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Journal of the Brazilian Chemical Society

Print version ISSN 0103-5053

J. Braz. Chem. Soc. vol.16 no.6a São Paulo Nov./Dec. 2005

http://dx.doi.org/10.1590/S0103-50532005000700012 

ARTICLE

 

Thallium trinitrate-mediated ring contraction of 1,2-dihydronaphthalenes: the effect of electron-donating and electron-withdrawing groups

 

 

Luiz F. Silva Jr.*; Raquel M. F. Sousa; Helena M. C. Ferraz*; Andrea M. Aguilar

Instituto de Química, Universidade de São Paulo,CP 26077, 05513-970 São Paulo-SP, Brazil

 

 


ABSTRACT

The oxidation of a series of 1,2-dihydronaphthalenes substituted in the aromatic ring was investigated with thallium trinitrate (TTN) in methanol or in trimethylorthoformate (TMOF) as solvent. In all cases, indans are produced, although the yield varied from excellent to poor, depending on the structure of the substrate. The presence of an electron-donating group in the substrate favors the rearrangement, whereas significant amounts of glycolic derivatives, as well as naphthalenes, were obtained in the oxidation of 1,2-dihydronaphthalenes bearing electron-withdrawing groups, such as Br and NO2. Mechanisms for the formation of each of these products are proposed.

Keywords: ring contraction, oxidation, indans, thallium(III)


RESUMO

A oxidação de uma série de 1,2-diidronaftalenos, substituídos no anel aromático, foi investigada com trinitrato de tálio (TTN) em metanol ou em trimetilortoformiato (TMOF) como solvente. Em todos os casos, indanos foram formados, embora o rendimento tenha variado de excelente a baixo, dependendo da estrutura do substrato. A presença de um grupo doador de elétrons no substrato favorece o rearranjo, enquanto que uma quantidade significativa de derivados glicólicos, bem como naftalenos, foi obtida na oxidação de 1,2-diidronaftalenos com um grupo retirador de elétrons, tais como Br e NO2. Mecanismos para a formação de cada um destes produtos foram propostos.


 

 

Introduction

The indan moiety constitutes the core of several molecules with important biological activity.1 Thus, a great effort has continuously been made toward the synthesis of such a class of compounds.2 A typical approach to obtain functionalized indans is the selection of a suitable 1-indanone as starting material, which is then elaborated into the desired target molecule.3 Considering that 1-tetralones are easily accessible and usually significantly cheaper than the corresponding 1-indanones, we initiated some years ago the development of short routes for the transformation of 1-tetralones into several types of functionalized indans, using a thallium(III)-promoted ring contraction as the key step.4-9 One of these approaches is the thallium(III)-mediated rearrangement of 1,2-dihydronaphthalenes, which are easily obtained from 1-tetralones by a reduction/dehydration sequence.6 Treatment of olefins, such as 1 (Scheme 1), with thallium trinitrate (TTN) in trimethylorthoformate (TMOF) gave indans in good yields, together with glycolic derivatives as minor components. However, trisubstituted alkenes, such as 4, led only to the addition product 5 (Scheme 1). Remarkably, this ring contraction is diastereoselective, leading exclusively to trans-1,3-disubstituted indans, when a 1-methyl-1,2-dihydronaphthalene is used as starting material.6 The efficiency of this selective reaction has recently been demonstrated in a short total synthesis of the sesquiterpene mutisianthol (Scheme 2).9 Furthermore, during our studies toward the synthesis of this natural product, we found that olefins bearing a methoxy group in para to the migrating carbon, such as 6, lead to the ring contraction product in nearly quantitative yield. This effect was rationalized considering that the methoxy group in para increases the migratory aptitude of the migrating carbon (8a in 7) by mesomeric effect, favoring the rearrangement (Scheme 2).8,9

 

 

 

 

Although several aspects of the oxidation of 1,2-dihydronaphthalenes with thallium trinitrate have been disclosed, the substituents in the aromatic ring have been restricted to methyl and/or methoxy groups (1 and 6, for example).6,8,9 Considering that indans substituted in the aromatic ring by groups such as halogens,10-14 hydroxy,15-17 nitro,15,18 acetamido,19 dimethyl,20 and dimethoxy14,17,20,21 are also important building blocks in organic synthesis, we decided to investigate further our approach based on the ring contraction reaction. The present article describes a detailed study of the TTN-mediated oxidation of 1,2-dihydronaphthalenes bearing different groups in the aromatic ring (Me, OMe, OH, NH2, NHAc, Br and NO2), better defining the scope of this reaction, which will facilitate future applications. In addition, a more clear picture of the mechanism of the thallium(III)-mediated oxidation of olefins could be drawn based on the new results.

 

Results and Discussion

Preparation of 1,2-dihydronaphthalenes

The transformation of the 1-tetralones 9 to 15 into the corresponding 1-tetralols was performed using NaBH4 (Table 1). The tetralols were then dehydrated under acidic conditions, for which two procedures were used. The first was the treatment of the alcohol with H3PO4 in THF, whereas the second was the use of a catalytic amount of p-TsOH in benzene or toluene. Table 1 summarizes the results obtained in the synthesis of 1,2-dihydronaphthalenes 16-22 from 1-tetralones 9-15.

 

 

The transformation of a tetralol into the corresponding 1,2-dihydronaphthalene may be troublesome. The preparation of 24 exemplifies well this statement, because when the dehydration step was performed with H3PO4, the reaction was not reproducible, leading in some runs to the desired product 24 and in others to the dimer 25. Thus, to obtain the necessary amount of the required substrate, it was preferable to use p-TsOH, although under this condition the olefin 24 was obtained together with the dimer 25 (Scheme 3). The dimerization can be rationalized by the formation of the benzylic carbocation 26, which then reacts with the formed olefin leading to the dimer 25, after losing a proton (Scheme 4). The positive charge in 26 is stabilized by the methoxy group of the carbon 6 through a mesomeric effect. Presumably, this stabilization makes the dimerization easier in the formation of 24 than in the other 1,2-dihydronaphthalenes, where a similar mesomeric effect is not present. Nevertheless, this dimerization could be overcome in the preparation of other similar olefins.8,9

 

 

 

 

Oxidation of 1,2-dihydronaphthalenes with thallium trinitrate

With a representative number of differently substituted 1,2-dihydronaphthalenes in hands, we were in position to investigate their behavior toward the oxidation with thallium(III). As shown in Table 2, the reaction of the olefins with TTN led in all cases to the ring contraction product, although the yield varied from excellent to poor. Addition and aromatization products were also formed in some cases. The reason for this variation is discussed on the following paragraphs for each substrate, based on the mechanism of the rearrangement of olefins mediated by thallium(III),22 which is exemplified for the 1,2-dihydronaphthalene (50) in Scheme 5. The first step in this mechanism is the formation of the thallonium ion 51, which gives the trans oxythallated adduct 52, after a ring-opening in a Markovnikov sense.23 The rearrangement takes place in this intermediate, giving the acetal 54, after addition of methanol to the oxonium 53, followed by deprotonation.

 

 

Treatment of the olefin 24, which bears two methoxy groups, with TTN gave the ring contraction product 27, as the only isolated product, in excellent yield (Table 2, entry 1). This result shows that the behavior of 24 is similar to 6, as expected.

The reaction of the olefin 16 with TTN gave the indan 28, in very good yield. However, in this case, the addition product 29 was also obtained as a minor component (entry 2). The high yield of the ring contraction can be explained considering the well-known hyperconjugative effect of the methyl groups, which increases the migratory aptitude of the migrating carbon.

