Stille-Heck coupling sequences applied in a versatile new access to steroid skeletons.
A variety of enantiomerically pure steroidal compounds was synthesized utilizing a sequence of Stille and Heck cross-coupling reactions and subsequent thermal 6pi-electrocyclizations. Highly chemoselective Stille couplings on the triflate moiety of several 2-bromocyclohex-1-enyl triflates with cis- and trans-fused bicyclo[4.3.0]nonenylstannanes furnished the corresponding tricyclic bromobutadienes in good to excellent yields (70-97%). These were subjected to Heck reactions with tert-butyl acrylate to provide pentasubstituted tricyclic 1,3,5-hexatrienes. A significant increase in efficiency could be achieved by applying a novel protocol with a precatalyst on the basis of the palladacycle prepared from Pd(OAc)2 and P(o-Tol)3 with added triarylphosphines as co-ligands (73-90% yield). Upon heating to 205-215 degrees C in decalin or to 140 degrees C in toluene (for certain cases), these hexatrienes yielded (78-90%) various unsaturated steroid analogues as single diastereomers. A particular oxohexatriene, obtained after deprotection of an adjacent carbonyl group, underwent 6pi-electrocyclization at the unusually low temperature of 140 degrees C to yield (75%) an interesting 7-carboxyl-substituted steroidal dienone. Attempts to remove the remaining protecting groups from some of the other new steroidal compounds under acidic conditions furnished a novel 3-oxo-7-carboxyl steroid analogue and a 3-hydroxy-substituted steroidal diene. A novel estradiol derivative could be obtained in 69% yield from the synthesized steroidal dienone. Deprotection furnished the corresponding unprotected 7-carboxylestradiol in 81% yield.
Sünnemann
Hans Wolf
HW
Institut für Organische und Biomolekulare Chemie, Georg-August-Universität Göttingen, Tammannstrasse 2, 37077 Göttingen, Germany.
Hofmeister
Anja
A
Magull
Jörg
J
de Meijere
Armin
A
D002384:Catalysis; D002625:Chemistry, Organic / Q000379:methods; D003432:Cross-Linking Reagents / Q000737:chemistry; D003500:Cyclization; D015394:Molecular Structure; D013237:Stereoisomerism; D013256:Steroids / Q000138:chemical synthesis* / Q000737:chemistry*; D013696:Temperature
D003432:Cross-Linking Reagents; D013256:Steroids