11-Aryl steroids, formation

Treatment of oestrone with tetraphenylbismuth monotrifluoroacetate gave oestrone phenyl ether and exemplified, in part, a new procedure for aryl ether formation.31 A detailed study was reported of the formation of benzyl ethers by sequential reaction of alcohols with chloro(phenylmethylene)dimethylammonium chloride and sodium hydrogen telluride.32 Steroidal alcohols, inter alia, were converted into hydrolytically stable silyl ethers by reaction with B N Sil or BulPh2I which were generated in situ from the selenosilane and iodine.33 The 5a-hydroxycholestane (21) was protected in this way. 

In the enantioselective synthesis of a cardenolide precursor, the congested quaternary carbon center and the cw-AB ring fusion in the steroid skeleton 224 were constructed by cyclization of the alkenyl triflate 223 [102]. Similarly critical quaternary carbon-aryl bond formation took place by the cyclization of the bromopyridine 225 to afford the pyridinomorphinan 226 using 60 mol% Pd triflu-oroacetate and PPhs [103]. 

Allenes also react with aryl and alkenyl halides, or triflates, and the 7r-allyl-palladium intermediates are trapped with carbon nucleophiles. The formation of 283 with malonate is an example[186]. The steroid skeleton 287 has been constructed by two-step reactions of allene with the enol trillate 284, followed by trapping with 2-methyl-l,3-cyclopentanedione (285) to give 286[187]. The inter- and intramolecular reactions of dimethyl 2,3-butenylmalonate (288) with iodobenzene afford the 3-cyclopentenedicarboxylate 289 as a main product) 188]. 

Allyl aryl ethers are used for allylation under basic conditionsfh], but they can be cleaved under neutral conditions. Formation of the five-membered ring compound 284 based on the cyclization of 283 has been applied to the syntheses of methyl jasmonate (285)[15], and sarkomycin[169]. The trisannulation reagent 286 for steroid synthesis undergoes Pd-catalyzed cyclization and aldol condensation to afford CD rings 287 of steroids with a functionalized 18-methyl group 170]. The 3-vinylcyclopentanonecarboxylate 289, formed from 288, is useful for the synthesis of 18-hydroxyestrone (290)[I7I]. 

Miscellaneous Methods of Preparing Phosphines. Palladium-catalysed formation of phosphorus-carbon bonds continues to be developed as a useful route to organophosphines. The reactions of primary or secondary phosphines with aryl- or vinyl-halides in the presence of a palladium catalyst, usually palladium acetate or a zerovalent palladium-phosphine complex, have been used in the synthesis of steroidal phosphines, e.g., (128), the cationic diphosphine system... 

STs are simple phenols such as 4-nitrophenol, phenolic catecholamine neurotransmitters such as dopamine, phenolic steroids such as the estrogens, non-phenolic hydroxy-steroids such as dehydroepiandrosterone (DHEA) and in plants, flavonols such as quercetin. Cytosolic STs are also actively involved in the Al-sulfation of alkyl- and aryl-amines, as well as alkyl- and arylamides leading in some cases to the formation of unstable metabolites. 

On the other hand, quinolinyl nucleophiles as the quinolinylzinc derivatives presented in the following example have been prepared by the in situ transmetallation of quinolinyllithium salts realized by direct halogen-metal exchange of 6-bromo quinoline derivative. The zinc salt was allowed to react with several aryl bromides, affording clean Negishi reactions for the formation of 6-substituted derivatives, which are potent inhibitors of steroid 5a reductases of types 1 and 2 ... 

Although the aryl-aryl C-C coupling of steroids, bearing the anisole fragment in their structure, with 1,2,4-triazinones results in the formation of two region-isomeric compounds, it demonstrates a successful application of the Sn methodology for C-H functionalization of this important class of bioregulators (Scheme 49) [158],... 

Steroid hormones can be inactivated by conjugation and degradation. Conjugation involves the formation of either glucuronides or aryl sulfates. Steroids are conjugated with glucuronic acid in the presence of a liver microsomal enzyme and UDP-glucuronic acid. 

Sulphate conjugates, once called ethereal sulphates because of their extraction characteristics, are of two major types aryl or alkyl sulphates (which are esters of phenols or alcohols) and steroid sulphates. The sulphate moiety is transferred from the cofactor adenosine-3 -phosphate-S -phosphosulphate (PAPS) to an acceptor by enzymes known as sulphotransferases or sulphokinases. The enzymes which catalyse the formation of PAPS as well as the sulphokinases are in the soluble fraction of liver ... 

Other Reactions with AgF. Treatment of vicinal di-bromo steroids with aqueous AgF results in the formation of epoxides.The AgF-initiated methanolysis of 2,2-dibromo-1,3-dimethylcyclopropanecarboxylic acid has also been studied in detail. Thiophilic heavy metal salts such as AgF have been used for ring opening of penicillin derivatives (eq 14), although other catalysts such as silver(I) oxide are better. Treatment of ( )-aryl- and -alkenylpentafluorosilicates with silver fluoride affords symmetrical ( , )-1,3-dienes in high yields (eq 15). ... 

The method developed by Cacchi and Lupi for the hydroxycarbonylation of various aryl triflates including steroidal substrates [69] was used effectively for the synthesis of an intermediate of the biologically active 8,10-di-O-methylbergenin [70]. The conversion of the rather unreactive aryl triflate substrate was achieved using DMSO as solvent that was shown to play a crucial role in the catalytic cycle by facilitating decomposition of the in situ formed acylpalladium complex and formation of the carboxylic acid product [69]. 

One of the first reports of a microwave-assisted palladium-catalyzed reaction for the formation of an arylphosphine oxide described the synthesis of progesterone antagonists (Scheme 4.198) [335]. The chemistry was based upon functionalization of the aromatic group on the lip-position of the steroid core. An aryl triflate and a secondary phosphine... 

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