title: Addition reactions at the 16(17) double bond of 3-methoxy-13alpha-estra-1,3,5(10),16-tetraene.
abstract: The epoxidation, the addition of hypobromous acid, and the hydroboration of 3-methoxy-13alpha-estra-1,3,5(10),16-tetraene 1 with diborane, catecholborane, and 9-BBN were investigated in order to determine the stereochemical outcome and to synthesize new 13alpha-estra-1,3,5(10)-trienes for biological and conformational investigations. It was shown that the sterically demanding reagent 9-BBN participated in a preferred beta attack (53% 16betaOH 10, 34% 17betaOH 8, 13% 16alphaOH 11). This stereochemical result is in agreement with that from another cis addition reaction, the recently described OsO4 dihydroxylation of 1 [Steroids 68 (2003) 113]. With smaller reagents such as B2H6, catecholborane, or magnesium monoperoxyphthalate, a diminished stereoselectivity was observed with only a slight excess of beta attack. The ionic trans addition of hypobromous acid gave two 17-bromo-16-alcohols with 16beta,17alpha (4, 76%) and 16alpha,17beta configuration (5, 24%) formed by trans cleavage of the 16,17alpha- and beta-bromonium ion at position 16. The same regioselective and stereoselective course was found for the cleavage of the 16alpha,17alpha- and 16beta,17beta-epoxides (3 and 2) with hydrazoic acid (3-->16betaN3,17alphaOH 7, 2-->16alphaN3,17betaOH 6). The stereochemistry of the addition reactions to 1 can be explained in terms of a twist-boat conformation involving the C ring of compound 1. From a synthetic viewpoint the synthesis of the beta-epoxide 2 from the bromohydrin 4, the cleavage of this epoxide to 16alpha-substituted-17beta-hydroxy compounds, such as 6, and hydroboration/oxidation with 9-BBN to the hitherto unknown 16beta-hydroxy compound 10 are useful procedures. The bromohydrin 5 is the first 13alpha-steroid with a 17beta-bromo substituent. X-ray analysis revealed twist-boat and 16beta-envelope conformations for rings C and D, respectively.
authors.affiliation: Department of Organic Chemistry, University of Szeged, Dóm tér 8, H-6720, Szeged, Hungary.
authors.forename: Erzsébet
authors.initials: E
authors.lastname: Mernyák
authors.forename: Bruno
authors.initials: B
authors.lastname: Schönecker
authors.forename: Corinna
authors.initials: C
authors.lastname: Lange
authors.forename: Manuela
authors.initials: M
authors.lastname: Kötteritzsch
authors.forename: Helmar
authors.initials: H
authors.lastname: Görls
authors.forename: János
authors.initials: J
authors.lastname: Wölfling
authors.forename: Gyula
authors.initials: G
authors.lastname: Schneider
mesh_terms: D001894:Borohydrides / Q000138:chemical synthesis / Q000737:chemistry; D001896:Boron Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis / Q000737:chemistry; D001959:Bromates / Q000737:chemistry; D002625:Chemistry, Organic / Q000379:methods; D004852:Epoxy Compounds / Q000737:chemistry*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D013237:Stereoisomerism; D014961:X-Ray Diffraction
chemical_list: D001894:Borohydrides; D001896:Boron Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001959:Bromates; D004852:Epoxy Compounds; C454803:9-borabicyclononane; D004958:Estradiol; C024731:diborane; C027664:hypobromous acid