LAUSR

Graphical abstract Figure. No Caption available. HighlightsTwo convenient approaches for the synthesis of 7&agr;‐hydroxypregnenolone are reported.Explanation of the stereoselectivity of reduction at C7‐ketone.Potential application to other steroid analogs oxygenated at C7. Abstract 7&agr;‐Hydroxypregnenolone is an endogenous neuroactive steroid that stimulates locomotor activity. A synthesis of 7&agr;‐hydroxypregnenolone from pregnenolone, which takes advantage of an orthogonal protecting group strategy, is described. In detail, the C7‐position was oxidized with CrO3 and 3,5‐dimethylpyrazole to yield a 7‐keto steroid intermediate. The resulting 7‐ketone was stereoselectively reduced to the 7&agr;‐hydroxy group with lithium tri‐sec‐butylborohydride. In contrast, reduction of the same 7‐ketone intermediate with NaBH4 resulted in primarily the 7&bgr;‐hydroxy epimer. Furthermore, in an alternative route to the target compound, the 7&agr;‐hydroxy group was successfully incorporated by direct C–H allylic benzoyloxylation of pregnenolone‐3‐acetate with CuBr and tert‐butyl peroxybenzoate followed by saponification. The disclosed syntheses to 7‐oxygenated steroids are amenable to potentially obtain other biologically active sterols and steroids.