Hydrogen transfer steroids

We recently reported that Cu/Si02 is an effective catalyst for the hydrogenation of cyclohexanones under very mild experimental conditions. Thus, a series of cyclohexanones with different substituents, including 3-oxo-steroids, could be reduced under 1 atm of H2 at 40-90°C, with excellent selectivity (5). The catalyst is non-toxic and reusable. This prompted us to investigate the reduction of cyclohexanones over a series of supported copper catalysts under hydrogen transfer (h.t.) conditions (2-propanol, N2, 83 °C) and to compare the results with those obtained under catalytic hydrogenation (n-heptane, 1 atm H2, 40-90°C) conditions. Here we report the results obtained in the hydrogenation of 4-tert-butyl-cyclohexanone, a molecule whose reduction,... 

The stereospecificity of hydrogen transfer for estradiol-17 and estradiol-17(3 dehydrogenases has been examined by George et a/.84>. These enzymes are both present in chicken liver, and have substrates which differ only in the chirality of their substituents at C—17. Both of these enzymes were shown to use the 4-pro-S or 4B proton of the NADPH. Since the steroid is a bulky substrate, the authors argue that the steric fit between pyridine nucleotide and steroid cannot be as important as the role played by the enzyme in directing the fit. This paper contains an interesting summary of other recent work on the stereospecificity of pyridine nucleotide dependent-steroid dehydrogenases. 

CHEMO-, REGIO- AND STEREOSELECTIVITY IN STEROID HYDROGENATION WITH CU/AI2O3. INTRA- AND INTERMOLECULAR HYDROGEN TRANSFER REACTIONS. 

The hydrogen transfer from different secondary alcohols to a steroidic conjugated enone and a saturated ketone in the presence of CU/AI2O3 has been investigated. The stereochemical pathway of the reaction has been studied and the results are compared with those obtained by conventional molecular hydrogen addition in the presence of the same catalyst. 

Preliminary investigation on the reduction of steroidic molecules via hydrogen transfer showed new and interesting features of selectivity3. 

Unsaturated A5-3p-hydroxy steroidic molecules undergo a facile isomerization in toluene solution at 60°C in the presence of Cu on alumina under inert atmosphere. The saturated ketones derived through a formal hydrogen transfer from the alcoholic to the olefinic moiety are formed, besides small amounts of A4-3-ketone. 

Stiver and Yates have studied the photochemical reactions of some hydroxy-keto steroids (28, 29). Irradiation of the isomeric compounds (28a, 29a) showed that the products obtained, (30) and (31) respectively, had retained the configuration of the carbon to which the hydroxy group is attached. The use of deuteriated derivatives (28b, 29b) has identified the hydrogen abstraction processes involved in the conversion of these ketones into the lactones (30b) and (31b) respectively. The authors " propose that there are two major factors which control the stereospecificity of the reactions. These are the shape of the hydroxy-bearing C-atom and the hydrogen transfer within the biradical formed on Norrish Type I fission. The stability of the biradical intermediate clearly plays an important part in determining the outcome of the reactions. 

Syntheses and photochemical behaviour of some azido-steroids have been described. Thermolytic and acid-catalysed reactions have also been studied and compared. Photolysis and thermolysis of azido-steroids led to alkyl migration products, endocyclic imines, and 1-2 hydrogen-transfer compounds, exocyclic imines giving ketones by hydrolysis. Pyrrolidine formation through a nitrene intermediate occurred only in the case of 6/3-azidopregnene. Mechanistic implications were fully discussed. 

Mass spectra of a series of 20-pyridyl steroids were measured, and the fragmentations discussed. Intramolecular hydrogen transfer in mass spectra rearrangements involving the loss of small neutral molecules has been reviewed.The loss of water and ammonia from hydroxy-amino- and amino-steroids was quoted. 

In the mass spectral fragmentation pattern of 3/ -N-demethyl-5a-20(jV)-conene (22), after [2H] labelling in positions 2 and 4, it was demonstrated that hydrogen transfer occurred from C-2 to C-4, giving an insight into the mechanism leading to ions a, characteristic of 3-amino-steroids 14... 

Hydrogenation of steroidal olefin 1 yields only one hydrogenation product 2. Hydrogen transfer occurs from the a-side in a clean cis fashion, indicating that the a-sidc of the molecule is more open for approach of the catalyst3. 

An isomerization step is also involved in the hydrogen transfer reaction of steroidal homoallylic alcohols which takes place in the presence of Cu/AlaOa 12). This process recently allowed us to obtain 95% 5P Isomer in the hydrogenation of ergosterol under inert atmosphere while 98% 5a isomer was obtained under Ha pressure with the same catalyst [3],... 

Many other workers have taken independent advantage of this tendency of radicals to undergo intramolecular hydrogen transfer through 6-membered cyclic transition states to yield highly specific products as in the Barton reaction (20) Most recently, the concept has been extended by Breslow to highly specific substitutions at much more remote sites in the steroid series.(21)... 

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