In our previous studies, when a trisubstituted olefin was treated with TTN in methanol, the formation of the ring contraction product has not been observed (see, for example, Scheme 1).6 However, the reaction of the trisubstituted olefin 55 with TTN in TMOF led to the indan 56, together with the addition products 57 and 58 (Scheme 6). This result shows that the presence of an electron-donating group indeed favors the rearrangement, partially changing the course of the oxidation of trisubstituted olefins by thallium(III). Another reason for the different behavior of 4 and 55 could be the modification of the solvent, because higher yields of the ring contraction products have been obtained for similar reactions in TMOF than in MeOH.6 The relative configuration of the compound 58 was assigned by comparison with the NMR data of similar compounds.24,25 The cis relationship of the hydroxy and the methoxy groups in 57 was analogously suggested.

 

 

The behavior of the 8-hydroxy-1,2-dihydronaphthalene 17 toward the oxidation with TTN in methanol (Table 2, entry 3) was somewhat similar to that of the olefins bearing a methoxy group in meta to the migrating carbon, such as 1 (Scheme 1), because the indan 30 was obtained in good yield, together with the product of addition of methanol 31. However, the yield of the ring contraction product was lower from 17, probably due to the instability of 30. An interesting aspect concerning the reaction of 17 with thallium(III) is that the oxidation of the phenol moiety, which has already been described,26 was not observed. For olefin 17, the ring contraction product was obtained in higher yield using methanol instead of TMOF. Thus, the oxidation of the following substrates was also examined in methanol.

The reaction of the nitrogenated 1,2-dihydronaphthalenes 18 and 19 with thallium(III) was then investigated. Considering the studies of Michael and Nkwelo concerning the thallium(III)-promoted cyclization of unsaturated nitrogenated compounds,27 we anticipated that difficulties would appear in the reaction of 18 and 19 with thallium(III). When TTN was added to the solution of 18 in methanol, the mixture immediately became black, which has never been observed in our long experience with thallium chemistry. TLC analysis showed a single spot corresponding to the starting material, even after more than 12 hours at room temperature. Later, NMR analysis showed that the resulting black oil consisted of the starting amine 18 impure, contaminated with other products formed by the easily oxidated amine moiety. On the other hand, the corresponding acetyl amide 19 reacted with TTN giving the ring contraction product 32 in moderate yield, together with addition (33 to 35) and aromatization (36) products (Table 2, entry 4).

Next, the TTN-mediated oxidation of the bromo alkenes 20 and 21 (entries 5 and 6, respectively) was performed. For these substrates the ring contraction product was obtained in modest yields (35-37%). Using a substrate with a more powerful electron-withdrawing group, the nitro alkene 22, the indan was obtained in even lower yield (entry 7). These results shows that the yield of the ring contraction products lowers as the electron-withdrawing power of the substituent in meta to the migrating carbon is increased, because its migratory aptitude is decreased.28 Other products formed in the oxidation of olefins 20-22 were those of the addition of two molecules of methanol (38, 42, 43 and 47), of the addition of methanol and nitrate (39, 44 and 48) and of aromatization (40, 45 and 49).

The results shown in Table 2 allowed additional conclusions. First, comparing the reaction times and temperatures (see, for example, entries 1, 5 and 7), it is possible to conclude that the presence of an electron-withdrawing group in the aromatic ring makes the oxidation of the double bond by thallium(III) slower. Presumably, the electron density of the double bond is decreased by the electron-withdrawing group, which would decrease the rate of the electrophilic addition step. There is also a clear correlation between the rate of oxidation and the yield of the ring contraction product. In fast oxidations, the yields are usually high (compare, for example, entries 1 and 7). This trend has also been observed in previous works.6,7

Second, in the formation of the addition products of methanol the trans diastereomer was formed either as the major compound (entries 4 and 6) or exclusively (entries 2, 3, 5 and 7). A similar selectivity has also been observed in the oxidation of cyclohexene with thallium triacetate (TTA) in anhydrous AcOH,23,29,30 whereas in the presence of water the cis diastereomer predominated.22 Moreover, 3-t-butylcyclohexene gave exclusively a trans diol, when treated with thallium(III) sulfate.31 The cis glycolic derivatives were obtained in the reaction of chromens with TTN32 and of steroidal olefins with TTA.33 In summary, the diastereoselectivity of the thallium(III)-mediated addition of nucleophilic species to cyclic olefins can not be easily predicted, because it depends on either the structure of the substrate or on the reaction conditions. Based on these previous works, a mechanism for the formation of the cis and trans isomers was proposed, as exemplified for the olefin 21 in Scheme 7. In the formation of the trans isomer, the oxythallated aduct 59 would originate the oxonium ion 60, by a reductive intramolecular displacement of the thallium(III). Addition of a second molecule of the solvent would give the trans-1,2-dimethoxylated isomer 42, after deprotonation. The cis isomer 43 would be produced directly from 59 by an intermolecular displacement of the thallium(III) by the methanol, followed by deprotonation.

 

 

The indans and the dimethoxylated addition products have a quite similar 1H NMR spectrum. However, these compounds can be easily distinguished by 13C NMR, where the signal around 107 ppm indicates the presence of the acetal unit of the ring contraction product, whereas for the addition products, two signals between 75 and 80 ppm are present. During the development of this work and others,6,8,9 a large number of indans, as well as cis- and trans-addition products, were obtained, which allowed us to find an easy way to differentiate this kind of compounds by 1H NMR. This was achieved after tabulating the coupling constants corresponding to the doublets of the hydrogen of the benzylic C1 carbon for the addition products and of the acetal for the indans. The coupling constants of the mentioned hydrogens of all these compounds fall in a very restricted and characteristic range. The coupling constant of the hydrogen of the acetal moiety is the highest of the three kinds of products (7.5 Hz). A similar value was found by Antus et al. for structurally related acetals.34 To assign the cis and trans isomers we considered that the coupling constant of the trans isomers should be higher than the cis, based on the well-established Karplus studies. Thus, for the hydrogen of the C1 carbon, the typical value for the cis isomer would be between 2.2 and 3.0 Hz, while for the trans isomer would be between 4.8 and 5.2 Hz (Figure 1). These values agree with that observed for the cis- and trans-1,2-dihydroxy-1,2,3,4-tetrahydronaphthalene and other related cis isomers,35 as well as with the cis-1,2-dimethoxychroman 61 (Figure 2).32 However, the values are not in accord to that determined by Ogibin et al. for the cis- and trans-1,2-dimethoxy-1,2,3,4-tetrahydronaphthalenes.36

 

 

 

 

Nitrate derivatives are not usually produced in the oxidation of olefins with TTN, although a few papers reported the isolation of these compounds.37 The somewhat unexpected formation of the trans-1-nitrate-2-methoxy derivatives 35, 39, 44 and 48 probably occurs from the oxonium ion 62, which reacts with a nitrate anion. These nitrates have a very characteristic signal in the 1H NMR spectrum. The hydrogen of the C1 carbon is deshielded when compared to the corresponding methoxy derivative, appearing as a doublet in ca. 6.0 ppm. The coupling constants, ranging from 4.0 to 4.4 Hz (Scheme 8), allowed us to suggest a trans-relationship between the two substituents (compare with Figure 1).

 

 

Naphthalene derivatives are usually produced in the oxidation of 1,2-dihydronaphthalenes with TTN, when the substrate has a low reactivity (entries 4 to 7, Table 2), as already observed in the oxidation of other 1,2-dihydronaphthalenes.6,7 There are two possible mechanisms to explain the formation of this kind of product, as illustrated for the olefin 22 in Scheme 9. The first would be the allylic oxidation of the 1,2-dihydronaphthalene,38 followed by the acid catalyzed dehydration of 64 (Path a), which is favored by the formation of an aromatic ring. The second possibility would be two consecutives acid-catalyzed eliminations of MeOH in the addition product 47, which would occur through the intermediate 65 (Path b).

 

 

In summary, the reaction of 1,2-dihydronaphthalenes with thallium trinitrate constitutes an efficient entry into indans, providing electron-withdrawing groups are not present in the aromatic ring. Moreover, these indans bear a masked aldehyde moiety, which could be useful for further transformations.

