A facile preparation of tetralins from arene-1,4-diones using titanium(IV) chloride and triethylsilane

Tetrahedron Letters 52 (2011) 6827–6830

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A facile preparation of tetralins from arene-1,4-diones using titanium(IV) chloride and triethylsilane Gang Li, Qiong Xiao, Chun Li, Xiaojian Wang ⇑, Dali Yin Department of Medicinal Chemistry, Beijing Key Laboratory of Active Substances Discovery and Drugability Evaluation, State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, PR China

a r t i c l e

i n f o

a b s t r a c t

Article history: Received 6 August 2011 Revised 9 October 2011 Accepted 11 October 2011 Available online 17 October 2011

A facile method for the synthesis of tetralins has been described which uses various substituted phenylpentane-1,4-diones as starting material with a combination of TiCl4/Et3SiH. The synthesis involves three reactions under mild conditions. A mechanism has been proposed for the reductive cyclization through ionic hydrogenation, and titanium(IV) chloride catalyzed cyclization. Ó 2011 Elsevier Ltd. All rights reserved.

Keywords: Tetralin Arene-1,4-dione Intramolecular cyclization Ionic hydrogenation

Tetralins are present as important structure motifs in many natural products and pharmaceuticals.1 Many methods have been developed to construct the tetralin structure frameworks, such as Darzens tetralin synthesis,2 hydrogenation of naphthalene,3 and intramolecular Friedel–Crafts type cyclization.4 Recently the metal catalyzed cyclization method regarded as intramolecular hydroarylation5 has been developed and widely used to generate the annulated arene heterocycles and carbocycles. However, each of these methods requires a suitable starting molecule that needs several steps to reach. We herein report a facile method which could convert substituted phenylpentane-1,4-diones directly to tetralin derivatives. We have serendipitously found that tetralin (B) was formed when 1,4-dione (A) was treated with titanium chloride and triethylsilane instead of the attempted reduction product (C)

(Scheme 1).6 It is anticipated that tetralins could be prepared with a combination of suitable Lewis acid and triethylsilane directly from the substituted phenylpentane-1,4-diones. Then we screened various Lewis acids and Brønsted acids that might promote the cyclization. The results indicated that only TiCl4 was found to be efficient to afford the desired compound B in good yield (Table 1). Meanwhile the combination of SnCl4/Et3SiH could reduce ketone but did not exert cyclization. The scope of the method for tetralin synthesis was then investigated. To our delight, the substituted 1-phenylpentane-1,4-dione substrates 1a–j smoothly underwent intramolecular reductive cyclization and gave tetralins (2a–j) in good yields (Table 2). It was noticed that the molecules with electron-donating groups, such as phenoxyl and alkyl gave higher yields (entries 5–10), while electron insufficient molecules with halogene substituents gave

O TiCl4/Et3SiH

TiCl4/Et3SiH O

B

A Scheme 1. Synthesis of tetralin in the presence of TiCl4 and Et3SiH.

⇑ Corresponding author. Tel./fax: +86 10 63165248. E-mail address: [email protected] (X. Wang). 0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2011.10.054

O C

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G. Li et al. / Tetrahedron Letters 52 (2011) 6827–6830

Table 1 Lewis or Brønsted acids for the reduction and cyclization of 1-phenylpentane-1,4-dione

O

O

Lewis or Bronsted acid Et3SiH O

+ OH

CH2Cl2 , rt

A Entry a

1 2b 3a 4a 5a 6a 7a a b c

B

D

Catalyst

Reagent

Solvent

Temperature

Time (h)

Yieldc (%)

TiCl4 TiCl4 AlCl3 BF3 ZnCl2 SnCl4 CF3COOH

Et3SiH Et3SiH Et3SiH Et3SiH Et3SiH Et3SiH Et3SiH

CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2

rt rt rt rt rt rt rt

6 10 6 6 6 6 6

B(86) D(0) B(72) D(0) No reaction No reaction No reaction B(0) D(65) No reaction

Using 3.8 equiv of the catalyst and 3.8 equiv of Et3SiH. Using 2.1 equiv of TiCl4 and 3.1 equiv of Et3SiH. Isolated yields.

Table 2 Reductive cyclization of selected substrates promoted by TiCl4 and Et3SiH Entry

Substrate

Product

Time (h)

Yielda (%)

6

86

4

80

5

75

6

72

2

87

3

85

2

90

O 1

O

2a

1a O

F

2

O

F

2b

1b O

Cl

3

O

Cl

2c

1c O Br

4

O

Br

2d

1d O 5

O

2e

1e O

6

O

2f

1f O

O

7

2g 1g

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G. Li et al. / Tetrahedron Letters 52 (2011) 6827–6830 Table 2 (continued) Entry

Substrate

Product

Time (h)

Yielda (%)

2

93

2

92

3

88

6

80

O O

8

O

O

2h

1h O

O O

O

9

2i

1i O

O O

10

O

O

O

2j

1j O

OH

11

2k

1k

a All the reactions were carried out in anhydrous dichloromethane at room temperature for 2–6 h, entries1–9 using TiCl4 (3.8 equiv), Et3SiH (3.8 equiv); entry 10 using TiCl4 (7.6 equiv), Et3SiH (7.6 equiv); entry 11 using TiCl4 (2 equiv), Et3SiH (2 equiv), Isolated yields.

