Simple Routes to Keto-norsteroids James R. Hanson* and Cavit Uyanik School of Chemistry, Physics and Environmental Science, University of Sussex, Brighton, Sussex BN1 9QJ, UK Ring A and B keto-norsteroids have been obtained by applying the McMurray low valency titanium cyclization to steroidal seco ring A and ring B nor-keto-esters which were readily available by cleaving the corresponding unsaturated ketones. Nor-steroids often have an interesting pharmacological proRle when compared to their six-membered analogues.1 The established methods2 for the preparation of keto- norsteroids involve a series of steps which do not always proceed in good yield.Here we describe simple alternative routes to these compounds utilizing the McMurray reac- tion.4 Oxidative cleavage of steroidal D4-3-ketones 1 with potassium permanganate�}sodium periodate a€orded the 5-oxo-3,5-seco-4-nor-3-oic acids 2 in good yield. The acids were methylated with caesium �Puoride and methyl iodide.6 The resultant keto-esters were then reductively cyclized with a low-valency titanium reagent derived from the titanium trichloride : dimethoxyethane complex and a zinc : copper couple.7 This a€orded the 5b-A-nor-3-ketone 4 as the major product (67%) accompanied by the 3(5)-alkene 3 as the minor product.The sequence was applied to testosterone acetate 1a, 19-nortestosterone acetate 1b, progesterone 1c and cholest-4-en-3-one 1d which were converted to their respective 5b-A-nor-3-ketones 4a�}d together with small amounts of the 3(5)-alkenes.A similar sequence was applied to the preparation of a B-norsteroid. The readily available dehydroisoandro- sterone (3b-hydroxyandrost-5-en-17-one) was converted via its 3b-iodo derivative into androst-5-en-17-one 5.9 The latter was oxidized with the chromium trioxide�}3,5-dimethyl- pyrazole complex10 to androst-5-en-7,17-dione 6. Cleavage of the unsaturated ketone with potassium permanganate�} sodium periodate and methylation with caesium �Puoride�} methyl iodide gave methyl 5,17-dioxo-5,7-seco-6-nor- androstan-7-oate 7.This keto-ester was reductively cyclized with low valency titanium to the B-norketone. The major product (47%) was the B-nor-5a-androstan-6,17-dione 8 accompanied by the cis isomer 9 (15%). C.U. wishes to thank Kocaeli University, Izmit, Turkey, for study leave and Rnancial assistance. Techniques used: IR, 1H NMR, chromatography References: 15 Received, 25th November 1997; Accepted, 30th December 1997 Paper E/7/08520F References cited in this synopsis 1 P.G. Marshall, in Rodd's Chemistry of Carbon Compounds, ed. S. Co€ey, Elsevier, Amsterdam, 1970, vol. IID, p. 281. 2 For a review see: R. M. Scribner, in Organic Reactions in Steroid Chemistry, ed. J. Fried and J. A. Edwards, van Nostrand:Reinhold, New York, 1972, vol. 2, p. 408. 4 A. Furstner and B. Bogdanovic, Angew. Chem., Int. Ed. Engl., 1996, 35, 2442. 6 T. Sato, J. Otera and H. Nozaki, J. Org. Chem., 1992, 57, 2166. 7 J. McMurray, T. Lectka and J. G. Rico, J. Org. Chem., 1989, 54, 3748. 9 J. R. Hanson, H. J. Wadsworth and W. E. Hull, J. Chem. Soc., Perkin Trans. 1, 1988, 1381. 10 W. G. Salmond, M. A. Barta and J. Havens, J. Org. Chem., 1978, 43, 2057. J. Chem. Research (S), 1998, 221 J. Chem. Research (M), 1998, 1032�}1042 *To receive any correspondence. J. CHEM. RESEAR