Benzylic tertiary alcohols

Herein we report the generation of benzylic lithiums via an iodine-lithium exchange reaction on benzylic iodides performed in continuous flow using t BuLi as the exchange reagent. The resulting benzylic lithium species are trapped in situ by carbonyl electrophiles under Barbier conditions, resulting in benzylic secondary and tertiary alcohols. This flow procedure further allows the generation of highly reactive heterobenzylic lithium compounds, which are difficult to generate under batch conditions. A general scale-up was possible without further optimization...

Hydrogenolysis of tertiary benzylic alcohols on palladium on carbon (Pd/C) generally proceeds with inversion of configuration. However, little is known about the hydrogenolysis mechanism of primary and secondary benzylic alcohols. Literature precedents suggest that these substrates may interact differently with the catalyst. To study the mechanism, we synthesized a pair of deuterated diastereoisomers with a chiral center at the benzylic position. Chemical derivatization of the hydrogenolysis products showed that the reaction proceeds with inversion of configuration for these substrates...

Electrochemical organic oxidation reactions are highly appealing because protons are often effective terminal electron acceptors, thereby avoiding undesirable stoichiometric oxidants. These reactions are often plagued by high overpotentials, however, that greatly limit their utility. Single-electron transfer (SET) from organic molecules generates high-energy radical-cations. Formation of such intermediates often requires electrode potentials far above the thermodynamic potentials of the reaction and frequently causes decomposition and/or side reactions of ancillary functional groups...

A conceptionally novel nucleophilic substitution approach to synthetically important alkyl bromides is presented. Using molecular bromine (Br2 ), readily available secondary benzyl and tertiary alkyl phenyl sulphides are converted into the corresponding bromides under exceptionally mild, acid- and base-free reaction conditions. This simple transformation allows the isolation of elimination sensitive benzylic β-bromo carbonyl and nitrile compounds in mostly high yields and purities. Remarkably, protic functionalities such as acids and alcohols are tolerated...

'Desymmetrization' of trans- 1,2-diaminocyclohexane by treatment with α,ω-dihalogenated alkylation reagents leads to mono-NH2 derivatives ('primary-tertiary diamines'). Upon reaction with formaldehyde, these products formed monomeric formaldimines. Subsequently, reactions of the formaldimines with α-hydroxyiminoketones led to the corresponding 2-unsubstituted imidazole N -oxide derivatives, which were used here as new substrates for the in situ generation of chiral imidazol-2-ylidenes. Upon O-selective benzylation, new chiral imidazolium salts were obtained, which were deprotonated by treatment with triethylamine in the presence of elemental sulfur...

A sustainable boron-based catalytic approach for chemoselective N-alkylation of primary and secondary aromatic amines and amides with primary, secondary, and tertiary benzylic alcohols have been presented. The metal-free protocol operates at low catalyst loading, tolerates several functional groups and generates H2O as the sole by-product. Preliminary mechanistic studies were performed to demonstrate the crucial role of boron catalyst for the activation of the intermediate dibenzyl ether and to identify the rate-determining step...

An efficient method for asymmetric synthesis of 4 H -3,1-benzoxazines was developed via kinetic resolution of 2-amido benzyl alcohols through chiral phosphoric acid catalyzed intramolecular cyclizations. A broad range of benzyl alcohols (both secondary and tertiary alcohols) could be kinetically resolved with high selectivities, with s factor up to 94. Mechanistic studies were performed to elucidate the mechanism of these reactions, in which the amide moieties reacted as the electrophiles. Gram-scale reaction and facile transformations of the chiral products well demonstrate the potential of this method in asymmetric synthesis of biologically active chiral heterocycles...

OBJECTIVE: Commercial ear drops contain ingredients reported to be inactive. We sought to evaluate such excipients for possible cytotoxicity on human and mouse tympanic membrane (TM) fibroblasts. STUDY DESIGN: Prospective, in vitro. SETTING: Tertiary academic center. SUBJECTS AND METHODS: Mouse and human TM fibroblasts were treated with 1:10 dilutions of benzalkonium chloride (BKC) 0.0025%, 0.006%, or 0.01%; benzyl alcohol 0...

The aging effects of sodium hydroxide (NaOH) on ion exchange membranes were systematically studied, including the membrane properties, desalination performance, and fouling behaviors. After aging in NaOH solution, there were minor changes in the cation exchange membrane (CEM) properties; however, functional groups (i.e., quaternary amines) on the anion exchange membranes (AEMs) were converted into benzylic alcohol, alkene and tertiary amines, respectively, by nucleophilic substitution, Hofmann elimination and ylide formation...

Fluorinated alcohols as solvents strongly influence and direct chemical reaction through donation of strong hydrogen bonds while being weak acceptors. We used 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) as activating solvent for a nitric acid and FeCl3 catalyzed aerobic oxidation of secondary alcohols to ketones. Reaction proceeded selectively with excellent yields with no reaction on primary alcohol group. Oxidation of benzyl alcohols proceeds selectively to aldehydes with only HNO3 as catalyst, while reaction on tertiary alcohols proceeds through dehydration and dimerization...

