Indium-Mediated Cleavage of the Trityl Group from Protected 1H-Tetrazoles

Abstract

On treatment with indium metal in MeOH/THF, the trityl group undergo reductive removal from 1-H protected tetrazoles; (including aliphatic, aromatic and heteroaromatic substituents), affording the corresponding free tetrazoles in excellent yields, without any decomposition of the tetrazole ring or reduction of any other group.

Zn/MeOH-Mediated Practical and Easy Detritylation of Protected 1-Trityltetrazoles

“…To compare the methodology described here with those using other metals such as lithium 13b or indium 16 already reported, Table 3 shows that, in general, yields are comparable in the three cases. However, the reaction times are shorter for lithium and longer for indium.…”

“…The starting materials 1 were prepared according to our previous reports. 13,16 When compounds 1 were allowed to react with zinc powder (1:1 molar ratio) in a mixture of methanol/THF (2:1) under reflux, the corresponding detritylated tetrazoles 2 were isolated after acidic work-up (Scheme 1 and Table 2). The reaction worked well for 5-aryl (entries 1, 2, and 10) and 5-alkyl (entries 2 and 9) derivatives, as well as for heterocyclic (entry 5) or benzylic substrates (entries 2 and 9).…”

“…5 Some reported procedures for the detritylation of N-Tr containing systems include: (a) acidic conditions (hydrogen chloride 6 and trichloro- 7 or trifluoroacetic acid 8 ), (b) palladium-catalyzed hydrogenation (with molecular hydrogen, 9 ammonium formate, 10 or polymethylhydrosiloxane 11 ), (c) alkali metals in solution (sodium/ammonia 12 or lithium/naphthalene cat. 13 ), (d) hydroxybenzotriazole derivatives in trifluoroethanol, 14 and (e) the use of other metals (such as ytterbium 15 or indium 16 ).…”

LiCl-mediated, easy, and low-cost removal of the trityl group from protected alcohols and diols

“…15l Other metals, such as indium 21 In the present paper we describe the deprotection of trityl protected alcohols and diols with lithium chloride. This methodology represents a milder procedure than those already described and therefore may be more compatible with other functional groups present in a molecule.…”

Indium-mediated cleavage of the trityl group from protected alcohols and diols

“…Among them, we investigated detritylation processes involving trityl ethers 9a and trityl amines. 9g In addition, more recently, we have explored the use of other metals, such as indium 11 or zinc, 12 in both cases in methanol, for the effective detritylation of 1-trityltetrazoles. 13,14 In this paper,…”