Regioselective bromination

Regioselective bromination of ketones at the mote highly substituted a-position is effected by photocatalytic bromination in the presence of 1,2-epoxycyclohexane (37). 

Regioselective bromination of phenols gave 2-bromo-, 4-bromo-, 2,6-dibromo-, 2,4-dibromo, 2-bromo-6-substituted, 4-bromo-2-substituted and 2,4-dibromo-6-substitutgd phenols, respectively. Especially, 2-bromo-, 2,6-dibromo- and 2-bromo-6-substituted phenols which were prepared via long steps, were obtained in NBS-amine (primary and secondary) system in high yields under ordinary conditions. The scope and their mechanisms were discussed. 

The distribution of the products was only slightly influenced by the added amount of the amine in the bromination. Even a 0.1 molar amount of diisopropylamine was sufficiently effective. From these results, it was concluded that the amine worked catalytically in the selective orf/io-bromination of phenol. Regioselective bromination of phenol was summarized in Scheme 2. 

STEREOSPECIFIC AND 100 % REGIOSELECTIVE BROMINATION OF A MODERATELY CONJUGATED OLEFIN... 

Al-Bromosuccinimide is also a highly regioselective brominating agent at other positions, including positions a to a carbonyl group, to a C=C triple bond, and to an aromatic ring (benzylic position). When both a double and a triple bond are in the same molecule, the preferred position is a to the triple bond. ... 

Porco s route to (—)-kinamycin C (3) began with 2,5-dihydroxybenzaldehyde (38), which was elaborated to the enone 35 by the sequence shown in Scheme 3.6. Regioselective bromination [25] followed by methylation and reduction of the aldehyde function afforded the primary alcohol 39. The alcohol 39 was dearomatized by treatment with bis(acetoxy)iodobenzene, to afford the quinone monoketal 41. Transketalization with 1,3-propanediol followed by silylation of the primary alcohol generated the silyl ether 42 in 72 % yield over three steps. 

Some time ago, Holliman and co-workers illustrated a method for synthesizing polysubstituted phenazines by reductive cyclization of o-nitrodiphenylamine. However, the yield was poor when competitive cyclizations occurred <70CC1423>. Recently, Kamikawa and co-workers reported a more efficient method to synthesize phenazines using sequential aniline arylation, which was first introduced by Buchwald <97JOC1264>. Regioselective bromination of o-nitrodiphenylamine 226 with bromine in the presence of sodium bicarbonate yielded 227 which was subjected to the Buchwald conditions to provide the desired phenazine 228 and the eliminated product 229 <00TL355>. The former compound is a proposed intermediate for the synthesis of the radical scavenger benthocyanin A. 

Commercially available 2,5-dibromothiazole can be alternatively generated by bromination of thiazole or 2-bromothiazole [5]. 2,4-Dibromothiazole and 2,5-dibromothiazole are among the most useful building blocks in the synthesis of thiazole-containing molecules. Regioselective bromination was achieved at C(4) when 2-amino-6-trifluoromethoxythiazole (4) was treated with bromine in acetic acid to afford 4-bromobenzothiazole 5 [6],... 

Having appropriate substituents on the imidazole ring, Haseltine et al. were able to carry out a regioselective bromination of l-benzyl-5-methyimidazole in excellent yield [8]. 

Nonetheless, to make imidazole-containing molecules, haloimidazoles may serve as electrophilic coupling partners for the Suzuki reaction. As described in section 9.1, regioselective bromination at the C(4) position could be achieved for a 1,5-dialkylimidazole using NBS in CH3CN. The Suzuki coupling of l-benzyl-4-bromo-5-methylimidazole with phenylboronic acid assembled the unsymmetrical heterobiaryl in 93% yield, whereas the corresponding Stille reaction with phenyltrimethyltin proceeded in only moderate yield (51%) [8]. 

Analogously, 5-tributylstannylimidazole 29 was easily obtained from the regioselective deprotonation of 1,2-disubstituted imidazole 28 at C(5) followed by treatment with tributyltin chloride [24]. In the presence of 2.6 equivalents of LiCl, the Stille reaction of 29 with aryl triflate 30 afforded the desired 1,2,5-trisubstituted imidazole 31 with 2,6-di-tert-butyl-4-methylphenol (BHT) as a radical scavenger. Reversal of the nucleophile and electrophile of the Stille reaction also provided satisfactory results. For example, the coupling reaction of 5-bromoimidazole 33, derived from imidazole 32 via a regioselective bromination at C(5), and vinylstannane 34 produced adduct 35 [24],... 

The required arylamine 921 was prepared in a straightforward manner starting from commercial 3-methylveratrole (789). Regioselective bromination of the veratrole 789 afforded the 4-bromo derivative 790 in 88% yield. Halogen-metal... 

Oxidation of 3-formyl-6-methoxycarbazole (97) with manganese dioxide and potassium cyanide in methanol afforded methyl 6-methoxycarbazole-3-carboxylate (104). Regioselective bromination of 97 afforded the 5-bromocarbazole 1031. Cleavage of the methyl ether to 1032, followed by nickel-mediated prenylation, provided micromeline (100) (547) (Scheme 5.154). 

Regioselective bromination of the pyrrolocarbazole 1157 with NBS led to the bromocarbazole 1158, which, on halogen-metal exchange with butyllithium and... 

Borowiak, T., Kubicki, M., Wysocka, W. and Przybyl, A. 1998. Regioselective bromination of multiflorine and structures of 3-bromomultiflorine and its molecular complex with succinimide. Journal of Molecular Structure, 442 103-113. 

Regioselective bromination of polyenes.1 The first steps in a biomimetic synthesis of concinndiol (4) from methyl geranylgeranate (2) involve regioselective bromination with 1 followed by cyclization with AgOAc in HOAc to 3 in 20% overall yield. 

Other highly regioselective brominating reagents are chlorotrimethylsilane/lith-ium bromide and hexamethyldisilane/pyridinium perbromide.88 An outline mechanism of the former reaction is formulated below and a preparative example is given in Expt 5.56. 

In contrast to the parent compound, activated quinolines undergo high yielding, regioselective bromination. 

Fig. 5.13, Regioselective bromination of a benzene derivative that contains a strong acceptor and a weak donor substituent.

Regioselective bromination. This reagent is superior to NBS for bromination of pyrrole to provide 2-bromopyrrole. After conversion to the N-boc derivative,... 

Regioselective bromination of 2-fluoroaniline is attained by DBDMH in DMF (equation 99)730. 

Lithium enol ethers of methyl / ,/ -unsaturated ketones are quenched by NBS to yield regioselective bromination of the methyl group (equation 135)918 ... 

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