title: Diversity-oriented synthesis of enantiomerically pure steroidal tetracycles employing Stille/Diels-Alder reaction sequences.
abstract: Various steroid analogues were synthesized by Stille coupling of bicyclo[4.3.0]nonenylstannanes cis-/trans-8 and 14 with cyclohexenol triflates 17 and 18 and subsequent Diels-Alder reactions of the resulting dienes. The enantiomerically pure bicyclo[4.3.0]nonenylstannanes cis- and trans-8 were prepared in good yields via the enol triflates cis- and trans-7, obtained from the bicyclo[4.3.0]non-2-en-3-one 5. The alkenylstannane 14 was obtained from the [2+2] cycloadduct 10 a produced from addition of dichloroketene to the enantiomerically pure and protected bishydroxycyclohexadiene 9 a (65 %). Treatment of 10 a with diazomethane, reduction of the dichloromethylene group, and trapping with tributyltin chloride after lithium-for-bromine exchange, yielded the bicyclo[4.3.0]nonenylstannane 14 (23 % over four steps). Stille couplings provided the tricyclic dienes cis-/trans-19 in good yields (73-77 %), whereas the tricyclic diene 20 was obtained in only 34 % yield at best. Diels-Alder reactions of trans-19 with various reactive dienophiles yielded the novel steroidal compounds trans-21 to trans-26 with complete diastereoselectivity. Heating the dienes cis-19 or 20 with maleic acid derivatives provided the corresponding tetracycles cis-23alpha,beta and 27alpha,beta with a cis-C,D ring junction, each as mixtures of two diastereomers. Less reactive dienophiles required higher temperatures to promote the relevant cycloaddition with trans-19 to furnish several stereoisomeric forms of trans-28 and trans-29 in significantly lower yields (31-45 %). The selected steroid analogues trans-22 and trans-23 were deprotected in two steps by using acid catalysis to provide trans-31 and trans-33 (91 and 80 % over two steps). Cyclopropanation of trans-30 yielded the cyclopropasteroid analogue 34 (74 %), treatment of which with trifluoroacetic acid furnished the cyclopropasteroid 35 and the 2-methyl-substituted steroid analogue 36 in 40 and 12 % yield, respectively. Aromatic B-ring steroids 38 (69 %) and 39 (5 %) were accessed by dehydrogenation of trans-24 with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone.
authors.affiliation: Institut für Organische und Biomolekulare Chemie der Georg-August-Universität Göttingen, Tammannstrasse 2, Göttingen, Germany.
authors.forename: Hans Wolf
authors.initials: HW
authors.lastname: Sünnemann
authors.forename: Martin G
authors.initials: MG
authors.lastname: Banwell
authors.forename: Armin
authors.initials: A
authors.lastname: de Meijere
mesh_terms: D047028:Macrocyclic Compounds / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008958:Models, Molecular; D013055:Spectrophotometry, Infrared; D013237:Stereoisomerism
chemical_list: D047028:Macrocyclic Compounds