 

Experimental

General

Information concerning general experimental methods was recently published.5 6-Methoxy-4,7-dimethyl-1,2-dihydronaphthalene (55) was prepared according to the procedure described by Zubaidha et al.39

Preparation of 1-tetralones

5-Hydroxy-1-tetralone (10). Under nitrogen, NaH (0.30 g, 7.5 mmol, 60% in mineral oil) was washed with anhydrous hexanes (2 x 1 mL). After a few minutes under nitrogen, anhydrous DMF (3.5 mL) was added. To this mixture was slowly added a solution of EtSH (3.9 mL, 53 mmol) in anhydrous DMF (3.9 mL) at 0 °C and the resulting solution was stirred for 20 min at room temperature. The 5-methoxy-1-tetralone (0.881 g, 5.00 mmol) was then added and the resulting mixture was stirred for 5 h at 140 °C, becoming light yellow. The mixture was cooled to the room temperature and a saturated solution of NH4Cl was added. The mixture was extracted with Et2O and the organic phase was washed with water, with brine, and dried over anhydrous MgSO4. The solvent was removed under reduced pressure and the resulting brown solid was purified by flash chromatography (silica gel 200-400 mesh, 30% AcOEt in hexanes) giving starting material (0.103 g, 0.586 mmol, 12%) and 1040 (0.590 g, 3.64 mmol, 73%), as a yellow-brown solid (mp 208.1-208.2 °C).

7-Amino-1-tetralone (11). To stirred solution of 15 (1.00 g, 5.23 mmol) in MeOH (65 mL) was added 10% Pd/C (0.11 g). The mixture was subjected to 1.5 atm of H2 for 2 h. The mixture was then filtered through a silica gel pad (200-400 Mesh, ca. 10 cm) and the filtrate was concentrated. The residue was purified by flash chromatography (silica gel 200-400 mesh, 50% EtOAc in hexanes) affording 1141 (0.708 g, 4.39 mmol, 84%), as a brown solid (mp: 137.7-137.8 °C), together with 7-amino-1,2,3,4-tetrahydronaphthalen-1-ol (0.0976 g, 0.598 mmol, 11%), also as a brown solid.

7-Acetamido-1-tetralone (12). In a solution of 11 (0.260 g, 1.61 mmol) and DMAP (0.0040 g) in Et3N (4.0 mL) under nitrogen was added Ac2O (0.5 mL). The mixture was stirred for 0.5 h at room temperature. MeOH was added and the solution was concentrated. The reaction was quenched with H2O, extracted with AcOEt, washed with brine, and dried over anhydrous MgSO4. The solvent was removed under reduced pressure giving 1241 (0.326 g, 1.60 mmol, 99%), as a yellow solid (mp 161.0-161.1 °C).

7-Bromo-1-tetralone (13) and 5-bromo-1-tetralone (14). To a three-necked flask equipped with a condenser, with a drying tube in a condenser and a mechanical stirrer terminating in a Teflon paddle, was added anhydrous AlCl3 (7.0 g, 0.050 mol). While the catalyst was stirred, 1-tetralone (3.0 g, 20 mmol) was slowly added providing a viscous brown mixture that was difficult to stir. The mixture was heated at 60 °C and then cooled to 0 °C, becoming easier to stir. Bromine (1 mL; 0.02 mol) was added at 0 °C and the resulting mixture was stirred for 1 h at 80 °C. The mixture was cooled to the room temperature and the resulting brown solid was added in portions to a solution of crushed ice (200 mL) and concentrated HCl (3 mL). More crushed ice was added in portions until a total volume of 500 mL and then concentrated HCl (12 mL). The mixture was stirred for 1 h and extracted with Et2O (four times). The organic phase was washed with water, saturated solution of NaHCO3, with brine, and dried over anhydrous Na2SO4. The solvent was removed under reduced pressure and the resulting residue was purified by flash chromatography (silica gel 200-400 mesh, 15% AcOEt in hexanes) giving the bromo-1-tetralones contaminated with unreacted starting material. These mixtures were submitted to a bulb-to-bulb distillation affording 1442 (1.4 g, 6.2 mmol, 30%), as a brown solid (mp 43.7-43.8 °C), and 1343 (0.96 g, 4.3 mmol, 21%), as a yellow solid (mp 74.7-75.6 °C). The NMR data of the compound 13 have not been reported: 1H NMR (200 MHz, CDCl3) d 2.14-2.19 (m, 2H), 2.65 (t, J 6.14 Hz, 1H), 2.91 (t, J 6.1 Hz, 2H), 7.14 (d, J 7.9 Hz, 1H), 7.56 (dd, J 2.2 and 7.9 Hz, 1H), 8.13 (d, J 2.2 Hz, 1H); 13C NMR (50 MHz, CDCl3) d 22.9, 29.1, 38.7, 120.6, 129.9, 130.6, 134.0, 136.0, 143.1, 196.8.

7-Nitro-1-tetralone (15). The nitration was performed following the procedure described by Zhang and Schuster,44 but the mixture of nitro-tetralones was separated by flash chromatography (silica gel 200-400 mesh, 30% AcOEt in hexanes) giving 1544 (1.51 g, 5.24 mmol, 34%), as pale yellow solid (mp 103.5-103.6 °C) and 5-nitro-1-tetralone44 (0.95 g, 4.99 mmol, 21%), as a pale yellow solid (mp 98.8-98.9 °C). The 13C NMR data of 15 and of 5-nitro-1-tetralone have not been reported. (15): 13C NMR (50 MHz, CDCl3) d 22.2, 29.7, 38.6, 122.5, 127.1, 130.2, 133.4, 147.1, 150.9, 195.9. 5-Nitro-1-tetralone: 13C NMR (50 MHz, CDCl3) d 22.1, 26.3, 38.1, 127.0, 128.8, 132.1, 134.5, 138.4, 149.4, 199.3.

Preparation of 1,2-dihydronaphthalenes

6,8-Dimethyl-1,2-dihydronaphthalene (16). To a stirred solution of 5,7-dimethyl-1-tetralone (0.348 g, 2.00 mmol) in a mixture of anhydrous THF (2 mL) and anhydrous MeOH (6 mL) under nitrogen, was added NaBH4 (0.378 g, 10.0 mmol) in portions at 0 °C. The mixture was stirred for 1 h at room temperature. The reaction was quenched with H2O (7 mL) and a 10% aqueous solution of HCl was added dropwise until pH around 7. The resulting solution was extracted with EtOAc, washed with brine, and dried over anhydrous MgSO4. The solvent was removed under reduced pressure giving 5,7-dimethyl-1-tetralol45 (0.331g, 1.90 mmol, 94%), as a white solid. To a stirred solution of the tetralol (2.19 g, 12.0 mmol) in anhydrous THF (18 mL), was added H3PO4 85% (10 mL). The mixture was heated for 10 min at 80 °C. NaHCO3 was added in portions and then was added a 5% aqueous solution of NaHCO3 until pH around 7. The resulting solution was extracted with EtOAc, washed with brine, and dried over anhydrous MgSO4. The solvent was removed under reduced pressure and the resulting oil was purified by flash chromatography (silica gel 200-400 mesh, 5% EtOAc in hexanes) affording 1646 (1.74 g; 11.0 mmol, 91%), as a pale yellow oil. The NMR data of 16 have not been reported: 1H NMR (300 MHz, CDCl3) d 2.22 (s, 3H), 2.25 (s, 3H), 2.27-2.33 (m, 2H), 2.69 (t, J 8.3 Hz, 2H), 5.97 (dt, J 4.3 and 9.6 Hz, 1H), 6.39 (dt, J 1.8 and 9.6 Hz, 1H), 6.70 (s, 1H), 6.82 (s, 1H); 13C NMR (75 MHz, CDCl3) d 19.1, 20.8, 23.1, 23.2, 124.8, 127.9, 128.2, 129.7, 130.5, 133.8, 134.8, 135.1.

