Methoxymethyl aryl ethers

Methoxymethyl aryl ethers, Ar0CH20CH3. These ethers can be prepared by treatment of phenols with NaH in ether-DMF followed by chloromethyl methyl ether. Ronald reports that these ethers show enhanced susceptibility at the orfho-position to halogen-metal exchange, particularly with f-butyllith-ium. Thus (1) can be converted into (2) in high yield by metalation, reaction with CO2, and then reaction with diazomethane. In contrast, the methyl ether of OT-cresol under similar conditions gives less than 1% yield of carboxylic acids. 

Ac, acetyl AIBN, azobis(isobutanonitrile) All, allyl AR, aryl Bn, benzyl f-BOC, ferf-butoxycarbonyl Bu, Butyl Bz, benzoyl CAN, ceric ammonium nitrate Cbz, benzyloxycarbonyl m-CPBA, m-chloroperoxybenzoic acid DAST, diethylaminosulfur trifluoride DBU, l,8-diazabicyclo[5.4.0]undec-7-ene DCC, /V. /V - d i eye I oh e x y I c ar bo -diimide DCM, dichloromethyl DCMME, dichloromethyl methyl ether DDQ, 2,3-dichloro-5,6-dicyano-l,4-benzoquinone DEAD, diethyl azodicarboxylate l-(+)-DET, L-(+)-diethyl tartrate l-DIPT, L-diisopropyl tartrate d-DIPT, D-diisopropyl tartrate DMAP, 4-dimethylaminopyridine DME, 1,2-dimethoxyethane DMF, /V./V-dimethylformamide DMP, 2,2-dimethoxypropane Et, ethyl Im, imidazole KHMDS, potassium hexamethyldisilazane Me, methyl Me2SO, dimethyl sulfoxide MOM, methoxymethyl MOMC1, methoxymethyl chloride Ms, methylsulfonyl MS, molecular sieves NBS, N-bromosuccinimide NIS, /V-iodosuccinimide NMO, /V-methylmorpho-line N-oxide PCC, pyridinium chlorochromate Ph, phenyl PMB, / -methoxvbenzyl PPTs, pyridiniump-toluenesulfonate i-Pr, isopropyl Py, pyridine rt, room temperature TBAF, tetrabutylammonium fluoride TBS, ferf-butyl dimethylsilyl TBDMSC1, f-butylchlorodimethylsilane Tf, trifhioromethylsulfonyl Tf20, trifluoromethylsulfonic anhydride TFA, trifluoroacetic acid THF, tetrahydrofuran TMS, trimethylsilyl TPAP, tetra-n-propylammonium perruthenate / -TsOH. / -toluenesulfonic acid... 

Many functional groups are stable under conditions for the alkylation of pseudoephedrine glycinamide enolates, including aryl benzenesulfonate esters (eq 18), rert-butyl carbamate and rerf-butyl carbonate groups (eq 19), tert-butyldimethylsilyl ethers, benzyl ethers, ferf-butyl ethers, methoxymethyl ethers, and alkyl chlorides. The stereochemistry of the alkylation reactions of pseudoephedrine glycinamide and pseudoephedrine sarcosinamide is the same as that observed in alkylations of simple A(-acyl derivatives of pseudoephedrine. 

Reductive cycHzations have been shown to be diastereoselective in the synthesis of bicyclic products as well as various macrocycles. There are also instances of chirahty transfer in intermolecular reductive couphngs. The synthesis of anti-1,2-diols has been demonstrated using a-alkoxyaldehydes with a methoxymethyl ether (MOM) protecting group and mono-aryl internal alkynes (Scheme 8.25) [49]. Dias-tereoselectivities are high for the formation of anfi-l,2-diols in cases where the aldehyde has a branched sp -P-carbon. 

Carbon-Oxygen Bond Formation. CAN is an efficient reagent for the conversion of epoxides into /3-nitrato alcohols. 1,2-cA-Diols can be prepared from alkenes by reaction with CAN/I2 followed by hydrolysis with KOH. Of particular interest is the high-yield synthesis of various a-hydroxy ketones and a-amino ketones from oxiranes and aziridines, respectively. The reactions are operated under mild conditions with the use of NBS and a catalytic amount of CAN as the reagents (eq 25). In another case, N-(silylmethyl)amides can be converted to A-(methoxymethyl)amides by CAN in methanol (eq 26). This chemistry has found application in the removal of electroauxiliaries from peptide substrates. Other CAN-mediated C-0 bondforming reactions include the oxidative rearrangement of aryl cyclobutanes and oxetanes, the conversion of allylic and tertiary benzylic alcohols into their corresponding ethers, and the alkoxylation of cephem sulfoxides at the position a to the ester moiety. 

The or//io-palladation of 3,4-dioxygenated benzylic tertiary amines by lithium tetrachloropalladate can be directed exclusively to either C-2 or C-6. Substitution at C-6 prevails when AcO, methylenedioxy, PhCH20, methoxymethyl ether, or HO substituents are attached to C-3, whereas palladation occurs exclusively at C-2 when C-3 bears methylthiomethyl ether or phenylthiomethyl ether substituents. The resulting organopalladium compounds are crystalline solids, stable to air and moisture, and can readily be carbonylated, alkylated, arylated, Kinetic studies of the acetoxylation of arenes by potassium peroxydisulphate and acetic acid in the presence of (2,2 -bipyridyl)palladium(ii) acetate catalyst have led to a revision of the mechanism. The reaction is now thought to proceed via... 

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