Stereoselective Alkylation of 7-Hydroxy-DHEA Derivatives

Abstract

A series of 7-hydroxysteroids were stereoselectively alkylated with a variety of electron-rich nucleophiles to give 7-α-substituted steroids.

alkylations - steroids - Lewis acids - stereoselective - eliminations

References and Notes

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For similar reactions on simple nonsteroidal substrates, see:

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Nomenclature: 13a refers to the product 13 with the a nucleophile at the 7-position.

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The Multimax is a device used to monitor reactions by heat flow. This is accomplished by comparing the system’s jacket temperature (T_j) and the reaction temperature (T_r). T_r-T_j when plotted in real time gives a measure of the course of the reaction.

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<A NAME="RS02507ST-10">10</A> For a related process, see: Rueping M. Nachtsheim BJ. Kuenkel A. Org. Lett.  2007,  9:  825 

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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 T_r-T_j profile and by TLC (50% EtOAc-hexane). After complete reaction, H₂O 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.