Intramolecular esters

This case study deals with an industrial Dieckmann condensation (intramolecular ester condensation Scheme 5.6) considering the laboratory and the operation scale. 

In a closely related approach, Yen and Chu have reported the preparation of tetra-hydro-/3-carbolinediketopiperazines employing a three-step Pictet-Spengler, Schot-ten-Baumann, and intramolecular ester amidation sequence (Scheme 6.233) [415]. Throughout the synthesis, the ionic liquid l-butyl-2,3-dimethylimidazolium hexa-fluorophosphate (bdmimPF6) was employed. In a typical experiment, (S)-tryptophan methyl ester was dissolved in a 1 1 mixture of the ionic liquid and tetrahydrofuran... 

The oxidative part starts with the oxidation of glucose 6-phosphate by glucose-6-phosphate dehydrogenase. This forms NADPH+H"" for the first time. The second product, 6-phosphogluconolactone, is an intramolecular ester (lactone) of 6-phospho-gluconate. 

DMSO resulted in an intramolecular ester condensation (Baker Venkataraman-type rearrangement) to give a Cl 5 phenol the cyclization of which furnished the 0-benzyl-protected flavone-C-glycoside. After deprotection, isoembigenin was obtained. 

The lactones are the intramolecular esters of the corresponding hydroxy fatty acids. They contribute to the aroma of butter and various fruits. 15-Pentadeca-nolide is responsible for the musk-like odor of angelica root oil. Of the naturally occurring bicyclic lactones, phthalides are responsible for the odor of celery root oil, and coumarin for woodruff. 

The macrolide systems described above are produced by formation of an intramolecular ester or amide linkage, utilizing appropriate functionalities in the growing polyketide chain. Macrolide formation does not always occur, and similar acetate-propionate precursors might also be expected to yield molecules which are essentially linear in nature. Good examples of such molecules... 

The overall process for this enzymatic resolution is compared with the conventional chemical process in Fig. 14. The enzymatic process can skip several tedious steps which are necessary in chemical resolution and this is a considerable practical advantage. There have been several reports on the application of enzymatic asymmetric hydrolysis to the optical resolution of pantolactone [141, 142], In these cases, esterified substrates, such as O-acetyl or O-formyl pantolactone, and lipases were used as the starting materials and catalysts, respectively. Since the lactonase of F. oxysporum hydrolyzes the intramolecular ester bond of pantolactone, it is not necessary to modify the substrate, pantolactone. This is one of the practical advantages of this enzyme. 

Intramolecular ester condensation reactions are called Dieckmann condensations and are very useful ring-forming reactions. Examples are shown in the following equations. In the second equation the yield is only 54% if sodium ethoxide is used as the base. 

Lactonase belongs to the esterase family, and can act on the intramolecular ester bonds of lactones. Like already-known esterases such as lipases,... 

Under Fischer esterification conditions, many hydroxycarboxylic acids i intramolecular esters (lactones). ... 

The carbonates and thiocarbonates may be classified quite simply into the following types, (i) Mixed Esters. In these esters, the carbonic acid or thiocarbonic acid is esterified with both an alcohol and a carbohydrate, (ii) Acid Esters. Here, a metal salt of a half-ester of a carbohydrate has been formed, (iii) Intermolecular Esters. Here, an ester has been formed between one molecule of the acid and two molecules of carbohydrate, (iv) Cyclic or Intramolecular Esters. Here, one molecule of the acid is di-esterified with one molecule of carbohydrate. 

In another case, 1 was used to deprotect the 2-(allyloxy)phenylacetyl group, employed as a protecting functionality in carbohydrate chemistry242. Thus, heating compound 266 with a palladium catalyst/proton sponge system results in an almost quantitative yield of compound 268 (equation 29). In accordance with a postulated relay mechanism, the phenolic allyl ether is cleaved by the transition metal followed by intramolecular ester cleavage by nucleophilic attack of the released hydroxyl. The aforementioned conditions... 

Stream of nitrogen. The initial product, the jS-keto sulfoxide II, undergoes intramolecular ester condensation with formation of the 1,3-indanedione system. Ill, which in the presence of hydrochloric acid undergoes Pummerer rearrangement to 2-chloro-2-methylmercapto-l,3-indanedione (IV). This crystalline product (m.p. 63°) is obtained in yield of 80% and is hydrolyzed in boiling water nearly quantitively to ninhydrin (V). 

Dimedon, 5,5-dimethylcyclohexane-l,3-dione, is prepared by an interesting process discovered by Vorlander. The reaction of 1 mole each of diethyl malonate, mesityl oxide, and sodium ethoxide in absolute ethanol probably involves a Michael addition followed by an intramolecular ester condensation to close the ring to give the diketo ester formulated (procedure of Shriner and Todd. Aqueous potassium... 

The addition reaction of enolates to activated cyclopropanes has also been applied to intramolecular reactions leading to cyclic and bicyclic products as the result of a subsequent intramolecular ester condensation ... 

Kim, D., Shin, K.J., Kim, I.Y., and Park, S.W., A total synthesis of (-)-reiswigin A via sequential Claisen rearrangement-intramolecular ester enolate alkylation. Tetrahedron Lett., 35, 7957, 1994. 

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