Esterifications Steglich

Neises, B. and W. Steglich, Simple method for the esterification of carboxylic acids. Angewandte Chemie International Edition in English, 1978.17(7) p. 522-524. 

Examples of nonasymmetric organocatalysts that were introduced in the 1950s include analogs of thiamine reported by Breslow in 1957 as an alternative to cyanide as a catalyst for the benzoin condensation [8]. Asymmetric versions of these thiazolium catalysts were used in organocatalytic benzoin condensations by Sheehan and Hunneman in 1966 [9]. In another important development, in 1969 the nucleophilic catalyst 4-(dimethylamino)pyridine (DMAP), which is now widely used for difficult esterifications, was reported by Steglich [10]. 

Steglich esterification-. DMAP, trace of tosic acid, DCC (dicyclohexylcarbodiimide)... 

Macrolactonization The original conditions of Steglich esterification are ineffective for lactonization of co-hydroxy carboxylic acids. However, addition of a soluble amine hydrochloride as a proton-transfer agent results in a useful method... 

Alternative reactions employ coupling reagents such as DCC (Steglich Esterification), preformed esters (transesterification), carboxylic acid chlorides or anhydrides. These reactions avoid the production of water. Another pathway for the production of esters is the formation of a carboxylate anion, which then reacts as a nucleophile with an electrophile (similar reactions can be found here). Esters may also be produced by oxidations, namely by the Baeyer-Villiger oxidation and oxidative esterifications. 

The Fukuyama Reduction allows the convenient and selective reduction of thioesters, which are easily prepared from the corresponding carboxylic acids, for example by the Steglich Esterification. 

The Steglich Esterification is a mild reaction, which allows the conversion of sterically demanding and acid labile substrates. It s one of the convenient methods for the formation of terf-butyl esters because r-BuOH tends to form carbocations and isobutene after a subsequent elimination under the conditions employed in the Fischer Esterification. 

Macrolactonization. This version of Steglich esterification was developed specifically for lactonization of 1 to (+ )-colletodiol 2. 

Steglich esterification of a carboxylic acid with 2,2,2-trichloroethanol using DCC-DMAP affords a mild and convenient method for preparing TCE esters [Scheme 6,88],203 More traditional methods involving the reaction of an acid chloride with trichloroethanol in the presence of pyridine have also been used. 

STEGLICH HASSNER Dir t esterification 361 STEPHEN Aldehyde synthesis 362 STEPHENS CASTRO Acetylene cyclophana synthesis 363... 

RCOOH with 1°, 2° and 3° alcohols in the presence of DCC (dicyclohexylcar-bodiimide) and DMAP gives the corresponding esters in good yield under mild conditions (Steglich esterification). ... 

Boden, E. P., Keck, G. E. Proton-transfer steps in Steglich esterification a very practical new method for macrolactonization. J. Org. Chem. 1985, 50, 2394-2395. 

Trichlorobenzoyl chloride a reagent for esterification of acids via a mixed anhydride, also used for large ring lactonization with DMAP (see also Steglich-Hassner, (see 1st edition). 

Boden and Keck [53] developed a practical method for macrolactonization by treatment with DCC and DMAP in the presence of DMAP-HCl the original esterification procedures using DCC and DMAP or 4-pyrrolidinopyridine were reported by Neises and Steglich [54] and Hassner and Alexanian [55] independently. This method worked very efficiently for the macrolactonization (92% yield) in the total synthesis of cytovaricin (196) (see Scheme 29 later in this chapter). 

STEGLICH HASSNER Dirad esterification Direct room temperature esterification of carboxylic acids with alcohols, Including ten alcohols with the help of dfcydohexytcartxxSimide (DCC) and S-dtekylamnopyridlne catalysts 3. 

Esterification of a carboxylic acid with 2-(trimethyIsilyI)elhanol (commercially available) using DCC-DMAP (Steglich esterification) [Scheme has... 

Fig. 7 Macrolactonizations mediated by (a) the Mitsunobu reaction (b) the Steglich esterification run in the presence of DMPA, which gives only an urea derivative and (c) high yields of lactones, which are obtained in the presence of a proton source (DMPA, HCl).

The second example is based on Steglich esterification, for which it was shown that the yield of esterification reaction using dicyclohexylcarbodiimide is greatly increased by the addition of 4-dimethylarninopyridine (DMPA). However, in the case of w-hydroxyacids under these reaction conditions, the N-acylurea derivative is formed almost exclusively (Fig. 7b), with almost no lactone formation. The reason for this failure appears to lie in the proton-transfer steps. By operating in the presence of a proton source (DMPA-HCl), the lactoniza-tion occurred in excellent yield (Fig. 7c). 

Macrolides. - The Steglich esterification procedure (DCC-DMAP) can be applied to the macrolactonization of u>-hydroxy-acids if, in addition, an excess of the hydrochloride salt of DMAP is... 

The first high-performance polymer with over 7% efficiency in its photovoltaic devices, namely PTB7, was constructed with BnDT as the donor and 2-ethylhexyl-3-fluorothieno[3,4-b]thiophene-2-carboxylate as the acceptor. The synthetic route is outlined in Scheme 15.7. Fluorine is first attached onto 4,6-dihydrothieno[3,4- ]thiophene-2-carboxylic acid by PhS02NF via electrophilic fluorination. This fluorinated intermediate then undergoes Steglich esterification to attach a solubilizing side chain. Finally, an oxidation by mCPBA, followed by the dehydration by acetic anhydride, affords the fluorinated thienothiophene. 

Organic Syntheses Based on Name Reactions STEGLICH-HASSNER Direct Esterification... 

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