Trapping of Transient Thienyllithiums Generated by Deprotonation of 2,3- or 2,5-Dibromothiophene in a Flow Microreactor

Abstract

Selective trapping of (4,5-dibromo-2-thienyl)lithium, known to undergo halogen dance, was achieved in a flow microreactor. This transient thienyllithium, generated by mixing 2,3-dibromothiophene and lithium diisopropylamide at –78 °C for 1.6 seconds, reacted with benzaldehyde. The reaction system is also applicable to other carbonyl compounds to afford the corresponding adducts in good yields. Moreover, the established conditions permit the conversion of 2,5-dibromothiophene into a mixture of the two constitutional isomers. The contrasting results are discussed on the basis of the reaction pathway.

Continuous‐Flow Divergent Lithiation of 2,3‐Dihalopyridines: Deprotolithiation versus Halogen Dance

“…It is also important to mention the recent report from Nagaki, who reported the continuous flow deprotolithiation using LDA on 2,3-and 2,5-dibromothiophene derivatives (Scheme 1, eq (c)). [12] This report clearly highlighted the challenging and tedious control of the formation of lithiated species, even in continuous flow at very low temperature and with very short residence times.…”

“…(c)). [12] This report clearly highlighted the challenging and tedious control of the formation of lithiated species, even under continuous flow at very low temperature and with very short residence times.…”

Ultrafast Halogen Dance Reactions of Bromoarenes Enabled by Catalytic Potassium Hexamethyldisilazide

“…However, although halogen dance reactions of thiophene, [6] pyridine, [7] and ferrocene [8] are well known, there are few examples of their successful application to other arenes [9] . Recently, much of our efforts have been devoted to extending the limited substrate scope and utilizing the hitherto unutilized arylmetal species of the halogen dance reaction of thiophene, [10a,b] azole, [10c] pyrrole, [10d–g] and benzene [10h,i] . Nevertheless, the general conditions remain underdeveloped, even for bromopyridines, which are the most investigated halogen dance reaction substrates.…”

Unsymmetrization of 1,8-Dibromonaphthalenes by Acid-Induced Halogen Dance Reaction

“…The rearrangement of a halo group, termed the halogen dance reaction, is an effective approach for obtaining unusual bromoarenes in which the reaction is induced by the addition of a strong base . The halogen dance reaction has been studied particularly for heteroarenes such as thiophene, pyridine, and thiazole because they have a relatively acidic proton. , However, the halogen dance reactions of aromatic hydrocarbons are limited and require the introduction of a directing or electron-withdrawing group . The acid-induced halogen dance reaction is an alternative approach .…”