Oxetane ethers are formed reversibly in the lithium-catalyzed Friedel–Crafts alkylation of phenols with oxetanols: Synthesis of dihydrobenzofurans, diaryloxetanes, and oxetane ethers
| Autor: | James A. Bull, Chulho Choi, James J. Mousseau, Rosemary A. Croft |
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| Přispěvatelé: | Engineering & Physical Science Research Council (EPSRC), Engineering & Physical Science Research Council (E, The Royal Society |
| Rok vydání: | 2018 |
| Předmět: |
Chemistry
Organic Ether Lithium 010402 general chemistry Oxetane 0305 Organic Chemistry 01 natural sciences Biochemistry Catalysis chemistry.chemical_compound Nucleophile Drug Discovery Organic chemistry Phenol PHASE ALKYLATION MEDICINAL CHEMISTRY Friedel–Crafts reaction FRAGMENTS Oxetanes Science & Technology STABILITY Dihydrobenzofurans DERIVATIVES 010405 organic chemistry Organic Chemistry ALCOHOLS PEPTIDES O-Alkylation 0304 Medicinal And Biomolecular Chemistry 0104 chemical sciences Chemistry chemistry Catalytic cycle Physical Sciences BIOISOSTERES Polar effect FUNCTIONALIZATION |
| Zdroj: | Tetrahedron. 74:5427-5435 |
| ISSN: | 0040-4020 |
| Popis: | Studies on the mechanism and intermediate products in the Friedel–Crafts reaction between oxetanols and phenols are presented. The formation of O-alkylated intermediates is identified using 1H NMR spectroscopy, in a reversible formation of the kinetic oxetane ether products. An interesting relationship between the electronic nature of the nucleophile and the degree of O-alkylation is uncovered. For phenols substituted with an electron withdrawing group such as CN, oxetane ethers are the only products isolated regardless of reaction time. Increasing the electron rich nature of the phenol leads to an increased proportion of the thermodynamic C-alkylated Friedel–Crafts products after just 1 h and as the sole product/s after extended reaction times. These studies have enabled a more complete catalytic cycle to be proposed. Using the same lithium catalyst and carefully selected reaction times, several examples of oxetane ethers are successfully isolated as novel bioisosteres for ester groups. |
| Databáze: | OpenAIRE |
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