Trimethylsilylmethylamine

Other radical cyclization approaches to the synthesis of piperidines include a CAN-mediated stereoselective cyclization of epoxypropyl cinnamyl amines <06TL705> and a cyclization of (-trimethylsilylmethylamine radical cation, generated via a photoinduced electron transfer reaction to a tethered -functionality <06JOC8481>. 

The amine is prepared by reaction of N-benzyl-N-trimethylsilylmethylamine with HCHO in CHjOH. 

The azomethine ylide was generated by treatment of A -benzyl-Af-(methoxy-methyl)-trimethylsilylmethylamine (155) with TFA and underwent the required cycloaddition step with chiral dipolarophile 156, stereocontrol being induced by Evan s auxiliary. The ot, p-unsaturated acid dipolarophile was tethered to a chiral oxazoladine in two easy, high-yielding steps. The auxiliary served three purposes to give asymmetric control to the reaction, to allow for separation of the reaction products by generating column separable diastereoisomers, and hnally to activate the olefin in the cycloaddition step (Scheme 3.45). 

The reaction of MSMAs with chloroacetates has been studied. It was stated that mixing trimethylsilylmethylamine with ethyl chloroacetate leads to the formation of the corresponding sarcosine after treatment with dilute hydrochloric acid.87... 

However, internal cycloaddition fails to give an adduct when an ethylenic moiety is linked to the ylid precursor. Even a styrene does not give any adduct and a diamine is obtained instead (note that in this instance zinc chloride was used instead of lithium fluoride). The same result is observed starting from the corresponding phenyl derivative, i.e., from /V-benzyl-/V-(methoxy methyl)trimethylsilylmethylamine. The proposed mechanism involves demethox-ylation under the action of the Lewis acid to form cation, K, which adds to the ylid to give the ethylenediamine framework.219... 

Trimethylsilylmethylamine itself has been shown to exert MAO inactivator activity. This is a remarkable finding, as the molecule is very simple and its activity should rely directly on the S-C-N framework. Oxidation of amines in the brain into aldimines and finally into aldehydes is a normal feature, but in diseases related to MAO, the level of its activity is not controlled inducing depletion of these amines. The mechanism... 

Mechanistically, it was suggested [92] that this cyclization does not involve the free a-amino radical formed by cleavage of the C—Si bond of the trimethylsilylmethyl-amine radical cation. Instead, it was pointed out that cleavage of the C—Si a-bond from the delocalized trimethylsilylmethylamine radical cation, produced by a vertical overlap of the C—Si bond and empty p-orbital of nitrogen, is assisted by the 71-orbitals of the olefin. This strategy was applied to the stereoselective synthesis of pyrrolizidine and indolizidine ring systems [93]. The synthetic utility of this reaction is also demonstrated by the synthesis of ( )-iso-retronecanol [94]. 

The same chiral auxiliary has been used in the cycloaddition of an optically active azomethine ylide to benzaldehyde and to l-nitro-2-(3,4-methylenedioxyphenyl)ethylene Ae ylide was generated in situ by treating (R)-(+)-/V-(l-phenylethyl)-A -cyanomethyl-A -trimethylsilylmethylamine (33) with silver fluoride. Unfortunately, no selectivity was observed in the first case and only a 3 2 preference was expressed in the second. Use of the azomethine ylide derived in the same manner from (/ )-(-)-N-(l-phenyl-2-methoxyethyl)-/V-cyanomethyl-N-trimethylsilylmethylamine (34) displayed a modest, but potentially useful, 4 1 diastereofacial selectivity in its reaction with l-nitro-2-(3,4-methylenedioxyphenyl)ethylene. The precise structure of the major and minor product was not determined (Scheme 25). 

The aminoolefin (82) obtained from the acetanilide 80 in a three-step sequence of reactions was converted to the formamide 83 in 88% yield by sequential formylation and methylation. Treatment of 83 with methyl trifluoromethanesulfonate followed by trimethylsilylmethylamine gave the formamidine 84 in 77% yield. Methylation of 84 with methyl trifluo-romethanesulfonate, followed by exposure of the resulting salt (24) to tetra-zi-butylammonium fluoride brought about a facile generation of the... 

The cycloaddition of azomethine ylides to alkenes is another elegant entry to pyrrolidines. The required 1,3-dipoles can be produced in a number of ways the example below is one of the most simple wherein a trimethylsilylmethylamine, an aldehyde and the alkene are simply heated in tetrahydrofuran. ... 

A novel route to ( + )-isofagomine from D-tartaric acid has been reported. In the presence of 1,4-dicyanonapthalene and light an a-trimethylsilylmethylamine radical cation is generated in an advanced alkynitol intermediate (Scheme 14). 

Dry CO2 passed at 20-50° into trimethylsilylmethylamine until no further weight increase is observed trimethylsilyl methylcarbamate (Y 90%) heated with phenyltridilorosilane at 105-110° methyl isocyanate (Y 82%). - This is a phosgene-free prepn. of isocyanates. F. e., also with isolation of intermediate silyl N-silylcarbamates, s. V. F. Mironov, V. P. Kozyukov, and V. P. Bulatov, 3C. 43, 2089 (1973) C. A. 80, 37216. 

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