Amino acids trimethylsilylation

Silyl esters are stable to nonaqueous reaction conditions, but are often too labile to mild acid or base or even neutral aqueous media to survive many simple manipulations. Thus, they have not found wide application in peptide synthesis. Due to easy formation and cleavage they may play an important role as intermediates in the synthesis of amino acid derivatives and for temporary carboxy protection in the preparation of small peptide fragments. The TMS group has been used for the solubilization of H-Arg-OH for the synthesis of Z-Arg(Z2)-OHP l and in the synthesis of Al -Nps- and Al -Tfa-protected amino acids.P Amino acid trimethylsilyl esters as well as the related A1 -TMS derivatives react rapidly with acylating agents and are used for the preparation of peptides with amino acid active esters, e.g. A-hydroxysuccinimide-, 4-nitrophenyl-, or 2,4,5-trichlorophenyl esters, or mixed anhydrides. 

Aldol Reactions.—N-(Trimethylsilyl)amino-acid trimethylsilyl esters, e.g. 

Preparation of Isothiocyanates.—A conventional synthetic method is illustrated in the preparation of AT-(isothiocyanato-acyl)-amino-acids, e.g. S C N (CH2) C0 NHCHR C02H, starting from the peptide trimethyl-silyl ester treatment with CSg and an alkyl chloroformate gives an alkoxycarbonyl dithiocarbamate which readily cyclo-eliminates COS and alkanol. Acylation of an amino-acid trimethylsilyl ester with SCN--(CH2) C0 C1 provides an alternative route cyclization of an a-isothio-cyanato-acid (158) to a 2-thio-oxazolidone (159) occurs readily in solution, ... 

From Thiocarbonylamino-acid Silyl Esters. Thiazolidine-2,5-diones (306) are accessible in high yield and purity by the cyclization of iV-(alkoxythio-carbonyl)amino-acid trimethylsilyl esters (305) by phosphorus tribromide. The reaction proceeds by an electrophilic attack of the acyl group on the sulphur atom, presumably involving intermediates of type (307). The... 

Me3SiNEt2- Trimethylsilyldiethylamine selectively silylates equatorial hydroxyl groups in quantitative yield (4-10 h, 25°). The report indicated no reaction at axial hydroxyl groups. In the prostaglandin series the order of reactivity of trimethylsilyldiethylamine is Cii > Ci5 C9 (no reaction). These trimethylsilyl ethers are readily hydrolyzed in aqueous methanol containing a trace of acetic acid. The reagent is also useful for the silylation of amino-acids. ... 

V,/V-Bis(trimethylsilyl) alkyl glycinates can be deprotonated and then alkylated on carbon (4) to give homologous a-amino-acid derivatives ... 

Although SiCh 57 has been employed, e.g., in the presence of sodium azide to convert ketones into tetrazoles (Section 5.3), to condense cyclopentanone in high yields into 1.2.3.4.5.6-tris(trimethylene)benzene (Section 9.2), or used for the condensation of amino acids to polyamides (Chapter 14) with formation of Si02, enol-trimethylsilyl ethers 107 a of ketones such as cyclohexanone are cleanly converted by SiCh 57 in the presence of Hg(OAc)2 into the trichlorosilylenol ether 116, which adds benzaldehyde in the presence of the asymmetric catalyst 117 to give... 

Benzaldehyde dimethyl acetal 121 reacts, for example, with the silylated allylic alcohol 645, in the presence of SnCl2-MeCOCl, via an intermediate analogous to 641, to the 3-methylenetetrahydrofuran 646 and methoxytrimethylsilane 13 a [182], whereas benzaldehyde dimethyl acetal 121 reacts with the silylated homoallylalco-hol 640 in the presence of TMSOTf 20 to afford exclusively the ds 4-vinyltetrahy-drofuran 647 and 13 a [183]. A related cyclization of an a-acetoxy urethane 648 containing an allyltrimethylsilane moiety gives the 3-vinylpyrrohdine 649 in 88% yield and trimethylsilyl acetate 142 [184, 185]. Likewise, methyl 2-formylamido-2-trimethylsilyloxypropionate reacts with allyltrimethylsilane 82 or other allyltri-methylsilanes to give methyl 2-formamido-2-aUyl-propionate and some d -unsatu-rated amino acid esters and HMDSO 7 [186] (Scheme 5.56). 

For a facial selective assembly ofthe stereogenic centers and the introduction of the amino functionality, chiral nitrogen-containing reagents, such as benzyl(2-pheny-lethyl)amine (2-19) and trimethylsilyl RAMP derivative 2-24 were applied. Treatment of diacrylates 2-18, 2-21, and 2-23 with 2-19 and 2-24, respectively, gave the protected amino acids 2-20, 2-22, and 2-25 in good yields as single isomers. 

Substitution of two chlorines in (l,2-benzenedioxy)trichlorophosphorane by N,0 bis(trimethylsilyl)amino acids gives 34 (X = Cl) further substitution of chlorine by phenol gives 34 (X = OPh) (Scheme 22) <1998S855>. The reaction of P(NMe2)3 with 2-aminophenols generates aminophosphoranes 33 (R = H, Buc) (Equation 20) <2000HAC11>. 

