Aminomethylation trifluoroacetic acid

Pyrrolidines have been prepared by 1,3-dipolar cycloaddition of N-(benzyli-dene)trimethylsilylamine/TMSOf 20 and methyl acrylate, N-methylmaleimide, or dimethyl maleate [35]. More recently, methyl trans-3-cyanociruiamate 1479 was reacted with N-benzyl-N-(trimethylsilylmethyl)aminomethyl methyl ether 1480 and trifluoroacetic acid in CH2CI2 at 0°C and 24°C to afford, via 1481, the pyrrolidine derivative 1482 in high yield and MeOSiMe3 13a [35a] (Scheme 9.20). Several... 

Aminomethylated polystyrene (DVB I %, 1.07 mmol Trifluoroacetic acid / dichloromethane (I/I, v/v), 10mL 3-Bromopropionic acid (97 %) (158 mg, I mmol) Cesium carbonate (99.9%) (652 mg, 2 mmol) Triethylamine Benzene Acetone... 

Added CO2 allows the synthesis of substituted maleic anhydrides. According to a novel aminomethylation, ethane or propane is reacted with /V./V-di alkyl methyl-amine A-oxides in the presence of trifluoroacetic acid and a catalytic amount of Cu(OAc)2 to afford A,A-dialkylaminomethylated alkanes in good yields 321 337 338... 

Abbreviations used Dde, N-[l-(4,4-dimethyl-2,6-dioxocyclohexadiene)]-ethyl DIEA, diisopropylethylamine DMF, N,N-dimethylformamide EDC, l-Ethyl-3-(3 -dimethylaminopropyl)carbodiimide hydrochloride HOBt, 1-hydroxybenzotriazole NHS, N-hydroxysuccinimide NMP, l-methyl-2-pyrroIidinone PAL, Peptide Amide Linker [5-(4-(9-fluorenylmethyloxycarbonyl) aminomethyl-3,5-dimethoxyphenoxy) valeric acid] PyBOP, Benzotriazole-l-yl-oxy-trispyrrolidino-phosphonium hexafluorophosphate TFA, trifluoroacetic acid. 

Our ongoing research on (aminomethyl)(lithiomethyl)silanes focuses on modification of the substituents at the nitrogen center. The unprotected 2-silyl-substituted pyrrolidine 5 is a very useful starting point for the synthesis of different A -substituted pyrrolidines like rac-6. The racemic compound rac-S and the enantioenriched compound (iS)-5 could be s)mthesized by reaction of the Af-Boc-protected compound rac-2 or (S)-2 trifluoroacetic acid (TFA) [10]. In subsequent reactions it was possible to introduce a methyl group at the nitrogen center by conversion of rac-S with methyl... 

A modification of the Sommelet reaction (see page 339) is to convert primary and secondary benzylamines into aldehydes by means of formaldehyde and hexamethylenetetramine. For instance, Greymore and Davies obtained benzaldehyde from benzylamine hydrochloride by this route 593 and 2-fluorene-carbaldehyde has been similarly prepared in 70% yield from 2-(aminomethyl)-fluorene hydrochloride.594 Papers by Snyder et al.595 and by M. M. Robison and B. L. Robison596 should be consulted for the reaction of tertiary amines with hexamethylenetetramine. Benzaldehydes can be synthesized by treating benzylamines with sodium nitrite and trifluoroacetic acid (molar ratio 1 2 3)... 

A modern adaptation uses trifluoroacetic acid as catalyst. That allows for formylation of aromatics such as toluene and xylene and even electron deficient phenols such as 2,4-difluorophenol under mild conditions in good yields.A high order of para regioselectivity is exhibited even for phenols.The mechanism involves fast aminomethylation followed by a rate-determining dehydrogenation step to the imine similar to that observed in the Sommelet reaction hydrolysis then gives the aldehyde (Eq 1.42). ... 

A variety of polyamine linkers were developed by Bradley and colleagues [152,162,163]. They mainly use an aminomethylated polystyrene resin 111 (Table 1). An urethane linkage was found to be cleavable using strong acidic conditions (lOequiv trifiuoromethanesulfonic acid-trifluoroacetic acid, TFMSA/TFA) and hence is potentially useful for resin screening purposes. Other linkers such as the trityl linkers (114, 116-120) (Table 1) are readily cleavable with TFA and are ideal for solution screening applications. 

---