Catalytic Oxidative Processes in Steroid Chemistry: Allylic Oxidation, β-Selective Epoxidation, Alcohol Oxidation and Remote Functionalization Reactions

Abstract

The preparation of steroids containing oxygenated functions in suitable positions of the steroid nucleus is of great importance and can be achieved by means of several oxidative processes. In this paper allylic oxidation,  -selective epoxidation, alcohol oxidation and remote functionalization reactions in steroid substrates are reviewed. Focus has been given to catalytic processes because of their major importance from the viewpoint of synthetic organic chemistry. Steroid compounds are widely distributed in nature. The living organism, both animal and vegetable, contains steroids which play an important role in its vital activity. Over the last decades, hundreds of steroid compounds have been isolated from natural sources and many thousands of them have been obtained synthetically. Moreover, steroids are challenging substrates for the synthesis of a wide variety of important biologically active molecules. The preparation of steroids containing oxygenated functions in the steroid nucleus is of major importance and can be performed by means of several oxidative processes. Among the available methods, allylic oxidation,  -selective epoxidation, alcohol oxidation and remote functionalization reactions were chosen to discuss in this review. Special emphasis has been given to the allylic oxidation of steroidal alkenes to the corresponding enones. The  5 -7-keto deri- vatives are of great importance due to their relevant bio- logical properties.  -Selective epoxidation has been consi- dered because the  -epoxides are normally difficult to obtain in organic synthesis. Moreover, this functionality has been found in a number of biologically active steroids, parti- cularly the 5 ,6 -epoxides. The oxidation of steroidal satu- rated, allylic and homoallylic alcohols is also reviewed. Of particular relevance is the synthesis of  4 -3-ketones, a typical functionality of the major class of steroidal hor- mones. Finally, remote functionalization in steroid substrates has been considered. Its practical goal lies in the possibility of obtaining bioactive compounds from readily available sterols or bile acid sources, through regio- and stereo- selective remote oxyfunctionalization of unactivated carbons, avoiding multistep syntheses. Environmentally benign and sustainable transformations are now considered to be basic goals and requirements in the development of modern organic synthesis. There has been a growing effort in the replacement of stoichiometric pro- cedures, using classical toxic waste-producing oxidants, with