Sequential alcohol oxidation/putative homo Claisen–Tishchenko-type reaction to give esters: a key process in accessing novel biologically active lactone macrocycles. Issue 68 (4th July 2016)

• Record Type: Journal Article
• Authors: Viana, Hugo; Carreiro, Elisabete P.; Goth, Albertino; Bacalhau, Patrícia; Caldeira, Ana Teresa; Martins, Maria do Rosário; Burke, Anthony Joseph
• Is Part Of: RSC advances. Volume 6:Issue 68(2016)
• Page Start: 63214
• Page End: 63223
• Publication Date: 2016-07-04
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c6ra07547a
• Languages: English
• ISSNs: 2046-2069

Abstract

Abstract : We report an efficient methodology for the direct oxidative esterification of primary alcohols to diether-esters using pyridinium chlorochromate (PCC). Abstract : We report an efficient methodology for the direct oxidative esterification of primary alcohols to diether-esters using pyridinium chlorochromate (PCC). Numerous studies were carried out to probe the reaction mechanism and at the same time optimize the reaction conditions. The reaction could be conducted with 1 equivalent of PCC and 1 equivalent of BF3 ·OEt2 . Indications based on literature precedent were that the reaction may proceed via a sequential alcohol oxidation to the aldehyde followed by a putative Cr or boron catalyzed Claisen–Tishchenko-type reaction. Using this efficient methodology, we synthesized a family of novel diether-esters in very good yields; some of these molecules were subsequently tested against both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). In addition, we also disclose a new synthetic strategy for the synthesis of lactam macrocycles with potential biological activity. This methodology included the regioselective borylation of the ester substrate and a subsequent Suzuki–Miyaura coupling to obtain the desired lactam macrocycle.