one (5), from the D1-3-keto enone, (5a,17b)-3-oxo-5-androst-1-en-17-yl acetate (1), through a strategy involving the reaction of D1-3-hydroxy allylic alcohol, 3b-hydroxy-5a-androst-1-en-17b-yl acetate (2), with SOCl2 , was revisited in order to prepare and biologically evaluate 5 as aromatase inhibitor for breast cancer treatment. Surprisingly, the followed strategy also afforded the isomeric D2-olefin 6 as a byproduct, which could only be detected on the basis ofNMR analysis. Optimization of the purification and detection procedures allowed us to reach 96% purity required for biological assays of compound 5. The same synthetic strategy was applied, using the D4-3-keto enone, 3-oxoandrost-4-en-17b-yl acetate (8), as starting material, to prepare the potent aromatase inhibitor D4-olefin, androst-4-en-17-one (15). Unexpectedly, a different aromatase inhibitor, the D3,5-diene, androst-3,5-dien-17-one (12), was formed. To overcome this drawback, another strategy was developed for the preparation of 15 from 8. The data now presented show the unequal reactivity of the two steroidal A-ring D1- and D4-3-hydroxy allylic alcohol intermediates, 3b-hydroxy-5a-androst-1-en-17b-yl acetate (2) and 3b-hydroxyandrost-4-en-17byl acetate (9), towards SOCl2 , and provides a new strategy for the preparation of the aromatase inhibitor 12. Additionally, a new pathway to prepare compound 15 was achieved, which avoids the formation of undesirable by-products. ; The authors thank FCT (FundaÅa˜o para a Cieˆncia e Tecnologia) for the strategic project PEst-OE/ SAU/UI0177/2011. Carla Varela also thanks FCT for a Ph.D. fellowship (SFRH/BD/44872/2008). We also acknowledge the Rede Nacional de RMN for access to the facilities. The Varian VNMRS 600 MHz spectrometer is part of the National NMR Network and was purchased with in the framework of the National Programme for Scientific Re-equipment, contract REDE/1517/RMN/2005, with funds from POCI 2010 (FEDER) and (FCT). The work was also funded by FEDER Funds through the Operational Competitiveness Program-COMPETE and by National Funds through FCT- FundaÅa˜o para a Cieˆncia e Tecnologia under the project FCOMP-01 – 0124-FEDER-020970 (PTDC/QUI-BIQ/120319/2010). The authors are also grateful to Laboratory of Mass Spectrometry (LEM) of the Node CEF/UC, integrated in the National Mass Spectrometry Network (RNEM) of Portugal, for the MS analyses.