Acylation method

The A-(l-acyloxyalkyl)amides or carbamates arc easily prepared from the corresponding hydroxy compounds by conventional acylation methods, such as heating with the required carboxylic acid in the presence of a strong acid or treatment with acyl halides or acid anhydrides1. 

Thus, these methodologies were used to resolve 1-hydroxyalkanephospho-nates 41 by either their enzyme-mediated acylation (Method A) or hydrolysis of the corresponding acyloxy derivatives 42 (Method B) (Equation 23). Selected examples are collected in Table 3. 

Illustrative yields for the two acylation methods catalyzed by -substituted imidazoles are given in the following tables. 

A number of new synthetic approaches to the tropane skeleton have been developed during recent years. The more characteristic ones are described in this section. In order to provide a representative picture of the whole field, a few of the earlier syntheses, starting from the classic ones of Willstatter and Robinson, are briefly reviewed. The earlier methods based on the transformation of the preformed tropane skeleton are noted only occasionally. However, the recently developed syntheses of the proteaceous tropane alkaloids based on new C-acylation methods for tropinone (124) are included. 

The insertion of carbon monoxide into o-alkylpalladium(II) complexes followed by attack by either alcohols or amines is a powerful acylation method. This carbonylation reaction has been applied in several different ways to the reactions and syntheses of indoles. Hegedus and coworkers converted o-allylanilines to indoline esters 315 in yields up to 75% [293], In most of the examples in this section, CO at atmospheric pressure was employed. 

A. Acylation Methods by a) Acetic anhydride-pyridine reagent (p333) b) Acetyl chloride (p335) and c) Phthalic anhydride (P336)... 

In connection with the elaboration of specific procedures for the manufacture of both of the isosorbide mononitrates, methods were developed to shift, with high regioselectivity, the course of the acylation reaction either towards the 5 (endo) or the 2 (exo) position, depending on the conditions applied.104-106 Thus, isosorbide 5-acylates are obtained in 70-85% yield when 3 is treated with the appropriate acid anhydride in the presence of lead(II) oxide or acetate for 20 to 40 h at room temperature. To avoid transesterifications to the appropriate 2-acylate, the workup procedures, especially during the distillation, have to be conducted under strictly neutral conditions. The contrary effect, a remarkable enrichment by the isosorbide 2-acylate (up to 90%) is realized by a transesterification process mediated by a small proportion of sodium or potassium carbonate, hydroxide, or meth-oxide, which are added to the acylation mixture from isosorbide at HOMO0, and subsequent removal of the 2-acylate by vacuum distillation.104 These two regioselective acylation methods may be used for aliphatic, as well as for aromatic, carboxylic acid anhydrides. 

Other research groups have made use of the acylation method, followed by reduction of the resulting ketone group, to prepare alkylated thiophenes e.g. C20 alkylthiophenes (8). 

The preparation of 3-methvl-2-f3 7Ur-trimethvldodecvrithiophene. This compound, which has a carbon skeleton resembling that of phytane, is often a major component of certain immature sediments Q). Previous syntheses of this compound have used the acylation method whereby 3-methylthiophene is acylated with 3,7,11-trimethyldodecanoic acid (1, 8). Reference to Figure 5 indicates that the required compound will be accompanied by the 2,4-isomer and this is indeed the case. The pure compound can, however, be prepared using a lithiated alkylthiophene and an aldehyde (Figure 23). 

Several different methods for the acylation of lFf-pyrrolo[2,3-6]pyridine (1) have been reported <82JHC665> and the results are summarized in Table 40. When reaction conditions which gave a 90% yield for the acylation of indole were tested on compound (1), an excellent yield (91%) of 1-acetylpyrrolo[2,3-6]pyridine was obtained <52JCS3592>. Other acylation methods afforded the 3-acyl derivative as the major product. 

As noted earlier, the development of new alkylation and acylation methods for compounds bearing carbonyl groups has fostered the use of enamines as reaction intermediates. 

As we have seen in these chapters on acylation methods in stepwise and segment condensation peptide synthesis, considerable progress towards efficient procedures to couple amino acids and peptides by an amide bond have been made, particularly in the areas of coupling agents, enzyme-catalyzed coupling, and ligation methods. Problems still arise when... 

A major disadvantage with the acylation method is that the starting material, cis-cyclopentene-3,5-diol, is not readily available and must be... 

Acylative Methods. Benzyl groups, as well as other alkyl groups, can be converted to various carbamates by a variation of the von Braun reaction. These can then be cleaved by conditions that are outlined in the section on carbamates. 

The usual work-up procedure of the reaction mixture made with Fe -KlO under optimum conditions (Table 2) resulted in 4 Ac-B15C5 with 55% yield. This result gives a practical preparative method which is really competitive with the 65-70% yield of the P2O5 or polyphosphoric acid acylation methods and eliminates their drawbacks difficult handling and mixing because of high viscosity, costly neutralization. 

The mixed carboxylic-triflic anhydride produced between the acyl chloride and triflic acid has been earlier described to give electrophilic acylation without any catalyst.This acylation method is advantageous in terms of the mild conditions employed and the easy availability of acyl chlorides. The aromatic substrates are mainly limited to electron-rich arenes. However, the methodology can be applied to unactivated aromatics such as benzene and chlorobenzene under special conditions. 

Gilbert, L. and Spagnol, M. 1997. Aromatic thioether acylation method. WO Patent 9,717,324. 

Diaryl ketones. A Friedel-Crafts acylation method is shown in the following equation ... 

Prepare a ketone from each of the following precursors by the Friedel-Crafts acylation method. 

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