Cu(OTf)2-catalyzed arylmethylation of terminal alkynes with benzylic alcohols under ligand-, base-, and additive-free reaction conditions

An effective, convenient, and mild coupling reaction of benzylic alcohols with terminal alkynes has been developed. As an effective Lewis acid, Cu(OTf)₂-catalyzed arylmethylation of terminal alkynes with benzylic alcohols generated the corresponding products in BrCH₂CH₂Br with good yields in the absence of ligand, base, and additive.     

Catalytic CN Bond Alkynylation of N‐Benzylic Sulfonamides with Terminal Alkynes

A new cross‐coupling reaction of N‐benzylic sulfonamides with terminal alkynes for the synthesis of internal alkynes is reported. In the presence of 5 mol% of (Tf)₂NH/Bi(OTf)₃ (1:1), a broad range of N‐benzylic sulfonamides react smoothly with arylacetylenes to afford structurally diverse internal alkynes in moderate to excellent yields. We reasoned that vinyl cations could be formed by the regioselective attack of terminal alkynes with benzyl cations generated in situ from N‐benzylic sulfonamides under acidic conditions, which then eliminated to form a carbon‐carbon triple bond.     

Metal-free one-pot oxidative conversion of benzylic alcohols and benzylic halides into aromatic amides with molecular iodine in aq ammonia, and hydrogen peroxide

Various primary alcohols, particularly benzylic alcohols, could be converted into the corresponding aromatic amides in good yields in a one-pot manner by treatment with molecular iodine in aq. NH₃, followed by reaction with ∼30% aq H₂O₂. Similarly, various benzylic halides could be also converted into the corresponding aromatic amides in good yields in a one-pot manner by treatment with molecular iodine in aq NH₃, followed by reaction with ∼30% aq H₂O₂. The present reactions involve the metal-free one-pot oxidative conversion of benzylic alcohols and benzylic halides into the corresponding aromatic amides, respectively.     

Stereospecific benzylic dehydroxyfluorination reactions using Bio’s TMS-amine additive approach with challenging substrates

Reactions involving the conversion of a benzylic alcohol into a benzylic fluoride using RSF₃ reagents are notoriously difficult to achieve with high stereochemical inversion (S_N2 reaction) due to competing dissociative S_N1 reaction processes. This Letter develops the methodology of Bio et al., and reports that the addition of a preformed 1:TMS-amine 1:RSF₃ (fluorination reagent) complex as the reagent in these reactions significantly suppresses the S_N1 process and promotes a highly stereospecific reaction generating benzylic fluorination products of high %ee.     

Catalytic Enantioselective Intermolecular Benzylic C(sp3)−H Amination

A practical general method for asymmetric intermolecular benzylic C(sp³)?H amination has been developed by combining the pentafluorobenzyl sulfamate PfbsNH₂ with the chiral rhodium(II) catalyst Rh₂(S‐tfptad)₄. Various substrates can be used as limiting components and converted to benzylic amines with excellent yields and high levels of enantioselectivity. Additional key features for the reaction are the low catalyst loading and the ability to remove the Pfbs group under mild conditions to give NH‐free benzylic amines.     

The nuclear magnetic resonance spectra of pyrazines—II : The influence of side-chain alkyl substitution on the benzylic coupling constants

The benzylic coupling constants ⁵J_m and ⁶J_p for a series of 2-alkyl-3-methoxypyrazines, in which the size of the 2-alkyl group is progressively increased, are reported and discussed. ⁵J_m remains virtually constant, while ⁶J_p falls steadily with increasing alkyl group size. These effects are largely attributed to variations in the time-averaged orientation of the benzylic protons and are consistent with the generally accepted mechanisms for meta and para benzylic coupling. The results illustrate the importance of taking conformational aspects into account when attempting to use benzylic coupling constants derived from substituted side-chains in making structural assignments.     

A new type of functionalization of the benzylic-type positions in alkylpyridines by DMSO-AC2O.

4-Methyl, 4-ethyl, 4-isopropylpyridine and 4-methylquinoline react with DMSO-Ac₂O giving a new type of reaction of the C-H benzylic type bond, mainly involving the substitution of the hydrogen atom by the CH₂SCH₃ group.     

Sodium iodide/boron trifluoride etherate: A mild reagent system for the conversion of allylic and benzylic alcohols into corresponding iodides and sulfoxides into sulfides

A variety of allylic and benzylic alcohols have been converted into the corresponding iodides using NaI/BF₃.Et₂O. Selective conversion of allylic and benzylic alcohols in preference to primary saturated alcohols has also been demonstrated. Further, the same reagent system has been used to convert sulfoxides into sulfides under mild conditions.     

