No abstract

Cycloaddition of dichloroketene to 3‐, 7‐, and 17‐methylene steroids affords the corresponding spirodichlorocyclobutanones, which can be reduced to monochloro‐ and unsubstituted spirocyclobutanones. Selective cycloaddition to the exo‐double bond is observed in the reaction of 3β‐acetoxy‐17‐methylene‐5‐androstene. The stereochemistry of spiro compounds is assigned on the basis of 1H‐ and 13C‐NMR spectra. Some steroidal spirolactones are obtained and their stereochemistry is assigned.

17β‐(3‐Oxocyclobutyl)androstane, prepared by the thermal [2 + 2] cycloaddition of dichloroketene to 3β‐acetoxypregna‐5,20‐diene, is the key intermediate in the new, efficient synthesis of steroids bearing the 17β‐butenolide fragment that characterizes cardenolides. The six‐step synthesis of 3β‐tert‐butyldimethylsilyloxy‐14α‐carda‐5,20(22)‐dienolide was achieved with a total yield of 32%. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

The reaction of dichloroketene and 3P-acetoxy-20a-homopregna-5,20-diene 1 is shown to give one diastereoisomeric cycloadduct 2 arising from attack at the rear side of the preferred rotamer l b of the steroid skeleton. The structure of dichlorocyclobutanone 2 was determined by X-ray crystallography. Reduction of 2 gives chlorocyclobutanone 3 and cyclobutanone 4. Examination of the cyclobutanones by CD, 'H and 13C NMR spectroscopy demonstrates that these techniques can be used for the determination of the configuration of 2 and 3.The reaction of dichloroketene (DCK) and methylene steroids provides the entry to steroidal spiro cyclobutanones.' Depending on the steric crowding around the two faces of the exocyclic double bond, the reaction resulted in formation of one (position 17) or two (positions 3 and 7) spiro cyclobutanone stereoisomers. In the light of these results, it seemed of interest to study the reaction of DCK with 3P-acetoxy-20ahomopregna-5,20-diene, 1. Two points were of interest: (i) the stereoselectivity of cycloaddition, (ii) the conformation of the side chain in compound 1 leading to the cycloadduct.

Diastereomeric [(3S)‐5α]‐ and [(3R)‐5α]‐2′,2′‐dichlorospiro‐[cholestane‐3,1′‐cyclobutan]‐3′‐ones (1 and 2), prepared by cycloaddition reaction of dichloroketene with 3‐methylene‐5α‐cholestane, served as starting material for the synthesis of the related spirane derivatives. Thus, the synthesis of spiro‐cyclopentane (3–6), spirocyclobutane (9, 11, 13, 17–20) and spirocyclopropane steroids (12, 14, 15) is described. The sterically dependent reaction of spiro‐α,α‐dichlorocyclobutan‐3‐ones with an excess of sodium methanolate in methanol is reported. Thus, the reaction of 1 with sodium methanolate gives 9, the product of the double cine substitution, while the corresponding reaction of compound 2, which is sterically more hindered for similar nucleophilic attack, gives mainly the spirocyclopropane 12. The stereochemistry of the spiro compounds is assigned on the basis of 1H‐ and 13C‐NMR spectra.