemical manipulations provided a general methodology to obtain the enantiomers of 3,5-dialkyl-gamma-lactones.     

Electrophilic fluorinating reagent mediated synthesis of fluorinated alpha-keto Ethers,benzil, and 6,6'-dialkoxy-2,2'-bipyridines

Interactions of various fluorinated and nonfluorinated alcohols with trans-stilbene in the presence of electrophilic reagents were studied. Under neat conditions, reactions of trans-stilbene (1) with fluorinated alcohols, R(f)OH (R(f) = CF3CH2-, CFH2CH2-, CF3CF2CH2-, CF2H(CF2)3CH2-, (CF3)2CH-, (CF3)3C- (2a-f) in the presence of an electrophilic reagent, 1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (Selectfluor) or N,N-difluoro-2,2'-bipyridinium bis(tetrafluoroborate) (MEC-31), gave alpha-keto ethers (3a-f) and benzil (4) in good to moderate yields. alpha-Keto ether and benzil formation was very much dependent on the reaction time, the degree of fluorination of the alcohols, and whether a solvent such as CH3CN, DMF or DMA was utilized. In solution, alpha-keto ethers and benzil did not form. Interestingly, under neat conditions, nonfluorinated alcohols, ROH (R = CH3-, CH3CH2-, CH3CH2CH2-, CH3CH2CH2CH2-, CH3CH2CH2CH2CH2CH2-) (5g-k) did not react with trans-stilbene in the presence of MEC-31 but gave 6,6'-dialkoxy-2,2'-bipyridines (6g-k), regioselectively, in excellent isolated yields. On the other hand, fluorinated alcohols did not react with MEC-31. Reaction of MEC-31 with an excess of diethylene glycol (7) gave the bipyridine derivative (8) in 88% isolated yield. Reaction of 8 either with diethylaminosulfur trifluoride (DAST) or bis(2-methoxyethyl)aminosulfur trifluoride (Deoxofluor) readily produced the corresponding difluoro derivative (9) in 85% isolated yield. All new compounds have been characterized by spectroscopic and elemental analysis.     

Highly (Z)-selective hydrosilylation of terminal alkynes catalyzed by a diphosphinidenecyclobutene-coordinated ruthenium complex: application to the synthesis of (Z,Z)-bis(2-bromoethenyl)arenes

[reaction: see text] Complex 1 bearing a diphosphinidenecyclobutene ligand (DPCB-OMe) catalyzes highly stereoselective hydrosilylation of diethynylarenes with HSiMe2Ph to afford (Z,Z)-bis(2-silylethenyl)arenes. Treatment of the hydrosilylation products with N-bromosuccinimide causes bromodesilylation in a stereospecific manner, giving (Z,Z)-bis(2-bromoethenyl)arenes in high geometrical purity (>98%).