Synthesis and Application of O-Xylylenebis(triphenylphosphonium Peroxymonosulfate) for Selective Oxidation of Benzylic Alcohols and Hydroquinones

Abstract

This article describes the oxidation of benzylic, allylic alcohols and hydroquinones under solvent-free conditions using o-xylylenebis(triphenylphosphonium peroxymonosulfate), which has been prepared by mixing an aqueous solution of o-xylylenebis(triphenylphosphonium bromide) with oxone at room temperature.     

Synthesis of 3,4-disubstituted isoquinolines via palladium-catalyzed cross-coupling of 2-(1-alkynyl)benzaldimines and organic halides

The palladium-catalyzed cross-coupling of readily available N-tert-butyl-2-(1-alkynyl)benzaldimines and aryl, allylic, benzylic, alkynyl halides, as well as a vinylic halide, provides a valuable new route to 3,4-disubstituted isoquinolines with aryl, allylic, benzylic, 1-alkynyl, and vinylic substituents, respectively, in the 4-position. The reaction appears to require an aryl group on the end of the acetylene furthest from the imine functionality. The reaction conditions have been optimized, and reasonably good yields have been obtained.     

Direct conversion of benzylic and allylic alcohols to phosphonates

Benzyl phosphonate esters often serve as reagents in Horner-Wadsworth-Emmons reactions. In most cases, they can be prepared from benzylic alcohols via formation of the corresponding halide followed by an Arbuzov reaction. To identify a more direct synthesis of phosphonate esters, we have developed a one-flask procedure for conversion of benzylic and allylic alcohols to the corresponding phosphonates through treatment with triethyl phosphite and ZnI(2).     

Divergent regioselectivity in the base-promoted reactions of cyclic eight-membered alpha-ketols with activated halides

[reaction: see text] Deprotonation of 2-hydroxycyclooctanone followed by exposure to an allylic or benzylic halide proceeds very selectively to give the product of C-alkylation. The effect of Delta(5,6)-unsaturation is to promote instead the formation of the O-alkylated derivative. This crossover in kinetic preference is attributed to an inability of the olefinic system to attain a conformation conducive to proton abstraction at C-2.     

Toward Daisy Chain Polymers: "Wittig Exchange" of Stoppers in

Two ammonium ion/crown ether-based [2]rotaxane monomers-each incorporating (i) a dumbbell-shaped component, possessing an exchangeable benzylic triphenylphosphonium stopper, and (ii) a ring component, bearing an aldehyde function-undergo a sequence of Wittig reactions in which the surrogate triphenylphosphonium stopper is exchanged for a ring component either (i) in the same rotaxane molecule to give cyclic daisy chains by an intramolecular, chain-terminating reaction or (ii) in another rotaxane molecule to give acyclic daisy chains by an intermolecular chain-propagating reaction.     

Regioselective Transition‐Metal‐Free Allyl–Allyl Cross‐Couplings

Readily prepared allylic zinc halides undergo S_N2‐type substitutions with allylic bromides in a 1:1 mixture of THF and DMPU providing 1,5‐dienes regioselectively. The allylic zinc species reacts at the most branched end (γ‐position) of the allylic system furnishing exclusively γ,α′‐allyl–allyl cross‐coupling products. Remarkably, the double bond stereochemistry of the allylic halide is maintained during the cross‐coupling process. Also several functional groups (ester, nitrile) are tolerated. This cross‐coupling of allylic zinc reagents can be extended to propargylic and benzylic halides. DFT calculations show the importance of lithium chloride in this substitution.     

Copper triflate/t-BuOOAc-catalyzed amidation of allylic and benzylic acetates with sulfonamides

A copper triflate/t-BuOOAc-catalyzed amidation of allylic and benzylic acetates has been developed which is suitable for the coupling of a wide variety of functionalized sulfonamide nucleophiles with acetate electrophiles. The methodology allows for the amidation of benzylic substrates which are not further activated by an additional adjacent alkene or alkyne, enabling simple allylic acetates and primary benzylic acetates to be used as reaction partners.     

Stereocontrolled preparation of a nonpeptidal (-)-spirobicyclic NK-1 receptor antagonist

The synthesis of a spirobicyclic NK-1 receptor (Substance-P) antagonist 1 antipode is described. Retrosynthetic analysis reveals an allylic halide A bearing the cyclopropoxy-substituted aryl group and a 2-phenyl-3-piperidone B. The stereochemistry in the spirobicyclic system bearing three chiral centers is initially set via a highly diastereoselective zinc-mediated coupling of the allylic bromide 23 to the optically active ketopiperidine 3. The remaining benzylic asymmetric center is set by a diastereoselective hydroboration followed by cyclization to the spirobicyclic system.     

