Methoxymethyl amine

As depicted in Scheme 1.1.2, the silyl ketones (S)-ll of high enantiomeric purity were converted into the Z-configured silyl enol ethers (S) -12, which were used in the aminomethylation step by treatment with dibenzyl(methoxymethyl)amine in the presence of a Lewis acid. The silylated Mannich bases S,R)-13 were obtained in excellent yields and diastereomeric excesses (de = 92-96%). Finally,... 

Preparation. These intermediates are readily prepared from an activated acid (acid chloride) and the methoxymethyl amine. 

Thus, the reaction has some value for the synthesis of known ureas derived from methoxymethyl amine such as the herbicide Linuron [see scheme 141] (Ref. 196). 

SPECIAL -NH PROTECTIVE GROUPS iV-Methoxymethyl amine (MOM NR2) CH3OCH2NR2 Formation Cleavage ... 

A -methoxymethyl-amines or-amides A -acetyloxymethyl-amines or -amides or A/, iV-dimethylfonnamide acetals, all react with phosphorus(III) esters in non-classical Michaelis-Arbuzov fashion. From these and similar reactions, quaternary salts of the type 186 have been isolated. The A-methylated dervative may be preformed or produced in situ in mixtures containing amide, formaldehyde and phosphite ester. The products of the reactions are A-acylated (acetyl, benzoyl, phthaloyl, pyridinecarbonyl or benzyloxycarbonyl) when derived from amides, or A,A-dialkyl derivatives from hydroxy (or methoxy)methylamines the use of Me2NCH(OMe)2 leads to dimethylaminomethyl-enebisphosphonic esters. Ivanov and coworkers have made a detailed study of the reactions which occur between phosphorus(III) amides Et2NPYZ and the substrates, RCONHOAc (Scheme 16). The reagent can attack the substrate by virtue of the nucle-... 

Chloroalkyl carbamates, prepared with phosgene (see Section 4.3.2 Carbamates ), react with hard nucleophiles such as methoxymethyl amine to afford known ureas such as the herbicide Linuron [219]. 

Progress has been made toward enantioselective and highly regioselective Michael type alkylations of 2-cyclohexen-l -one using alkylcuprates with chiral auxiliary ligands, e. g., anions of either enantiomer of N-[2-(dimethylamino)ethyl]ephedrine (E. J. Corey, 1986), of (S)-2-(methoxymethyl)pyrrolidine (from L-proline R. K. EHeter, 1987) or of chiramt (= (R,R)-N-(l-phenylethyl)-7-[(l-phenylethyl)iinino]-l,3,5-cycloheptatrien-l-amine, a chiral aminotro-ponimine G. M. Villacorta, 1988). Enantioselectivities of up to 95% have been reported. 

Aldol condensation of the methoxymethyl ether of m-methoxybenzaldehyde (83) with cyclohexanone affords the conjugated ketone 84. Michael addition of dimethyl amine leads to the ami noketone Reduction of the ketone... 

Asymmetric induction may also derive from chirality in the amine part of the enamine. The reaction of the enamine (S)-l-(l-cyclohexenyl)-2-(methoxymethyl)pyrrolidine with ( )-(2-ni-troethenyl)arenes gives, after hydrolysis, a single diastereomeric product in >90% ee30. 

Aryl alcohol oxidase from the ligninolytic fungus Pleurotus eryngii had a strong preference for benzylic and allylic alcohols, showing activity on phenyl-substituted benzyl, cinnamyl, naphthyl and 2,4-hexadien-l-ol [103,104]. Another aryl alcohol oxidase, vanillyl alcohol oxidase (VAO) from the ascomycete Penicillium simplicissimum catalyzed the oxidation of vanillyl alcohol and the demethylation of 4-(methoxymethyl)phenol to vanillin and 4-hydro-xybenzaldehyde. In addition, VAO also catalyzed deamination of vanillyl amine to vanillin, and hydroxylation and dehydrogenation of 4-alkylphenols. For the oxidation of 4-alkylphenol, the ratio between the alcohol and alkene product depended on the length and bulkiness of the alkyl side-chain [105,106]. 4-Ethylphenol and 4-propylphenol, were mainly converted to (R)-l-(4 -hydroxyphenyl) alcohols, whereas medium-chain 4-alkylphenols such as 4-butylphenol were converted to l-(4 -hydroxyphenyl)alkenes. 

For conversion of functionalized diorganozincs into tertiary amines, aromatic compounds which contain a directed metallation group, such as Af,Af-dialkylbenzamides, methoxymethyl phenyl ether, phenyl oxazolines and phenyl Af,Af-dialkylcarbamates, were ortho-lithiated, transmetallated and then aminated with 2a in good yields, but with a slower reaction rate (Scheme 19). 

Schistosoma japonicum. The carbobenzoxy (CBz) protected template 160 was initially converted to the a, p-dehydrolactone 161 via the phosphate ester, before undergoing cycloaddition to ylide 162, generated in situ by acidic treatment of A(-benzyl-A(-(methoxymethyl)trimethylsilyl amine. The resultant cycloadduct (163) was isolated in 94% yield as a single diastereoisomer. Destructive template removal, by catalytic hydrogenation, released (5)-( )-cucurbitine, after ion-exchange chromatography, as the free amino acid in 90% yield (Scheme 3.46). 

Treatment of isopropyl 6-hydroxy-4-methoxymethyl-/3-carboline-3-carboxylate 189 with a primary amine in the presence of an excess of manganese dioxide produces the oxazolo[4,5-g]-/3-carboline 190 in moderate yield (Equation 125) <1998H(48)31>. The efficiency of the reaction is limited by the formation of by-products. 

Kolb and Barth 229) synthesized oc-substituted optically active amines or amino acids (223). Again the authors employed a derivative of naturally occurring (S)-proline, namely (—)-(S)-l-dimethoxymethyl-2-methoxymethyl-pyrrolidine (221) as chiral auxiliary agent. The metalation of the amidines (160) leads to azaallyl anions homologous with (222). After alkylation and hydrolysis, the desired a-substituted amines and amino acids, respectively, are obtained with some stereoselectivity. 

It has been demonstrated that TMS iodide (in combination with cesium fluoride) or TMS triflate in various solvents (THF, MeCN, HMPA) are excellent reagents to promote the generation of azomethine ylids from A-methoxymethyl-A-(trimethylsilylmethyl)aIkyl-amines and their cycloaddition to electron deficient alkenes with yields ranging from moderate to nearly quantitative. The geometry of the double bond in the alkene is preserved in the cycloadduct.410... 

Pyrrolidine-based thrombine inhibitors are prepared by condensation of the ylid derived from /V-benzyl-iV-(methoxymethyl)trimethylsilyl methyl amine, with methyl m-trifluoromethyl cinnamate.420... 

The same Dutch-Russian group has reported several varieties of this method, which allows the preparation of iV-methoxymethyl thietanylidene amines 49 and 50 (Scheme 18 Equation 18) <2004RJ0131> or 2,3-thietes 51 (Scheme 14) <2004RJ0753>. 

Fig. 13.34. Enders SAMP method for the generation of enantiomerically pure a-alky-Lated carbonyl compounds SAMP, (S)-aminoprolinol methyl ether = (5)-2-methoxymethyl-l-pyrrolidin-amine, or S-l-amino-2-(methoxymethyl)pyrrolidine (which is the name according to IUPAC rules).

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