UUmann synthesis

Sjwyer and coworkers have developed an efficient alternative UUmann synthesis of diaryl ethers, diaryl thioethers, and diarylamines using the SnAt reaction. Phenol, thiophenol, or aniline reacts v/ith an appropriate aryl halide, In the presence of KF-aliunina and 18-crovm-6 In acetonitrile or DMSO to give the corresponding diaryl ether or diaryl thio ether as shovm In Eqs. 9.6 and 9.7. ... 

As a variation on the base-catalyzed nucleophilic displacement chemistry described, polysulfones and other polyarylethers have been prepared by cuprous chloride-catalyzed polycondensation of aromatic dihydroxy compounds with aromatic dibromo compounds. The advantage of this route is that it does not require that the aromatic dibromo compound be activated by an electron-withdrawing group such as the sulfone group. Details of this polymerization method, known as the UUmann synthesis, have been described (8). 

Parrick and colleagues used the photochemical Graebe-UUmann method to synthesize a series of dialkoxycarbo-lines (Scheme 8, equation 1) [43]. Warburton and Stephenson prepared several a-carbolines via an ortho-phosphoric acid-mediated synthesis (150-200 °C) [44], andNantka-Namirski summarized his work on the synthesis of numerous a-carbolines using phosphoric acid [45]. In 1993, Alvarez-Builla and coworkers reported the first use of microwave irradiation in a one-pot Graebe-UUmann synthesis (equation 2) [46]. The intermediate A-pyridylbenzotriazole was not... 

The UUmann synthesis of symmetrical biaryls Preparation of 2,2 -dimethoxy-4,4 -dimetho3 carbonyibiphenyl (64) [15]... 

Acyl phenols are sufficiently stable to permit their occasional use in the UUmann synthesis [131] and they are normally unreactive towards thionyl chloride and the phosphorus halides. This property permits the preparation of acid chlorides of protected phenolic acids which are employed widely in the synthesis of esters and depsides [122, 124, 125, 126, 127]. Fully acylated phenols are, in contrast to certain alkylated phenols, stable to a range of oxidants such as permanganate and chromic acid and using this property the dihydroxyphenanthra-quinone (76) was prepared from (75) [132]. 

The application of the Graebe-UUmann earbazole synthesis to the carboline series has led to syntheses of a-, /3-, and y-carboline. This reaction has already been reviewed in Vol. Ill of this series.419 The only point worth reemphasizing at this stage is the fact that Graebe-Ullmann cyclization of 1 -/J-pyridylbenztriazole (189) gives mainly, if not only, j8-carboline—cyclization taking place at C-4 of the pyridine ring—in marked contrast to the results obtained in the Fischer cyclizations. 

UUmann ether synthesis. The original Ullmann ether synthesis9 involved melting the salt of a phenol with an aryl bromide in the presence of copper metal. Yields are low. Williams et al.10 found that the reaction can be carried out at lower temperatures by using as solvent pyridine, which forms a complex with copper salts (cuprous chloride preferred), which provides catalysis for the reaction reflux temperature is then sufficient. 

UUmann diphenyl ether synthesis. Copper or one of its salts or oxides has been used to effect this reaction between an aromatic halide and a phenol. Cava... 

Ut. ApSimon (ed.). The Total Synthesis of Natural Products, vols. I-to. New York Wiley 1971-1997 Blum, The Toxic Action of Marine and Terrestrial Alkaloids, Fort Collins Alaken Inc. 1995 Blum, Chemistry and Toxicology of Diverse Classes of Alkaloids, Fort Collins Alaken Inc. 1996 Helv. Chim. Acta 75,647 - 688 (1992) (Review) Manske (53 vols. up to 2000) Molhes, SchUlle, and Luckner, Biochemistry of Alkaloids, Weinheim Verl. Chemie 1985 Pelletier, Alkaloids Biological Perspectives, vols. I -6, New York Wiley 1983-1988 vols. 7-9, Oxford Pergamon 1992-1995 Rodd s Chem. Carbon Compds. (2.) 4B (1997) (complete volume) Pharmazie 52, 546 (1997) (history) Saxton (ed. 1971-1975) and Grundon (ed. 1976-1983), The Alkaloids. Specialist Periodical Reports, 13 vols. up to 1983, London Royal Soc. Chem. 1971-1983 Southon and Buckingham (eds.). Dictionary of Alkaloids, London Chapman Hall 1989 UUmann (5.) A I, 353-407 Waterman (ed.). Alkaloids and Sulphur Compounds, London Academic Press 1993. -[HS293910-293990 ... 

The synthesis is comparatively simple. An UUmann reaction is followed by reduction with lithium aluminium hydride and a one-carbon elongation of the side-chain with cyanide. 

The adaptation of the Graebe-UUmann carbazole synthesis to indoles was apparently first described by Schmid s group [27, 28], but Wender and Cooper parlayed the... 

J. Li, and J.M. Cook (2005) Graebe-UUmann carbazole synthesis, in Name Reactions in Heterocyclic Chemistry, (ed. J.J. Li), John Wiley Sons, Hoboken, New Jersey, pp. 132-134. 

For the synthesis of quinazoHnones 147, a domino UUmann-type cou-pling/aerobic oxidative C-H amidation/oxidation process was successfully utilized by Fu et ol. [79]. 

As noted in the introduction to this section, UUmann also reported the formation of biaryl ethers from phenol and phenyl bromide in the presence of copper and a base. This UUmann ether synthesis has been used extensively to prepare biaryl ethers. " However, the original reaction conditions involved high temperatures (150-200 C), neat phenol or highly polar aprotic solvents, and stoichiometric amounts of copper complexes. The yields for the reactions of unactivated aryl halides were often low. Conditions with catalytic amounts of copper at lower temperatures with broader scope have now been developed. 

DoM-UUmann Cross-Coupling. Synthesis of Ar-X-Ar (X=0, N, S) under Modified UUmann Reaction Conditions 1124... 

A copper-catalyzed synthesis of benzo[f)]thiophenes and benzothiazoles using thiocarboxylic acids as sulfur source and coupling partner in the presence of Cul and 1,10-phenanthroline (1-10 phen) was developed this year (13JOC8898). The reaction proceeds by UUmann-type C—S bond coupling followed by Wittig condensation. 

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