Abstract
A series of 7-hydroxysteroids were stereoselectively alkylated with a variety of electron-rich nucleophiles to give 7-α-substituted steroids.
Key words
alkylations - steroids - Lewis acids - stereoselective - eliminations
References and Notes
1 Rabasseda X.
Silvestre J.
Castañer J.
Drugs Future
1999,
24:
488
2 McMahon EG.
Curr. Opin. Pharmacol.
2001,
1:
190
3a Pearson WH.
Schkeryantz JM.
J. Org. Chem.
1992,
57:
2986
3b Malkov AV.
Davis SL.
Baxendale IR.
Mitchell WL.
Kocovsky P.
J. Org. Chem.
1999,
64:
2751
3c Malkov AV.
Davis SL.
Baxendale IR.
Mitchell WL.
Kocovsky P.
J. Org. Chem.
1999,
64:
2764
4 Nomenclature: 13a refers to the product 13 with the a nucleophile at the 7-position.
5 Negi AS.
Dwivedy I.
Roy R.
Ray S.
Steroids
1995,
60:
470
6 Pearlman BA, Padilla AG, Havens JL, Mackey SS, and Wu H. inventors; WO 2003082895 A2. For an alternative approach to alkylating the 7-position of a steroid with 2-methylfuran, see:
7 Wuts PGM.
Ashford SW.
Anderson AM.
Atkins JR.
Org. Lett.
2002,
5:
1483
8 The Multimax is a device used to monitor reactions by heat flow. This is accomplished by comparing the system’s jacket temperature (Tj ) and the reaction temperature (Tr ). Tr -Tj when plotted in real time gives a measure of the course of the reaction.
9 Ha TBT.
Djerassi C.
Tetrahedron Lett.
1985,
26:
4031
10 Rueping M.
Nachtsheim BJ.
Kuenkel A.
Org. Lett.
2007,
9:
825
11
Typical Experimental
A solution of diacetate 1 (2.0 g, 5.15 mmol) and 2-methyl-furan (2.0 mL) in 20 mL of MeCN was equilibrated to 20 °C in the Mettler Multimax. Then Sc(OTf)3 (200 mg, 0.46 mmol) was added. The reaction was monitored by observing the Tr -Tj profile and by TLC (50% EtOAc-hexane). After complete reaction, H2 O was added to the mixture and the product isolated with EtOAc. Crystallization from EtOAc-hexane afforded 1.71 g of product. The mother liquors were chromatographed on silica gel with 25% EtOAc-hexane to afford an additional 350 mg for a total of 97% yield.
