Kinetic Resolution of Racemic Carboxylic Acids Using Achiral Alcohols by the Promotion of Benzoic Anhydrides and Tetramisole Derivatives: Production of Chiral Nonsteroidal Anti‐Inflammatory Drugs and Their Esters

Abstract

A variety of optically active carboxylic esters were produced by kinetic resolution of racemic carboxylic acids by using achiral alcohols, benzoic anhydrides, and Birman's tetramisole‐type catalysts. Bis(α‐naphthyl)methanol is a very effective reagent for producing the corresponding esters with high ee values in the presence of 4‐methoxybenzoic anhydride (PMBA) as the coupling reagent by promotion of benzotetramisole derivatives (BTM, α‐Np‐BTM, and β‐Np‐BTM). This protocol directly provides chiral carboxylic esters from free carboxylic acids and achiral alcohols by utilizing a transacylation process to generate the mixed anhydrides from the acid components with benzoic anhydride derivatives in the presence of chiral catalysts.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Kinetic Resolution of α‐Substituted Alkanoic Acids Promoted by Homobenzotetramisole

“…BTM 3 reacted more slowly and displayed somewhat reduced enantioselectivity when used in conjunction with di(1-naphthyl)methanol ( Scheme 3. BTM-catalyzed KR of arylpropionic acids by Shiina et al [17] R = di(1-naphthyl)methyl, PMBA = p-methoxybenzoic anhydride. Both 3 and 2 produced negligible selectivity factors and low rates when isopropanol was used (Table 1, entries 7 and 8).…”

Kinetic Resolution of Secondary Alcohols Using Amidine-Based Catalysts

“…6 In addition to our own efforts in this area, several other groups have subsequently explored the use of ABCs in this transformation and made important contributions by broadening their known substrate scope, establishing new reaction protocols, and exploring additional variations of the catalyst design. 7–11 Furthermore, we and others have demonstrated the utility of ABCs in other types of transformations as well, such as desymmetrization of meso- diols, 6g KR of oxazolidinones and β-lactams via enantioselective N-acylation, 12 intramolecular ketene [2+2] and [2+4] cycloadditions, 13 Steglich rearrangement, 14,15 KR of chiral acyl donors via enantioselective alcoholysis, 16,17 epoxide opening, 18 O-silylation, 19 and Michael additions. 20 …”

6.08 Acylation-Type Reactions: Synthesis of Esters via Acyl Transfer

“…66 The best results were obtained by utilizing bis(α-naphthyl)methanol, catalyst 157, and pivalic anhydride for the KR of various 2-arylpropanoic acids ( Table 21). 70 In summary, amidine-based catalysts (e.g., 130, 131, and 157) are excellent catalyst for enantioselective acyl transfer reactions. The synthesis of the catalysts can be achieved in a few steps from commercially available starting materials.…”