Aryl halides with alkoxides

In contrast to the borylation of alkane C-H bonds, the coupling of aryl halides with amines was based on a literature precedent from another group published about a decade before our initial studies. Kosugi, Kameyama and Migita published the coupling of aryl halides with tin amides." Mechanistic studies we conducted on this process led us to the perhaps obvious realization that the reaction" could be conducted with amines and a silylamide base instead of tin amides (equation 4)." Surveys of bases with similar p a values led Janis Louie to conduct reactions with alkoxide bases. Similar studies were conducted at nearly the same time by Steve Buchwald and coworkers."... 

The first palladium-catalyzed formation of aryl alkyl ethers in an intermolecular fashion occurred between activated aryl halides and alkoxides (Equation (28)), and the first formation of vinyl ethers occurred between activated vinyl halides and tin alkoxides (Equation (29)). Reactions of activated chloro- and bromoarenes with NaO-Z-Bu to form /-butyl aryl ethers occurred in the presence of palladium and DPPF as catalyst,107 while reactions of activated aryl halides with alcohols that could undergo /3-hydrogen elimination occurred in the presence of palladium and BINAP as catalyst.110 Reactions of NaO-/-Bu with unactivated aryl halides gave only modest yields of ether when catalyzed by aromatic bisphosphines.110 Similar chemistry occurred in the presence of nickel catalysts. In fact, nickel catalysts produced higher yields of silyl aryl ethers than palladium catalysts.108 The formation of diaryl ethers from activated aryl halides in the presence of palladium catalysts bearing DPPF or a CF3-subsituted DPPF was also reported 109... 

In 1995, Hartwig and Buchwald published concurrently their two groups results on tin-free amination of aryl halides [79,80], Instead of isolating or generating a tin amide in situ, the amination reactions were conducted by reacting an aryl halide with the combination of an amine and either an alkoxide or silylamide base (Eq. (5)). These reactions were typically conducted between 80 and 100 °C in toluene solvent. The catalysts used initially were 1, 3, or a combination of [Pd2(dba)3] (Sa) (dba = trans, trans-dibenzylidene acetone) and P(o-C6H4Me)3. Catalysts used subsequently will be described below. As shown in Table 7.1, secondary amines were viable substrates, but primary amines gave substantial yields with... 

There is presumably more than a subtle difference between the reactions of alkyl and aryl halides with organocopper compounds, as a straightforward nucleophilic displacement of aryl halide by the d electrons of a copper species is hardly likely. Simple aryl halides are nearly all inert to the usual nucleophiles, such as alkoxides, unless strongly activated by electron-attracting groups in the ortho and para positions. However, coordination of the halogen to copper may be sufficient to... 

Certain ethers can be prepared by the reaction of unusually active aryl halides with sodium alkoxides. For example ... 

Scheme 1.6. Palladium-catalyzed synthesis of ether by cross-coupling of an aryl halide with a metal alkoxide.

In chemistry related to the reactions of alkali metal alkoxides with late metal halide complexes, late metal alkoxides have been formed by the reaction of alcohols with metal halides in the presence of a base. This process has been used to form arylpalladium alkoxides during the coupling of aryl halides with alcohols discussed in Chapter 19 (cross-coupling). In addition, Milstein used an intramolecular version of this process to prepare the metallaoxetane in Equation 4.68. ... 

Other metal salts and complexes also catalyze the formation of C-N, C-O, and C-S bonds from organic electrophiles. Thus, a mixture of [Ni(COD)2] and a bidentate phosphine catalyzes the formation of aryl ethers from aryl halides and alkoxides [410]. In some cases, the reactions occur under milder conditions and with higher yields than when catalyzed by Pd complexes. 

Nickel plays a prominent role in C—N bond formation. The first nickel-catalyzed C—N coupling has been reported using Ni(cod)2-dppf and Ni(cod)2-l,10-phenanthroline for the synthesis of aryl amine (Scheme 20.29) [65]. The use of Ni/bipyridine [66], Ni/C-dppf [67], and Ni(II)-(NHC) [68, 69] has been subsequently described for the coupling of aryl halides with amines in the presence of sodium alkoxide. Ackermann and coworkers used Ni(cod)2-dppf for... 

Alkoxide or aryloxide anions are also reputed to be inactive in Sr I reactions. There is, however, one example of such a reaction at an sp carbon the nitro-derivative of 4-nitrocumyl reacts with phenoxide and 1-methyl-2-naphthoxide ions yielding the corresponding ethers (Kornblum et al., 1967). A similar reaction has been reported for halobenzenes in t-butyl alcohol upon stimulation by sodium amalgam (Rajan and Sridaran, 1977). This reaction could not, however, be reproduced (Rossi and Pierini, 1980) and other attempts to make phenoxide ions react at sp carbons have been equally unsuccessful (Ciminale et al, 1978 Rossi and Bunnett, 1973 Semmelhack and Bargar, 1980). It has been found, more recently, that phenoxide ions react with a series of aryl halides under electrochemical induction, but that the coupling occurs at the p- or o-phenolic carbon rather than at the phenolic oxygen (Alam et al, 1988 Amatore et al, 1988). This is... 

Ziegler catalysis involves rapid polymerization of ethylene and a-ole-fins with the aid of catalysts based on transition-element compounds, normally formed by reaction of a transition-element halide or alkoxide or alkyl or aryl derivative with a main-group element alkyl or alkyl halide (1,2). Catalysts of this type operate at low pressures (up to 30 atm), but often at 8-10 atm, and, in special cases, even under reduced pressure, and at temperatures up to 120°C, but often as low as 20-50°C. Approximately 2,200,000 tons of polyethylene and 2,900,000 tons of polypropylene are produced per year with the aid of such catalysts. The polyeth-... 

The method is an extension of the well-known Grignard synthesis in ethers to the use of nonsolvating media, and is a development of procedures previously reported.2-6 A version of it has been employed with straight-chain primary alkyl chlorides, bromides, and iodides from C2 to Cu,5-7 and in solvents (or an excess of the halide) which permit reaction temperatures above 120°, with simple aryl halides such as chlorobenzene and 1-chloro-naphthalene. Branched-chain primary, secondary, and tertiary alkyl halides, allyl, vinyl, and benzyl halides either fail to react or give extensive side reactions. Better results are reported to be obtained in such cases with the use of catalytic quantities of a mixture of an alkoxide and an ether such as diethyl ether or tetrahydrofuran in a hydrocarbon medium, but the products are not, of course, completely unsolvated.4... 

An alternative pathway when soluble alkoxide or silylamido bases are used, involves reaction of a palladium amido aryl complex with the alkoxide or silylamide to form an intermediate alkoxide or amide. These complexes can react with amines to form the required amido aryl intermediate. This pathway seems to occur for aryl halide animations catalyzed by complexes with chelating ligands. The inorganic... 

Work on other halides is much more limited. Gera-dibromocyclopropanes give modest yields of alkoxycarbonylation with alkoxide bases419. Aryl iodides may be carbonylated by catalytic mixtures of Fe(CO)5-Co2(CO)8 predominantly to the carboxylic acids or predominantly to the benzophenones, depending upon conditions420. 

In 1995, Hartwig and Buchwald published concurrently their respective groups results on tin-free amination of aryl halides [98, 99]. Instead of isolating or generating a tin amide in situ, the amination reactions were conducted by allowing an aryl halide to react with a combination of an amine and either an alkoxide or silylamide base (Eq. (5)). 

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