Silylated amino acid

A-Methyl-N-trimethylsilylacetamide. This reagent has been used prepa-ratively to silylate amino acids. 

Kricheldorf HR, Greber G (1971) N-silylated amino acid N-carboxylic acid anhydrides (oxazolidine-2.5-diones). Chem Ber 104 3131... 

Syntheses of Peptides from Silylated Amino Acids and CDI... 

Application of amino acid silyl esters or A-silyl amino acid silyl esters as amino components is very convenient in peptide synthesis with CDI, because the resulting peptide silyl esters are easily hydrolyzed to dipeptides during the usual work up. They need not be saponified in a separate step, as would be the case with the corresponding alkyl esters. Furthermore, no racemization occurs with this method.tl8],tl9]... 

Table 5-2. Polypeptides from silylated amino acids and CDI.

A slight modification of the synthesis involves the application of silylated amino acids which are more soluble in organic solvents (equation 159). In this case reactions occur rapidly (0.5-1 h) at lower temperatures (40-50 °C, DMF) to give the corresponding silatranones (128-134) in good yields. l-Methylsilatrane-3,7,10-trione (134) was isolated as a complex with DMF382. 

A further application of silylated amino acids is the formation of /3-lactams by treating N-TMS-0-amino acid-TMS-esters (497) with Grignard reagents under cycli-zation262 (Scheme 74). From N-TMS-a-phenyl-/ -alanin-TMS-ester (497) via the silylated product (498), 3-phenyl-2-azetidinone (499) can be obtained. 

Figure 6.17. An e-aminocaproic acid can not be directly transformed (area shaded grey) into the corresponding e-aminocaprolactam nonetheless, the transformation can be performed indirectly (area shaded red) the intermediate formation of the O-silylated amino acid ester C makes the crucial difference because it precludes the deactivation of the substrate as an ammonium carboxylate.

Silylated amino acid esters have been prepared by a dynamic kinetic asymmetric transformation of this type. Slow addition (by syringe pump) of (R,R) DPEC maintained insertion slow relative to interconversion and afforded the silyl-substituted amino acid esters in Eq. 36 with ee values of 80, 68, and 83%. The ester 38c (R=TMS) was too base-sensitive to permit removal of the chiral diol, but transesterification of the other /J-hydroxyethyl esters 38 to the corresponding methyl esters was straightforward [22]. 

Scheme 71 Acylation of Transiently N,0-Silylated Amino Acids or PeptidesI ...

Liu, G., Sieburth, S. M. Enantioselective a-Silyl Amino Acid Synthesis by Reverse-Aza-Brook Rearrangement. Org. Lett. 2003, 5,4677-4679. 

More complex, but nevertheless straightforward, is the genesis of 44 from bis-silylated amino acids 9070. The following sequence of events involving cyclization via silyloxy transfer (91 -+ 92), decarbonylation (92 -+ 93) and /7-cleavage (loss of a Schiff base) was suggested (reaction 44). 

Taneptine was detected only after silyliaton with A -methyl-A -trimethylsilyltri-fluoroacetamideinCH2Cl2.Themostprominentpeakswererecordedatm/z = 217 amu, which was assigned to the silylated amino acid chain [NH2-(CH2)g-C0-0-Si(Me)3], and m/z =117 amu, which was assigned to the C0-0-Si(Me)3 fragment. 

General.—A number of new routes to some C-silylated amino-acids have been described. Treatment of malonyl peroxides with triphenylphosphine generates malonyl anhydrides and the corresponding ketens, by two distinct decomposition modes of the intermediate (2) (Scheme 8). 

---