Tetralone derivatives

Superacids such as HF-SbF effect cyclo alkylation of aryl alkyl ketones to give tetralone derivatives (58). Tandem iatramolecular cyclo alkylatioas can be achieved when functional groups are located ia close proximity (59). 

The diastereoselective addition to imines proceeds well with aromatic enolsi-lanes (249). Propiophenone- and tetralone-derived enolsilanes provide good levels of diastereoselectivity (>95 5) and excellent enantioselectivity (>98% ee) with selective formation of the anti diastereomer. Nonaromatic enolsilanes are somewhat less selective although cyclohexanone enolsilane still provides useful levels of diastereoselectivity and enantioselectivity (92 8 anti/syn and 88% ee at -78°C). A one-pot procedure using glyoxylate, sulfonamide, and enolsilane as coupling partners was developed subsequently, leading to the product in comparable yields and selectivities (250, 251). 

Aboul-Enein, H.Y. and Ali, I., A comparative study of the enantiomeric resolution of several tetralone derivatives on macrocyclic antibiotic chiral stationary phases using HPLC under normal phase mode, Pharmazie, 334, 258, 2001. 

It has been suggested that the benzo[c]furan (245) is formed from the tetralone derivative (244) on treatment with o-phthalaldehyde in acetic acid-sulfuric acid (71JCS(C)2175). 

MeCN-water-AcOH 60 40 0.03 Tetralone derivatives Chiralpak AD-R... 

O. 5 mL/min flow rate was found suitable for this study. It is interesting to note that there was no improvement in resolution when the flow rate was decreased below 0.5 mL/min. In another study, Aboul-Enein and Ali [94] optimized the chiral resolution of certain tetralone derivatives (Fig. 18) on a Chiralpak AD-RH CSP. The results of these findings are given in Table 6, where kx and k2 are, respectively, negative and positive retention factors. Similarly, the flow rates were varied from 0.5 mL/min to 2.0 mL/min. It was observed that the 0.5 mL/min flow rate was suitable for the chiral resolution of most of the derivatives. All the tetralone derivatives studied resolved completely at 0.5 mL/min when water-acetonitrile-triethylamine (50 50 0.03, v/v/v) served as the mobile phase. However, partial resolution of tetralone derivative IV was observed at 0.5 mL/min when water-acetonitrile-acetic acid (60 40 0.03, v/v/v) was the mobile phase. This study shows that the optimization of chiral resolution can be achieved by adjusting the flow rate. 

FIGURE 18 Chemical structures of econazole, miconazole, sulconazole, tetralone derivatives, and aromatase inhibitors. 

TABLE 6 Effects of Flow Rate and Substituents on the Chiral Resolution of Tetralone Derivatives (Fig. 18)... 

FIGURE 4.5 Chromatograms of (a-e) tetralone derivatives on ristocetin A CSP using hexane-ethanol-TEA (12 8 02, v/v/v), (f) 3-amino-3-phenyl propionic acid [methanol-water (60 40, v/v)], (g) midodrine [methanol-1% triethyl ammonium acetate buffer, pH 7 (20 80, v/v)], (h) A-FMOC-glycy 1-arginine [methanol-water (60 40, v/v)], (i) thyroxine [methanol-1% triethyl ammonium acetate buffer, pH 7 (20 80, v/v)], (j) trihexyphenidyl [methanol-1% triethyl ammonium acetate buffer, pH 7 (20 80, v/v)] and (k) verapamil [methanol-1% triethyl ammonium acetate buffer, pH 7 (20 80, v/v)] on avoparcin CSP (From Refs. 8 and 14.)... 

There are also a few examples of poly-amino add catalyzed epoxidation of non-linear enones. These indude tetralone derivatives 47, which can be epoxidized with good yields and enantiomeric excesses the best results were achieved for R = p-02N-QH4 and n = 1 (85% 96% ee) [84]. Other examples are the epoxidation of "iso-chalcone 48 (78% 59% ee) [69] or of bis-benzylidene cyclohexanone 49, which affords the corresponding bis-epoxide of good optical purity [69]. 

LXXXVin gave the tetralone derivative LXXXIX in 99% yield. A modification of the phosphorus oxychloride method was used to cyclize... 

Denny (5) prepared 5-substituted tetralone derivatives, (VII), which were effective as farnesyl transferase inhibitors, and used for treating uncontrolled or abnormal tissue proliferation such as in cancer. 

In the laboratory of J.D. White, the asymmetric total synthesis of (+)-codeine was accomplished. The Robinson annulation was the method of choice to build a phenanthrenone precursor starting from a substituted tetralone derivative. As it is usuaiiy the case, the isolation of the Michael adduct allowed the intramolecular aldol reaction to proceed cleanly and to afford a higher yield of the annulated product. 

Superacids such as HF-SbFs have been used to cyclize alkyl phenyl ketones to the corresponding tetralone derivatives in good yield, as shown by the example in equation (111), ... 

