L,6-Dibromo-2-naphthol

Further bromination of 3,4,6-tribromo-5-hydroxybenzo[6]thio-phene affords the 2,3,4,6-tetrabromo derivative in the absence of acetate ion, and 3,4,4,6-tetrabromo-4,5-dihydrobenzo[6]thiophen-5-one in the presence of acetate ion. 421 On treatment of 3,4-dibromo-, 4,6-dibromo-, 3,4,6-tribromo-, or 2,3,4,6-tetrabromo-5-hydroxybenzo-[6]thiophene with nitric acid in acetic acid, the corresponding unstable orange crystalline 4-bromo-4-nitro-4,5-dihydrobenzo[6]thio-phen-5-one is obtained.152,421 Hence, once both positions ortho to the hydroxyl group in 5-hydroxybenzo[6]thiophene are occupied by bromine, the properties of these compounds are analogous to the properties of l-bromo-2-naphthol which, on bromination in acetic acid in the presence of acetate ion, affords l,l-dibromo-l,2-dihydro-naphthalen-2-one whereas, in its absence, it affords l,6-dibromo-2-naphthol.616 The behavior of l-bromo-2-naphthol and its derivatives on nitration is similar to that of 4,0-dibromo-5-hydroxybenzo[6]thio-phene and its derivatives.162,616... 

Figure 15 shows the absorption spectra of several 1- and 2-naphthol derivatives. The very broad absorption band of 5-cyano-1-naphthol looks like a red-shifted 1-naphthol spectra where the spectrum of l,6-dibromo-2-naphthol resembles the two-band absorption spectrum of 2-naphthol shifted to the red by about 20 nm. The broad absorption spectrum of 1-naphthol is retained in the absorption spectra of l-naphthol-3,6-disulfonate, but the spectrum becomes much more structured. In contrast, the familiar spectral features of 2-naphthol become blurred in the case of 2-naphthol-6,8-disulfonate and l,6-dibromo-2-naphthol, which are considerably red-shifted and appear wider and almost featureless. In fact, the two spectra resemble each other more than they resemble the spectrum of either the parent 2-naphthol molecule or the 1-naphthol isomer. In addition, no clear correlation exists between the shape of the spectra and the pK of the photoacid, the three 2-naphthol derivatives and l-naphthol-3,6-disulfonate all having a p that falls within 1 pK unit... 

Scheme 16 Site-selective cross-coupling of l,6-dibromo-2-naphthol...

We will not go through every detail of the synthesis. Suffice it to say that the known l,6-dibromo-2-naphthol (102) was first converted to )8-ketoester... 

FIGURE 15. Absorption spectra at 20 °C of 5-cyano-l-naphthol (5C1N), l-naphthol-3,6-disulfonate (3,6DS1N), 2-naphthol-3,6-disulfonate (3,6DS2N), 2-naphthol-6,8-disulfonate (6,8DS2N) and 1,6-dibromo-2-naphthol (l,6DBr2N) measured in water at acidic pH values from 4 to 7 ... 

In 1997, Kobayashi and colleagues reported the first truly catalytic enantioselective Mannich-type reactions of aldimines 24 with silyl enolates 37 using a novel chiral zirconium catalyst 38 prepared from zirconium (IV) fert-butoxide, 2 equivalents of (R)-6,6 -dibromo-l,l -bi-2-naphthol, and N-methylimidazole (Scheme 13) [27, 28], In addition to imines derived from aromatic aldehydes, those derived from heterocyclic aldehydes also worked well in this reaction, and good to high yields and enantiomeric excess were obtained. The hydroxy group of the 2-hydroxyphenylimine moiety, which coordinates to the zirconium as a bidentate ligand, is essential to obtain high selectivity in this method. 

The Stacker reaction has been employed on an industrial scale for the synthesis of racemic a-amino acids, and asymmetric variants are known. However, most of the reported catalytic asymmetric Stacker-type reactions are indirect and utilize preformed imines, usually prepared from aromatic aldehydes [24]. A review highlights the most important developments in this area [25]. Kobayashi and coworkers [26] discovered an efficient and highly enantioselective direct catalytic asymmetric Stacker reaction of aldehydes, amines, and hydrogen cyanide using a chiral zirconium catalyst prepared from 2 equivalents of Zr(Ot-Bu)4, 2 equivalents of (R)-6,6 -dibromo-1, l -bi-2-naphthol, (R)-6-Br-BINOL], 1 equivalent of (R)-3,3 -dibromo-l,l -bi-2-naphthol, [(R)-3-Br-BINOL, and 3 equivalents of N-methylimida-zole (Scheme 9.17). This protocol is effective for aromatic aldehydes as well as branched and unbranched aliphatic aldehydes. 

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