Alcohols with aryl halides

Another method for the hydrogenoiysis of aryl bromides and iodides is to use MeONa[696], The removal of chlorine and bromine from benzene rings is possible with MeOH under basic conditions by use of dippp as a ligand[697]. The reduction is explained by the formation of the phenylpalladium methoxide 812, which undergoes elimination of /i-hydrogen to form benzene, and MeOH is oxidized to formaldehyde. Based on this mechanistic consideration, reaction of alcohols with aryl halides has another application. For example, cyclohex-anol (813) is oxidized smoothly to cyclohexanone with bromobenzene under basic conditions[698]. 

Vinyl substitution of primary or secondary allylic alcohols with aryl halides usually produces 3-aryl aldehydes or ketones, respectively. The reaction is believed to involve an addition of the intermediate arylpalladium halide to die double bond, placing the aryl group mainly on the more distant carbon from the hydroxy group, followed by palladium hydride elimination, a reverse readdition and another elimination with a hydrogen atom on the carbon bearing the hydroxy group. The product is probably a ir-com-plex of the enol which ultimately either dissociates or collapses to a a-complex with palladium on the... 

After obtaining this encouraging result, the Rh2(OAc)4 catalyst was evaluated with several other alcohols using diisopropylsilane (Scheme 24). The reaction works with primary, secondary and tertiary alcohols (Table 5). Alcohols with aryl halide functionality also work, however the reaction failed with alcohols containing double and triple bonds because hydrosilylation and/or hydrogenation of double and triple bonds is believed to be a major side reaction as judged by NMR analysis of crude mixture. 

Emphasis on the employment of transition metal catalysts to achieve useful synthetic transformations is illustrated by three procedures in this volume. The reaction of allylic alcohols with aryl halides in the presence of a palladium derived catalyst can be used to prepare various /3-arylaldehydes. This is illustrated by the preparation of 2-METHYL-... 

Thus, the transition metal catalyzed arylation reactions of amines and alcohols would constitute powerful tools for synthetic chemists. We have been developing practical procedures for the palladium-catalyzed arylation of amines and alcohols with aryl halides or sulfonates. During the course of our investigations [9] as well as those of John Hartwig and co-workers [10] the substrate scope of these transformations has been incrementally expanded. With each cycle of this catalyst improvement process, advances in mechanistic understanding and ligand design have also been made. 

P-A/y/ aldehydes (7, 274). These aldehydes can be obtained by reaction of allylic alcohols with aryl halides and a base (usually triethylamine) in the presence of PdlOAc), (equation I). 

Arylation of ailylic alcohols with aryl halides. - This reaction can be realized... 

Reactions of Alcohols with Aryl Halides Involving /3-Carbon Elimination... 

A unique method of oxidation of primary and secondary alcohols was found by Tamaru, who reported that the Pd-catalyzed oxidation of alcohols with aryl halides proceeds under basic conditions involving /3-H elimination of the alkoxypalladium 1 [1]. Guram et al. reported that cheaply available chlorobenzene can be used for the oxidation of benzyl alcohols and some secondary aliphatic alcohols in toluene at 105 °C using biphenylyl(dicyclohexyl)phosphine (IV-2) as a ligand. Sterically hindered aliphatic alcohol was oxidized using /-BuONa as a base [la]. 

The C—O cross-coupling of primary and secondary alcohols with aryl halides has been synthetically challenging due to p-hydride elimination (Schane 20.38, see Scheme 20.2). This has been overcome using binaphthyl-based phosphines L98 and L90 [112]. Buchwald and coworkers have explored sterically hindered phosphines for the alkoxylation of aryl substrates with secondary alcohols, and ligands L99-L100 with 1-phenyl and naphthyl backbone exhibited superior results (Scheme 20.39) [113]. 

Seller and coworkers reported the coupling of primary alcohols with aryl halides using Pd(OAc)2 with a series of ligands L2, L13, L21, LlOl-LllO, and L105 (Scheme 20.40) [114]. 

Scheme 18.6 Proposed mechanism for anaerobic oxidation of secondary alcohols with aryl halides (Ar = aryl X = 1, Cl, Br) [17],...

The Pd-catalysed arylation of tertiary allylic alcohols with aryl halides (equation 4), in the presence of a base, produces aryl substituted allyl alcohols in varying yields, and a mechanistic scheme has been proposed. 

When allylic alcohols are used as an alkene component in the reaction with aryl halides, elimination of /3-hydrogen takes place from the oxygen-bearing carbon, and aldehydes or ketones are obtained, rather than y-arylated allylic alcohoIs[87,88]. The reaction of allyl alcohol with bromobenzene affords dihydrocinnamaldehyde. The reaction of methallyl alcohol (96) with aryl halides is a good synthetic method for dihydro-2-methylcinnamaldehyde (97). 

