Ullmann reaction discussion

Figure 1 Ullmann reaction (left) and electrochemical catalytic alternative (right). Results and Discussion...

Cycloamidation has been used extensively to prepare 17-membered cycloisodityrosines. The acyclic biaryl ether precursors were prepared by methods including the Ullmann reaction 2-5 and nucleophilic aromatic substitution (SNAr)J6 7 Since these methods have all been used intramolecularly in cyclization reactions, they will be discussed in Sections 9.5.3 and 9.5.4. Evans and co-workers employed the pentafluorophenyl ester method of macrolactamization 8] to prepare 11, an intermediate in their total synthesis of OF4949-III (7) (Scheme 2)J3 In this case, the acidic removal of a Boc group was employed to release the cyclization substrate, although hydrogenolysis of a Z group is also effective 3 ... 

The term Ullmann reaction is often expanded to also include copper-mediated nucleophilic substitution reactions (of almost any kind) to iodo- or bromoaromatic compounds. The discussion of Figure 16.3 provided all the necessary mechanistic information. Figure 16.6 shows that Ullmann reactions in the above sense allow a large number of functionalizations of... 

The Ullmann reaction (Figure 13.4) represents another synthesis of substituted biphenyls. In this process an aryl iodide or—as in the present case—an aryl iodide/aryl chloride mixture is heated with Cu powder. It is presumed that under standard conditions the aryl iodide reacts in situ with Cu to form the aryl copper compound. Usually, the latter couples with the remaining aryl iodide and a symmetric biphenyl is formed. In a few instances it is also possible to generate asymmetric biaryls via a crossed Ullmann reaction. In these cases one employs a mixture of an aryl iodide and another aryl halide (not an iodide ) the other aryl halide must exhibit a higher propensity than the aryl iodide to couple to the arylcopper intermediate. It is presumed that the mechanism of the Ullmann reaction parallels the mechanism of the Cadiot-Chodkiewicz coupling, which we will discuss in Section 13.4. 

Discussions of oxazolines as chiral directing groups are included in the previous sections under the appropriate reaction classifications. Meyers has already published a recent review of chiral oxazolines (1998) that focused primarily on their use in aromatic reactions and Ullmann coupling reactions in particular. The examples of oxazolines as chiral directing groups described in this section will include reactions that are not discussed in any previous section of this chapter. 

General properties of ammonia are discussed in Mellot(Ref 6), Gmelin(Ref 13), Thorpe(Ref 15),ChemRevs(Ref 17a), Kirk Othmer(Ref 32) and in Ullmann(Ref 59). Franklin(Ref 1) described the reactions of liq ammonia Von Braun et al(Ref 16) reported a violent and explosive reaction of liq ammonia with some organic halogen compds. For example, when the reaction between liq ammonia and BrHaC—CHaBr was carried out at RT, there occurred a spontaneous evolution of heat resulting in a violent expln. 

The biaryl synthesis by Ullmann coupling, as well as a large number of related coupling reactions, constitutes another type of copper-mediated or -catalyzed reaction used extensively for the formation of carbon-carbon and carbon-heteroatom bonds. These transformations have been reviewed recently17,177,177a,177b and will not be discussed in detail here. 

Two reviews have detailed the reactions of aryl halides with copper and copper compounds these are (1) the Ullmann biaryl synthesis, by Fanta 113) and (2) copper-promoted reactions, by Bacon and Hill (9). The mechanism of the Ullmann biaryl synthesis was discussed the possible routes are shown in Eq. (110). No evidence had been obtained... 

The effects of ultrasound on the reactivity of copper metal as a stoichiometric reagent have been documented in the literature in two cases, the Ullmann coupling 2 and the reaction with salicylidene-aniline to form uncharacterized copper complexes.33 These reactions are discussed in Ch. 5 (pp. 171 and 208). In addition, ultrasound has been used to enhance the reduction of Cu salts by alkali metals to form highly reactive copper dispersions. ... 

It should also be noted that copper-catalyzed Ullmann-type coupling of aryl halides with amines yields substituted products [206], and reaction with diphenylamine has been used to form triaryl-amines [207], Triarylamines may also be formed in a variation of the Meyers reaction [47] by displacement by lithium amides of fluoro- or methoxy-substituents activated by an ort/io-ester function [208], The oxidation of a-adducts is discussed in Chapter 11, but it should also be mentioned that aminated products may also be produced by the oxidation of adducts formed by the addition of amide or alkylamide ions at ring carbon atoms carrying hydrogen [209]. 

The question of the possible intervention of various copper oxidation states in Ullmann and Goldberg reactions has been discussed from time to time (see the summarising discussion in [159]). Although the reduction of copper(II) to copper... 

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