Aryl chlorides, reactions with

The sterically hindered alkylmonophosphines provide an improved catalyst system (Table 7.5) [132]. In this case, reactions occur at 100 °C over 8 h for activated or deactivated aryl bromides and with electron-poor or electron-neutral aryl chlorides. Reactions of ortho-substituted aryl halides were surprising, providing a mixture of 1-and 3-substituted indoles. However these aryl halides were suitable substrates when the 3-position of the indole was substituted. The origin of this C- versus N-arylation is unknown. 

A full account of the scope and limitations of the amination chemistry of these ligands has recently appeared [158]. With ligand 15, a number of aminations were conducted at room temperature. In the absence of an ortho substituent, couplings of primary amines with unactivated aryl chlorides at room temperature required 5 mol % catalyst. However, a variety of secondary amines, both cyclic and acyclic, reacted with activated or deactivated aryl chlorides at room temperature. Thirteen examples were demonstrated. The scope of this process was broader, however, when reactions were conducted at 80 or 110 °C. Under these conditions, unactivated aryl chlorides reacted with a variety of amines in high yields. In favorable cases, such as reactions of aryl chlorides bearing one ortho methyl group, reactions of N-methyl... 

The palladium-catalyzed reaction of aryl halides with cyanides to give cyanobenzenes takes place under relatively mild conditions compared to the conventional method using a stoichiometric amount of CuCN [74]. Thus, palladium catalysis has been often employed. Recently, a number of effective methods for the cyanation have been reported. The reaction of aryl iodides with NaCN under two-phase conditions [75] and those of aryl triflates [76, 77] and aryl chlorides [78] with Zn(CN)2 occur with good efficiency, while these are considered to proceed via mechanism B. 

A highly active catalytic system for direct arylation reactions of nonactivated arenes relied on a homobimetallic rhodium complex. Thus, treatment of [bis(2-pyridyl) amino]diphenylphosphane (109) with [Rh(cod)Cl]2 led to the formation of a complex 108, which, according to X-ray crystal structure analysis, consisted of [Rh(cod) Cl2] anion and a rhodium cation stabilized by two P,N-ligands (Scheme 9.34) [73]. This bimetallic rhodium complex (108) allowed the direct arylation of benzene (87) with the aryl chloride 106 with a turnover number (TON) of 780 under comparably mild reaction conditions. 

The carbamates LXXXIX are also obtained upon treatment of XC with a variety of acids, such as hydrogen chloride, carboxylic acids, and phosphoric acid Reaction of XC with amines yields the 0,N-acetals XCII. For example, the monosubstituted products, derived from phenols (XC, R = aryl) upon reaction with alkyl amines afford the corresponding 0,N-acetals, which are useful herbicides... 

Uemura has shown that aryl chlorides which are T -bound to Cr(CO)3 are remarkably reactive coupling partners in Suzuki reactions [23, 24]. Even in the presence of the electron-donating, deactivating ortho-methoxy substituent, the aryl chloride couples with an arylboronic acid (Equation 2.13). Furthermore, no homo-coupled 4 -bromobiphenylboronic acid is observed, establishing that highly selective activation of a C—Cl bond is occurring in the presence of a typically more reactive C—Br bond. 

The synthetic route to iV-aryl [3.2.2] cryptands 5a and 5b is shown in the Scheme. Starting from the A-aryl diethanolamine, reaction with two equivalents of chloro-acetic and /-BuOK in t-BuOH followed by conversion of the diacid to the diester for purification gave la and lb in yields of 49 and 25%, respectively. Subsequent acid-catalyzed hydrolysis produced the dicarboxylic acid amine hydrochlorides 2a and 2b quantitatively. Attempts to form the diacid chloride of 2a resulted in an unreactive deep blue-colored substance of unknown identity. Ring closure was effected by adaptation of a method from peptide synthesis [8]. Mixed anhydrides 3a and 3b formed by reaction with two equivalents of isobutyl chloroformate in the presence of triethylamine were cyclized with l,10-diaza-18-crown-6 in toluene to produce the corresponding cryptand diamides 4a and 4b in 36 and 32% yields, respectively. Reduction with borane-dimethyl sulfide in THF provided 74% yields of 5a and 5b. 

The synthesis of the sterically hindered 2-ketoesters succeeded in a simple fashion and in excellent yields by the esterification of ethyl oxalyl chloride with the lithium salt of 2,6-di-f rt-butyl-4-methoxyphenol followed by the chemose-lective nucleophilic addition of methyl or ethyl Grignard reagents to the unsym-metrical ethyl aryl oxalate. Reaction with (S)-l-amino-2-(methoxymethyl)pyrro-... 

Palladium-catalyzed cross-coupling reactions of aryl chlorides 5 with hydrazine afforded intermediate arylhydrazines 6 at ambient temperatures, which reacted further with P-diketones to give 1,3,5-trisubstituted pyrazoles 7 in one-pot (13AG(E)3434). Palladium-catalyzed Heck car-boxylative cross-coupling reactions of aryl iodides with acetone afforded the in situ 1-aryl-1,3-butadiones, which reacted with an aqueous solution of hydrazine in ethanol to give 3-methyl-5-arylpyrazoles in moderate yields (13CEJ12624). 

Alkyl and aryl iodides usually react with magnesium more rapidly than the corresponding bromides, and the bromides very much more rapidly than the chlorides. Aryl (as distinct from alkyl) chlorides have usually only a slow reaction with magnesium and are therefore very rarely used. With alkyl and aryl iodides in particular, however, a side reaction often occurs with the formation of a hydrocarbon and magnesium iodide ... 

Reaction with chlorosulphonic acid ( chlorosulphonyl-ation ). Sulphonamides. Many aryl hahdes, either alone or in chloroform solution, when treated with excess of chlorosulphonic acid afford the corresponding sulphonyl chlorides in good yield (compare Section IV.106) the latter may be readily converted into the aryl sulphonamides by reaction with concentrated ammonia solution or with sohd ammonium carbonate. 

Aryl sulphonic acids, either free or in the form of tlieir sodium or potassium salts, are converted into the acid chlorides by reaction with phosphorus peutu-chloride or phosphorus oxychloride, for example ... 

Arenediazonium salts are also used for the couplina[563], (Z)-Stilbene was obtained unexpectedly by the reaction of the ti-stannylstyrene 694 by addition-elimination. This is a good preparative method for cu-stilbene[564]. The rather inactive aryl chloride 695 can be used for coupling with organostannanes by the coordination of Cr(CO)3 on aromatic rings[3.565]. 

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