I n 1993, the first cinchona-catalyzed enantioselective Mukaiyama-type aldol reaction of benzaldehyde with the silyl enol ether 2 of 2-methyl-l -tetralone derivatives was achieved by Shioiri and coworkers by using N-benzylcinchomnium fluoride (1, 12 mol%) [2]. However, the observed ee values and diastereoselectivities were low to moderate (66-72% for erythro-3 and 13-30% ee for threo-3) (Scheme 8.1). The observed chiral inductioncan be explained by the dual activation mode ofthe catalyst, that is, the fluoride anion acts as a nucleophilic activator of the silyl enol ethers and the chiral ammonium cation activates the carbonyl group of benzaldehyde. Further investigations on the Mukaiyama-type aldol reaction with the same catalyst were tried later by the same [ 3 ] and another research group [4], but in all cases the enantioselectivities were too low for synthetic applications. 

Several other substituted benzophenone systems [li] such as aminobenzophe-nones (Mischler s ketone and others), trimethylsilylbenzophenones, alkylthiobenzo-phenones [156], aryloxy benzophenones [157], maleimidophenoxyl benzophe-nones [158], polycyclic aromatic ketones (such as tetralone derivatives) were shown to exhibit some interesting properties. 

This reaction, similar to the reductions of other cyclic ketones, shows higher selectivity when nonfermenting baker s yeast is used 89,155. Bicyclic /J-keto esters from 1- or 2-tetralone derivatives are also accepted as substrates and are transformed selectively by yeast89,151 153. 

Aza-annulation of a number of dimethoxy-substituted P-tetralone derivatives, such as those represented by 136, with acrylamide was used to produce 137. In turn, 137 was an important intermediate in the synthesis of conformationally restricted congeners of dopamine (eq. 30).53... 

A very low yield (1.2%) of benzodiazocinone (12) is obtained as a minor, undesired side product upon rearrangement of the oxime generated in situ from a tetralone derivative (Equation (17)) <86JHC975>. The Tiemann rearrangement allows the preparation of perhydro-l,3-diazocin-2-one (22) <83JOC1694>, while a modification of this rearrangement provides cyclic carbodiimide (7), also prepared by mercuric oxide oxidation of 2-thione derivative (14) (Scheme 12) <83JOCl694>. 

Asymmetric epoxidation of tetralone-derived enones can be accomplished using the immobilized synthetic peptide poly-L-Ieucine (i-PLL), urea-peroxide, and DBU in a medium of isopropyl acetate. Yields are variable and substrate-dependent, but can be quite good, as... 

A soln. of startg. N-protected (S)-phenylalanine in 1,2-dichloroethane treated with PCI5 at 0, stirred at 0° for 30 min then at room temp, for 16 h, the soln. added dropwise within 1 h to a suspension of AICI3 same solvent, stirred for a further 24 h at room temp., and worked up at 0° - (S)-2-phthalimido-l-indanone. Y 83%. Other Lewis acids were ineffective. Reaction proceeds with retention of chirality. F.e. incl. tetralone derivs. s. F. Effenberger et al., Chem. Ber. 727, 125-30 (1988) inter-molecular process s. ibid. 117-23. 

Optically active cobalt(ii) complexes have been used as catalysts for the enan-tioselective borohydride reduction of aromatic ketones employing pre-modified borohydride. A DKR was observed for the reduction of a 2-ethoxycarbonyl-1-tetralone derivative using pre-modified borohydride arising from NaBH4, tetrahydrofurfuryl alcohol (THFA) and ethanol (Scheme 2.72). 

The reaction has been extended to synthesis of tetralone derivatives. Thus treatement of 31 with polyphosphoric acid leads to the substituted 3-tetralone 32, which can be also converted to l-phenyl-3-aminotetraline 33 providing a complementary synthetic route to that one for 30 illustrated above. 

The tetralone derivatives produced by the Haworth reaction are important synthetic intermediates. However, in Haworth s original work, his efforts were directed toward the synthesis of phenanthrene fi-om naphthalene. Thus the synthesis of tetralone derivative 12 by the standard Haworth conditions is followed by a Clemmensen " or Wolff-Kishner reduction of the ketone... 

The Haworth synthesis of tetralone derivatives has found substantial utility in natural product and small molecule synthesis. Zubaidha and co-workers performed the Haworth reaction on 2-methylanisole (15) to yield 18 as an intermediate in the synthesis of ( )-heritol (19), a potent itchthyotoxin. Beginning with 15, acylation to yield 16 is followed by the Clemmensen reduction to produce 17. Subsequent intramolecular Friedel-Crafts acylation results in the formation of tetralone 18. Ferraz and coworkers have also synthesized 18 in the same manner as an intermediate for the synthesis of ( )-mutisianthol (20), a potential antitumor agent. In addition, this substrate 18 has been used for the synthesis of various a-tetralols as substrates for enzymatic resolution studies. ... 

The Haworth phenanthrene synthesis has been extensively used in the synthesis of derivatives of chrysene,an environmental pollutant which exhibits tumorigenic and mutagenic properties. For example Harvey and coworkers treated 61 with succinic anhydride under Friedel-Crafts conditions to produce 62. Reduction of the ketoacid under Wolff-Kishner conditions is followed by esterification to yield 63. Dehydrogenation of 63 is followed by saponification to yield carboxylic acid 64. Intramolecular Friedel-Crafts acylation produces tetralone derivative 65, which undergoes carbonyl reduction and dehydrogenation to produce 66. 

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