Boranes, pyridyl

Pyridyl)hydrazine (Aldrich), 4-acetylpyridine (Acros), N,N,N -trimethylethylenediamine (Aldrich), methylrhenium trioxide (Aldrich), InQj (Aldrich), Cu(N0j)2-3H20 (Merck), Ni(N03)2-6Il20 (Merck), Yb(OTf)3(Fluka), Sc(OTf)3 (Fluka), 2-(aminomethyl)pyridine (Acros), benzylideneacetone (Aldrich), and chalcone (Aldrich) were of the highest purity available. Borane dimethyl sulfide (2M solution in THE) was obtained from Aldrich. Methyl vinyl ketone was distilled prior to use. Cyclopentadiene was prepared from its dimer immediately before use. (R)-l-acetyl-5-isopropoxy-3-pyrrolin-2-one (4.15) has been kindly provided by Prof H. Hiemstra (University of Amsterdam). 

Under the phase-transfer catalysis conditions, 2-bromo-8-methylquino-line (67) was coupled with 2-pyridylboronic ester 68 to furnish 2-(2-pyridyl)-8-methylquinoline (69) in 56% yield (91JOC6787). At this point, it is opportune to mention that the simple 2-pyridylborane, in contrast to 3- and (4-pyridyl)boranes, is considered an unsuitable Suzuki coupling partner because it forms an unusually stable cyclic dimer resembling a dihydroanthracene. In this case, the obstacle was circumvented by using 2-pyridylboronic ester in place of 2-pyridylborane (Scheme 9). 

Two additional examples of the Suzuki coupling using diethyl (3-pyridyl)borane include the coupling with 4-chloro-2,3 -bipyridine l -oxide (40) to give terpyridine 41 [7] and the coupling with 1,8-dibromonaphthalene to afford a mixture of two atropisomers 42 and 43 of l,8-di(3 -pyridyl)naphthalene [33, 34], Interestingly, the N atoms in 42 and 43 provide enough steric and spectral differentiation to make the detection of atropisomers possible at room temperature. 

Li and Yue observed an ethyl transmetalation during the Suzuki coupling of diethyl (3-pyridyl)borane and 3-bromoquinoxaline 44 [35]. In the presence of a strong base (NaOH), the Suzuki reaction of diethyl (3-pyridyl)borane with 3-bromo-6,7-dichloroquinoxalin-2-ylamine (44) proceeded to give 52% of the 3-pyridylquinoxaline 45 accompanied by 21% of 3-ethylquinoxaline 46. 

Chloropyrimidine was coupled with diethyl (3-pyridyl)borane in the presence of Pd(Ph3P)4, Bt NBr, and KOH to afford 3-(2 -pyrimidinyl)pyridine [23]. Likewise, the Suzuki coupling of 2-bromopyrimidine with diethyl (4-pyridyl)borane (47) led to 4-(2 -pyrimidinyl)pyridine (48) in 50% yield, whereas 2-chloropyrimidine produced 48 in only 20% yield under the same conditions [24], Diethyl (4-pyridyl)borane (47), on the other hand, was readily accessible from sequential treatment of 4-bromopyridine with n-BuLi and diethylmethoxyborane. 

In equation 7.1. a 4-chloropyridine was coupled with diethyl(3-pyridyl)borane.3 The reaction was run in aqueous THF in the presence of potassium carbonate. The role of the base is to facilitate the transmetalation step through the formation of a borate ion, as organoboranes are usually not nucleophilic enough to transfer their organic moiety onto the palladium. An alternate function of the base is to increase the electrophilicity of the palladium through exchange of the halide to carbonate. 

A similar transformation was reported using a polyfunctional phthalazine derivative (7.2.) 4 It is interesting to note that the transmetalation of the borane was not selective with respect to the pyridyl group, formation of the product resulting from the transfer of the ethyl group was also observed. 

Both diethyl (3-pyridyl)borane and diethyl (4-pyridyl)borane are readily accessible from 3-bromopyridine and 4-bromopyridine, respectively, via halogen-metal exchange and reaction with triethylborane [29-32], The two pyridylboranes have been coupled with a variety of aryl and heteroaryl halides, as exemplified by the coupling of diethyl (3-pyridyl)borane and 2-nitrophenylbromide to form phenylpyridine 39 [30, 31]. 

Bis(phosphoranimine) ligands, chromium complexes, 5, 359 Bis(pinacolato)diboranes activated alkene additions, 10, 731—732 for alkyl group functionalization, 10, 110 alkyne additions, 10, 728 allene additions, 10, 730 carbenoid additions, 10, 733 diazoalkane additions, 10, 733 imine additions, 10, 733 methylenecyclopropane additions, 10, 733 Bisporphyrins, in organometallic synthesis, 1, 71 Bis(pyrazol-l-yl)borane acetyl complexes, with iron, 6, 88 Bis(pyrazolyl)borates, in platinum(II) complexes, 8, 503 Bispyrazolyl-methane rhodium complex, preparation, 7, 185 Bis(pyrazolyl)methanes, in platinum(II) complexes, 8, 503 Bis(3-pyrazolyl)nickel complexes, preparation, 8, 80-81 Bis(2-pyridyl)amines... 

Diethyl(3-pyridyl)borane (3.38 g, 23 mmol) from Aldrich Chemical Co. Ltd. was added to a stirred solution of 3p-acetoxyandrosta-5,16-dien-17-yl trifluoromethanesulphonate (6.94 g, 15 mmol) in THF (75 ml) containing bis(triphenylphosphine)palladium(II) chloride (0.105 g, 0.15 mmol). An aqueous solution of sodium carbonate (2 M, 30 ml) was then added and the mixture heated, with stirring, by an oil bath at 80°C for 1 h, and allowed to cool. The mixture was partitioned between diethyl ether and water, the ether phase was dried (Na2C03), filtered through a short plug of silica, and concentrated. Chromatography, on elution with light petroleum-diethyl ether (2 1), afforded the 3 5-acetoxy-17-(3-pyridyl)androsta-5,16-diene (4.95 g, 84%) which crystallised from hexane, m.p. 144-145°C. 

Diethyl-(3-pyridyl)borane can also be prepared from 3-lithiopyridine by the sequence shown (83CPB4573) in Scheme 4. 

Some examples of attempted isolation of resulting borates such as tributyl 3-pyridyl-, 3-quinolyl-, or 4-isoquinolyl borates by quaternization of the ring nitrogen with various allylic bromides have been reported (87JHC377). Alternatively, diethyl(3-pyridyl)borane obtained by the method mentioned previously reacts with potassium cyanide, and then, with alkyl halides, to afford cyanoborate betaines (20) in high yields (83CPB4573) (Scheme 7). 

Fig. 3. I3C chemical shift data for diethyl(2-, 3-, and 4-pyridyl)boranes and for pyridine. 8ppm given in CDC13.

Terashima employed diethyl-(3-pyridyl)borane as the boron partner in a Suzuki cou-... 

An optimized temperature of < 0°C, employed for the generation of 3-pyridyllithium used for the preparation of diethyl-3-pyridyl borane on the pilot scale, was achieved by careful selection of solvent and addition order (Scheme 12.2, eq. 3). The optimized procedure employed an inverse addition of 3-bromopyridine in hexane to a solution of -BuLi in hexane containing a quantity of... 

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