Direct and carbonylative vinylation of steroidal triflates in the presence of homogeneous palladium catalysts Rita Skoda-FiJldes,* Liszl6 Koil6r,* Fabio Marinelli,~" and Antonio ArcadH" * University of Veszpr~m, Department of Organic Chemistry, Veszpr~m, Hungary t Universita de L "Aquila, Dipartimento di Chimica, L 'Aquila, Italy The palladium-catalyzed vinylation of several steroid 2-enyl- and 3,5-dienyl-3 triflates and estrone-3-triflate was systematically examined using vinyltributylstannane as a vinylating agent. In carbon monoxide atmosphere the insertion of a CO molecule took place and unsaturated ketones were obtained. In this way new steroid derivatives containing unsaturated side chain were produced, which can serve as starting material far further functionalization of the steroid skeleton. (Steroids 59:691-695, 1994) Keywords:triflate esters; homogeneouscatalytic vinylation;carbonylativevinylation;palladium-containingcatalysts Introduction The homogeneous catalytic cross-coupling reactions serve as a very powerful method in organic synthesis. The palladium-catalyzed coupling of unsaturated com- pounds containing trifluoromethanesulfonate (triflate) leaving group with organostannanes (Stille reaction 1'2) is a very easy and elegant method for carbon-carbon bond formation. The reaction of organostannanes with various simple molecules like 4-acetylphenyl triflate, 4-formylphenyl triflate, 4-methoxyphenyl triflate has been carefully studied L3 but only a few examples of this reaction can be found in the literature for more complicated molecules (e.g., uridine triflate4). Biologi- cally important compounds and their precursors can be produced in similar reactions (e.g., quinoline alkaloid dubamin~). When the coupling reaction between the organic electrophile and the organostannane is carried out under moderate CO pressure beside the coupling CO insertion also takes place 5 and unsaturated ketones can be produced. The efficiency of homogeneous coupling and carbonylation reactions in steroid chemistry has been proved in our laboratory. Pregna-16,20-diene was synthesized in the Stille reaction and its hydroformyla- tion was studied in order to introduce 0t-formyl-ethyl functionalilty. 6 The same reaction sequence was used for Address reprint requests to Lfiszl6 Koll~tr, University of Veszprrm, Department of Organic Chemistry, H-8200 Veszprrm, Egyetem u. 8. (P.O. Box 158),Hungary. ReceivedApril 8, 1994; accepted June 20, 1994. the synthesis of 3-(2-formyl-ethyl)-estrone. The hydro- formylation step was highly stereoselectivite by using different platinum- and rhodium-containing catalysts) The present work was initiated by the increasing demand for functionalized steroids containing un- saturated systems (e.g., enon or diene derivatives) which are important precursors of various novel skeletons. As described above, the vinyl functionality enables the introduction of a novel asymmetric center into the steroidal backbone via carbonylation reactions and are excellent starting materials for the synthesis of products possessing an additional ring annulated to ring-A. In this work the direct and carbonylative vinylation of several steroid 2-enyl- and 3,5-dienyl-3 triflates and estrone-3- triflate will be described. Experimental Pd(PPh3)4 and Pd2(dba)a'CHC13 (where dba is dibenzyli- deneacetone) were prepared as described previously. 7's Solvents were dried over sodium and distilled under argon. The IH and 13C NMR spectra were recorded in CDCI a with TMS as internal standard on a VARIAN UNITY 300 spectrometer at 300 and 75.4 MHz, respectively. GLC analyses were carried out on a Shimadzu GC-14A gas chromatograph fitted with a 10 m HP-17 column. Gas chromatography-mass spectroscopy (GC-MS) measurements were made on a Hewlett Packard 5971A GC-MSD, mass spectra of solid samples (3b,4b) were recorded on a VG-16F mass spectrometer. Infrared (IR) spectra were recorded in KBr pellets on a Specord-IR 75 instrument. (~) 1994 Butterworth-Heinemann Steroids, 1994, vol. 59, December 691