Hydride as a leaving group in the reaction of pinacolborane with halides under ambient Grignard and Barbier conditions. One-pot synthesis of alkyl, aryl, heteroaryl, vinyl, and allyl pinacolboronic esters

Grignard reagents (aliphatic, aromatic, heteroaromatic, vinyl, or allylic) react with 1 equiv of 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (pinacolborane, PinBH) at ambient temperature in tetrahydrofuran (THF) to afford the corresponding pinacolboronates. The initially formed dialkoxy alkylborohydride intermediate quickly eliminates hydridomagnesium bromide (HMgBr) and affords the product boronic ester in very good yield. Hydridomagnesium bromide (HMgBr) in turn disproportionates to a 1:1 mixture of magnesium hydride (MgH(2)) and magnesium bromide (MgBr(2)) on addition of pentane to the reaction mixture. DFT calculations (Gaussian09) at the B3LYP/6-31G(d) level of theory show that disproportionation of HMgBr to MgH(2) and MgBr(2) is viable in the coordinating ethereal solvents. This reaction also can be carried out under Barbier conditions, where the neat PinBH is added to the flask prior to the in situ formation of Grignard reagent from the corresponding organic halide and magnesium metal. Pinacolboronic ester synthesis under Barbier conditions does not give Wurtz coupling side products from reactive halides, such as benzylic and allylic halides. The reaction between PinBH and various Grignard reagents is an efficient, mild, and general method for the synthesis of pinacolboronates.     

On the synthesis of vinyl and phenyl C-furanosides by stereospecific debenzylative cycloetherification

Open-chain benzyl-ether-protected polyols in which one of the alcohols is either allylic or benzylic are synthesised by addition of organometallic vinyl or phenyl reagents to benzyl-ether-protected carbohydrate hemiacetals. The diastereoselectivity of addition is dependent on whether a Grignard reagent or a trialkylzincate reagent is used. The open-chain compounds undergo a stereospecific cyclisation reaction on treatment with catalytic strong Brønsted acid with heating to form tetrahydrofurans with inversion of configuration at the allylic or benzylic carbon (C-1) and loss of hydroxyl from this position. A short synthesis of the starting material, 1,2,4,6-tetra-O-benzyl-d-galactose, from lactose is described.     

PCC-mediated novel oxidation reactions of homobenzylic and homoallylic alcohols

A new PCC-mediated carboncarbon bond cleavage reaction during oxidation of homobenzylic alcohols leading to the formation of benzylic carbonyl compounds has been observed. Homobenzylic alcohols with no benzylic substitution (R¹=H) gave benzylic aldehydes without further oxidation, while those with benzylic substitution (R¹=Me, Et, Ar) gave benzylic ketones. In contrast, homoallylic alcohols gave products arising from double bond migration, cis- to trans-olefin isomerization and/or allylic oxidation.     

The Kharasch type reaction of allylic halides with Grignard reagent in the presence of transition metal halides

The reaction of allylic halide with Grignard reagent in the presence of transition metal chloride has been investigated. Three reactions of allylic halide occurred competitively; (i) reduction to olefin, (ii) coupling with Grignard reagent to olefin (cross-coupling) and (iii) coupling with itself to 1,5-diene (homo-coupling). The relative importance of these reactions depends on both the structures of allylic halide and Grignard reagent, as well as on the transition metal salt utilized. The mechanism was discussed in terms of the allylic transition metal intermediate.     

Rearrangements of the carbanions derived from allyl benzyl thioether

The metalation of allyl benzyl thioether involves the benzylic or the allylic hydrogens. The benzylic carbanion undergoes a rapid[2,3] sigmatropic shift whereas the allylic carbanion gives rise to various rearrangements, among them migration of the allylic unit to the para position with allylic inversion. The temperature dependence of the ratio of products arising from the benzylic carbanion vs those from the allylic carbanion shows that the allylic-to-benzylic carbanion transformation occurs only under special conditions: (a) with slow addition of the base; (b) with thioether in excess relative to the base, and (c) on raising the temperature of the reaction medium from ?78° to ?15°. In the last instance, the proton transfer is intramolecular as shown with labeled thioethers. The extent of the different rearrangements depends on the temperature and solvent. A choice of mechanism cannot be made at this time for the para migration 5→9a. A leaving group effect on the reaction regioselectivity of the carbanion from allyl methyl thioether with benzyl halides has been noticed. The presence of dibenzyl indicates that, in addition to S_N2 reactions, some electron transfer process is occurring.     

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.     

Metal-free oxidative C-C bond formation of active methylenic sp C-H bonds with benzylic sp C-H and allylic sp C-H bonds mediated by DDQ

An efficient and simple method for the oxidative coupling of benzylic and allylic sp³ C-H bonds with active methylenic sp³ C-H bonds under metal-free conditions was developed by employing 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) as an oxidant. The reaction was shown to proceed smoothly for various 1,3-dicarbonyl compounds with a range of benzylic and allylic substrates in good to excellent yields.     

