A-aminomethylation

Silylated cyanohydrins have also been prepared via silylation of cyanohydrins themselves and by the addition of hydrogen cyanide to silyl enol ethers. Silylated cyanohydrins have proved to be quite useful in a variety of synthetic transformations, including the regiospecific protection of p-quinones, as intermediates in an efficient synthesis of a-aminomethyl alcohols, and for the preparation of ketone cyanohydrins themselves.The silylated cyanohydrins of heteroaromatic aldehydes have found extensive use as... 

Chemical Name a -(aminomethyl)-4-hvdroxybenzene-methanol hydrochloride Common Name Norsympatol hydrochloride norsynephrine hydrochloride Structural Formula hochcHjKHj... 

The enzymatic conversion of a-(aminomethyl)pyrroles is also used by nature to produce porphyrinogens like uroporphyrinogen III (see introduction, compound 8), which is the key building block in the biosynthesis of all known porphinoid natural products. This biomimetic method is a powerful tool for the synthesis of different porphyrins, e.g. for the preparation of JV,Af, V ,Ar"-tetramethylporphyrin-2,3,7,8,12,13,17,18-octaacetic acid dibromide 12.36... 

Simple 1,2,4-triazole derivatives played a key role in both the synthesis of functionalized triazoles and in asymmetric synthesis. l-(a-Aminomethyl)-1,2,4-triazoles 4 could be converted into 5 by treatment with enol ethers <96SC357>. The novel C2-symmetric triazole-containing chiral auxiliary (S,S)-4-amino-3,5-bis(l-hydroxyethyl)-l,2,4-triazole, SAT, (6) was prepared firmn (S)-lactic acid and hydrazine hydrate <96TA1621>. This chiral auxiliary was employed to mediate the diastereoselective 1,2-addition of Grignard reagents to the C=N bond of hydrazones. The diastereoselective-alkylation of enolates derived from ethyl ester 7 was mediated by a related auxiliary <96TA1631>. 

Bis(a-aminomethyl)phosphines having a mobile hydrogen atom could be expected to undergo a borylation reaction with borane, hydrogen being evolved. In fact, bis(Af-phenylaminomethyl)-phenylphosphine (199) and its sulfide (200) appeared to interact with borane under mild conditions, yielding a new type of phosphorus-boron-containing heterocycle—2-... 

In a similar manner, starting from 2-methylchloride-naphtho[l,8-de][l,2,3]triazine and magnesium, via a novel sonication-promoted Barbier reaction, an a-aminomethyl carbanion equivalent is generated which reacts in situ with a variety of carbonyl compounds. Subsequent catalytic hydrogenolysis of the triazine moiety yields the corresponding amines <00TL4685>. Sterically controlled regiospecific cyclization of aldose-5-ethyl-l,2,4-... 

Amino-3-mercaptopropanoic acid, c411 1-Amino-2-methoxyethane, m77 a-(Aminomethyl)benzyl alcohol, a257... 

Problem 18.62 Synthesize from benzene, toluene, naphthalene (NpH), and any aliphatic or inorganic compounds (a) a-(p-nitrophenyl)ethylamine, (b) -(p-bromophenyl)ethylamine, (c) l-(a-aminomethyl) naphthalene, (d) 2-naphthylamine, (e) -NpCH2NH2. 

Knoevenagel condensation of 2-formylquinuclidine (75) with cyanoacetic108 and malonic129 esters was used to make /9-(quinuclid-2-yl)propionic acid (95) and its a-aminomethyl derivative (96). 

IUPAC name (-)-3,4-dihydroxy-OC- [(methylamino)methyf benzyl alcohol (-)-a(aminomethyl)-3,4- dihydroxybenzyl alcohol... 

S)-15-Aminoethyl-14-hydroxy-5,5-dimethyl-2,8-dithia[9](2,5)pyridinophanc, 29-30 0-Aminoglutarate, 265 Aminomcrcuration, 315 a-Aminomethyl ketones, 274, 352-353... 

Most reports in this category deal with asymmetric processes. For example, classic Mannich reaction of unmodified ketones, aqueous formaldehyde, and aromatic amines produces a-aminomethylation of the ketones in >99% ee, using L-proline as catalyst. 24 Methyl ketones regioselectively reacted on the methylene carbon. The method is simple, using wet solvents in the presence of air. 

While studying the conversion of the adducts, obtained from aldehydes, it was discovered that upon thermolysis they lose diphenyl-phosphine oxide (Ph2P0H) to form a-aminomethyl ketones 7. The overall reaction thus results in a-aminomethylation of the parent al-... 

Chemical Name a-(Aminomethyl)-4-hydroxybenzene-methanol hydrochloride... 

Firstly, the possibility of generating an a-aminomethyl anion equivalent under mild and neutral conditions and in the presence of the electrophilic receptor via the fluoride ion cleavage of the Si-C bond was investigated by Patel and Joule,11 who observed the addition product of the anion to the starting material. Katritzsky and Sengupta12 then found that fluoride-mediated desilylation could be carried out in the presence of an aldehyde, allowing the facile synthesis of aminoethanols. 

Proline and its derivatives also catalyze the classical asymmetric Mannich reaction between aqueous formaldehyde, anilines, and ketones. This was the first successful direct catalytic a-hydroxymethylation of ketones, and the corresponding a-aminomethyl ketones were isolated in excellent yields with up to >99 % ee (Scheme 4) [34]. 

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