8-Hydroxy-1,2-dihydronaphthalene (17). The reduction was performed following the procedure described for 16, but using 10 (1.72 g, 10.6 mmol), anhydrous THF (11 mL), anhydrous MeOH (32 mL), NaBH4 (2.0 g, 53 mmol) and reaction time of 1 h. The reaction was quenched with H2O. The solvent was removed under reduced pressure giving 5-hydroxy-1-tetralol (1.71 g, 10.4 mmol, 98%), as a white solid. The tetralol (1.29 g, 7.84 mmol) was used without purification in the next step, which was performed using anhydrous THF (12 mL), H3PO4 85% (6.4 mL), and reaction time of 1 h at 80 °C. The resulting solid was purified by flash chromatography (silica gel 200-400 mesh, 40% EtOAc in hexanes) affording 1747 (0.732 g, 5.01 mol, 64%), as white needles (mp 53.3-54.6 °C). The NMR data of 17 have not been reported: 1H NMR (200 MHz, CDCl3) d 2.26-2.37 (m, 2H), 2.75 (t, J 8.0 Hz, 2H), 4.92 (s, 1H), 6.01 (dt, J 4.0 and 9.6 Hz, 1H), 6.46 (dt, J 1.8 and 9.7 Hz, 1H), 6.64 (d, J 7.9 Hz, 2H), 7.01 (t, J 8.0 Hz, 1H); 13C NMR (50 MHz, CDCl3) d 19.5, 22.5, 114.5, 119.2, 120.6, 126.7, 127.6, 128.5, 135.4, 152.1.

6-Amino-1,2-dihydronaphthalene (18). The reduction was performed following the procedure described for 16, but using 11 (0.707 g, 4.38 mmol), anhydrous MeOH (62 mL), NaBH4 (0.22 g, 5.7 mmol), and reaction time of 30 min at room temperature, giving the 7-amino-1-tetralol (0.679 g, 4.16 mmol, 95%) as red-brown solid (mp: 91.7-91.8 °C). The tetralol (0.391 g, 2.45 mmol) was used without purification in the next step, which was performed toluene (36 mL), a few crystals of p-TsOH, and reaction time of 18 h at 130 °C, using a Dean-Stark apparatus. The resulting oil was purified by flash chromatography (silica gel 200-400 mesh, 70% EtOAc in hexanes) affording 18 (0.307 g, 2.12 mmol, 86%), as a gray solid: mp: 43.7-44.5 ºC. IR (KBr) nmax/cm-1: 868, 1442, 1606, 1729; 1H NMR (200 MHz, CDCl3) d 2.22-2.33 (m, 2H), 2.68 (t, J 8.1 Hz, 2H), 3.40-3.49 (m, 2H), 5.97-6.06 (m, 1H), 6.36 (d, J 9.7 Hz, 1H), 6.42 (s, 1H), 6.48 (dd, J 2.2 and 7.5 Hz, 1H), 6.90 (d, J 7.9 Hz, 1H); 13C NMR (50 MHz, CDCl3) d 23.7, 26.6, 113.2, 113.4, 125.8, 127.8, 128.1, 129.1, 134.8, 144.8; m/z 145 (M+, 80%), 144 (100). Anal. Calc. for C10H11N: C, 82.72; H, 7.64; N, 9.65. Found: C, 82.72; H, 7.59; N, 9.92.

6-Acetamido-1,2-dihydronaphthalene (19). The reduction was performed following the procedure above described for 16, but using 12 (0.30 g, 1.48 mmol), anhydrous MeOH (21 mL), NaBH4 (0.073 g, 1.92 mmol), and reaction time of 30 min at room temperature, giving 7-acetamido-1-tetralol (0.26, 1.29 mmol, 87%), as a brown solid: mp: 135.8-136.0 °C. IR (KBr) nmax/cm-1: 1497, 1665, 2938, 3285; 1H NMR (200 MHz, CDCl3) d 1.49-1.99 (m, 5 H), 2.10 (s, 3H), 2.70 (d, J 5.7 Hz, 2H), 4.67 (s, 1H), 7.02 (d, J 8.3 Hz, 1H), 7.38 (d, J 8.34 Hz, 1H), 7.45 (s, 1H), 7.76 (s, 1H); 13C NMR (50 MHz, CDCl3) d 19.0, 24.3, 28.7, 32.2, 68.0, 119.8, 120.0, 129.4, 133.2, 135.9, 139.4, 168.6; m/z 205 (M+, 30%), 43 (100). Anal. Calc. for C12H15NO2: C, 70.22; H, 7.37; N, 6.82. Found: C, 70.01; H, 7.50; N, 6.63.

The tetralol (0.250 g, 1.20 mmol) was dehydrated using toluene (18 mL), a few crystals of p-TsOH, and reaction time of 1 h at 130 °C, using a Dean-Stark apparatus. The resulting oil was purified by flash chromatography (silica gel 200-400 mesh, 50% EtOAc in hexanes) affording 19 (0.191 g, 1.02 mmol, 84%), as a brown solid: mp: 51.2-54.6 °C. IR (KBr) nmax/cm-1: 886, 1497, 1661, 2927, 3430; 1H NMR (200 MHz, CDCl3) d 2.13 (s, 3H), 2.23-2.32 (m, 2H), 2.73 (t, J 8.1 Hz, 2H), 5.97-6.06 (m, 1H), 6.37 (d, J 9.7 Hz, 1H), 7.00 (d, J 7.5 Hz, 1H), 7.19 (s, 1H), 7.19-7.26 (m, 1H), 7.81 (s, 1H); 13C NMR (50 MHz, CDCl3) d 22.3, 23.4, 25.9, 116.9, 117.5, 126.6, 126.7, 128.2, 130.5, 133.6, 135.3, 167.6; m/z 187 (M+, 51%), 43 (100). Anal. Calc. for C12H13NO: C, 76.98; H, 7.00; N, 7.48. Found: C, 76.54; H, 6.93; N, 7.39.

6-Bromo-1,2-dihydronaphthalene (20). The reduction was performed following the procedure described for 16, but using 13 (0.78 g, 3.5 mmol), anhydrous MeOH (25 mL), NaBH4 (0.17 g, 4.5 mmol), and reaction time of 1 h at room temperature. The reaction was quenched with H2O. The solvent was removed under reduced pressure giving 7-bromo-1-tetralol (0.77 g, 3.4 mmol, 98%) as a solid (mp 57.7-58.6 °C). The tetralol (0.62 g, 2.7 mmol) was used without purification in the next step, which was performed using toluene (12 mL), p-TsOH (0.05 g, 0.27 mmol), and reaction time of 15 min at 130 °C. The mixture was cooled to the room temperature and washed with 10% aqueous solution of NaHCO3, with brine, and dried over anhydrous Na2SO4. The solvent was removed under reduced pressure giving 2042 (0.52 g, 2.5 mmol, 91%), as light brown oil. The 13C NMR data of 20 have not been reported: (75 MHz, CDCl3) d 23.0, 26.9, 119.8, 126.7, 128.5, 129.0, 129.4, 130.1, 134.2, 136.0.

8-Bromo-1,2-dihydronaphthalene (21). The reduction was performed following the procedure described for 16, but using 14 (0.30 g, 1.3 mmol), anhydrous MeOH (6.7 mL), and NaBH4 (0.07 g, 1.7 mmol), giving 5-bromo-1-tetralol (0.10 g, 0.44 mmol, 98%), as white needles (mp: 64.7-65.9 °C). The tetralol (0.34 g, 1.5 mmol) was used without purification in the next step, which was performed using benzene (3.4 mL), p-TsOH (0.03 g, 0.15 mmol), and reaction time of 15 min at 80 °C. The mixture was cooled to the room temperature and washed with 10% aqueous solution of NaHCO3, with brine, and dried over anhydrous MgSO4. The solvent was removed under reduced pressure giving 2142 (0.29 g, 1.4 mmol, 92%), as yellow oil. The 13C NMR data of 21 have not been reported: (75 MHz, CDCl3) d 23.1, 27.0, 124.3, 125.4, 127.6, 127.8, 129.6, 131.2, 134.9, 136.4.