First attempts to combine pyrolysis with in situ HMDS silylation of organic art materials were reported by Chiavari et al., who were successful in obtaining trimethylsilyl derivatives of fatty acids [52], amino acids [53] and carbohydrates [54]. The same authors also applied pyrolysis-silylation to the analysis of different kinds of natural resins and for each of them diagnostic silylated compounds were identified, even if many were difficult to assign precise structures [55],... 

The preparation of optically active analogues of the natural amino acids has proven reasonable using the reaction of tris(trimethylsilyl) phosphite with chiral aldimines prepared from optically active amines.225 The asymmetric induction has been observed to be as high as 80%, a significant competitive process compared to the multistep approaches available.226227 An alternative one-step approach involving asymmetric induction upon addition to an aldimine derived from a chiral N-substituted urea provided a product with less desirable optical purity.228... 

Addition of (trimethylsilyl)acetylides to chiral a-aminoalkyl- (413) and a-alkoxyalkyl-(BIGN) (292) nitrones proceeds stereoselectively. Successive desi-lylation (BU4NF, THF) and transformation of the ethynyl group into carboxyl (RuCl3-NaIC>4) led to the synthesis of diastereomerically pure /V-hydroxy-a-amino acids (414) and a-amino acids (415) (Scheme 2.185) (199, 202, 652, 660). 

The a-arylation of carbonyl compounds (sometimes in enantioselective version) such as ketones,107-115 amides,114 115 lactones,116 azlactones,117 malonates,118 piperidinones,119,120 cyanoesters,121,122 nitriles,125,124 sul-fones, trimethylsilyl enolates, nitroalkanes, esters, amino acids, or acids has been reported using palladium catalysis. The asymmetric vinylation of ketone enolates has been developed with palladium complexes bearing electron-rich chiral monodentate ligands.155... 

Strecker reactions provide one of the most efficient methods for the synthesis of a-amino nitriles, which are useful intermediates in the synthesis of amino acids and nitrogen-containing heterocycles. Although classical Strecker reactions have some limitations, use of trimethylsilyl cyanide (TMSCN) as a cyano anion source provides promising and safer routes to these compounds.133-351 Consequently, we focused our attention on tributyltin cyanide (Bu3SnCN), because Bu3SnCN is stable in water and is also a potential cyano anion source. Indeed, the Strecker-type reactions of aldehydes, amines, and Bu3SnCN proceeded smoothly in water (Eq. 9).1361 It should be noted that no surfactants are required in this reaction. Furthermore, Complete recovery of the toxic tin compounds is also possible in the form of bis(tributyltin) oxide after the reaction is over. Since conversion of bis(tributyltin) oxide to tributyltin cyanide is known in the literature, this procedure provides a solution to the problem associated with toxicity of tin compounds. 

FIGURE 7.19 Reagents for preparing A-protected amino-acid fluorides,55-5661 Boc2-amino-acid fluorides (CyNF),58-59 and a nonbasic acid scavenger (BSA).62 CyNF = cyanuric fluoride DAST = diethylaminosulfur trifluoride TFFH = tetramethylfluoroformamidinium hexafluo-rophosphate BSA = b (trimethylsilyl)acetimide. 

The advantage of trimethylsilyl (TMS) derivatives lies in the simplicity of the derivatization procedure, which is carried out by the addition of N,0-bis(trimethylsilyl)trifluoroacetamide (BSTFA) in acetonitrile and heating for approximately 2 h at 150 °C under anhydrous conditions in a sealed tube. However, there may be problems owing to the formation of multiple derivatives of each amino acid. Another technique involves the formation of n-butyl esters of the amino acids and their subsequent trimethylsilylation by a similar procedure. The n-butyl esters are formed by heating the amino acids for 15 min in n-butanol and HC1 and these are then converted to the A-TMS-n-butyl ester derivatives. A-acyl amino acid alkyl esters are commonly used. Acetylation of the butyl, methyl or propyl esters of amino acids,... 

The unusual amino acid (S)-2-amino-(Z)-3,5-hexadienoic acid (269), which is a component of the toxic y-glutamyl dipeptide isolated from the defensive glands of the Colorado beetle [209], has been synthesized along Scheme 17, after two initial attempts had proved unsuccessful due to the instability of 269 towards various oxidation conditions [210]. Scheme 17 relies on the hydrolysis of an ortho ester to generate the required carboxylic acid. Thus, the L-serine aldehyde equivalent 270 was treated with ( )-l-trimethylsilyl-l-propene-3-boronate to give the addition product 271. Reaction of 271 with KH gave the stereochemically pure (Z)-diene 272. Mild acid treatment of 272 followed by... 

Silyl Acid Linker 4-[l-Hydroxy-2-(trimethylsilyl)ethyl]-benzoic acid Silyl Amide Linker 4-[(l-Amino)-2-(trimethylsilyl)ethyl]-phenoxyace-... 

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