A convenient preparation of cyclobutyl ketones: Naphthalene-catalyzed reductive cyclization of substituted 1,4-dihalobutanes

Tetrahedron Letters

Volumn 37, Issue 4, 1996, Pages 443-446

  Ramig, Keith ^a   Dong, Yong ^b   Van Arnum, Susan D ^c  

^a Ohmeda Inc   (United States)

^b BOEHRINGER INGELHEIM PHARMACEUTICALS INC   (United States)

^c HOFFMANN LA ROCHE INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLOBUTANE DERIVATIVE;

ARTICLE; DRUG SYNTHESIS; REACTION ANALYSIS;

EID: 0030031720     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/0040-4039(95)02194-9     Document Type: Article

References (18)

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2. Overberger, C.G.; Lebovits, A. J. Am. Chem. Soc. 1954, 76, 2722. Heisig, G.B.; Stodpla, F.H. Org. Syn. Coll. Vol. III 1955, 213. Mariella, R.P.; Raube, R. Org. Syn. Coll. Vol. IV 1963, 288. Rathke, M.W.; Cowan, P.J. J. Org. Chem. 1985, 50, 2622.
3. Overberger, C.G.; Lebovits, A. J. Am. Chem. Soc. 1954, 76, 2722. Heisig, G.B.; Stodpla, F.H. Org. Syn. Coll. Vol. III 1955, 213. Mariella, R.P.; Raube, R. Org. Syn. Coll. Vol. IV 1963, 288. Rathke, M.W.; Cowan, P.J. J. Org. Chem. 1985, 50, 2622.
4. Overberger, C.G.; Lebovits, A. J. Am. Chem. Soc. 1954, 76, 2722. Heisig, G.B.; Stodpla, F.H. Org. Syn. Coll. Vol. III 1955, 213. Mariella, R.P.; Raube, R. Org. Syn. Coll. Vol. IV 1963, 288. Rathke, M.W.; Cowan, P.J. J. Org. Chem. 1985, 50, 2622.
5. Field, G.; Vermeulen, J.; Zally, W. US 5,001,140, 1991.
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16. The following is a representative example. Under a nitrogen atmosphere, naphthalene (42.4 mg, 0.331 mmol) was added to Li ribbon (919 mg, 132 mmol) in 30 mL of dry THF. The mixture was cooled to 0°C and a solution of dibromide 2e (2.00 g, 6.62 mmol) in THF was added all at once. The mixture was stirred at room temperature overnight and was followed by an extractive workup with diethyl ether. After purification (radial chromatography, pentane, 5% diethyl ether/pentane), 301 mg (32%) of 2f was obtained as a pale oil. Similarly, 77.3 mmol of diiodide 2d was reacted as above and the crude reaction mixture was treated with 5% HCl at room temperature. An extractive workup was followed by an atmospheric distillation (BP = 135°C) to yield 3.0 g (45%) of cyclobutyl methyl ketone (2) as an oil.
17. All new compounds gave satisfactory spectral data and high resolution mass spectral data.
18. Despite the fact that ketal 2f and ketone 2 were the only products observed by TLC, our crude and isolated material balances were low. This was attributed to the volatility of the products. In support of this hypothesis, the higher molecular weight propyl derivative afforded a significantly better yield of isolated products.