Imino esters acylation

Hoesch reaction. In most cases, a Lewis acid is necessary zinc chloride is the most common. The reaction is generally useful only with phenols, phenolic ethers, and some reactive heterocyclic compounds (e.g., pyrrole), but it can be extended to aromatic amines by the use of BCls. Acylation in the case of amines is regioselectively ortho. Monohydric phenols, however, generally do not give ketones " but are attacked at the oxygen to produce imino esters. Many nitriles... 

The formation of tluorinated Q -hydroxy-jS-imino esters (180) by treatment of fluorinated imino ethers (179) with lithium 2,2,6,6-tetramethylpiperidide has been reported. A possible explanation for this interesting intramolecular rearrangement is proposed in Scheme 64. Acyclic imides derived from primary benzylic amines and amino acid esters have been found to undergo a novel nitrogen to carbon acyl migration via a base-generated carbanion to yield the corresponding a-amino... 

An interesting bifunctional system with a combination of In(OTf)3 and benzoyl-quinine 65 was developed in p-lactam formation reaction from ketenes and an imino ester by Lectka [Eq. (13.40)]. High diastrereo- and enantioselectivity as well as high chemical yield were produced with the bifunctional catalysis. In the absence of the Lewis acid, polymerization of the acid chloride and imino ester occurred, and product yield was moderate. It was proposed that quinine activates ketenes (generated from acyl chloride in the presence of proton sponge) as a nucleophile to generate an enolate, while indium activates the imino ester, which favors the desired addition reaction (66) ... 

When hydrazine is added to the keto-ester an imine is formed with the ketone but acylation occurs at the ester end to give an amide rather than the imino-ester we had designed. The product is a dihydropyridazolone. 

Alkylation and acylation of imino esters proceeds at the nitrogen of the imino ester function. In many cases it is not advisable to use alkyl halides or acyl halides for such reactions because the iminium salts (89) or (90 Scheme 8) are readily dealkylated by the halide anions. This can be prevented by the use of stronger alkylating reagents, e.g. tertiary oxonium salts, dialkyl sulfates or alkyl triflates, which produce in the course of the alkylation only anions with low nucleophilicity. Heterocycles containing... 

Azabuta-l,3-dienes have been prepared in which the imino group is conjugated with an enol ester acylation of carbanions derived from N-(diphenylmethyl)arylmethanimines affords a wide range of the 2-azadienes (Scheme 197). The site selectivity for the attack of the electrophile on the aza-allyl anion depends upon the substituents on the carbanion, and on the hardness of the... 

Acyl carbonates (234), alkoxyquinones (235) as vinylogous esters, imino ethers (236), and diketene (237) react with ethyleneimine to give the corresponding acylated ethyleneimines. 

In solution-phase peptide synthesis, acylation of amino acids or peptides with N-protected azetidine-2-carboxylic acid is performed via the active esters, e.g. A-hydroxysuccin-imide 100 111-112 or pentachlorophenyl ester, m 117 as well as by the mixed anhydride 101114 or carbodiimide 118 methods. An attempt to prepare the A-carbonic acid anhydride by cycli-zation of A-(chloroformyl)azetidine-2-carboxylic acid with silver oxide in acetone or by addition of triethylamine in situ failed, presumably due to steric hindrance. 111 In SPPS, activation of the Fmoc-protected imino acid by HBTU 119,120 is reported. In solution-phase peptide synthesis, coupling of N-protected amino acids or peptides to C-protected azetidine-2-carboxylic acid or related peptides may be performed by active esters, 100 118 121 mixed anhydrides, 95 or similar methods. It may be worth mentioning that the probability of pip-erazine-2,5-dione formation from azetidine-2-carboxylic acid dipeptides is significantly reduced compared to proline dipeptides. 111 ... 

Due to the extremely low nucleophilicity of the imino group, 187,188 acylation of thiazolidine-4-carboxylic acid (11) is not a trivial procedure. In fact, N-protected Thz derivatives can be prepared by standard procedures, but strong acylating conditions are required. The related N-Boc derivative is obtained only by prolonged reaction times with Boc-N3 U2,189 or with Boc20. 113 For preparation of the N-Z derivative, silylation of Thz with, for example, chlorotrimethylsilane is recommended prior to the reaction benzyl chloroformate. 200 Due to the stability of thiazolidine-4-carboxylic acid to acids its methyl ester is obtained by HC1 catalyzed reaction with methanol, 190 whereas the amide is formed by reacting Thz N-carboxyanhydride with ammonia.1 89 Derivatives of thiazolidine-4-carboxylic acid are listed in Table 8. 

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