Naphthol derivatives, addition with

Collier et al. (10) demonstrated that HPLC was an effective technique for the separation of aromatic hydrocarbon metabolites in exposed marine organisms. Radioactive bioconversion products were studied in liver and gall bladder of coho salmon dosed with H-naphthalene. Quantitative identifications of glucuronide, sulphate, dihydrodiol, glycoside, and 1-naphthol derivatives were obtained. Three additional polar compounds of unknown structure were found. A typical HPLC profile is shown in Figure 2. 

The first systematic investigations of the catalytic Friedel-Crafts-type reaction with alcohols and olefines were performed by Yamamoto and colleagues. After reporting the development of a Pd-catalyzed method for the allylation of different naphthol derivatives [24], the authors used Mo(CO)g for the Friedel-Crafts-type alkylation of electron-rich arenes with allyl acetates [25], The same molybdenum catalyst was additionally used for a Friedel-Crafts-type alkylation of arenes using 1-phenylethanol and styrene as alkylating reagents [26], However, Mo(CO)g is toxic and must be handled under strictly inert conditions. Thus, more stable Lewis acids were necessary. 

Naphthol derivatives with an acrylic pendant (251) undergo a conjugate addition of Grignard reagents, catalysed by Cu(I)-(254). The resulting magnesium enolate (252) can be oxidatively coupled in situ by copper(II) to afford spirocyclic cyclohexenones (253) in >20 1 dr and <94%... 

On the other hand, Yang etal. [33] have developed an organocatalyzed enantioselective FC-type addition reaction of 2-naphthol 212 with p,y-unsaturated a-ketoesters 209 using a cinchona alkaloid-derived thiourea catalyst 213 (Scheme 2.30). The resulting product 214 is in rapid equilibrium with the cyclic hemiketal 215, which was dehydrated with a catalytic amount of concentrated H SO in a one-pot fashion, providing the naphthopyran derivatives 216 with moderate to good yields (51-91%) and enantioselectivities (57-90% ee). 

A solvent-free synthesis of substituted spiroindolinonaphth[2,l-fo][l,4]oxazines through condensation of 2-methylene-l,3,3-trimethylindoline derivatives with 1-nitroso-2-naphthol under microwave irradiation has been described by Fedorova and colleagues (Scheme 6.263) [453], In a typical reaction, an equimolar mixture of the two starting materials was irradiated at 65-110 °C for 15 min to produce the desired spiroindolinonaphth[2,l-fo][l,4]oxazines, which are useful as photochromic compounds. In a related procedure, addition of morpholine to the reaction mixture led to the formation of the corresponding 6 -amino-functionalized spiroindolino-naphth[2,l-fo][l,4]oxazines, which exhibit a strong hypsochromic color shift (not shown) [453]. 

The reaction with the siloxy derivative 29 is an interesting example because the product 30 is a 1,5-dicarbonyl derivative (Equation (36)).96 1,5-Dicarbonyls are classically prepared by a Michael addition, but the synthesis of 30 by a Michael addition is not possible because it would require addition to the keto form of 1-naphthol. The acetoxy derivative 31 resulted in a different outcome, leading to the direct synthesis of the naphthalene derivative 32 (Equation (37)).96 In this case, the combined C-H activation/Cope rearrangement intermediate was aromatized by elimination of acetic acid before undergoing a reverse Cope rearrangement. 

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. 

Stereoselective chelate-controlled addition of Grignard reagents to tetrahydrooxepine derivatives (Equation 3) involves Zr-catalyzed kinetic resolution with (i )-[EBTHI]Zr-BINOL (BINOL= l,l -bi-2-naphthol) <1996JA4291, 1997JA6205, 1999JOC854>. 

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