6-Nitro-1,2-dihydronaphthalene (22). The reduction was performed following the procedure described for 16, but using 15 (0.51 g, 2.7 mmol), anhydrous MeOH (25 mL), NaBH4 (0.13 g, 3.5 mmol), and reaction time of 1.5 h at room temperature, giving 7-nitro-1-tetralol48 (0.51 g, 2.6 mmol, 98%), as white solid (mp 109.0-109.1 °C). The 13C NMR data of 7-nitro-1-tetralol have not been reported: (50 MHz, CDCl3) d 18.7, 29.4, 32.1, 67.9, 122.2, 123.7, 129.9, 140.6, 144.9, 146.6. The tetralol (0.203 g, 1.05 mmol) was used without purification in the next step, which was performed using toluene (22 mL), a few crystals of p-TsOH, and reaction time of 3.5 h at 130 °C, using a Dean-Stark apparatus. The resulting oil was purified by flash chromatography (silica gel 200-400 mesh, 30% EtOAc in hexanes) affording 2248 (0.161 g, 0.919 mmol, 88%), as solid (mp 33.3-33.7 °C). The 13C NMR data of 22 have not been reported: (50 MHz, CDCl3) d 22.5, 27.4, 120.2, 121.7, 126.4, 128.1, 131.2, 135.2, 142.9, 146.9.

6,7-Dimethoxy-1,2-dihydronaphthalene (24). To a stirred solution of 6,7-dimethoxy-1-tetralone (0.207 g, 1.00 mmol) in anhydrous EtOH (2 mL) under nitrogen, was added NaBH4 (0.0504 g, 1.20 mmol) in small portions during 10 min at room temperature. The resulting mixture was stirred for 6 h at room temperature. The solvent was removed under reduced pressure. To the residue was added H2O (2 mL) and a 10% aqueous solution of HCl until pH around 7. The resulting solution was extracted with Et2O, washed with brine, and dried over anhydrous MgSO4. The solvent was removed under reduced pressure affording a yellow oil that was diluted in toluene (2 mL). A few crystals of p-TsOH were added to this solution and the mixture was heated under reflux for 30 min. The mixture was cooled to the room temperature and hexane was added. The resulting solution was washed with saturated aqueous solution of NaHCO3 (twice), with brine, and dried over anhydrous Na2SO4. The solvent was removed under reduced pressure giving a oil, which was purified by flash chromatography (silica gel 200-400 mesh, 30% EtOAc in hexanes) affording the olefin 2449 (0.0844 g, 0.444 mmol, 45%) as a white solid (mp 56.7-56.7 °C), together with the dimer 25 (0.0703 g, 0.185 mmol, 41%).

1,2-dihydro-3-(1,2,3,4-tetrahydro-6,7-dimethoxy naphthalen-4-yl)-6,7-dimethoxynaphthalene (25).49 Pale brown solid. The analytical data of this compound has not been reported: mp: 54.8-55.0 °C. IR (film) nmax/cm-1: 1511, 2931; 1H NMR (300 MHz, CDCl3) d 1.63-1.83 (m, 2H), 1.85-1.94 (m, 2H), 2.04-2.24 (m, 2H), 2.68-2.73 (m, 4H), 3.58-3.62 (m, 1H), 3.76 (s, 3H), 3.85 (s, 3H), 3.86 (s, 6H), 6.10 (s, 1H), 6.59 (d, J 5.7 Hz, 2H), 6.68 (d, J 2.2 Hz, 2H); 13C NMR (75 MHz, CDCl3) d 21.3, 25.4, 28.4, 28.6, 29.4, 46.7, 55.8, 55.9, 56.0, 56.1, 109.7, 111.4, 111.6, 112.1, 124.4, 127.1, 127.7, 129.7, 129.9, 143.7, 147.1, 147.3, 147.4, 147.5; m/z 380 (M+, 42%), 190 (100).

Oxidation of 1,2-dihydronaphthalenes with TTN. General procedure for the thallium(III) mediated oxidation of 1,2-dihydronaphthalenes

Oxidation of 16 with TTN. To a stirred solution of 16 (0.166 g, 1.05 mmol) in TMOF (5.2 mL), was added TTN.3H2O (0.518 g, 1.20 mmol) at 0 °C, which promptly dissolved. The mixture was stirred for 1 minute at room temperature and an abundant precipitation was observed. The resulting suspension was filtered through a silica gel pad (200-400 Mesh, ca. 10 cm), using CH2Cl2 as eluent. The filtrate was washed with H2O (twice), with brine, and dried over anhydrous MgSO4. The solvent was concentrated under reduced pressure giving a yellow solid. The residue was purified by flash chromatography (silica gel 200-400 mesh, 5% EtOAc in hexanes) immediately after concentration of the solvent, affording 28 (0.181 g, 0.860 mmol, 82%), together with traces of impure 29.

1-(Dimethoxymethyl)-4,6-dimethyl-indan (28). White neddles. mp: 37.1-37.3 °C. IR (KBr) nmax/cm-1: 1052, 2831; 1H NMR (300 MHz, CDCl3) d 1.90-2.02 (m, 1H), 2.14-2.25 (m, 1H), 2.21 (s, 3H), 2.30 (s, 3H), 2.64-2.86 (m, 2H), 3.37 (s, 3H), 3.43 (s, 3H), 3.42-3.43 (m, 1H), 4.33 (d, J 7.4 Hz, 1H), 6.83 (s, 1H), 7.07 (s, 1H); 13C NMR (75 MHz, CDCl3) d 19.0, 21.2, 27.1, 29.5, 47.6, 53.0, 54.1, 107.4, 123.4, 128.7, 133.3, 135.9, 140.6, 142.7; m/z 220 (M+, 1%), 75 (100). HRMS calc. for C14H20O2: 220.14633, found 220.13807.

trans-1,2-Dimethoxy-5,7dimethyl-tetrahydronaphthalene (29). The compound 29 was obtained in low yield and purity which precluded its characterization. The characteristic signal of the hydrogen of the C1 carbon appears as a dublet in 4.20 ppm (J 4.9 Hz).

Oxidation of 17 with TTN. The reaction was performed following the general procedure, but using 17 (0.074 g, 0.51 mmol), MeOH (2.5 mL), TTN.3H2O (0.25 g, 0.56 mmol), and reaction time of 1 min at 0 °C. The resulting brown solid was purified by flash chromatography (silica gel 200-400 mesh, 20-40% EtOAc in hexanes) affording the unstable indan 30 (0.063 g, 0.30 mmol, 60%) and 31 (0.01 g, 0.07 mmol, 6%).

