Trimethylsilyl urethane

Hydrolysis of the trimethylsilyl urethane (1 R=C02SiMe3), prepared by the action of trimethylsilyl iodide on the methyl carbamate (1 R = C02Me), with methanol at -78 °C yields the carbamic acid (1 R = C02H). On allowing a CDC13 solution of the carbamic acid to warm to room temperature, decarboxylation takes place to yield the deep red, highly unstable 1//-azepine (1 R=H) (80AG(E)1016>. 

The second solution is to carry out acylations in the presence of trimethysilyl trifluoroacetamide or trimethylsilyl urethane, (CH3)3SiNHCOOC2Hs, both of which are readily hydrolyzed by HCl to an amide and trimethylchlorosilane. Collidine is a poor acceptor of HCl in these acylations. 

Trimethylsilyl trichloroacetate, K2CO3, 18-crown-6, 100-150°, 1-2 h, 80-90% yield.This reagent silylates phenols, thiols, carboxylic acids, acetylenes, urethanes, and /3-keto esters, producing CO2 and chloroform as byproducts. 

The Cunius degradation of acyl azides prepared either by treatment of acyl halides with sodium azide or trimethylsilyl azide [47] or by treatment of acyl hydrazides with nitrous acid [f J yields pnmarily alkyl isocyanates, which can be isolated when the reaction is earned out in aptotic solvents If alcohols are used as solvents, urethanes are formed Hydrolysis of the isocyanates and the urethanes yields primary amines. 

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). 

Whereas the repeated lithiation-trimethylsilylation sequence of trimethyl-silylbicyclopropylidene 43 a yielded predominantly the cyclopropene derivative 51 [54], bicyclopropylidenecarboxylates 42-Me, 42-fBu after repeated deprotonation and carboxylation retain the bicyclopropylidene moiety and give 2,2-disubstituted products 52-R only (Scheme 9) [55]. So far, alkylbicyclopropyl-idenes 43 e, f, g have not been induced to undergo deprotonation and a second substitution [56a]. The urethane 53 with a nitrogen directly attached to the skeleton, more easily than any other bicyclopropylidene derivative, rearranges to... 

The sensitivity of Si chemical shifts to structural changes and the technique of silylating compounds for more favourable analysis or synthesis have been combined by several researchers to produce a powerful structure elucidation technique for monofunctional or polyfunctional compounds. (135-141) Specifically, the trimethylsilyl derivatives of imidophosphoryl compounds, (141) sugars, (138-140) steroids, (140) amines, amides, and urethanes, (135,136) and amino-, hydroxy-, and mercaptocarboxylic acids (137) have all been studied within the past three years. 

As has been demonstrated, 2-(trimethylsilyl)ethoxymethyl (SEM) esters are selectively removed from amino acids and peptide derivatives in the presence of the most common N- and O-protecting groups applied in peptide chemistry including the urethane-type Boc, Z, Fmoc, and Troc as well as Bzl, tBu, and TBDMS ethers.The SEM ester is removed by acidolysis or with a fluoride ion source, e.g. TBAF in THF or HMPA or with aqueous HF in MeCN (—10°C).f l Deprotection with magnesium bromide in EtjO represents an even milder alternative that allows increased selectivity toward fluoride-labile silyl ethers or Fmoc groups. The SEM esters are prepared in 60-80% yield by stirring a mixture of 0.25 M N-protected amino acids in DMF with 0.8 equivalents of SEM-Cl and 1.1 equivalents of lithium carbonate at room temperature for 16 hours. 

Of all the methods described, the most convenient laboratory preparation of NCAs is the reaction of Boc-protected amino acids with thionyl chloride in THF. The method provides NCAs in good yields, which may then be purified by crystallization. Typically, a urethane-protected amino acid in THF is treated with 1.1-4 equivalents of thionyl chloride at 0°C. The NCA is formed in 30 minutes to 24 hours, depending on the annino acid and the urethane protecting group. Conversely, direct phosgenation of an amino acid is the preferred industrial process and modifications, such as trimethylsilylation, allow preparation of NCAs... 

The use of 2-(trimethylsilyl)ethanol allows the very mild and selective conversion of the initially formed urethanes into the cyclopropylamines with tetrabutylammonium fluoride, e.g. the synthesis of 2,2-dimethyl-3-(2-methylprop-l -enyl)cyclopropylamine (13) from /ra i-chrysanthemic acid (11). ... 

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