TiCl4 O OH

E

F

NaBH4

TiCl4

Et3SiH

Et3SiH

TiCl4 OH G

B Scheme 2. Exploration of the mechanism.

lower yields (entries 2–4). However, when ketone 1k was used as substrate, the reaction did not give five-membered ring but a reduced product (entry 11). There are two possible pathways to realize the reductive cyclization. One way is the ketone intermediate cyclized in the assistance with a Lewis acid, then the tertiary alcohol is reduced by

triethylsilane. Another is the ketone reduced to alcohol first, then cyclization takes place to form tetrahydronaphthalene. When ketone E was treated first with TiCl4, then with triethylsilane, the major product was 1-methylnaphthalene (F) whereas no tetralin (B) formed. If triethylsilane was added first and followed by titanium chloride, tetralin (B) was obtained. When alcohol G was treated with TiCl4, tetralin (B) was formed exclusively (Scheme 2). The last question remained is which one of the two carbonyl is reduced first. When a mixture of 1,4-dione (1g) and TiCl4 was treated with 1 equiv of Et3SiH, three products were isolated while phenylnaphthalene was not observed. The results indicated that the methyl ketone is reduced prior to the benzyl ketone (Scheme 3). With above observations, a mechanism of the reductive cyclization was proposed. The aliphatic carbonyl is converted to siloxane, then benzyl carbonyl is reduced to methylene. Cyclization of siloxane generates the 1-methyl-tetrahydronaphthalene (Scheme 4). In summary, we have described a mild and efficient method for the synthesis of tetralins via ionic hydrogenation and cyclization in the presence of TiCl4 and Et3SiH from the substituted phenylpentane-1,4-dione substrates. This method involves three reactions under mild conditions, ionic hydrogenation of remote ketone to hydroxyl, deoxygenation of benzyl ketone, and cyclization catalyzed by TiCl4. Although the method is not suitable to generate five-membered arene carbocycles, it could potentially be useful

O

O

2eq TiCl4 O

1g

OH

OH

+

1eq Et3SiH

H

I

Scheme 3. Reduction of arene-1,4-dione (1g) with 2 equiv TiCl4 and 1 equiv Et3SiH.

+

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G. Li et al. / Tetrahedron Letters 52 (2011) 6827–6830

Ti4+

Ti4+ O

O

O 4+

Et3SiH

2 Ti O

O

O Et3Si

Ti4+

Ti4+

-H+

2 Et3SiH H

O Ti4+

SiHEt3

H

Scheme 4. Proposed mechanism for tetralin synthesis via reductive cyclization.

in selective cases and complementary to the existing methods for the synthesis of tetralins. Acknowledgments

2. 3. 4.

The authors are grateful to National Major Scientific and Technological Special Project (No. 2009ZX09301-003) and Taisho Pharmaceuticals, Japan, for the financial support.

5.

Supplementary data

6.

Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.tetlet.2011.10.054. References and notes 1. (a) Perrone, R.; Berardi, F.; Colabufo, N. A.; Leopoldo, M.; Tortorella, V.; Fiorentini, F.; Olgiati, V.; Ghiglieri, A.; Govoni, S. J. Med. Chem. 1995, 38, 942; (b) Welch, W. M.; Kraska, A. R.; Sarges, R.; Koe, B. K. J. Med. Chem. 1984, 27, 1508; (c) Wyrick, S. D.; Booth, R. G.; Myers, A. M.; Owens, C. E.; Kula, N. S.; Baldessarini,

R. J.; McPhail, A. T.; Mailman, R. B. J. Med. Chem. 1993, 36, 2542; (d) Hook, B. B.; Cortizo, L.; Johansson, A. M. J. Med. Chem. 1996, 39, 4036. (a) Cook, J. W.; Hewett, C. L. J. Chem. Soc. 1933, 1098; (b) Bergmann, E. Chem. Rev. 1941, 29, 529. Hiyoshi, N.; Miura, R.; Rode, C. V.; Sato, O.; Shirai, M. Chem. Lett. 2005, 34, 424. (a) Bogert, M. T.; Davidson, D.; Apfelbaum, P. M. J. Chem. Soc. 1934, 56, 959; (b) Roblin, R. O.; Davidson, D.; Bogert, M. T. J. Chem. Soc. 1935, 57, 151; (c) Kropp, P. J.; Breton, G. W.; Craig, S. L.; Crawford, S. D.; Durland, W. F.; Jones, J. E.; Raleigh, J. S. J. Org. Chem. 1995, 60, 4146. (a) Youn, S. W.; Pastine, S. J.; Sames, D. Org. Lett. 2004, 6, 581; (b) Xie, K.; Wang, S.; Li, P.; Li, X.; Yang, Z.; An, X.; Guo, C.-C.; Tan, Z. Tetrahedron Lett. 2010, 51, 4466. General procedure for the reductive cyclization of 1-phenylpentane-1,4-dione (1a): To a magnetically stirred solution of 1-phenylpentane-1,4-dione (2.84 mmol) in dry dichloromethane (10 mL) was added dropwise a solution of Et3SiH (1.73 mL, 10.8 mmol) at rt under an atmosphere of nitrogen. TiCl4 (1.20 mL, 10.8 mmol) was then added with a syringe to the reaction mixture cooled with an ice bath. The contents were stirred at rt for 6 h. The solution was poured slowly into ice water and the aqueous phase was extracted with dichloromethane. The organic layers were combined, washed with brine, dried over Na2SO4, and the solvent was removed. Flash chromatography of the residue over silica gel using petroleum ether as the eluent afforded the pure 1-methyl-tetralin (2a). The product was identified by NMR and MS and the data are identical to the reported values.