Biaryls, synthesis

Pyrimidine, 4-fluoro-2-isopropyl-synthesis, 3, 140 Pyrimidine, 4-fluoro-2-methoxy-synthesis, 3, 140 Pyrimidine, 4-fluoro-2-methyl-NMR, 3, 63 Pyrimidine, halo-aleoholysis, 3, 100 aminolysis, 3, 99 as antitumour agents, 3, 152 bipyrimidines from, 3, 103 Buseh biaryl synthesis, 3, 103 hydrolysis, 3, 101... 

Scheme 24 Diastereoselective biaryl synthesis via double benzannulation...

Although the copper mediated Ullmann reaction is a well known method for biaryl synthesis, drastic conditions in the range of 150-280 °C are required. Zerovalent nickel complexes such as bis(l,5-cyclooctadiene)nickel or tetrakis(triphenylphosphine)nickel have been shown to be acceptable coupling reagents under mild conditions however, the complexes are unstable and not easy to prepare. The method using activated metallic nickel eliminates most of these problems and provides an attractive alternative for carrying out aryl coupling reactions(36,38). 

The Ullmann biaryl synthesis(lQl,102) invokes the reaction of copper powder with aryl halides at relatively high temperatures, typically 100-300 °C, to give biaryl products. The intermediacy of arylcopper species is presumed but not specifically proven due to the instability of the arylcopper at the temperatures required for reaction. The Ullmann reaction has seen appreciable usage as it allows considerable functionality to be incorporated in the products. 

In a more recent study, Wang and coworkers have discussed microwave-assisted Suzuki couplings employing a reusable polymer-supported palladium complex [141]. The supported catalyst was prepared from commercial Merrifield polystyrene resin under ultrasound Bonification. In a typical procedure for biaryl synthesis, 1 mmol of the requisite aryl bromide together with 1.1 equivalents of the phenyl-boronic acid, 2.5 equivalents of potassium carbonate, and 10 mg of the polystyrene-... 

Biaryl synthesis from aryl halides is a more interesting reaction due to the value of these molecules and their difficult access by chemical methods. The first electrosyntheses were simultaneously done in 1979-80 by three groups [21-23] who used NiCljPPha (1-20%) as catalyst precursor in the presence of excess PPhs. Later, several groups investigated the use of bidentate phosphines like dppe associated with nickel in the synthesis of various biaryls, and notably 2,2 -bipyridine and of 2,2 -biquinoline from respectively 2-chloropyridine and 2-chloroquinoline [24], More recently new nickel complexes with l,2-bis(di-2-alkyl-phosphino)benzene have been studied from both fundamental and synthetic points of view [25]. They have been applied to the coupling of aryl halides. 

The lactone concept is not restricted to the simple model biaryl synthesis presented here. It has been successfully expanded to a broad series of structurally diverse biaryl substrates (e.g., lactones with additional stereocenters and functional groups, configurationally stable lactones, seven-membered lactones, and again configurationally unstable biaryl hydroxy aldehydes ), to different activation modes in the ring-opening step (e.g., use of metallated nucleophiles, carbonyl activation by Lewis acids, (Ti -complexation, etc.), and for various strategies of stereoselection (e.g., external vs. internal asymmetric induction). ... 

In addition to the synthetic route shown in Scheme 32, Armstrong approached the synthesis from the other direction, by converting the initial resin-bound iodide to a supported pinacolatoboronate 30 under platinum catalysis (Scheme 33). This was then coupled in the usual way with a solution-phase aryl iodide in high yield, and with much more satisfactory results than were obtained with the vinylboronates 29. This chemistry was later shown to be useful in solution for one-pot biaryl synthesis by genera-... 

Frenette, R. Friesen, R. W. Biaryl Synthesis via Suzuki Coupling on a Solid Support, Tetrahedron Lett. 1994, 35, 9177-9180. 

Benzyltriethylammonium chloride, (56-37-1), 66, 204 68, 220 N-Benzyl-N-(trimethylsilyl)methylamine Benzenemethanamine, N [(trimethyl-silyI)methyl]- (53215-95-5), 67, 133 BETA-LACTAM, 65, 135, 140 BIARYL SYNTHESIS, 66, 67... 

Scheme 8.23 Biaryl synthesis by vinylogous Michael reaction.

In 1996, workers at GlaxoWellcome disclosed the solution-phase preparation of 2-aminothiazole combinatorial libraries [99], Utilizing 20 glass vials and a DPC liquid dispensing robot, they prepared a library of 2500 compounds by this procedure. Also in 1996, Argonaut reported the use of their computer-controlled fluid delivery system for biaryl synthesis via a Suzuki coupling reaction [61],... 

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. ... 

Fig. 16.5. Biaryl synthesis via arylcopper compounds II— in-situ preparation of the nucleophile with the classical Ullmann procedure ("variant 1"), with a procedure that may also be applied to aryl bromides ("variant 2") and with a crossed classical Ullmann coupling (bottom-most reaction example).

S. P. Stanforth, Catalytic Cross-Coupling Reactions in Biaryl Synthesis, Tetrahedron 1998, 54, 263-303. 

This synthetic plan, which initially involved an efficient asymmetric biaryl synthesis, suffered from two weaknesses, namely in the manipulation of configurationally fragile intermediates and in the epimerization at the biaryl axis during the decarboxylation step. These... 

Frenette R, Friesen RW, Biaryl synthesis via coupling on a solid support, Tetrahedron Lett., 35 9177-9180, 1994. 

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