Visible-Light Photoredox-Catalyzed Remote Difunctionalizing Carboxylation of Unactivated Alkenes with CO2

Remote difunctionalization of unactivated alkenes is challenging but a highly attractive tactic to install two functional groups across long distances. Reported herein is the first remote difunctionalization of alkenes with CO₂. This visible-light photoredox catalysis strategy provides a facile method to synthesize a series of carboxylic acids bearing valuable fluorine- or phosphorus-containing functional groups. Moreover, this versatile protocol shows mild reaction conditions, broad substrate scope, and good functional-group tolerance. Based on DFT calculations, a radical adds to an unactivated alkene to smoothly form a new carbon radical, followed by a 1,5-hydrogen atom-transfer process, the rate-limiting step, generating a more stable benzylic radical. The reduction of the benzylic radicals by an Ir^II species generates the corresponding benzylic carbanions as the key intermediates, which further undergo nucleophilic attack with CO₂ to generate carboxylates.     

Stereodivergent Quaternization of 2‐Alkyl‐2‐p‐tolylsulfinylacetonitriles: NMR Spectroscopic Evidence of Planar and Pyramidal Benzylic Carbanions

Enantiomerically enriched α,α‐disubstituted phenylacetonitriles have been readily prepared by stereoselective quaternization of 2‐alkyl‐2‐[2‐(p‐tolylsulfinyl)phenyl]acetonitriles with different alkylating electrophiles in the presence of bases. The use of potassium hexamethyldisilazane (KHMDS)/[18]crown‐6 ether and NHMDS with alkyl halides afforded S,S_S and R,S_S diastereoisomers, respectively, in high enantiomeric purities, thus providing stereodivergent processes for synthesizing both isomers. The dependence of the stereochemical course of the reactions on the experimental conditions (mainly on the counterion) has been rationalized by assuming a planar or pyramidal structure for the benzylic carbanions. This hypothesis has been supported by NMR spectroscopic studies, which permit one to assign a chelated pyramidal structure to the sodium benzylic carbanions and an almost planar naked carbanionic structure to the potassium benzylic carbanions generated in the presence of [18]crown‐6 ether.     

Benzylic C(sp3)?H Perfluoroalkylation of Six‐Membered Heteroaromatic Compounds

Successful benzylic C(sp³) H trifluoromethylation, pentafluoroethylation, and heptafluoropropylation of six‐membered heteroaromatic compounds were achieved as the first examples of a practical benzylic C(sp³) H perfluoroalkylation. In these reactions, BF₂C_nF_2n+1 (n=1–3) functioned as both a Lewis acid to activate the benzylic position and a C_nF_2n+1 (n=1–3) source. The perfluoroalkylation proceeded at both terminal and internal positions of the alkyl chains. Perfluoroalkylated products were obtained in moderate to excellent yields, even on gram scale, and in a sequential procedure without isolation of the intermediates. By using this method, trifluoromethylation of a bioactive compound, as well as introduction of a CF₃ group into a bioactive molecular skeleton, proceeded regioselectively.     

Benzylic C(sp3)H Perfluoroalkylation of Six‐Membered Heteroaromatic Compounds

Successful benzylic C(sp³)? H trifluoromethylation, pentafluoroethylation, and heptafluoropropylation of six‐membered heteroaromatic compounds were achieved as the first examples of a practical benzylic C(sp³)? H perfluoroalkylation. In these reactions, BF₂C_nF_2n+1 (n=1–3) functioned as both a Lewis acid to activate the benzylic position and a C_nF_2n+1 (n=1–3) source. The perfluoroalkylation proceeded at both terminal and internal positions of the alkyl chains. Perfluoroalkylated products were obtained in moderate to excellent yields, even on gram scale, and in a sequential procedure without isolation of the intermediates. By using this method, trifluoromethylation of a bioactive compound, as well as introduction of a CF₃ group into a bioactive molecular skeleton, proceeded regioselectively.     

Non-heme iron catalysts for the benzylic oxidation: a parallel ligand screening approach

Ethylbenzene and 4-ethylanisole were used as model substrates for benzylic oxidation with H₂O₂ or O₂ using a range of non-heme iron catalysts following a parallel ligand screening approach. Effective oxidation was found for Fe complexes based on tetra- and pentadentate nitrogen ligands affording the corresponding benzylic alcohol and ketone.     

An Enantioselective Bidentate Auxiliary Directed Palladium‐Catalyzed Benzylic C−H Arylation of Amines Using a BINOL Phosphate Ligand

A new enantioselective palladium(II)‐catalyzed benzylic C?H arylation reaction of amines is enabled by the bidentate picolinamide (PA) directing group. This reaction provides the first example of enantioselective benzylic γ‐C?H arylations of alkyl amines, and proceeds with up to 97 % ee. The 2,2′‐dihydroxy‐1,1′‐binaphthyl (BINOL) phosphoric acid ligand, Cs₂CO₃, and solvent‐free conditions are essential for high enantioselectivity. Mechanistic studies suggest that multiple BINOL ligands are involved in the stereodetermining C?H palladation step.     

