Alkenes steroidal double bonds

Acetoxy-l,7-octadiene (40) is converted into l,7-octadien-3-one (124) by hydrolysis and oxidation. The most useful application of this enone 124 is bisannulation to form two fused six-membered ketonesfl 13], The Michael addition of 2-methyl-1,3-cyclopentanedione (125) to 124 and asymmetric aldol condensation using (5)-phenylalanine afford the optically active diketone 126. The terminal alkene is oxidi2ed with PdCl2-CuCl2-02 to give the methyl ketone 127 in 77% yield. Finally, reduction of the double bond and aldol condensation produce the important intermediate 128 of steroid synthesis in optically pure form[114]. 

In the carbonylation of trans,trans,cis-CDT, the trans double bond is attacked preferentially to give the monoester 10, and then the diester 11. Attack of the cis double bond to give the triester is slow[15]. Only the C-16 alkene was carbonylated regio- and stereoselectively to give the Ibo-carboxy-late 12 by carbonylation of the C-5 and C-16 unsaturaied steroid[]6]. 

Bromo [ F]fluoride (Section 3.9.1) addition across a double bond was used in the synthesis of fluorine-18-labelled steroids of high specific radioactivity. After addition, the bromine is removed by reduction or by dehydrobromination. [ F]Fluoro-5a-dihydrotestosterone was obtained in about 3% radiochemical yield (Scheme 17) [64] and 6a-p F]fluoroprogesterone in only 0.3% [65]. The yields were quite low but sufficient to allow for animal studies. These reactions had been tested out successfully with simpler model alkenes [66]. 

The discussion of the planar C=C chromophore will be divided into two classes in the first, substituted cyclic alkenes will be discussed, while the second class will present the aliphatic planar moiety. In the first class, we will concentrate mostly on small cyclic compounds rather than on steroidal compounds containing a double bond. Among the first cycloalkenes studied was 3-methylcyclobutene28. Its absorption was reported in the... 

Reductive desulfonylation.1 A stereocont rolled method for addition of the steroid side chain to a 17-keto steroid is outlined in scheme (I). The various steps proceed selectively to the sulfone 5. Reductive desulfonylation of 5 with Na/Hg, Na2HP04 in CH3OH gives the desired 6 (57% yield) and the undesired alkene in a 2 1 ratio. The desired stereoselectivity was obtained with lithium in ethylamine. The final step was hydrogenation of the 17(20)-double bond to give a protected cholesterol (7). 

Another approach to improved chemoselectivity utilizes sterically hindered alkenes, as reported by Konoike et al. (Scheme 3.25) [115]. Ursolic add 12, a steroid with a highly congested trisubstituted double bond, undergoes allylic hydroxylation at the C-ll position with MCPBA and tetrakis(pentafluorophenyl)porphyrin iron chloride [Fe(PFPP)Cl] as a catalyst to give a single diastereomer 13 in 91% yield. With sterically less encumbered systems only epoxidation was observed. 

Although epoxidation reactions are treated in detail elsewhere in these volumes, it should be mentioned here that a template ester attached to a steroid alkene can direct epoxidation to remote double bonds using the general concepts of remote functionalization. Steroidal diene (5) underwent the epoxidation shown (Scheme 13) with excellent regiochemical and stereochemical control. The product was formed in quantitative yield, although the reaction was carried through to only 25% conversion. 

In contrast to lead tetraacetate, simple addition to the double bond does not occur as a side re-action. While allylic rearrangement is common and mixtures of products are frequently obtained, the reaction often proceeds in very high yield and is simple to carry out the alkene is simply heated in an appropriate solvent with mercury(II) acetate until reaction is complete. Mercury(II) acetate has also been us for dehydrogenation, particularly in the steroid field. One interesting example incorporating simultaneous dehydrogenation and allylic oxidative rearrangement is seen in the reaction of abietic acid (37 equation 16). ... 

The reaction of alkenes with iodosobenzene in acetic acid in the presence of sodium azide offers a simple and high yield route to 1,2-diazides (Table 3)76. a-Azido ketones are side products or the exclusive product from the reaction with conjugated alkenes. Allylic azides or oxonitriles, resulting from oxidative cleavage of the C-C double bond, are alternatively obtained from trisubstituted steroid alkenes77. 

Arnone et al. studied the epoxidation of various olefins 220 with perfluorinated oxaziridine 80 (Equation 10) <1996JOC8805>. Alkyl-substituted olefins are epoxidized with this oxaziridine under particularly mild conditions. Electron-deficient substrates can also be epoxidized, and the more electron deficient the double bond is, the more severe the reaction conditions become. The reaction is chemoselective and stereoselective, with air-alkenes affording air-epoxides. Various complex and polyfunctionalized substrates of natural origin (monoterpenes, sesquiterpenes, and steroids) have been epoxidized effectively with this reagent (Table 18). 

The hydrogenation of alkenes conjugated to aromatic systems is usually much less difficult than partial reduction of polyenes, as the aromatic ring is less susceptible to reduction. Many catalysts of Group 10 metals have been used for this transformation, including Raney nickel, Pd adsorbed on carbon, Pd adsorbed on calcium carbonate, Pd on barium sulfate, metallic palladium, PtOa, chloroplatinic acid or platinum metal. Normally, the stereochemistry of the reduced product arises from syn addition of a hydrogen molecule to the less-hindered face of the double bond, as exemplified in the catalytic hydrogenation of a steroidal styrene over metallic palladium (Scheme 93). ... 

Vinyl halides represent yet another important class of intermediates in the conversion of ketones to alkenes. The most widely applied conditions for the conversion of ketones into vinyl halides are those developed by Barton et a/. ° for the conversion of 3p-acetoxyandrost-5-ene-17-one into 3P-hydroxyandrosta-5,16-diene (Scheme 44). These conditions of vinyl halide formation and subsequent reduction have been useful in a number of steroid systems for the introduction of a A -carbon-carbon double bond and have been shown to be compatible with such functional groups as alcohols, isolated double bonds and acetals. The scope of vinyl iodide formation from hydrazones has been studied by Pross and Stemhell, and recently the original reaction conditions were improved by using sterically hindered guanidine bases rather than triethylamine. Haloalkenes have also been prepared from the corresponding ketones by treatment with iodoform and chromium chloride or with phosphorous penta-halides. ... 

A very interesting way to control alkene epoxidation was introduced by Breslow and Meresca. In the steroid diene, 77, epoxidation takes place exclusively at the 4,5 double bond using Mo(CO)6 and TBHP. However, by attaching a template, as in 78, to the alcohol, the regioselectivity could be inverted so that epoxidation takes place only at the 17,20 double bond. It was concluded that the appendage did not act as a steric shield, but the remote tertiary alcohol moiety was transformed in situ to a hydroperoxide resulting in the observed selectivity by intramolecular epoxidation. This approach was then extended to other functionalized polyenes, such as famesol and geranylgeraniol. ... 

Alkenes and polyenes (alkenes with several carbon-carbon double bonds) are common in nature. Ethene, the simplest alkene, is a plant growth substance involved in fruit ripening, senescence and leaf fall, and responses to environmental stresses. Isoprenoids, or terpenes, are polyenes built from one or more isoprene units. Isoprenoids include steroids, chlorophyll and other photos)mthetic pigments, and vitamins A, D, and K. 

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