Alkyl aryl ethers, reduction

In the asymmetric reduction of ketones, stereodifferentiation has been explained in terms of the steric recognition of two substituents on the prochiral carbon by chirally modified reducing agents40. Enantiomeric excesses for the reduction of dialkyl ketones, therefore, are low because of the little differences in the bulkiness of the two alkyl groups40. In the reduction of ketoxime ethers, however, the prochiral carbon atom does not play a central role for the stereoselectivity, and dialkyl ketoxime ethers are reduced in the same enantiomeric excess as are aryl alkyl ketoxime ethers. Reduction of the oxime benzyl ethers of (E)- and (Z)-2-octanone with borane in THF and the chiral auxiliary (1 R,2S) 26 gave (S)- and (R)-2-aminooctane in 80 and 79% ee, respectively39. 

Cyclic alkyl aryl ethers lead also to functionalized organolithium compounds by reductive carbon-oxygen bond cleavage in arene-catalyzed lithiation process. Thus, the treatment of 2,3-dihydrobenzofuran (47) with an excess of lithium in the presence of a catalytic amount of DTBB in THF at 0°C gives the dianion (48) which after reaction with different carbonyl compounds and final hydrolysis with water leads to... 

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. ... 

In addition to /3-H elimination, olefin insertion, and protonolysis, the cr-metal intermediate has also proved to be capable of undergoing a reductive elimination to bring about an alkylative alkoxylation. Under Pd catalysis, the reaction of 4-alkenols with aryl halides affords aryl-substituted THF rings instead of the aryl ethers that would be produced by a simple cross-coupling mechanism (Equation (126)).452 It has been suggested that G-O bond formation occurs in this case by yy/z-insertion of a coordinated alcohol rather than anti-attack onto a 7r-alkene complex.453... 

Asymmetric reduction of alkyl aryl ketones with trialkoxysilanes is promoted by a catalytic amount of chiral nucleophiles [39]. The reactive species is a transiently prepared hypervalent silicon hydride. 2, 4, 6 -Trimethylacetophenone was reduced with equimolecular amounts of trimethoxysilane in the presence of the monolithio salt of (R)-BINAPHTHOL (substrate Li=20 l) in a 30 1 ether-TMEDA mixed solvent at 0 °C to afford the R product in 90% ee (Scheme 21) [40]. The presence of TMEDA was crucial to achieve high yield and enantiose-lectivity. Reduction of less hindered ketonic substrates preferentially gave the... 

Reduction by LiAlH of RAsClj or RjAsCl (R = alkyl, aryl) occurs in ethers ... 

Reviews devoted to Se chemistry or Raney nickel show that these are efficient reagents in reductive deselenations. Of course the advantages and drawbacks encountered with desulfurizations (see Section 4.3.1.2) must also be taken into consideration with deselenations. Raney Ni, often freshly prepared, is generally used in excess in solvents such as EtOH, ether, THE or DME, and under conditions milder than those for desulfurizations. From the numerous works published, it appears that the procedure tolerates alkyl and aryl ethers, - ketals, ketones, "" esters,"" lactones" and sulfonamides. A few representative examples are given in Scheme 18. 

Shintou, T., Mukaiyama, T. Efficient Methods for the Preparation of Alkyl-Aryl and Symmetrical or Unsymmetrical Dialkyl Ethers between Alcohols and Phenols or Two Alcohols by Oxidation-Reduction Condensation. J. Am. Chem. Soc. 2004,126, 7359-7367. 

The mixed hydride is the reagent of choice for the reduction of diaryl ketones, alkyl aryl ketones, and certain aryl alcohols to the corresponding hydrocarbons. Usually best yields are obtained if an equimolecular mixture of the ketone and aluminum chloride in ether is added to the I 1 LiAlHj AICI3 reagent. 

The C-4 acids (183 and 184) have also been subjected to borane reduction conditions to afford alcohol 195 in 23-50% yield or 64% yield as the C-8 epimeric mixture (195 and 196, Scheme 29) [34, 49, 64]. The C-8 alcohol epimers 195 and 196 have been treated separately as a common intermediate for a number of C-4 derivatives including esters, ethers, and amines [34, 49, 64], Alcohols 195 and 196 was subjected to DCC, DMAP, and desired acid chloride or carboxylic acid in CH2CI2 affording ester analogs in 50-92% yield [64], Esters prepared include alkyl, aryl, and fluorenylmethyloxycarbonyl (Fmoc) protected amino acid derivatives (197 and 198) [64]. Ethers were prepared with various alkyl halides and Ag20 in CH3CN at 40 °C. Alkyl, allyl, and benzyl ethers were prepared in 45-80% yield (199 and 200) [34,64]. Alcohols 195 and 196 were then activated to the triflates and displaced by a variety of amines by treatment with trifluoromethanesulfonic anhydride and desired amine in 22% - quantitative yield over two steps (201 and 202)... 

Fuchs elegant approach to the morphinan skeleton utilized an intramolecular conjugate addition/alkylation sequence, in which connections C12-C13 and C9-C14 were formed as a result of one tandem process.73-74 Mitsunobu condensation between alcohol 164 (from 2-allylcyclohexene-l,3-dione in five steps and 43% overall yield) and phenol 163 (from isovanilline in 6 steps and overall yield of 40%)73c gave the ether 165, Scheme 19. TBDMS deprotection followed by an oxidation/reduction sequence set the aryl ether... 

The methods discussed above all require chemically aggressive reagents. Freudenberg and his co-workers,41 however, found that benzyl ethers can also be cleaved by catalytic hydrogenation alkyl benzyl ethers can be converted into toluene and an alcohol by hydrogenation under very mild conditions in presence of platinum metals or Raney nickel reductive cleavage of aryl benzyl ethers is best carried out in presence of palladium-charcoal. 

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