TMPZnCl·LiCl is a novel, mild, and efficient base used for the metallation of aromatic rings, resulting in anions that await electrophilic attack.
The University of Munich published an article in the OPRD journal discussing how the presence or absence of magnesium chloride affects regioselectivity when using TMPZnCl·LiCl as a base. Let’s take a look at the reaction.
Reaction Process
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Compound 1 via pathway a, without magnesium chloride, yields compound 5.
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Compound 1 via pathway b, with magnesium chloride, yields compound 6.
Iodination Case
Preparation of TMPZn·LiCl
A dry and argon-flushed 1.0 L Schlenk flask, equipped with a magnetic stirring bar and a rubber septum, was charged with 2,2,6,6-tetramethylpiperidine (59.5 mL, 350 mmol) freshly dissolved in THF (350 mL). This solution was cooled to −40 °C, and n-BuLi (2.3 M in hexane, 152.2 mL, 350 mmol) was added dropwise. After the addition was complete, the reaction mixture was allowed to warm up slowly to −10 °C for 1 h. ZnCl2 (1.0 M in THF, 368 mL, 368 mmol, 1.05 equiv) was added dropwise, and the resulting solution was stirred for 30 min at −10 °C and then for 30 min at 25 °C. The solvents were then removed under vacuum, affording a yellowish solid. Freshly distilled THF was then slowly added under vigorous stirring until the salts were completely dissolved. The freshly prepared TMPZnCl·LiCl (2) solution was titrated prior to use at 25 °C with benzoic acid using 4-(phenylazo)diphenylamine as an indicator. A concentration of 1.35 M in THF was obtained.
References
Org. Process Res. Dev. 2017, 21, 660−663