A Selective C−H Deprotonation Strategy to Access Functionalized Arynes by Using Hypervalent Iodine

Abstract

Described here is an efficient method to access highly functionalized arynes from unsymmetrical aryl(mesityl)iodonium tosylate salts. The iodonium salts are prepared in a single pot from either commercially available aryl iodides or arylboronic acids. The aryne intermediates are generated by ortho‐C−H deprotonation of aryl(mesityl)iodonium salt with a commercially available amide base and trapped in a cycloaddition reaction with furan in moderate to good yields. Coupling partners for the aryne intermediates beyond furan are also described, including benzyl azide and alicyclic amine nucleophiles. The regio‐ and chemoselectivity of this reaction is discussed and evidence for the spectator aryl ligand of the iodonium salt as a critical control element in selectivity is presented.

Regioselective Synthesis of 1,2,3,4‐Tetrasubstituted Arenes by Vicinal Functionalization of Arynes Derived from Aryl(Mes)iodonium Salts**

“…We found that the equivalents of 2 a and NaO t Bu had the largest impact on yield and that higher temperature had a relatively small or even negative impact on yield (Scheme 3, right) [23] . Ultimately, the 2 3 design improved the yield from ≈50 % under our previous conditions (using 1 equiv NaO t Bu, 2 equiv 2 a , and 50 °C) [16] as estimated from equ. S1 [23] to 69 % yield of 3 aa at room temperature and in shorter reaction time (Scheme 3, bold circle).…”

“…Reaction development and scope . Our previous conditions to generate arynes from aryl(Mes)iodonium salts used two different bases, LiHMDS or NaO t Bu, [16] and we applied these in our initial survey of conditions. We used compound 1 a as an aryne precursor and arynophile 2 a [22] to access 1,2,3,4‐substituted aryl diazapinone 3 aa (Scheme 3).…”

“…The computed selectivity for aryne precursors 1 a – n with different substituents (R 1 and R 2 ) range from 0.94–6.8 kcal mol −1 , which corresponds to 4.9:1 on the low end to >90,000:1 on the high end ( 1 m and 1 g , respectively, Scheme 5 B). Based on our previous work [16] and literature precedent, we anticipated that the proximal R 2 substituent would be the singular factor in controlling site selectivity of deprotonation. In fact, because the observed selectivity values were uniformly so high and generally beyond detection limit, it was impossible to observe the effects of the distal R 1 substituent experimentally [23] .…”

“…This approachb uilds upon our previousr eport [16] on the generation of arynesv ia deprotonation ortho to an iodonium leaving group. [17][18][19] In the present work, we delineate thei nfluence of reactionc onditions on generation and trapping of arynes, and demonstrate that the iodomesitylene leaving group enables exceedingly mild and rapid reactions relative to more traditional halide leaving groups.…”

Nucleophilic Aromatic Substitution of Polyfluoroarene to Access Highly Functionalized 10-Phenylphenothiazine Derivatives

“…However, the high cost of organometallic catalysts and contamination of the resulting products with metal traces represent major drawbacks of such methods. Alternative methods for transition-metal-free synthesis of arylamine derivatives have been achieved using hypervalent iodine reagents [ 22 , 23 , 24 , 25 , 26 , 27 ], sulfonium reagents [ 28 ], nitorarenes [ 29 , 30 , 31 , 32 , 33 ], or electrochemical conditions [ 34 ]. The S N Ar reaction also offers an alternative method without the use of transition metals, which is therefore potentially applicable in the facile synthesis of organic functional materials containing substituted arenes.…”