Approaches to the Synthesis of 2,3-Dihaloanilines. Useful Precursors of 4-Functionalized-1H-indoles

Abstract

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Combined directed ortho-zincation and palladium-catalyzed strategies: Synthesis of 4,n-dimethoxy-substituted benzo[b]furans

“…Considering the steric hindrance of the required position ( o , o -disubstituted) we employed a copper- and solvent-free methodology for the Sonogashira coupling that uses tetrabutylammonium fluoride as base [42] (Table 2, method A). Subsequently, we checked that the selective coupling could be carried out under standard Pd–Cu catalysis by controlling the reaction temperature [43–44] (Table 2, method B).…”

Highly ortho‐Selective Chlorination of Anilines Using a Secondary Ammonium Salt Organocatalyst

“…[12] They are difficult to achieve by using conventional synthetic methods,b ut can easily be prepared using this mild and efficient secondary ammonium salt catalytic protocol. [13] Furthermore,t he reaction was found to be readily scalable.For instance,10mmol of the aniline 8fwas subjected to the reaction and 2.84 grams (99 %y ield) of the desired ortho-chlorinated product 9f was obtained (Scheme 2). The secondary ammonium salt catalyst 1g could be recovered by aqueous extraction followed by evaporation of the water.…”

“…While secondary ammonium salts have been widely utilized as the organocatalysts in various transformations through the formation of iminium or aminal intermediates,t heir application to site-selective aromatic halogenation remains unknown. [9] With the optimized reaction conditions in hand, we examined the compatibility of different Nsubstituents.I tw as realized that the reaction still could proceed smoothly when replacing the Ns group with Ts and Ms.Arange of carbonyl substituents including Boc, acetyl, and benzoyl could also be tolerated (entries [11][12][13][14][15]. In the absence of catalyst, no reaction was observed after 14 hours (entry 1).…”

“…Interestingly,d ouble ortho-chlorination of 2h proceeded readily to give 3h.A gain, the reaction was found to be highly ortho selective.The substrate 2i,which has athiophene core,c ould also be converted into 3i in 90 %y ield. [13] Furthermore,t he reaction was found to be readily scalable.For instance,10mmol of the aniline 8fwas subjected to the reaction and 2.84 grams (99 %y ield) of the desired ortho-chlorinated product 9f was obtained (Scheme 2). 9k could be furnished smoothly when using the naphthyl substrate 8k.…”

“…Ab rief survey of the reaction media revealed the superior performance of toluene as the solvent in the secondary ammonium salt catalyzed electrophilic orthochlorination of aniline. [9] With the optimized reaction conditions in hand, we examined the compatibility of different Nsubstituents.I tw as realized that the reaction still could proceed smoothly when replacing the Ns group with Ts and Ms.Arange of carbonyl substituents including Boc, acetyl, and benzoyl could also be tolerated (entries [11][12][13][14][15]. Prompted by these results,o ther substrates with N-Ns and N-Boc substituents were investigated since Ns and Boc groups can easily be removed under mild reaction conditions, and this advantage is of great importance for late-stage manipulation and derivatization.…”