(2‐Pyridyl)sulfonyl Groups for ortho‐Directing Palladium‐ Catalyzed Carbon–Halogen Bond Formation at Functionalized Arenes

Abstract

We describe an efficient palladium-catalyzed selectiveC -H ortho-monohalogenation (X = I, Br, Cl, F) of various functionalized (2-pyridyl)arylsulfones. ortho-, meta-and para-functionalization is tolerated at the arene group which undergoes C-H halogenation. Some modifications are also possible on the 2-(arylsulfonyl)heteroaryld irecting groups.A comparison of the halogenation efficiency suggests that bromination is the practical method of choice, while chlorination and fluorination are possible but more challenging. Under forcingc onditions ortho-dihalogenation can also be achieved.

A comprehensive overview of directing groups applied in metal-catalysed C–H functionalisation chemistry

“…Arylation with benzoyl peroxides was reported by Sun, and halogenation with NXS by Hierso ( Scheme 150A and B ). 871 , 904 Several yields were <70% for both reports, and product mixtures were obtained in the case of halogenation (mono- + dihalogenated products). Interestingly, modification (oxidation to sulfone, reduction to sulphide), desulphurisation (to 2-arylpyridines), and cleavage of the DG (obtaining thiols) was demonstrated by Sun ( Scheme 146 ).…”

Sequential ortho-C–H and ipso-C–O Functionalization Using a Bifunctional Directing Group

“…Of particular note, in contrast to that of the phenol substrates (Figure b), C–H activation occurred exclusively at the ortho position with remarkable regioselectivity ( ortho :others >20:1). Comparably, other ortho -selective directing groups such as 2-pyridyl ( T 1 ) and 2-pyrimidyl ( T 2 ) groups only gave the products in a yield of 62% and 58%, respectively, with 3:1 to 4:1 regioselectivity under the same conditions (see Figure S1 in the SI). Meanwhile, almost quantitative starting materials were recovered when using 4,6-dimethoxy-2-triazinyl group ( T 3 ) as a directing group .…”

Metal–free Efficient Method for the Synthesis of N‐(2‐haloethyl)benzamides through the Ring‐opening of2‐oxazolines

“…For example, halogenated quinolones could be applied in biological and pharmacological studies as excellent bioisostere, and extensive efforts have been devoted to the C‐5 or C‐7 position halogenation transitionof 8‐aminoquinolines derivatives, including the metal‐free synthesis and transition metal‐catalyzed synthesis (Scheme a) . In 2017, Hierso and colleagues described the efficient palladium‐catalyzed selective C–X ortho‐monohalogenation of various functionalized 2‐(arylsulfonyl)pyridines (X =I, Br, Cl, and F) . To the best of our knowledge, the amide functionality acts as a directing group for C−H functionalization of the aromatic ring with halogens in those reports.…”