Vinyl-aryl ethers

Another synthesis of the cortisol side chain from a C17-keto-steroid is shown in Figure 20. Treatment of a C3-protected steroid 3,3-ethanedyidimercapto-androst-4-ene-ll,17-dione [112743-82-5] (144) with a tnhaloacetate, 2inc, and a Lewis acid produces (145). Addition of a phenol and potassium carbonate to (145) in refluxing butanone yields the aryl vinyl ether (146). Concomitant reduction of the C20-ester and the Cll-ketone of (146) with lithium aluminum hydride forms (147). Deprotection of the C3-thioketal, followed by treatment of (148) with y /(7-chlotopetben2oic acid, produces epoxide (149). Hydrolysis of (149) under acidic conditions yields cortisol (29) (181). 

The catalysed -elimination of hydrogen bromide from 2-bromoethyl and 1,2-dibromoethyl sulphides, using 9.1.1 or 9.1.2, provides a convenient route to vinyl and alkynyl sulphides, respectively [17, 18], which, as their sulphoxides or sulphones, have considerable utility as dienophiles. Aryl vinyl ethers (>90%) have been obtained by analogous procedures from 2-chloroethyl ethers [19]. 

Diarylethenes, 1,1-diarylallylalcohols and aryl vinyl ethers were succesfully hydroformylated in water/toluene or water/cyclohexane biphasic mixtures with a catalyst prepared in situ from[ RhCl(COD) 2] and TPPTS (Scheme 4.15). Yields of the desired linear aldehyde product were around 80%. This method was applied for the synthesis of the neuroleptics Fluspirilen and Penfluridol (Scheme 4.16) and for other pharmaceutically active compounds containing the 4,4-bis(p-fluorophenyl)butyl group [153]. 

Whereas carbenoid character is definitely present in metalated alkyl vinyl ethers, lithiated alkyl and aryl vinyl sulfides and thioesters, which are easily available by hydrogen-lithium exchange, do not display carbenoid-typical reactions . They rather behave like nucleophilic reagents, so that their discussion is beyond the scope of this overview despite their utility in synthesis The same appiies to various derivatives of enamines, deprotonated in the vinyiic a-nitrogen position - . 

A third mechanistically distinct [3 -1- 2] cycloaddition between vinyl ethers and vinyl-carbenoids was discovered and reported in 2001 [26]. This reaction is remarkable because when Rh2(S-DOSP)4 is used as the catalyst, the cis-cyclopentenes 142 are formed in up to 99% enantiomeric excess. The reaction occurs between vinylcarbenoids unsubstituted or alkyl-substituted at the vinyl terminus and vinyl ethers substituted with an aryl or vinyl group. Some illustrative examples are shown in Tab. 14.12. The reaction is considered to be a concerted process, which would be consistent with the highly stereoselective nature of the reaction [26]. Contrary to the [3-1-2] cycloaddition derived by means of vinylogous carbenoid reactivity, this latest [3 -1- 2] cycloaddition is not influenced by solvent effects. Due to steric demands on the carbenoid, the [3-1-2] cycloaddi-tion only occurs with cis-vinyl ethers. 

Dittami et al. (170,171) was able to generate a carbonyl ylide via photocycliza-tion of an aryl vinyl ether (Scheme 4.85). The photocyclization proceeded through a six-electron rearrangement providing initially the carbonyl ylide, then subsequent to the cyclization, a dipolar cycloaddition takes place with a pendant olefinic tether. 

There are very few examples of photolysis being used for preparation of a carbonyl ylide. The Dittami protocol follows work completed from his lab with aryl vinyl sulfides. Photolysis, followed by cycloaddition, led to the cycloadduct 305 in excellent yield and stereoselectivity. If the aryl vinyl ether 304 was subjected to irradiation in a mixed solution of toluene-methanol at 366 nm rather than a single solvent of toluene, cyclized product was obtained, but no cycloadduct was formed. If a simple phenyl aryl ether was subjected to the same tandem conditions, the cyclized product was generated, but no cycloadduct was detected. 

Diaryl amines, ethers or sulphides, or their aryl vinyl analogues, provide another 6-electron system related to stilbene, but for these a pair of electrons is provided by the single heteroatom (ArXAr or ArXC=C). With dtaryl compounds the initial photocydized product is a zwitterion that undergoes a proton shift to give, for example, N-methyl-4a,4b-dihydrocarbazole from methyldiphenylamine, with subsequent oxidation to N-methylcarbazole (3.74). With the aryl vinyl analogues the product after the proton shift can normally be isolated (3.751. An especially useful variation of this reaction employs... 

Vinyl ethers yield acylated vinyl ethers when they are reacted with aroyl chlorides or 3-thienylcarbo-nyl chloride, triethylamine and a palladium acetate catalyst at 60-70 C (equation 43).103 The products of this reaction are useful 1,3-dicaibonyl equivalents. At higher temperatures the reaction yields arylated vinyl ethers. It is interesting that the acylations of vinyl ethers are regioselective while the direct aryla-tions are usually not.104... 