Use of allylzinc halide as a source of halide: Differential addition of nucleophiles to Ts-aziridines and aldehydes under similar reaction conditions

We have observed that the allylic zinc halide under identical reaction conditions acts in different modes for different electrophiles. For Ts-aziridines the halide part of the allylic halide has been introduced as a nucleophile and for the carbonyl compounds the simple allylation reaction occurs. To the best of our knowledge this is the first report where the allylic zinc halide is the source of halide acting as nucleophile. The main advantages of the present procedure are easy to handle, no need of inert atmosphere, mild reaction conditions, and applicability to a wide variety of substrates for aziridines and carbonyl compounds.     

Facile coupling of propargylic, allylic and benzylic alcohols with allylsilane and alkynylsilane, and their deoxygenation with Et(3)SiH, catalyzed by Bi(OTf)(3) in [BMIM][BF(4)] ionic liquid (IL), with recycling and reuse of the IL

Allyltrimethylsilane (allyl-TMS) reacts with propargylic alcohols in the presence of 10% Bi(OTf)(3) in [BMIM][BF(4)] solvent to furnish the corresponding 1,5-enynes in respectable isolated yields (87-93%) at room temperature. The utility of Bi(OTf)(3) as a superior catalyst was demonstrated in a survey study on coupling of allyl-TMS with employing several metallic triflates (Bi, Ln, Al, Yb) as well as, B(C(6)F(5))(3), Zn(NTf(2))(2) and Bi(NO(3))(3)·5H(2)O. Coupling of cyclopropyl substituted propargylic alcohol with allyl-TMS gave the skeletally intact 1,5-enyne and a ring opened derivative as a mixture. Coupling of propargylic/allylic alcohol with allyl-TMS resulted in allylation at both benzylic (2 isomers) and propargylic positions, as major and minor products respectively. The scope of this methodology for allylation of a series of allylic and benzylic alcohols was explored. Chemoselective reduction of a host of propargylic, propagylic/allylic, bis-allylic, allylic, and benzylic alcohols with Et(3)SiH was achieved in high yields with short reaction times. The same approach was successfully applied to couple representative propargylic and allylic alcohols with 1-phenyl-2-trimethylsilylacetylene. The recovery and reuse of the ionic liquid (IL) was gauged in a case study with minimal decrease in isolated yields after six cycles.     

Crystal structure and solid state computational (DFT/Hirshfeld surface) study for probing a new efficient and recyclable oxidation reagent, 1,2-ethandiylbis(triphenylphosphonium) peroxodisulfate dihydrate

A new, efficient and recyclable reagent, 1,2-Ethandiylbis(triphenylphosphonium) peroxodisulfate dihydrate, for the oxidation of benzylic alcohols has been synthesized and characterized by IR, NMR spectroscopy, and single crystal X-ray crystallography. Using the title compound, the results indicate that the oxidation reactions are rapid, take place under mild reaction conditions, easily to work-up and high yielding. The Hirshfeld surface and associated finger print plots were derived from the X-ray structure to visualize the significant nonclassical C-H ??? O/π interactions in the crystal packing. The geometry, vibrational spectroscopy and electronic properties of the bis(triphenylphosphonium) dication have also been investigated by various DFT computational methods.     

Iridium‐Catalyzed Asymmetric Allylic Aromatization Reaction

Described herein is an asymmetric allylic aromatization (AAAr) strategy that employs readily accessible equivalents of benzylic nucleophiles in iridium‐catalyzed allylic substitution reactions with the concomitant formation of aromatic rings by aromatization. The optimized reaction conditions involving a catalyst derived from a commercially available iridium precursor and the Carreira ligand are compatible with equivalents of benzylic nucleophiles derived from 4‐ or 5‐methyloxazoles, 5‐methylthiazoles, 4‐ or 5‐methylfurans, 2‐ or 3‐methylbenzofurans, 3‐methylbenzothiophene, 3‐methylindole, 1‐methylnaphthalene, and methylbenzene. This strategy provides straightforward accesses to valuable heterocyclic aromatic compounds, bearing a homobenzylic stereogenic center, in an enantiopure form and would be difficult to access otherwise. The versatility of the reaction was showcased by the further elaboration of the products into useful building blocks and a drug analogue.     

Catalyzed cross-coupling of allyl bromides with allyl tin reagents

The reaction of allyl bromides with allyl tin reagents, catalyzed by palladium or zinc chloride gives cross-coupled products without allylic transpostion in the allyl halide partner but with predominate allylic rearrangement from the tin partner.