Thermolytic removal of t-butyloxycarbonyl (BOC) protecting group on indoles and pyrroles

Efficient and selective cleavage of the tert-butoxycarbonyl (Boc) group under basic condition

“…3 However, selective cleavage of the di-t-butylimidodicarbonate, oftenly found as valuable intermediates in Mitsunobu 4 and Gabriel type 5 processes towards the synthesis of several bio-active molecules, protected α-amino acids to mono-Boc compounds still lacks efficient and milder methods. Numerous methods are available for the removal of the Bocgroup, 7 including trifluoroacetic acid, 8 trimethylsilyl iodide, 9 hydrochloric acid in ethyl acetate, 10 ceric ammonium nitrate, 11 tin tetrachloride, 12 tetrabutylammonium fluoride, 13 zinc bromide, 14 boron trifluoride, 15 thermolytic removal 16 etc. However, there are very few methods for the selective cleavage 17a-f of the di-Boc protected α-amino acids to mono-Boc compounds.…”

Five‐Membered Heterocycles: Pyrrole and Related Systems

“…For example, 1-(tert-butoxycarbonyl)pyrrole (158) [285] is efficiently lithiated at C2 by LiTMP, and subsequent quenching with aldehydes or acid chlorides gives the corresponding pyrrol-2-yl methanols 265 (Scheme 4.74) and 2-acylpyrroles, respectively. The Boc group may be removed by treatment with sodium methoxide in methanol [406], under thermal conditions [407] or using acid, which may, however, not always be compatible with electron rich substrates. Similar metallation of 158 followed by quenching with trimethyl borate and subsequent hydrolysis provides a route to the useful boronic acid 266 [239].…”

Solvent-Free Mechanochemical Deprotection of <i>N</i>-Boc Group

“…As far as we are aware, ball milling technique was only used in amine Boc protection with di-tert-butyl dicarbonate [4] and synthetic methods for solvent-free removal of Boc group were reported in several papers. These include grinding in a mortar with iodine [5], thermolysis at 180˚C -185˚C [6], or by thermolysis on silica gel at mild temperature (50˚C) at reduced pressure [7] [8]. Microwave-assisted thermolytic deprotection was achieved on silicagel within 1 min [9] or by MW heating on neutral alumina with AlCl 3 in 1 min [10].…”