Trost has used vinyl thioethers to add two carbons with terminal functionalization (3). Vinyl ethers and vinyl acetate give mixtures of products while isopropenyl acetate reacts selectively with aryl halides and at least one vinylic halide. 

The distinction between electrophilic and electron-transfer mechanisms of addition reactions to vinyl double bonds of ArX—CH=CH2 (X = S, O, Se) has been achieved by studying substituent effects. Specifically, the effects of meta and para substituents on the rates of electrophilic additions correlated with Hammett radical cations correlates with statistical tests. The ofclcctrophilicj/o-1 (FT) dichotomy is in accord with the conventional paradigm for cr/cr+ correlations and further support has been found by ah initio calculations. Interestingly, the application of this criterion to the reactions of aryl vinyl sulfides and ethers with tetracyanoethylene indicates that cyclobutanes are formed via direct electrophilic addition to the electron-rich alkene rather than via an electron-transfer mechanism.12... 

Heck arylation of vinyl ether 160 with 4-bromoacetophenone and 1-bromonaphthalene, respectively, catalyzed by [Pd(C3Hs)Cl]2 and using Tedicyp, as a ligand, gave dioxepanes 163 and 164 together with a mixture of regioisomeric aryl vinyl ethers 161 and 162 (Scheme 44) <2006EJ0765>. 

Addition to quinone monoketals and quinol ethers.2 Complexation of quinone monoketals or quinol ethers with MAD permits 1,4-addition of organo-lithium and Grignard reagents. Highest yields obtain with aryl, vinyl, and acetylenic organometallics. 

The reaction mechanism of photocyclization of aryl vinyl ethers was derived from results obtained by means of flash photolysis. The ground state intermediate rearranges by mono-or bi-molecular 1,4-hydrogen shifts to yield the products (Scheme 62) (81JOC978). The photocyclization of 2-aryloxyenones was used in the total synthesis of ( )-lycoramine (77JA8065). The formation of dihydrobenzo[6 ]furans by radical cyclization from o-allenyl-oxyarenediazonium salts with tri-n-butyltin(IV) hydride was successful (81CC136). 

Singular examples to form aromatic ethers are a base-catalyzed, multistep, one-pot reaction of aryl methyl ketones with the appropriate fluorinated arylidenemalonitriles, the mercury acetate assisted synthesis of pentahalophenylvinyl ethers from vinyl acetate and the corresponding phenol, and the radical displacements in aryloxycyclohexadienones (e.g., 27) by halophenols. 2,3-Dichloro-5,6-dicyanohydroquinone (28) and products such as 29 are readily formed when cyclohexadienone 27 is treated with different phenols. 

The photocyclodimerization of JV-vinylcarbazole, which was reported by Ledwith and Shirota, can be accounted for by this mechanism [71-73]. A chain process is involved in this photoreaction, and the quantum yield exceeds unity (the maximum quantum yield is 66). The hole transfer from the cyclobutane radical cation to a neutral JV-vinylcarbazole is a key reaction for the chain process. Similar photodimerizations of electron-rich alkenes such as aryl vinyl ethers [74-76], indenes [29, 77, 78], styrenes [79-80] and enamines [71] have been reported by several groups. The DCA-sensitized photodimerization of phenyl vinyl ether gives cis- and trans-1,2-diphenoxycyclobutanes. This photoreaction also involves a chain process although the chain length is short [75]. 

Dehydrohalogenation. Aryl vinyl ethers are prepared conveniently by dehy-drohalogenation of aryl 2-haloethyl ethers with aqueous sodium hydroxide with tetra-n-butylammonium hydrogen sulfate as phase-transfer catalyst (equation I). 

Reaction of aryl vinyl ethers, however, invariably gives mixtures of diazetidines and oxadiazines. The ratio is mainly dependent on the nature of the substituent on the phenyl group and, in part, on the nature of the alkyl group of the dialkyl diazenedicarboxylate and the solvent substituents which enhance the nucleophilicity of the alkene and the electrophilicity of the diazene, and polar solvents that favor a polar mechanism, result in concurrent formation of the diazetidine as the predominant product and vice versa15, l< Similarly, diazetidines 7 and oxadiazines 8 are formed in comparable yields in the reactions of vinyl sulfides with dimethyl diazenedicarboxylate, the ratio is principally dependent on the nature of the sulfur substituent (aryl, alkyl)17. 

Reaction of diphenyl diselenide or dimethyl diselenide with hydrazine hydrate and sodium hydroxide generates the corresponding selenolates smoothly in solvents like DMF or diethyl ether and in the presence of tetrabutylammonium chloride as a phase-transfer catalyst [13]. The selenolates react with organic halides to give various selenides (Scheme 9). Similar conditions have been applied to the synthesis of aryl vinyl selenides from diaryl diselenides and acetylene [14]. 

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