Ullmann couplings

Homocoupling of aryl iodides in the presence of Cu or Ni or Pd to afford biaryls. 

The overall transformation of Phi to PhCuI is an oxidative addition process. Example H 

Example 2, CuTC-catalyzed Ullmann coupling (CuTC, Copper(I)-thiophene-2- 

Name Reactions A Collection of Detailed Mechanisms and Synthetic Applications, DOI 10.1007/978-3-319-03979-4 277, Springer International Publishing Switzerland 2014 

Ullman Coupling. In Name Reactions for Homologations-Part 7 Li, J. J., Ed. Wiley Hoboken, NJ, 2009 pp 255-267. (Review). 

Name Reactions, 4th ed., DOI 10.1007/978-3-642-01053-8 258, Springer-Verlag Berlin Heidelberg 2009 

(a) Ullmann, F. Bielecki, J. Ber. 1901, 34, 2174-2185. Fritz Ullmann (1875-1939), bom in Fiirth, Bavaria, studied under Graebe at Geneva. He taught at the Technische Hochschule in Berlin and the University of Geneva, (b) Ullmann, F. Ann. 1904, 332, 38-81. 

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In a synthesis of decinine, a phenol was protected as a methanesulfonate that was stable during an Ullmann coupling reaction and during condensation, catalyzed by calcium hydroxide, of an amine with an aldehyde. Aryl methanesulfonates are cleaved by warm sodium hydroxide solution. 

In general, imines are too reactive to be used to protect carbonyl groups. In a synthesis of juncusol, however, a bromo- and an iodocyclobexylbnine of two identical aromatic aldehydes were coupled by an Ullmann coupling reaction modified by Ziegler. The imines were cleaved by acidic hydrolysis (aq. oxalic acid, THE, 20°, 1 h, 95% yield). Imines of aromatic aldehydes have also been prepared to protect the aldehyde during ring metalation with. -BuLi. ... 

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. 

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... 

The first series of soluble oligo(/ ara-phenylene)s OPVs 24 were generated by Kern and Wirth [48] and shortly after by Heitz and Ulrich [49]. They introduced alkyl substituents (methyls) in each repeat unit and synthesized oligomers 24 up to the hexamer. Various synthetic methods, like the copper-catalyzed Ullmann coupling, the copper-catalyzed condensation of lithium aryls, and the twofold addition of organomelallic species to cyclohexane-1,4-dione, have been thereby investigated. 

It has been shown that the imidoyl chloride moiety of 2(lff)-pyrazinones can imdergo an easy addition/elimination reaction with alkyl amines [24], while reactions with anilines proceed under harsher conditions. Ullmann coupling [109-113] of 2(lff)-pyrazinones with substituted anilines could open the way to the libraries of physiologically active compounds useful in inhibiting HIV replication [7]. Polymer-bound pyrazinone was successfully... 

Asymmetric syntheses of warfarin <96TL8321> and the axially chiral bicoumarin, isokotanin A <96TL3015> have been reported. The former is based on a Rh-catalysed asymmetric hydrogenation of a 3-(a,P-unsaturated ketone) substituted coumarin, whilst the key steps of the latter are an asymmetric Ullmann coupling and a selective demethylation. The stereochemistry of the fused dihydrocoumarin resulting from Li/NHs reduction of... 

We investigated the catalytic performance of the CU2O coated copper nanoparticles for Ullmann coupling reactions. When the coupling reactions using aryl bromides such as 2-... 

Nicolaou and coworkers reported efficient enantioselective syntheses of ( )-kinamycin C (3), ( )-kinamycin F (6), and ( )-kinamycin J (10) [39], Nicolaou s retrosyntheses of these targets are shown in Scheme 3.13. The authors envisioned that all three metabolites could be accessed from the common precursor 82. The a-hydroxyketone function of 82 was envisioned to arise from an intramolecular benzoin reaction of the ketoaldehyde 83. This key bond disconnection would serve to forge the cyclopentyl ring of the kinamycin skeleton. The ketoaldehyde 83 was deconstructed by an Ullmann coupling of the aryl bromide 84 and the a-iodoenone 85. The latter were anticipated to arise from the bromojuglone derivative 86 and the enantiomerically enriched enone 87, respectively. 

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... 

Picryl chloride has been used successfully in a number of copper-mediated Ullmann coupling reactions. 2,2, 4,4, 6,6 -Hexanitrobiphenyl has been synthesized by heating picryl chloride with copper powder. The same reaction in the presence of a hydride source (hot aqueous alcohol) yields 1,3,5-trinitrobenzene (TNB). The Ullmann reactions between picryl chloride and isomeric iodonitrobenzenes with copper bronze in DMF has been used to synthesize 2,2, 4,6-, 2,3, 4,6-, and 2,4,4, 6-tetranitrobiphenyls. ... 

Amino derivatives of polynitrobiphenyls often exhibit high thermal stability. The thermally insensitive explosive (156) is synthesized in three synthetic steps from 3,5-dimethoxychlorobenzene (154) in a route employing nitration, Ullmann coupling and ammonolysis. 3,3 -Diamino-2,2, 4,4, 6,6 -hexanitrobiphenyl (DIPAM) (157) is synthesized from 3-chloroanisole by a similar route. DIPAM (m.p. 304 °C, d = 1.82 g/cm ) is... 

The formation of the dibenzofuran nucleus by intramolecular Ullmann coupling of bis(2-iodophenyl) ethers has been little exploited, although the method offers potential. Mazere et al. have obtained 2,3,7,8-tetramethyl-dibenzofuran (47), and Carvalho and Sargent have obtained the dibenzofuran 21 (Scheme 6), by this method. 

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. 

TABLE 8.30 DIASTEREOSELECTIVITY IN ULLMANN COUPLING REACTIONS (SCHEME 8.158), 466... 

The Ullmann coupling is the classical example of Cu-catalyzed biaryl coupling, wherein (a) a phenol and arylhalide substrate are converted to a bis-arylether or (b) two arenes are coupled to form a bis-arene species. These coupling reactions are of great importance for general organic synthesis as well as pharmaceutical and fine chemicals. The copper-catalyzed phenol coupling to arrive at chiral biphenol derivatives is used extensively as a test reaction for the catalytic activity of new copper complexes [254,255]. 

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