Carboxylic acid silyl esters amines

In the first step amine 11 is coupled with carboxylic acid 15 to form an amide The method employed here for coupling an a-chiral carboxylic acid with an amine was developed in the context of peptide synthesis. Its success is based on DCC-mediated formation (see Chapter 5) of the reactive 1-hydroxy benzotriazole ester 55, which reacts with an amine to give the corresponding amide. In most cases reaction takes place without raccmi/ation, and often in the absence of side reactions that cause other procedures to The alcohol is converted into a silyl ether in the second step. 

Alkylation or acylation of ketones, sulfides, and amines. This reagent generally reacts with alcohols or carboxylic acids to form 2,2,2-trifluoroethyl ethers or esters in satisfactory yields, except in the case of alcohols prone to dehydration. The reaction of these ethers provides a simple synthesis of unsymmctrical sulfides (equation I). A similar reaction can be used for preparation of secondary amines or amides (equation II). Enolatc anions (generated from silyl cnol ethers with KF) can be alkylated or acylated with a or b (equation III). Use of Grignard reagents in this type of coupling results in mediocre yields. 

Photochemical Fe(CO)5-induced rearrangement of silylated allyl amine 9 gave N-silylated enamine 1015, which on subsequent Cu-catalyzed cyclopropanation by methyl diazoacetate afforded cyclopropane derivative 11. The use of an optically active catalyst gave an asymmetric induction of 56% ee for the cis isomer and 20% ee for the trans isomer. Further acid-induced ring cleavage afforded the -formyl ester 12, whereas reduction and desilylation produced aminocyclopropane carboxylic acid 13 (equation 2). 

Microwave irradiation of a mixture of an acid anhydride, an amine adsorbed on silica gel, and TaCl5/Si02 is a solvent-free method for the synthesis of A-alkyl and A-aryl-imides [47]. Ni(II) promotes the conversion of an acrylamide to ethyl acrylate via a Diels-Alder adduct with (2-pyridyl)anthracene [48], Aromatic carboxylic acids [49] and mandelic acid [50] are efficiently esterified with Fc2(S04)3 XH2O as catalyst. Co(II) perchlorate in MeOH catalyzes the methanolysis of acetyl imidazole and acetyl pyrazole [51]. Hiyama et al. used FeCb as a catalyst for the acylation of a silylated cyanohydrin. The resulting ester was then cyclized to 4-amino-2(5H)-furanones (Sch. 5) [52]. 

Total extracts and/or liquid chromatographic subfractions are then analyzed by capillary colnmn gas chromatography nsing a flame ionization detector. Except for hydrocarbon fractions, derivatization is commonly applied to render polar lipids more volatile in order to reduce gas chromatographic retention times and to improve peak shape at the detector. Carboxylic acids are usually transformed into their methyl esters, and hydroxyl or amine gronps into their trimethylsilyl ether derivatives. Alternatively, both acid and hydroxyl groups can be silylated. Acetate formation is another common derivatization method. A variety of derivatization reagents are conunercially available for this purpose. 

Over the last decade, a considerable number of reactions has been studied (11,35) (i) olefins oxidation (38,39), hydroboration, and halogenation (40) (ii) amines silylation (41,42), amidation (43), and imine formation (44) (iii) hydroxyl groups reaction with anhydrides (45), isocyanates (46), epichloro-hydrin and chlorosilanes (47) (iv) carboxylic acids formation of acid chlorides (48), mixed anhydrides (49) and activated esters (50) (v) carboxylic esters reduction and hydrolysis (51) (vi) aldehydes imine formation (52) (vii) epoxides reactions with amines (55), glycols (54) and carboxyl-terminated polymers (55). A list of all the major classes of reactions on SAMs plus relevant examples are discussed comprehensively elsewhere (//). The following sections will provide a more detailed look at reactions with some of the common functional SAMs, i.e hydroxyl and carboxyl terminated SAMs. 

A new route to racemic a-amino-acids in general consists of an overall a-amination of simple carboxylic acid esters in a relative of the Japp-Klingermann reaction, a method which is usually only successful with active methylene compounds such.as malonates. Thus, 0-silyl-enolates of esters (464) condense with benzenediazonium tetrafluoroborate to give, after isomerization,... 

Silylation is the most widely used derivatization technique for GC. Some functional groups are problematic for GC as a result of acidic or basic properties that promote intermolecular hydrogen bond formation and thus involatility thus hydroxyl, carboxylic acid, amine, thiol, even phosphate ester groups, can be derivatized by... 

The efficiency of HMDS-mediated silylations can be markedly improved by conducting reactions in polar aprotic solvents. For example, treatment of methylene chloride solutions of primary alcohols or carboxylic acids at ambient temperatures with HMDS (0.5-1 equiv) in the presence of catalytic amounts of TMSCl (0.1 equiv) gives the corresponding silyl ether and the trimethylsilyl ester, respectively (eq 4). Af-SUylation of secondary amines occurs in preference to primary alcohols when treated with 1 equiv of HMDS and 0.1 equiv TMSCl (eq 5). The silylation of secondary amines cannot be effected in the absence of solvent. Secondary and tertiary alcohols can also be silylated at ambient temperatures in dichloromethane with HMDS and TMSCl mixtures however, stoichiometric quantities of the sUyl chloride are required. 

Currently, these molecular systems are studies as SAMs on a metal surface. An additional method of preparing ordered monolayers of molecular devices is the use of Langmuir-Blodgett (LB) films. Therefore, a compound with hydrophilic and hydrophobic subunits with the central nitroaniline core similar to 70 was synthesized as in Scheme 3.40. n-Hexylbenzene was easily brominated on neutral alumina and coupled to TMSA followed by silyl removal and coupling to the nitroacetanilide core intermediate, 68, to afford 88. The methyl ester, intermediate 90, was synthesized by the coupling of methyl 4-ethynylbenzoate (89) to 88. The amine was unmasked and the methyl ester was saponified with lithium hydroxide to afford molecular scale device 91. Compound 91 is suitable for the formation of a LB film due to its hydrophilic carboxylic acid end-group and the hydrophobic n-hexyl end-group. 

The reaction may be of some preparative interest for obtaining alkylbenzonitriles and various a-functionalized alkylbenzonitriles starting from polynitriles (see Scheme 4.10 and Scheme 4.11) [56,57]. Donors that can be conveniently used as the precursors of the radicals include Jt donors, such as alkenes [58,59] and alkyl aromatics [60-63], heteroatom-centered donors, such as carboxylic acids [64] and ierf-butyl esters [65], ethers [66], ketals [67] (as well as cyclopropanone sUyl ketals) [68] and amines, organometallic donors such as silanes, silyl ethers, and silyl amines [69-71] as well as germanes, stannanes, and borates [72]. 

Aminations which afford 6-aminocarboxylates are of interest in relation to monobactam antibiotics. A secondary aminomethyl group can be introduced at the -position of carboxylic esters by reaction of hexahydro-1,3,5-triazines with ketene silyl acetals in the presence of a catalytic quantity of trifluoromethanesulphonic acid (Scheme 25). The triazine (10) is considered to be converted into an N-silylated methyleneiminium salt which undergoes addition of the ketene silylacetal (11). 

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