1-(Dimethoxymethyl)-indan-4-ol (30). Viscous colorless oil. IR (film) nmax/cm-1: 1591, 1709, 2942; 1H NMR (300 MHz, CDCl3) d 1.97-2.09 (m, 1H), 2.18-2.30 (m, 1H), 2.71-2.95 (m, 2H), 3.37 (s; 3H), 3.42-3.52 (m, 1H), 3.43 (s; 3H), 4.34 (d, J 7.5 Hz, 1H), 6.66 (d, J 7.8 Hz, 1H), 7.00-7.10 (m, 2H); 13 C NMR (75 MHz, CDCl3) d 27.1, 27.3, 48.1, 53.1, 54.3, 107.2, 113.3, 118.0, 127.8, 130.1, 145.2, 151.8; m/z 208 (M+, 8%), 150 (100). The analyses were performed as soon as the compound 30 was isolated. The instability of this phenol precluded to obtain elemental analysis.

trans-5,6,7,8-Tetrahydro-5,6-dimethoxynaphthalen-1-ol (31). Viscous colorless oil. 1H NMR (500 MHz, CDCl3) d 1.96-2.02 (m, 1H), 2.10-2.16 (m, 1H), 2.60-2.73 (m, 2H), 3.46 (s, 3H), 3.73-3.75 (m, 1H), 3.51 (s, 3H), 4.25 (d, J 4.8 Hz, 1H), 6.67 (d, J 7.8 Hz, 1H), 6.96 (d, J 7.6 Hz, 1H), 7.08 (t, J 7.8 Hz, 1H); 13C NMR (125 MHz, CDCl3) d 19.0, 22.1, 56.6, 57.5, 77.0, 79.1, 114.0, 122.4, 123.3, 126.6, 135.8, 153.0; m/z 208 (M+, 8%), 150 (100). HRMS Calc. for: C12H16O3 208.10994, found 208.10865.

Oxidation of 19 with TTN. The reaction was performed following the general procedure, but using 19 (0.190 g, 1.02 mmol), MeOH (5.1 mL) and TTN.3H2O (0.50 g, 1.0 mmol), which was added at 0 °C. The mixture was stirred for 1 h at room temperature. The resulting oil was purified by flash chromatography (silica gel 200-400 mesh, eluent: EtOAc (90%) and hexanes (10%)) affording the indan 32 (0.148 g, 0.527 mmol, 52%), 33 (0.0322 g, 0.115 mmol, 11%), 34 (0.0050 g, 0.018 mmol, 2%) and a mixture of the 35 and 36.

1-(Dimethoxymethyl)-6-amide-indan (32). Pale yellow solid. mp: 81.8-81.9 °C. IR (KBr) nmax/cm-1: 1052, 1112, 1498, 1662, 2984, 3292; 1H NMR (200 MHz, CDCl3) d: 1.88-2.02 (m, 2H), 2.05-2.24 (m, 1H), 2.14 (s, 3H), 2.70-3.01 (m, 2H), 3.37 (s, 3H), 3.43 (s, 3H), 4.32 (d, J 7.0 Hz, 1H), 7.13 (d, J 7.9 Hz, 1H), 7.38 (dd, J 1.5 and 8.1 Hz, 1H), 7.45 (s, 1H), 7.51 (s, 1H); 13C NMR (50 MHz, CDCl3) d 24.4, 27.5, 30.9, 47.6, 53.2, 54.3, 107.2, 117.5, 119.3, 124.4, 136.1, 140.9, 143.6, 168.3; m/z 217 (M+-32, 17%), 43 (100). Anal. Calc. for C14H19NO3: C, 67.45; H, 7.68; N, 5.62. Found: C, 67.22; H, 7.59; N, 5.57.

trans-1,2,3,4-Tetrahydro-1,2-dimethoxy-7-amide naphthalene (33). Yellow solid. mp: 90.7-92.3 °C. IR (KBr) nmax/cm-1: 1089, 1123, 1498, 1658, 2931, 3291; 1H NMR (200 MHz, CDCl3) d: 1.80-1.93 (m, 1H), 2.04-2.19 (m, 1H), 2.14 (s, 3H), 2.61-2.89 (m, 2H), 3.45 (s, 3H), 3.52 (s, 3H), 3.66-3.73 (m, 1H), 4.23 (d, J 4.8 Hz, 1H), 7.05 (d, J 8.3 Hz, 1H), 7.32 (s, 1H), 7.38 (dd, J 2.0 and 8.1 Hz, 1H), 7.45 (s, 1H); 13C NMR (50 MHz, CDCl3) d 23.7, 24.5, 25.0, 56.6, 57.6, 76.4, 79.7, 119.7, 120.9, 129.0, 133.0, 135.4, 135.8, 168.2; m/z 249 (M+, 19%), 191 (100). HRMS Calc. for C14H19NO3: 249.13649, found 249.13649.

cis-1,2,3,4-Tetrahydro-1,2-dimethoxy-7-amidenaphthalene (34). Yellow solid. 1H NMR (200 MHz, CDCl3) d 1.91-1.99 (m, 1H), 2.16 (s, 3H), 2.16 (m, 1H), 2.65-2.82 (m, 1H), 2.91-3.05 (m, 1H), 3.47 (s, 3 H), 3.49 (s, 3H), 3.61-3.69 (m, 1H), 4.33 (d, J 2.6 Hz, 1H), 7.08 (d, J 7.9 Hz, 1H), 7.22 (s, 1H), 7.32 (dd, J 2.4 and 8.1 Hz, 1H), 7.50 (d, J 2.2 Hz, 1H); 13C NMR (50 MHz, CDCl3) d 22.5, 24.5, 26.4, 56.5, 57.4, 77.2, 78.0, 120.1, 121.1, 129.3, 132.7, 135.4, 168.2. The compound 34 was obtained in low yield and purity which precluded its full characterization.

Oxidation of 20 with TTN. The reaction was performed following the general procedure, but using 20 (0.16 g, 0.72 mmol), MeOH (4.6 mL) and TTN.3H2O (0.35 g, 0.79 mmol), which was added at 0 °C. The mixture was stirred for 45 min at room temperature. The resulting light brown oil was purified by flash chromatography (silica gel 200-400 mesh, 10% AcOEt and 10% CH2Cl2 in hexanes) affording the indan 37 (0.072 g, 0.27 mmol, 37%), 39 (0.028 g, 0.094 mmol, 13%), 38 (0.032 g, 0.12 mmol, 16%), and 40 (0.014 g, 0.065 mmol, 9%).

6-Bromo-1-(dimethoxymethyl)-indan (37). Colorless oil. IR (film) nmax/cm-1: 1061, 1122, 1469, 2039; 1H NMR (200 MHz, CDCl3) d 1.87-2.02 (m, 1H), 2.05-2.29 (m, 1H), 2.68-2.96 (m, 2H), 3.37-3.49 (m, 1H), 3.37 (s, 3H), 3.43 (s, 3H), 4.30 (d, J 7.5 Hz, 1H), 7.06 (d, J 7.9 Hz, 1H), 7.28 (dd, J 1.5 and 8.1 Hz, 1H), 7.54 (s, 1H); 13C NMR (50 MHz; CDCl3) d 27.5, 30.9, 47.5, 52.9, 54.3, 106.8, 119.8, 125.7, 128.6, 129.8, 143.7, 145.3; m/z 241 (M+ -OCH2, 3%), 75 (100). Anal. Calc. for C12H15BrO2: C, 53.15; H, 5.58. Found: C, 53.20; H, 5.52.

trans-7-Bromo-1,2,3,4-tetrahydro-1,2-dimethoxynaphthalene (38). Colorless oil. IR (film) nmax/cm-1: 855, 1097, 1481, 2931; 1H NMR (200 MHz, CDCl3) d 1.83-2.17 (m, 2H), 2.59-2.88 (m, 2H), 3.44 (s, 3H), 3.53 (s, 3H), 3.66-3.74 (m, 1H), 4.18 (d, J 4.8 Hz, 1H), 6.97 (d, J 8.3 Hz, 1H), 7.30 (dd, J 2.0 and 8.1 Hz, 1H), 7.48 (d, J 2.2 Hz, 1H); 13C NMR (50 MHz, CDCl3) d 23.2, 24.9, 56.6, 57.9, 77.6, 79.3, 119.4, 130.2, 130.7, 132.5, 135.9, 137.0; m/z 270 (M+-H, 3%), 212 (100). Anal. Calc. for C12H15BrO2: C, 53.15; H, 5.58. Found: C, 53.10; H, 5.43.

trans-7-Bromo-2-methoxy-1-nitrate-1,2,3,4-tetrahydro naphthtalene (39). White solid. mp: 53.1-53.2 °C; IR (KBr) nmax/cm-1: 855, 1081, 1270, 1621, 2932; 1H NMR (200 MHz, CDCl3) d 2.01-2.09 (m, 2H), 2.63-2.95 (m, 2H), 3.46 (s, 3H), 3.76-3.83 (m, 1H), 5.97 (d, J 4.4 Hz, 1H), 7.04 (d, J 8.3 Hz, 1H), 7.40 (dd, J 2.0 and 8.1 Hz, 1H), 7.45 (d, J 1.8 Hz, 1H); 13C NMR (50 MHz; CDCl3) d 23.3, 24.1, 57.1, 75.6, 79.4, 119.9, 130.6, 131.0, 132.3, 133.0, 137.1; m/z 256 (M+-46, 5%), 115 (100). Anal. Calc. for C11H12BrNO4: C, 43.73; H, 4.00. Found: C, 43.82; H, 3.93.

