Pyridyl bromide

An alternative route for installing a methyl ketone is the three component carbonylative-Stille coupling with tetramethyltin. An indolopyridine alkaloid, naucletine (58), was prepared using such a sequence from pyridyl bromide 57 <95CC1675>. 

Boron-substituted pyridine reagents can be used to construct the bipyridine ring system by coupling them with halopyridines in the presence of a Pd° catalyst and a base (Suzuki method). Various ligands have been made in this manner in moderate to high yields, including 2,3-bipyridine (85%)41 and 3,5-dimethyl bipyridine (60%) 42 One valuable feature of the Suzuki method is that it is compatible with stannanes. A pyridyl diethylborane has been coupled to a tributyl tin-functionalized pyridyl bromide.43 This compatibility is useful for polypyridine syntheses because subsequent Stille coupling of the bipyridyl stannane is possible. 

C. 5-Methyl-2,2 -bipyridine (3). The 4- and 6-methyl-2,2 -bipyridines may also be prepared using the following procedure. A 500-mL, two-necked, round-bottomed flask (Note 2) with a Teflon-coated magnetic stirrer is placed in a dry ice/acetone bath (-78°C), then 80 mL of tetrahydrofuran (THF) (Note 11) and tert-butyllithium (tert-BuLi) (1.75 M in pentane, 52 mL, 91.0 mmol) Note 12) are added to it, followed by dropwise addition of 2-bromopyridine (7.13 g, 4.3 mL, 45.1 mmol) (Note 13). The canary yellow THF solution becomes reddish-brown upon addition of the pyridyl bromide. After the solution is stirred at -78°C for 30 min, anhydrous zinc chloride (ZnCI2) (13.3 g, 97.4 mmol) (Note 14) is added, and the reaction is stirred at 25°C for 2 hr. The 5-methyl-pyridyl triflate (2) (8.95 g, 37.1 mmol), lithium choride (LiCI) (3.18 g, 75.2 mmol) Note... 

The unsubstituted pyrrole-2-boronic acid 93 was coupled with pyridyl bromide 94 on a Wang resin to afford nicotinic acid derivative 95 after cleavage [69]. 

Derivatives of cephalosporins can serve as selective class C P-lactamase inhibitors and therefore routes to their preparation are of value [101]. Pyridyl analog 287 could be prepared in one of two ways, which differed only in the nature of the reacting partners. p-Lactam stannane 286 could be coupled with pyridyl bromide 19 to afford 287. Alternatively, pyridyl stannane 236 was reacted with bromide 288 to generate 287. 

M. L. Trudell and Cheng synthesized a chelating bis-NHC ligand (L15) that was optimized specifically for the synthesis of A -heteroaryl-7-azabicyclo[2.2.1]heptanes.50 They demonstrated that this ligand could aminate various pyridyl bromides and chlorides to give the desired product in low to moderate yields. 

Moreover, since the cross-coupling reaction of hexaalkyidistannane with aryl halides strongly depends on the reactivity of the latter, a chemoselective cross-coupling of two different aryl halides has become of practical value. Thus Zhang described a simple and versatile method for synthesis of unsymmetrical biaryls from 2-bromopyridines (more reactive) and various phenyl- and 3-pyridyl bromides (less reactive) to afford the appropriate biaryls in moderate to high yields [106]. For example, 5-cyano-2-bromopyridine (167) was cross-coupled with 4-nitro-bromobenzene (168) to give the biaryl 169 in 67% yield [106], respectively, Scheme 23. 

In 1994, Aliprantis and coworkers studied the catalytic intermediates in the Suzuki reaction by ESI-MS [1]. The currently accepted catalytic cycle involves oxidative addition, transmetalation, isomerization, and reductive elimination (Scheme 4.1). In order to form the protonated intermediates detectable by ESI-MS, pyridyl bromide and three phenylboronic acids were chosen for the reaction. Intermediate ions of [(pyrH)Pd(PPh3)2Br], diaryl Pd(II) species, and some other derivative palladium species were detected in the reaction mixture. 

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