The unconjugated alkenyl oxirane 133 reacts with aryl halides to afford the arylated allylic alcohol 134. The reaction is explained by the migration of the Pd via the elimination and readdition of H—Pd—1[107]. 

This reaction is similar to 13-1 and, like that one, generally requires activated substrates. With unactivated substrates, side reactions predominate, though aryl methyl ethers have been prepared from unactivated chlorides by treatment with MeO in HMPA. This reaction gives better yields than 13-1 and is used more often. A good solvent is liquid ammonia. The compound NaOMe reacted with o- and p-fluoronitrobenzenes 10 times faster in NH3 at — 70°C than in MeOH. Phase-transfer catalysis has also been used. The reaction of 4-iodotoluene and 3,4-dimethylphenol, in the presence of a copper catalyst and cesium carbonate, gave the diaryl ether (Ar—O—Ar ). Alcohols were coupled with aryl halides in the presence of palladium catalysts to give the Ar—O—R ether. Nickel catalysts have also been used. ... 

Palladium-catalyzed cyclization reactions with aryl halides have been used to synthesize pyrazole derivatives. V-Aryl-lV-(c>-bromobenzyl)hydrazines 26 participated in a palladium-catalyzed intramolecular amination reaction to give 2-aryl-2W-indazoles 27 . Palladium-catalyzed cascade intermolecular queuing-cyclocondensation reaction of o-iodophenol (28) with dimethylallene and aryl hydrazines provided pyrazolyl chromanones 29 <00TL7129>. A novel one-pot synthesis of 3,5-disubstituted-2-pyrazolines 32 has been achieved with an unexpected coupling-isomerization sequence of haloarene 30, propargyl alcohol 31, and methylhydrazine <00ACIE1253>. 

In addition to /3-H elimination, olefin insertion, and protonolysis, the cr-metal intermediate has also proved to be capable of undergoing a reductive elimination to bring about an alkylative alkoxylation. Under Pd catalysis, the reaction of 4-alkenols with aryl halides affords aryl-substituted THF rings instead of the aryl ethers that would be produced by a simple cross-coupling mechanism (Equation (126)).452 It has been suggested that G-O bond formation occurs in this case by yy/z-insertion of a coordinated alcohol rather than anti-attack onto a 7r-alkene complex.453... 

Mowery and DeShong reported on the use of siloxanes 72 (Figure 16) as versatile transmetallation agents for Pd(dba)3-catalyzed couplings with aryl halides and allylic alcohol derivates, in the presence of TBAF and at high temperature (95 They later used aryl silatrane 73 (Figure 16) as a suitable partner for the fluoride-promoted... 

Bromination of the enol ether product with two equivalents of bromine followed by dehydrobromination afforded the Z-bromoenol ether (Eq. 79) which could be converted to the zinc reagent and cross-coupled with aryl halides [242]. Dehydrobromination in the presence of thiophenol followed by bromination/dehydrobromination affords an enol thioether [243]. Oxidation to the sulfone, followed by exposure to triethylamine in ether, resulted in dehydrobromination to the unstable alkynyl sulfone which could be trapped with dienes in situ. Alternatively, dehydrobromination of the sulfide in the presence of allylic alcohols results in the formation of allyl vinyl ethers which undergo Claisen rearrangements [244]. Further oxidation followed by sulfoxide elimination results in highly unsaturated trifluoromethyl ketonic products (Eq. 80). 

Although isocyanates have been known for some time, the isomeric cy-anates were unknown until 1964. The latter were first prepared almost simultaneously by two different methods (1) thermolysis of 5-aryl- or 5-alkyloxy-l,2,3,4-thiatriazoles67 and (2) by reaction of phenols or alcohols with cyanogen halides.8 Since their synthesis, cyanates have ac-... 

The reaction of allylic alcohols and aryl halides in the presence of a palladium catalyst has been used in the past to prepare various 0-arylal-dehydes. The procedure described here is essentially that of Heck and Melpolder.3 A similar reaction has been carried out with bromobenzene and 2-methyl-2-propen-l-ol in hexamethylphosphoric triamide (HMPT) as solvent with sodium bicarbonate as base. A variety of other bases have also been used.4 2-Methyl-3-phenylpropanal has been prepared by reacting palladium acetate and phenylmercuric acetate with 2-methyl-2-propen-l-ol.5... 

A Pd(0)-catalyzed three-component coupling of propargylic alcohols and aryl halides with a suitable Michael-acceptor to yield alkylidene tetrahydrofuran derivatives has been developed. Upon decarboethoxylation of these compounds with potassium fet7-butoxide, 3-benzylfurans are eventually formed (Scheme 22) <2001JOC4069>. The reaction sequence can be carried out as a one-pot procedure with acceptable yields. 

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