2-Bromonaphthalene (40).50 Yellow solid. mp 49.2-51.0 °C. The NMR data of the compound 40 have not been reported: 1H NMR (300 MHz, CDCl3) d 7.46-7.51 (m, 2H), 7.54 (dd, J 2.0 and 8.8 Hz, 1H), 7.72-7.82 (m, 2H), 7.73 (d, J 2.3 Hz, 1H), 8.00 (d, J 1.0 Hz, 1H); 13C NMR (75 MHz; CDCl3) d 119.8, 126.3, 126.9, 127.0, 127.8, 129.2, 129.6, 129.9, 131.8, 134.5.

Oxidation of 21 with TTN. The reaction was performed following the general procedure, but using 21 (0.305 g, 1.46 mmol), MeOH (7.3 mL), TTN.3H2O (0.71 g, 1.60 mmol), and reaction time of 1 h at room temperature. The resulting brown oil was purified by flash chromatography (silica gel 200-400 mesh, 5% EtOAc and 5% Et2O in hexanes) affording the indan 41 (0.139 g, 0.512 mmol, 35%), 42 (0.073 g, 0.269 mmol, 18%), 43 (0.010 g, 0.037 mmol, 3%), 44 (0.0796 g, 0.264 mmol, 18%) and 45 (0.0264 g, 0.128 mmol, 9%).

4-Bromo-1-(dimethoxymethyl)-indan (41). Colorless oil. IR (film) nmax/cm-1: 1059, 1113, 1451, 2940; 1H NMR (200 MHz, CDCl3) d 1.91-2.09 (m, 1H), 2.13-2.31 (m, 1H), 2.77-3.07 (m, 2H), 3.37 (s, 3H), 3.42 (s, 3H), 3.46-3.60 (m, 1H), 4.31 (d, J 7.0 Hz, 1H), 7.03 (t, J 7.7 Hz, 1H), 7.32 (s, 1H), 7.36 (s, 1H); 13C NMR (50 MHz, CDCl3) d 26.1, 32.9, 48.8, 53.0, 54.4, 107.1, 119.8, 124.4, 128.0, 130.0, 144.8, 145.1; m/z 241 (M+ -OCH2, 3%), 75 (100). Anal. Calc. for C12H15BrO2: C, 53.15; H, 5.58. Found: C, 53.12; H, 5.54.

trans-5-Bromo-1,2,3,4-tetrahydro-1,2-dimethoxynaphthalene (42). Yellow oil. IR (film) nmax/cm-1: 1094, 1446, 2932; 1H NMR (200 MHz, CDCl3) d 1.91-2.20 (m, 2H), 2.77 (t, J 6.8 Hz, 2H), 3.43 (s, 3H), 3.49 (s, 3H), 3.69-3.76 (m, 1H), 4.20 (d, J 4.8 Hz, 1H), 7.06 (t, J 7.9 Hz, 1H), 7.30 (d, J 7.5 Hz, 1H), 7.48 (dd, J 1.1 and 7.7 Hz, 1H); 13C NMR (50 MHz, CDCl3) d 22.9, 26.5, 56.9, 57.8, 76.7, 79.6, 125.4, 127.4, 129.6, 132.2, 136.8, 137.1; m/z 270 (M+ -H, 2%), 212 (100). Anal. Calc. for C12H15BrO2: C, 53.15; H, 5.58. Found: C, 53.48; H, 5.46.

cis-5-Bromo-1,2,3,4-tetrahydro-1,2-dimethoxynaphthalene (43). Yellow oil. The compound 43 was obtained in low yield and purity which precluded its characterization. The characteristic signal of the hydrogen of the C1 carbon appears as a dublet at 4.33 ppm (J 2.6 Hz).

trans-5-Bromo-2-methoxy-1-nitrate-1,2,3,4-tetrahydro naphthalene (44). White solid. mp: 57.2-57.3 °C. IR (KBr) nmax/cm-1: 855, 1110, 1273, 1445, 1635, 2936; 1H NMR (200 MHz, CDCl3) d 1.96-2.23 (m, 2H), 2.82 (t, J 6.6 Hz, 2H), 3.46 (s, 3H), 3.78-3.85 (m, 1H), 6.01 (d, J 4.0 Hz, 1H), 7.12 (t, J 7.7 Hz, 1H), 7.30 (d, J 7.5 Hz, 1H), 7.58 (dd, J 1.3 and 7.2 Hz, 1H); 13C NMR (50 MHz, CDCl3) d 23.0, 25.6, 57.0, 75.1, 80.2, 125.3, 127.7, 129.8, 131.2, 133.5, 137.7; m/z 254 (M+ – 48, 7%), 115 (100). Anal. Calc. for C11H12BrNO4: C, 43.73; H, 4.00; N, 4.64. Found: C, 44.17; H, 4.10; N, 4.29.

Bromonaphthalene (45). Yellow oil. Commercially available.

Oxidation of 22 with TTN. The reaction was performed following the general procedure, but using 22 (0.161 g, 0.922 mmol), MeOH (4.6 mL) and TTN.3H2O (0.451 g, 1.01 mmol), which was added at room temperature. The mixture was stirred for 20.5 h at room temperature. The resulting oil was purified by flash chromatography (silica gel 200-400 mesh, 10% AcOEt and 10% CH2Cl2 in hexanes) affording the indan 46 (0.0294 g, 0.124 mmol, 13%), 48 (0.0663 g, 0.261 mmol, 28%), 47 (0.0534 g, 0.225 mmol, 24%), and 49 (0.0236 g, 0.136 mmol, 15%).

1-(Dimethoxymethyl)-6-nitro-indan (46). Pale yelllow solid. mp: 42.6-42.7 °C. IR (KBr) nmax/cm-1: 1060, 1122, 1347, 1519, 1471, 2940; 1H NMR (200 MHz, CDCl3) d 1.99-2.16 (m, 1H), 2.21-2.39 (m, 1H), 2.83-3.13 (m, 2H), 3.40 (s, 3H), 3.46 (s, 3H), 3.50-3.58 (m, 1H), 4.35 (d, J 7.0 Hz, 1H), 7.32 (d, J 8.3 Hz, 1H), 8.06 (dd, J 2.2 and 8.3 Hz, 1H), 8.24 (s, 1H); 13C NMR (50 MHz, CDCl3) d 27.4, 31.6, 47.4, 53.2, 54.8, 106.7, 120.9, 122.7, 124.6, 144.7, 147.3, 152.7; m/z 206 (M+ -OCH3, 6%); 75 (100). Anal. Calc. for C12H15NO4: C, 60.75; H, 6.37; N, 5.90. Found: C, 60.59; H, 6.25; N, 6.04.

