Oxidative fragmentation of pregna-14,16-dien-20-ones to 14 beta-hydroxyandrost-15-en-17-ones.
Two methods have been developed for efficient conversion of pregna-14,16-dien-20-ones into 14 beta-hydroxyandrost-15-en-17-ones. One procedure consists of treatment of the ring-D dienone successively with sodium borohydride and singlet oxygen. The reaction is illustrated by the conversion of pregna-14,16-dien-20-one 1 into 14 beta-hydroxyandrost-15-en-17-one 3, via the corresponding allylic alcohol 2. Although this two-step procedure is simple, it provides 3 in relatively low yield, accompanied by a smaller amount of the isomeric 14 alpha-hydroxyandrost-15-en-17-one 6. An alternative one-step conversion is achieved by treatment of dienone 1 with a peroxyacid in the presence of a strong protic acid. This process is illustrated by the two-step conversion of dienone 1 into hydroxy ketone 11 in 51% overall yield (Scheme 5) and by the analogous conversion of dienone 13 into hydroxy ketone 24 in 61% overall yield (Scheme 11).
Fell
Jennifer D
JD
Center for New Directions in Organic Synthesis, Department of Chemistry, University of California, Berkeley, California 94720, USA.
Heathcock
Clayton H
CH
D002301:Cardiac Glycosides / Q000138:chemical synthesis / Q000737:chemistry; D002384:Catalysis; D002625:Chemistry, Organic / Q000379:methods*; D006915:Hydroxytestosterones / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry; D011245:Pregnadienes / Q000737:chemistry*; D013237:Stereoisomerism
D002301:Cardiac Glycosides; D006915:Hydroxytestosterones; D011245:Pregnadienes; D010100:Oxygen