1. Aqueous phosphoric acid as a mild reagent for deprotection of tert-butyl carbamates, esters, and ethers
Bryan Li, et al. J Org Chem. 2006 Nov 24;71(24):9045-50. doi: 10.1021/jo061377b.
Aqueous phosphoric acid (85 wt %) is an effective, environmentally benign reagent for the deprotection of tert-butyl carbamates, tert-butyl esters, and tert-butyl ethers. The reaction conditions are mild and offer good selectivity in the presence of other acid-sensitive groups, including CBZ carbamates, azetidine, benzyl and methyl esters, TBDMS, and methyl phenyl ethers. The mildness of the reaction is further demonstrated in the synthesis of clarithromycin derivative, in which a tert-butyl ester is removed in the presence of cyclic carbamate, lactone, ketal, acetate ester, and epimerizable methyl ketone functionalities. The reaction preserves the stereochemical integrity of the substrates. The reactions are high yielding, and the workup is convenient.
2. Yb(OTf)3-Catalyzed and Di- tert-butyl Dicarbonate-Mediated Decarboxylative Etherification and Esterification Reactions
Arshpreet Kaur, Arshdeep Pannu, Deshkanwar S Brar, Surinder K Mehta, Deepak B Salunke ACS Omega. 2020 Aug 13;5(33):21007-21014. doi: 10.1021/acsomega.0c02516. eCollection 2020 Aug 25.
Protecting group chemistry has invariably captured the fascination of chemists because of its extensive viability in chemical synthesis. The present report describes our pioneer work of applying ytterbium triflate as a catalyst, for the reaction of alcohols with di-tert-butyl dicarbonate (Boc2O) leading to the formation of tert-butyl ethers. There exists no recorded evidence for the use of Yb(OTf)3 as a catalyst for the protection of alcohols to tert-butyl ethers, despite its excellent utility in various reactions. Yb(OTf)3 has been used predominantly in the catalytic deprotection studies such as selective deprotection of tert-butyl esters to carboxylic acids as well as prenyl ethers to alcohols. This study involved the critical evaluation of solvent, time, and temperature that finally led to an efficient protocol for the formation of tert-butyl ethers. Yb(OTf)3 catalyzed the formation of tert-butyl ethers, notably reducing the reaction time, which is exemplified by the achievement of up to 92% conversion of alcohols to tert-butyl ethers within an hour. Additionally, the report demonstrates the utility of this synthetic protocol for the protection of carboxylic acids.
3. Alcohols and di-tert-butyl dicarbonate: how the nature of the Lewis acid catalyst may address the reaction to the synthesis of tert-butyl ethers
Giuseppe Bartoli, Marcella Bosco, Armando Carlone, Renato Dalpozzo, Manuela Locatelli, Paolo Melchiorre, Letizia Sambri J Org Chem. 2006 Dec 22;71(26):9580-8. doi: 10.1021/jo061402d.
The reaction between alcohols and Boc2O leads to the formation of tert-butyl ethers and/or Boc-alcohols, depending on the nature of the Lewis acid catalyst. Product distribution is mainly tuned by the anionic part of the salt. Perchlorates and triflates, anions with highly delocalized negative charge, give prevalent or exclusive ether formation. On the other hand, Boc alcohols are the main or exclusive products with un-delocalized isopropoxide or low-delocalized acetate ions. The metal ion influences only the reaction rate, roughly following standard parameters for calculating Lewis acidity. A reaction mechanism is supposed, and a series of experimental evidences is reported to support it. These studies allowed us to conclude that, to synthesize tert-butyl ethers, in reactions involving aliphatic alcohols, Mg(ClO4)2 or Al(ClO4)3 represents the best compromise between costs and efficiency of the reaction, while, in reactions involving phenols, Sc(OTf)3 is the best choice, since aromatic tert-butyl ethers are not stable in the presence of perchlorates.