trans-1,2,3,4-Tetrahydro-1,2-dimethoxy-7-nitro naphthalene (47). Yellow solid. mp: 28.8-29.0 °C. IR (KBr) nmax/cm-1: 1089, 1187, 1460, 1347, 1519, 2935; 1H NMR (200 MHz; CDCl3) d 1.92-2.21 (m, 2H), 2.74-3.03 (m, 2H), 3.45 (s, 3H), 3.57 (s, 3H), 3.74-3.81 (m, 1H), 4.25 (d, J 4.4 Hz, 1H), 7.26 (d, J 8.8 Hz; 1H), 8.05 (dd, J 2.6 and 8.3 Hz, 1H), 8.22 (d, J 2.2 Hz, 1H); 13C NMR (50 MHz; CDCl3) d 22.5, 25.3, 56.7, 58.2, 76.8, 78.8, 122.5, 125.3, 129.5, 136.4, 144.9, 146.4; m/z 206 (M+ -OCH3, 9%), 115 (100). Anal. Calc. for C12H15NO4: C, 60.75; H, 6.37; N, 5.90. Found: C, 60.72; H, 6.23; N, 6.10.

trans-7-Nitro-2-methoxy-1-nitrate-1,2,3,4-tetrahydro naphthtalene (48). Yellow oil. IR (film) nmax/cm-1: 849, 1094, 1173, 1273, 1347, 1460, 1528, 1543, 2938; 1H NMR (200 MHz, CDCl3) d 1.98-2.25 (m, 2H), 2.79-3.12 (m, 2H), 3.48 (s, 3H), 3.83-3.90 (m, 1H), 6.05 (d, J 4.0 Hz, 1H), 7.35 (d, J 8.8 Hz, 1H), 8.14 (dd, J 2.4 and 8.6 Hz, 1H), 8.23 (d, J 2.2 Hz, 1H); 13C NMR (50 MHz, CDCl3) d 22.8, 24.6, 57.1, 74.9, 78.5, 123.9, 125.9, 130.1, 130.5, 145.9, 146.6; m/z 191 (M+ -ONO2 – CH3), 115 (100). Anal. Calc. for C11H12NO6: C, 49.26; H, 4.51; N, 10.44. Found: C, 49.21; H, 4.53; N, 10.22.

2-Nitronaphthalene (49).50 Yellow needles. mp 76.1-77.9 °C. The NMR data of 49 have not been reported: 1H NMR (200 MHz; CDCl3) d 7.60-7.74 (m, 2H), 7.94-8.06 (m, 3H), 8.24 (dd, J 2.2 and 9.2 Hz, 1H), 8.80 (d, J 1.7 Hz, 1H). 13C NMR (50 MHz; CDCl3) d 119.3, 124.6, 127.9, 128.0, 129.5, 129.7, 130.0, 132.0, 135.8, 145.6.

Oxidation of 24 with TTN. The reaction was performed following the general procedure, but using 24 (0.101 g, 0.533 mmol), TMOF (2.7 mL), TTN.3H2O (0.259 g, 0.583 mmol), and reaction time of 1 min at 0 °C. The resulting oil was purified by flash chromatography (silica gel 200-400 mesh, 20% EtOAc in hexanes) affording 27 (0.118 g, 0.47 mmol, 92%).

5,6-Dimethoxy-1-(dimethoxymethyl)-indan (27). Light yellow oil. IR (film) nmax/cm-1: 2830, 2859; 1H NMR (300 MHz, CDCl3) d 1.91-2.03 (m, 1H), 2.16-2.27 (m,1H), 2.74-2.94 (m, 2H), 3.38 (s, 3H), 3.39-3.42 (m, 1H), 3.44 (s, 3H), 3.85 (s, 3H), 3.87 (s, 3H), 4.28 (d, J 7.6 Hz, 1H), 6.75 (s, 1H), 6.99 (s, 1H); 13C NMR (75 MHz, CDCl3) d 27.7, 31.2, 47.4, 52.7, 54.3, 55.9, 56.0, 107.5, 107.5, 109.0, 134.4, 136.4, 147.8, 148.5; m/z 252 (M+, 9%), 75 (100). HRMS Calc. for: C14H20O4 252.13616, found 252.13301.

Oxidation of 55 with TTN. The reaction was performed following the general procedure, but using 55 (0.152 g, 0.806 mmol), TMOF (4.0 mL), TTN.3H2O (0.394 g, 0.887 mmol), and reaction time of 1 min at 0 °C. The resulting oil was purified by flash chromatography (silica gel 200-400 mesh, 10% EtOAc and 10% CH2Cl2 in hexanes) affording the indan 56 (0.0477 g, 0.234 mmol, 29%), 58 (0.0388 g, 0.155 mmol, 19%), and 57 (0.0535 g, 0.226 mmol, 28%).

1-(6-Methoxy-5-methyl-indan-1-yl)-ethanone (56). Colorless oil. IR (film) nmax/cm-1: 1707; 1H RMN (300 MHz, CDCl3) d 2.15 (s, 3H), 2.19 (s, 3H), 2.22-2.43 (m, 2H), 2.82-3.06 (m, 2H), 3.80 (s, 3H), 4.03 (dd, J 8.3 and 5.9 Hz, 1H), 6.71 (s, 1H); 7.03 (s, 1H); 13C RMN (75 MHz, CDCl3) d 16.4, 27.3, 29.2, 31.2, 55.6, 59.4, 106.6, 126.4, 126.7, 135.8, 139.2, 157.0, 209.5; m/z 204 (M+, 37%), 161 (100). Anal. Calc. for C13H16O2: C, 76.44, H, 7.90. Found C, 76.25, H, 7.88.

cis-2,7-Dimethoxy-1,6-dimethyl-1,2,3,4-tetrahydro naphthalen-1-ol (57). Colorless oil. IR (film) nmax/cm-1: 3549, 1099, 1250; 1H RMN (300 MHz, CDCl3) d 1.46 (s, 3H), 1.95 (dddd, J 1.8, 6.6, 11.7, and 14.7 Hz, 1H), 2.15 (s, 3H), 2.16-2.28 (m, 1H), 2.52-2.61 (m, 1H), 2.74-2.88 (m, 1H), 3.31 (sl, 1H), 3.44 (s, 3H), 3.45-3.47 (m, 1H), 3.83 (s, 3H), 6.82 (s, 1H), 7.10 (s, 1H); 13C RMN (75 MHz, CDCl3) d 15.7, 22.1, 23.3, 29.4, 55.5, 56.8, 82.7, 108.2, 125.7, 126.3, 130.1, 140.6, 156.6; m/z 236 (M+, 19%), 163 (100). HRMS Calc. for C14H20O3 236.14124, Found 236.14143.

trans-1,2,7-Trimethoxy-1,6-dimethyl-1,2,3,4-tetrahydronaphthalene (58). Colorless oil. IR (film) nmax/cm-1: 1252, 1104, 1075; 1H RMN (300 MHz, CDCl3) d: 1.46 (s, 3H), 1.68-1.82 (m, 1H), 2.15-2.24 (m, 1H), 2.17 (s, 3H), 2.77 (dd, J 4.2 and 8.8 Hz, 2H), 3.08 (s, 3H), 3.53 (s, 3H), 3.72 (dd, J 3.5 and 11.5 Hz, 1H), 3.82 (s, 3H), 6.83 (s, 1H), 6.87 (s, 1H); 13C RMN (75 MHz, CDCl3) d 15.8, 24.8, 25.2, 27.4, 50.3, 55.6, 57.2, 77.6, 80.5, 107.7, 126.1, 128.3, 130.3, 138.3, 156.7; m/z 250 (M+, 18%), 177 (100). HRMS calc. for C15H22O3 250.15689, Found 250.15646.

 

Acknowledgments

We are grateful for the financial support provided by FAPESP, CNPq and CAPES.

 

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Received: May 21, 2005
Published on the web: September 15, 2005
FAPESP helped in meeting the publication costs of this article

 

 

* e-mail: luizfsjr@iq.usp.br; hmferraz@iq.usp.br