Steroid Olefins

An indication of the most frequently used routes for the synthesis of common steroid olefin systems follows below. 

Several steroid olefins, especially A -steroids, do not give exclusive a-epoxidation. The a-oxirane usually predominates in the epoxidation mixture, its proportion varying from 50% to 90% or greater when either perbenzoic acid or monoperphthalic acid is employed. The claims that the ratio of a- to p-epoxide is high in compounds containing a keto group d or a j5-substituent at may be misleading since epoxidation of 17a,20 20,... 

As electrophilic substitutes for peracids, the use of borate ester induced decomposition of alkyl hydroperoxides and molybdenum VI peroxy-complexes have been reported in the recent literature. Although these reagents have led to the epoxidation of olefins in greater than 90% yield there are no reports yet of their application to steroid olefins. 

The addition proceeds most smoothly with highly functionalized (more polar) steroids as seen in examples by Bernstein and others. The polar reaction conditions pose solubility problems for lipophilic androstane, cholestane and pregnane derivatives. Improved yields can be obtained in some cases by using dimethyl sulfoxide or t-butanol " as solvents and by using sodium A-bromobenzenesulfonamide or l,3-dibromo-5,5-dimethyl hydantoin (available from Arapahoe Chemicals) as a source of positive bromine. The addition of bromo acetate and bromo formate to steroid olefins has been studied to a limited extent. ... 

Among the more exotic methods which have been used for the direct epoxidation of steroid olefins are chromic acid, ozone, e.g., (84), and photochemical oxygenation. Ozone is useful for the epoxidation of the unreactive 8,9-olefin, but the results of the other unusual methods can usually be duplicated by the methods of epoxidation discussed above. 

The Addition of Hypobromous Acid HOBr) to Steroid Olefins... 

The elements of bromine azide have been added to steroid olefins. The addition can be rationalized as proceeding through a positive bromonium ion under the ionic conditions of Hassner and Boerwinkle (bromine plus sodium azide and hydrochloric acid in nitromethane-dichloromethane) or Ponsold (A-bromosuccinimide or A-bromoacetamide in chloroform contain-... 

Additions of the halogen fluorides to unsaturated steroids [62, 95, 96, 97, 98, 99] and carbohydrates [62, 75] are well known Typical reagent combinations include l,3-dibromo-5,5-dimethylhydantoin (DBH) or the Af-halosuccinimides with hydrogen fluoride Reversal of the expected regiochemistry can be observed with certain steroidal olefins [JOO, 101] (equation 7)... 

Nitrosyl fluoride reacts with steroidal olefins to give, ultimately, a-fluo-roketones [131], with steroidal vinyl lluorides, the reaction provides a,a di fluoroketones from intermediate nitroimines [197] (equation 34)... 

Tnmethyl(trifluororaethyl)tin can also be prepared via in situ formation and capture of tnfluorometbide by trimethyltin chlonde [13, 14] (equation 9) This tin analogue has been used as a precursor for difluorocarbene either by thermal decomposition or by reaction with sodium iodide m 1,2-dimethoxyethane This carbene generation procedure has been used to study difluorocarbene selectivity with steroidal olefins [75] (equation 10). 

Oxidation of the steroidal olefin (XXVII) with thallium(III) acetate gives mainly the allylic acetates (XXXI)-(XXXIII) (Scheme 15), again indicating that trans oxythallation is the preferred reaction course (19). Addition of the electrophile takes place from the less-hindered a-side of the molecule to give the thallinium ion (XXVIII), which by loss of a proton from C-4 would give the alkylthallium diacetate (XXIX). Decomposition of this intermediate by a Type 5 process is probably favorable, as it leads to the resonance-stabilized allylic carbonium ion (XXX), from which the observed products can be derived. Evidence in support of the decomposition process shown in Scheme 15 has been obtained from a study of the exchange reaction between frawr-crotylmercuric acetate and thallium(III) acetate in acetic acid (Scheme 16) (142). 

The RDA reaction is often observed from steroid molecular ions, and it can be very indicative of steroidal stmcture. [107,110,113,114] The extent of the RDA reaction depends on whether the central ring junction is cis or trans. The mass spectra of A -steroidal olefins, for example, showed a marked dependence upon the stereochemistry of the A/B ring juncture, in accordance with orbital symmetry rules for a thermal concerted process. In the trans isomer the RDA is much reduced as compared to the cis isomer. The effect was shown to increase at 12 eV, and as typical for a rearrangement, the RDA reaction became more pronounced, whereas simple cleavages almost vanished. This represented the first example of such apparent symmetry control in olefinic hydrocarbons. [114]. 

Flanagan, V. P. and Ferretti, A. 1974. Characterization of two steroidal olefins in nonfat dry milk. Lipids 9, 471-475. 

Several tr-allyl palladium chloride complexes have been prepared from steroidal olefins. Reaction of cholest-4-ene (65), for example, with bis(benzonitrile)palladium dichloride produced dimeric complexes of structures (66) and (67) (76). 

Figures 4a—c. Capillary column gas chromatograms of the aromatic hydrocarbon fraction of selected samples from the Nordlinger Ries. M+ = molecular ion, BP = base peak in the corresponding mass spectra. The sample from 151.5 m of well NR-10 contains steroid olefins due to incomplete liquid chromatography separation.

RATE DATA FOR SOME STEROIDAL OLEFINS RELATIVE TO CYCLOHEXENE... 

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