Steroidal cyclobutanones. Part 2. Diastereofacial selection in the cycloaddition of dichloroketene and 3β-acetoxy-20a-homopregna-5,20-diene. Crystal structure of the cycloadduct, (20S)-3β-acetoxy-20,24-cyclo-22,22-dichlorochol-5-en-23-one

Abstract

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.

Enantiomerically Pure Cyclobutane Derivatives and Their Use in Organic Synthesis

“…Natural products with alkenes incorporated in a chiral carbon framework are abundant. Ketenes will add to steroids , and dehydro cyclic acetals derived from sugars − to give the corresponding optically pure cyclobutanones. Dichloroketene, being more reactive than the parent ketene, is often used as a ketene equivalent.…”

Steroid reactions and partial synthesis

“…41 The crystal structure of the adduct (41) of dichloroketene and 3pacetoxy-20a-homopregna-5,20-diene (40) has been described. 42 Various novel conditions for the allylic oxidation of A5steroids have been reported including the use of t-butylhydro- The reaction of 7-norandrost-5-enes (e.g. 45) with bromine and silver acetate afforded4' the fragmentation product (46) as well as the allylic substitution products (47) and (48).…”

Synthetic Organic Chemistry Based on Small Ring Compounds

“…These include [2ϩ2] cycloaddition reactions via photolytic [25][26][27][28][29][30][31][32] and thermolytic [33][34][35][36][37][38][39][40][41][42] processes, enantioselective alkylation, 43) ring contraction of cyclic acetals, 44) radical cyclization, 45) and chemical 46) and enzymatic 47) resolution of racemates or prochiral precursors. In contrast to these well documented methods described above, there have been few studies on the asymmetric induction of the ring expansion reaction of cyclopropane rings to form cyclobutanes.…”