Silver Nitrate‐Catalyzed Selective Air Oxidation of Benzylic and Allylic Alcohols to Corresponding Aldehydes or Ketones

The liquid phase selective air oxidation of benzylic and allylic alcohols to corresponding aldehydes or ketones has been achieved in high yields with catalytic amount of AgNO₃ and in the presence of Na₂CO₃.     

Reductive Benzylation of Dimetallo Hexaaryl[70]Fullerenes on the Equatorial Region

Dianions of dimetallic hexa(organo)[70]fullerene [(C₅R₅)₂Ru₂C₇₀Ar₆]^2? (R=H, Me; Ar=Ph, 4‐MeC₆H₄, 4‐tBuC₆H₄) react with benzylic bromide to yield the dibenzylated product dimetallic octa(organo)[70]fullerene (C₅R₅)₂Ru₂C₇₀Ar₆(CH₂Ar′)₂ (Ar′=Ph, 4‐MeO₂CC₆H₄), where the benzylic groups are attached to the equatorial belt region of [70]fullerene; this region is generally considered to be rather unreactive. This unusual structure was unambiguously determined by X‐ray crystallography. Theoretical studies on the electronic properties of the monoanionic intermediate indicated that the highest spin density resides on the two carbon atoms in the belt region; one of them then couples with a benzylic radical to yield the octa(organo)fullerene product after ionic substitution of the fullerene anion with a benzylic bromide. Electrochemical analysis of the hexa(organo) and octa(organo) ruthenium complexes suggests that the modification of the belt region does not affect the electronic communication between the two metal centers.     

Selective Benzylic and Allylic Alkylation of Protic Nucleophiles with Sulfonamides through Double Lewis Acid Catalyzed Cleavage of sp3 Carbon–Nitrogen Bonds

The acid‐catalyzed benzylic and allylic alkylation of protic nucleophiles is fundamentally important for the formation of carbon? carbon and carbon? heteroatom bonds, and it is a formidable challenge for benzylic and allylic amine derivatives to be used as the alkylating agents. Herein we report a highly efficient benzylic and allylic alkylation of protic carbon and sulfur nucleophiles with sulfonamides through double Lewis acid catalyzed cleavage of sp³ carbon–nitrogen bonds at room temperature. In the presence of a catalytic amount of inexpensive ZnCl₂‐TMSCl (TMSCl: chlorotrimethylsilane), 1,3‐diketones, β‐keto esters, β‐keto amides, malononitrile, aromatic compounds, thiols, and thioacetic acid can couple with a broad range of tosyl‐activated benzylic and allylic amines to give diversely functionalized products in good to excellent yields and with high regioselectivity. Furthermore, the cross‐coupling reaction of 1,3‐dicarbonyl compounds with benzylic propargylic amine derivatives has been successfully applied to the one‐step synthesis of polysubstituted furans and benzofurans.     

Applications of rare earth complexes as nmr shift reagents in elucidating the structure of organic molecules

The present state of affairs concerning shift reagents is reviewed and some new data on lanthanide-1,10-phenanthroline and lanthanide-2,2'-dipyridyl systems are presented. The use of Pr(TTA)₃ as an NMR shift reagent for benzylic systems has been reviewed and it is concluded that this complex possesses useful properties as a “two-way” shift reagent. Both high field and low field shifts for benzylic protons have been observed.     

Silica Chloride (SiO2-Cl), a New Heterogeneous Reagent,for the Selective and Efficient Conversion of Benzylic Alcohols to Their Corresponding Chlorides and Iodides

Abstract

Structurally different benzylic alcohols were efficiently converted to their corresponding chlorides by silica chloride (SiO₂-Cl) in CHCl₃ at room temperature. Silica chloride is also able to convert benzylic alcohols to their iodides in the presence of NaI in a mixture of CH₃CN/CHCl₃ in excellent yields.     

Application and Mechanistic Studies of a Water‐Oxidation Catalyst in Alcohol Oxidation by Employing Oxygen‐Transfer Reagents

By using a dimeric ruthenium complex in combination with tert‐butyl hydrogen peroxide (TBHP) as stoichiometric oxidant, a mild and efficient protocol for the oxidation of secondary benzylic alcohols was obtained, thereby giving the corresponding ketones in high yields within 4 h. However, in the oxidation of aliphatic alcohols, the TBHP protocol suffered from low conversions owing to a competing Ru‐catalyzed disproportionation of the oxidant. Gratifyingly, by switching to Oxone (2 KHSO₅ ? KHSO₄ ? K₂SO₄ triple salt) as stoichiometric oxidant, a more efficient and robust system was obtained that allowed for the oxidation of a wide range of aliphatic and benzylic secondary alcohols, giving the corresponding ketones in excellent yields. The mechanism for these reactions is believed to involve a high‐valent Ru^V–oxo species. We provide support for such an intermediate by means of mechanistic studies.