Ullmann synthesis, of biaryls

Meyers has also reported the use of chiral oxazolines in asymmetric copper-catalyzed Ullmann coupling reactions. For example, treatment of bromooxazoline 50 with activated copper powder in refluxing DMF afforded binaphthyl oxazoline 51 as a 93 7 mixture of atropisomers diastereomerically pure material was obtained in 57% yield after a single recrystallization. Reductive cleavage of the oxazoline groups as described above afforded diol 52 in 88% yield. This methodology has also been applied to the synthesis of biaryl derivatives. 

The Ullmann reaction (Figure 16.5) represents another synthesis of biaryls that reliably leads to the formation of symmetric biaryls (upper and middle reaction examples), but, in particular cases, is also suitable for the synthesis of unsymmetrical biaryls (lower reaction example). To prepare a symmetric biaryl in the traditional way, an aryl iodide is heated with Cu powder in order to prepare the parent compound of biaryls, i.e., biphenyl, one starts with iodobenzene. The metal reduces 50% of the substrate to phenylcopper in situ. The latter... 

The name Ullmann is not only associated with the biaryl synthesis (Figure 16.4, 16.5), but is also known from the synthesis of diaryl ethers (Ullmann synthesis of diaryl ethers). An example is given in the topmost reaction of Figure 16.6. Remember Side Note 5.6, where we asked the following question How can diphenyl ethers be prepared Now you are ready to give a correct answer, which is By way of Ullmann synthesis. ... 

An interesting synthesis of biaryl systems which is a modification of the Ullmann method was recently given by Cornfonh and Wallace [7]. It consists in acting upon m-dinitrobenzene with aryl iodides under the influence of copper r-butoxide (I). 

Cu-catalyzed Ullmann biaryl ether synthesis Cu-mediated synthesis of biaryl ethers by coupling aryl halides and phenols. 464... 

Ullmann reaction. During a study of the synthesis of biaryls with nickel catalysts (4, 33 6, 654), Tsou and Kochi2 found that nickcl(II) complexes such as 1 readily yield biaryls on treatment with an aryl halide and that they are important intermediates in the radical-chain process of nickel-catalyzed Ullmann reactions. 

Over the past century, several methods have been developed for the synthesis of biaryl compounds [7]. Among these are the Ullmann-type coupling [8,9], the Scholl reaction [10], the Gomberg-Bachmann reaction [11], and recently transition-metal-catalyzed cross-coupling reactions [12], In particular, palladium-catalyzed crosscoupling reactions have been successfully applied to the synthesis of biaryls due to their generally high yields and excellent selectivities. 

The formation of a biaryl by the condensation of two molecules of an aryl halide in the presence of finely divided copper is known as the Ullmaim reaction [1-4]. Although several newer methods for synthesis of biaryls were developed, the Ullmann reaction still remained its importance in some specific cases. Due to its efficiency and simplicity, the reaction is very useful in the synthesis of simple symmetrical and some classes of unsymmetrical biaryls. More than a century old, the classical Ullmaim reaction involves heating the mixture of the aryl halide(s) (I) with the copper powder or bronze at 100-360 °C in or without any solvent. Products of this reaction are the biaryl(s) (II) and the corresponding copper(I) halide. Scheme 1. 

The Ullmann synthesis of unsymmetrical biaryls has been employed in a number of cases with remarkable selectivity if the aryl halides were properly selected [2-6,37-41]. Some representative synthesis in the phenyl series are shown in the Table 2. 

The Ullmann synthesis of unsymmetrical biaryls Preparation of l-(2-methoxycarbonyl-4-nitrophenyl)-4-nitronaphthalene (30) [38]... 

Using other chiral 1,2-diols such as 1,2-diphenyl-1,2-ethanediol or 2,3-butanediol, the Lipshutz approach allows to rich very high diastereoselectivity [19]. Among reactions that have been used in the diastereoselective synthesis of unsymmetrical axially chiral biaryls, beside Ullmann and Lipshutz reactions, are the Suzuki-Miyaura and Meyers synthesis of biaryls. 

Some aromatic sulphonic acids are decomposed on strong heating and hence must be protected during the Ullmann synthesis of sulphonated biaryls. For this purpose sulphonic acid groups are usually converted into the phenyl esters [21], e.g.. Fig. 10.9. Other examples are given in the Tables in Fanta s reviews of the Ulhnann synthesis of biaryls [22]. 

Traditionally, the synthesis of symmetrical biaryls was routinely accomplished using the Ullmann reaction. Recently, palladium-catalyzed homocoupling of aryl halides has also been demonstrated to rival the utility of the Ullmann coupling. As illustrated in Scheme 21, using Pd(OAc)2 as the... 

Chan has discovered a completely atropdiasteroselective synthesis of a biaryl diphosphine by asymmetric intramolecular Ullmann coupling or Fe(m)-promoted oxidative coupling. A chiral atropisomeric biaryl bisphosphine ligand 2 was synthesized through this central-to-axial chirality transfer.38 Recently, a xylyl-biaryl bisphosphine ligand, Xyl-TetraPHEMP, was introduced by Moran, and is found to be effective for the Ru-catalyzed hydrogenation of aryl ketone.39... 

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 ... 

There are two different transformations referred as the Ullmann Reaction. The classic Ullmann Reaction is the synthesis of symmetric biaryls via copper-catalyzed coupling, the Ullmann-type Reactions include copper-catalyzed Nucleophilic Aromatic... 

Hennings, D. D. Iwama, T. Rawal, V. H. Palladium-catalyzed (Ullmann-type) homocoupling of aryl halides a convenient and general synthesis of symmetrical biaryls via inter- and intramolecular coupling reactions. Org. Lett. 1999, 1, 1205-1208. 

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