Carboxylic acid esters ketene addition

Carboxylic acid anhydrides. A soln. of triflic anhydride in ethylene dichloride added dropwise to a soln. of Ph3PO in the same solvent at 0° under N2 after 15 min a soln. of / -toluic acid in ethylene dichloride added followed by EtjN, and stirred for 15 min - p-toluic anhydride. Y 93%. Redox side reactions are avoided, and ketones, esters and ethers unaffected. F.e. inch ketenes, carboxylic acid esters (incl. aryl esters) and amides, amidines from carboxylic acid amides, benzimidazoles, and intramolecular ar. acylation, also using N-diphenylphosphinyl-N -methylpiperazine (without the need for an additional base), s. J.B. Hendrickson, M.S. Hussoin, J. Org. Chem. 54, 1144-9 (1989) alternative prepn. of reagents cf. D. Crich, H. Dyker, Tetrahedron Letters 30, 475-6 (1989). 

However, in subsequent work it was found that carboxylic acid groups readily add to ketene acetals to form carboxyortho ester linkages (24). These are very labile linkages and on hydrolysis regenerate the carboxylic acid group which then exerts its catalytic function. Because carboxylic acids add so readily to ketene acetals, very labile polymers can be prepared by the addition of diacids to diketene acetals. The utilization of such polymers is currently under investigation. 

Among the procedures which have been developed for /J-lactam syntheses (as reviewed [58] [59]) are the cyclization of /3-haIopropionamides [60] from azetidine-2-carboxylic acids and esters [61] the addition of ketenes to Schiff bases [62] ring-contraction procedures [63] [64] [65] [3+1] cyclizations of a-phenylthioacetamide [66] the cyclization of aminoacids [67], and styrene and N-chlorosulphonyl isocyanate [68]. 

Asymmetric Mannich-type reactions provide useful routes for the synthesis of enantiomerically enriched P-amino ketones or esters [48a, 48b]. For the most part, these methods involve the use of chirally modified enolates or imines. Only a handful of examples has been reported on the reaction of imines with enolates of carboxylic acid derivatives or silyl ketene acetals in the presence of a stoichiometric amount of a chiral controller [49a, 49b, 49c]. Reports describing the use of a substoichiometric amount of the chiral agent are even more scarce. This section contains some of the most recent advances in the field of catalytic enantioselective additions of lithium enolates and silyl enol ethers of esters and ketones to imines. 

Due to the unique bivalent carbene and diversity of the N-heterocyclic motif, NHCs have been demonstrated to be efficient organocatalysts for various enantioselective reactions. In addition to the traditional thioazolium and imidazolium NHCs, triazolium NHCs have become the most successful organocatalysts. Recently, NHC/Lewis acid cocatalysis and bifunctional NHCs have shown a very promising future. Beyond the classic NHC-catalysed umpolung of aldehydes, the extended umpolung of functionalised aldehydes are extremely successful. A series of NHC-catalysed reactions of ketenes have been developed for the synthesis of various enantioriched heterocycles. Esters, anhydrides, carboxylic acids and even Michael acceptors are useful alternative substrates for NHC-catalysed reactions. With increasing interest and rapid development of NHC catalysis, new structures of the catalysts, new reaction modes, and synthetic applications can be expected in the near future. 

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). 

Another conjugate addition strategy used the sodium enolate of 4.62 in a reaction with ketene 4.63 to give 4.64. In this particular example, both the amino and the carboxyl moieties of the final amino acid were present in the starting material (4.62). Aqueous acid hydrolysis of the ester groups and the amide was accompanied by decarboxylation to give 2-amino-3-methylenebutanedioic acid, 4.55.33... 

Other reports deal with a pyrrolidine-catalysed homo-aldol condensation of aliphatic aldehydes (further accelerated by benzoic acid), a diastereoselective aldol-type addition of chiral boron azaenolates to ketones,the use of TMS chloride as a catalyst for TiCU-mediated aldol and Claisen condensations, a boron-mediated double aldol reaction of carboxylic esters, gas-phase condensation of acetone and formaldehyde to give methyl vinyl ketone, and ab initio calculations on the borane-catalysed reaction between formaldehyde and silyl ketene acetal [H2C=C(OH)OSiH3]. ... 

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