Direct Arylation of C(sp2)–H Bonds in Anilines

Abstract

Anilines selectively arylated at their ortho-, meta- or para- positions are useful building blocks in synthesis and have found applications in many areas. The most straightforward method for their synthesis relies on the direct arylation of a C(sp2)-H bond of anilines, an attractive strategy avoiding the prefunctionalization of the starting anilines provided that such arylations proceed with high levels of regioselectivity. Such reactions are presented and discussed, in a comprehensive manner, in this review article, with an emphasis on the regioselectivity of the processes and factors governing both the reactivity and selectivity.

Rhodium‐Catalyzed Direct ortho‐Arylation of Anilines

“…[1] The synthesis of functionalized anilines is therefore of utmost importance and in this context, their regioselective arylation represents a key transformation. [2] While a range of processes have been developed over the years for the direct meta- [3] and para- [4] selective arylation of C(sp 2 )À H bonds in anilines with high levels of regioselectivity and with readily available arylating agents, their direct ortho-arylation is still challenging, despite the importance of ortho-aryl-anilines. They are indeed found in numerous natural products as well as biologically active molecules including alkaloids such as ismine [5] and dihydronitidine [6] or drugs and agrochemicals like fluxapyroxad, [7] boscalid [8] or revefenacin [9] (Figure 1.A).…”

“…To date, the direct ortho-arylation of anilines, [2,10] which avoids the use of pre-functionalized anilines (Figure 1.B1), mostly relies on aryldiazonium [11] or diaryliodonium [4] salts and aryne precursors, [12] which poses problems in terms of availability and/or safety in addition to affording limited levels of regioselectivity (Figure 1.B2). More attractive aryl halides have been reported as arylating agents (Figure 1.B3) but in this case, a strong base is required, which clearly limits the functional group compatibility, and the reaction is limited to the use of chlorobenzene [13] or the arylation proceeds with limited levels of regioselectivity.…”

“…Anilines are ubiquitous scaffolds found at the core structure of a broad variety of molecules of interest, notably in the pharmaceutical or agrochemical industries, and they represent building blocks commonly utilized for the synthesis of polymers, pigments, rubber products, or explosives, among other uses [1] . The synthesis of functionalized anilines is therefore of utmost importance and in this context, their regioselective arylation represents a key transformation [2] . While a range of processes have been developed over the years for the direct meta ‐ [3] and para ‐ [4] selective arylation of C(sp 2 )−H bonds in anilines with high levels of regioselectivity and with readily available arylating agents, their direct ortho ‐arylation is still challenging, despite the importance of ortho ‐aryl‐anilines.…”