Herein we describe the synthesis of tertiary alkyl fluorides via a formal radical deoxyfluorination process. This light-mediated, catalyst-free methodology is fast and broadly applicable allowing for the preparation of C-F bonds from (hetero)benzylic, propargylic, and unactivated tertiary alcohol derivatives. Preliminary mechanistic studies support that the key step of the reaction is the single electron oxidation of caesium oxalates - which are readily available from the corresponding tertiary alcohols - with in situ generated TEDA 2+• , a radical cation derived from Selectfluor®...

Phosphonate-directed catalytic asymmetric hydroboration (CAHB) of β-aryl/heteroaryl methylidenes and trisubstituted alkenes by pinacolborane enables facile access to functionalized, chiral tertiary benzylic boronic esters. Hydroboration is catalyzed by a chiral rhodium catalyst prepared in situ from a Rh(I)-precursor in combination with a simple TADDOL-derived chiral cyclic monophosphite in a 1:1 ratio. The regio- and stereochemistry arises from the combined effects of the relative disposition of the directing group to the alkene, the alkene substitution pattern, and the necessity of an aryl substituent attached to the alkene...

Toluene and its derivatives are petroleum-derived raw materials produced from gasoline by catalytic reformation. These abundant chemical feedstocks are commonly used as solvents in organic synthesis. The C(sp3 )-H functionalization of these unactivated substrates has been widely used to directly introduce benzylic motifs into diverse molecules to furnish important compounds. Despite these advances, progress in asymmetric catalysis remains underdeveloped. Here, we report photoinduced radical-based enantioselective C(sp3 )-C(sp3 ) coupling reactions of activated ketones with toluene and its derivatives by means of chiral acid catalysis...

We present an in-depth study of the acetylation of benzyl alcohol in the presence of N,N-diisopropylethylamine (DIPEA) by NMR monitoring the reaction from 1.5 seconds to several minutes. We have adapted the NMR setup to be compatible to microreactor technology, scaling down the typical sample volume of commercial NMR probes (500 μL) to a microfluidic stripline setup with 150 nL detection volume. In line spectra are obtained to monitor the kinetics and unravel the reaction mechanism of this industrially relevant reaction...

This perspective showcases our development of benzylic and allylic amine and alcohol derivatives as electrophiles for stereospecific, nickel-catalyzed cross-coupling reactions, as well as the prior art that inspired our efforts. The success of our effort has relied on the use of benzyl ammonium triflates as electrophiles for cross-couplings via C-N bond activation and benzylic and allylic carboxylates for cross-couplings via C-O bond activation. Our work, along with others' exciting discoveries, has demonstrated the potential of stereospecific, nickel-catalyzed cross-couplings of alkyl electrophiles in asymmetric synthesis, and enables efficient generation of both tertiary and quaternary stereocenters...

Water addition to α,β-unsaturated nitriles would give facile access to the β-hydroxy-nitriles, which in turn can be hydrogenated to the γ-amino alcohols. We have previously shown that alcohols readily add in 1,4-fashion to these substrates using Milstein's Ru(PNN) pincer complex as catalyst. However, attempted water addition to α,β-unsaturated nitriles gave the 3-hydroxynitriles in mediocre yields. On the other hand, addition of benzyl alcohol proceeded in excellent yields for a variety of β-substituted unsaturated nitriles...

The silver hexafluoroantimonate/ N-bromosuccinimide (NBS)-catalyzed synthesis of α-alkylated aryl ketones with a tertiary carbon center from internal alkynes and benzyl alcohols is reported. This reaction proceeds via the etherification of benzyl alcohols with an in situ generated benzyl bromide, formed by the reaction of benzyl alcohol with a catalytic amount of NBS and AgSbF6 . Ag-catalyzed C-O cleavage of the ether leads to a tolyl radical, which undergoes addition to the alkyne, ultimately leading to the α-alkylated aryl ketone products...

Without the requirement for base or other additives, Co2 Rh2 /C can selectively catalyze both mono- and bis-N-alkylation through the coupling of simple alcohols with amines, yielding a range of secondary and tertiary amines in good to excellent isolated yields. The reaction can be applied to benzyl alcohol with optically active 1-phenylethan-1-amines, and secondary amines were isolated in quantitative yields with an excellent enantiomeric excess (ee > 94%). Selectivity is achieved by varying the reaction temperature and amount of catalyst used...

The decarboxylative acetoxylation of carboxylic acids using a combination of PhI(OAc)2 and I2 in a CH2 Cl2 /AcOH mixed solvent is reported. The reaction was successfully applied to two types of carboxylic acids containing an α-quaternary and a benzylic carbon center under mild reaction conditions. The resulting acetates were readily converted into the corresponding alcohols by hydrolysis.

We report the first homogeneous palladium-based transfer hydrogenolysis of benzylic alcohols using an in situ formed palladium-phosphine complex and formic acid as reducing agent. The reaction requires a catalyst loading as low as only 1 mol % of palladium and just a slight excess of reductant to obtain the deoxygenated alkylarenes in good to excellent yields. Besides demonstrating the broad applicability for primary, secondary and tertiary benzylic alcohols, a reaction intermediate could be identified...