Aryl ethers with lithium

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). 

Aryl and alkyl trimethylsilyl ethers can often be cleaved by refluxing in aqueous methanol, an advantage for acid- or base-sensitive substrates. The ethers are stable to Grignard and Wittig reactions and to reduction with lithium aluminum hydride at —15°. Aryl -butyldimethylsilyl ethers and other sterically more demanding silyl ethers require acid- or fluoride ion-catalyzed hydrolysis for removal. Increased steric bulk also improves their stability to a much harsher set of conditions. An excellent review of the selective deprotection of alkyl silyl ethers and aryl silyl ethers has been published. ... 

A solution of the sodium salt of yV-methylaniline in HMPA can be used to cleave the methyl group from aryl methyl ethers ArOMe + PhNMe —> ArO + PhNMca- This reagent also cleaves benzylic groups. In a similar reaction, methyl groups of aryl methyl ethers can be cleaved with lithium diphenylphosphide (PH2PLi). " This reaction is specific for methyl ethers and can be carried out in the presence of ethyl ethers with high selectivity. 

Aromatic ketones 569, benzylic alcohols 570 and 571 as well as alkyl aryl ethers 572 reacted with lithium under ultrasonic irradiation in the presence of catalytic amounts of DTBB (2%) in THF to give, after alkylation with an alkyl iodide at 0°C and final... 

MeOC6H4, respectively. The titanium enolates were converted into silyl enol ethers 54 by treatment with chlorotrimethylsilane and lithium isopropoxide. Additionally, cyclic enones lb and Ic, and linear enones Id and le, are also good substrates for the asymmetric conjugate addition of phenyltitanium triisopropoxide, giving the corresponding arylation products with over 97% enantioselectivity. 

IV,N,N -Tris(trimethylsilyl)amidines have been used recently as precursors for a number of inorganic heterocycles and metallacycles,1 some of which are being studied in light of their unusual solid state properties2. Boere et al. reported the synthesis of several aryl-substituted persilylated benzamidines and the related compound /V,N,N, N",N",Ar" -hexakis(trimethylsilyl)-l,4-benezenedicarboximidamide (hereafter referred to as HBDA) 3 the present syntheses, which are generally based on the same reaction of an aryl-substituted carbonitrile with lithium bis(trimethylsilyl)amide, offer more facile routes to representative mono- and polyfunctional carboximidamides (i.e., amidines) as well as the prototypal derivative N,N,N -tris(trimethyl-silyl)formimidamide.4 As before, the crystalline diethyl ether adduct of lithium bis(trimethylsilyl)amide5 is favored over the nonsolvated amide in these syntheses the preparation of the diethyl ether adduct is also described here. 

Secondary and tertiary dialkylcuprates, lithium dialkenyl-, and even diphenyl-cuprates, add in very good yields to the reactive propionaldehyde diethyl acetal. The syn addition products may be trapped with a variety of electrophiles such as alkyl, alkenyl, alkynyl and aryl halides. The method has been used for the synthesis of several natural products. Substituted alkynic acetals also react with lithium dialkylcuprates in ether to furnish stable dialkenylcuprates of type (128) which do not eliminate to the corresponding alkoxy allenes (129) if the temperature is maintained below -20 C.164-179... 

Ruveda and co-workers have shown that the /5-hydroxyleucine, of which the aryl ether function in frangulanine is constructed, is present in the erythro-L-form (21). Dihydrofrangulanine was reduced with lithium in methylamine to an enol ether of /3-hydroxyleucine which on hydrolysis generated the free amino acid. It was shown that the hydroxyleucine in the hydrolysate is degraded by snake venom l-aminooxidase but not by pig kidney D-aminooxidase. Inasmuch as reo-hydroxyamino acids are attacked by neither enzyme it follows that the /3-hydroxyleucine, of hydrolytic origin, is the L-erythro form. 

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. 

Cleavage of alkyl aryl ethers ArOR - ArOH. Alkyl aryl ethers are cleaved in high yield when treated with lithium iodide in dry 2,4,6-collidine. The reaction mixture becomes mildly basic as the cleavage proceeds but can be buffered with an acid such as benzoic acid. The reactions can also be carried out with Lil-3H20 at 180-200° in the absence of solvent. 

Chiral boronic esters react with organolithium reagents to form diorganylalkoxyboranes (borinic esters). Subsequent reaction with the anion of dichloromethyl methyl ether then yields chiral ketones by rearrangement of both of the groups on boron (Scheme 42). No racemization is observed in this sequence and alkyl-, aryl- or alkynyl-lithium reagents can be used. 

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