User's guide to accessing arynes from arenes. Collectively, our observations over the course of these studies can be distilled down to a user's guide for generating and trapping an aryne derived from a simple arene. We have demonstrated that the two strategies, using an aryl thianthrenium or an aryl(Mes)iodonium salt as an intermediate, are essentially complimentary with respect to the arene scope. For several classes of arene only the aryl thianthrenium salt can be synthesized obviating the use of aryl(Mes)iodonium salts for these substrates; in other cases the aryne cannot be accessed from the aryl thianthrenium and therefore the aryl(Mes)iodonium salts critically expand the arene scope. Our general strategy, shown in Scheme 11a, involves either a one-pot (for aryl thianthrenium) or two-pot (for diaryliodonium) process for net dehydrogenation and functionalization of arenes. The site of aryne formation largely depends on the substitution pattern of the arene and in most cases very high selectivity is observed (Scheme 11b). In mono-substituted arenes the aryne is formed exclusively at the 3,4-position (highlighted blue) because both thianthrenium and iodonium groups are installed with very high para-selectivity (4-position) and deprotonation occurs exclusively ortho to the leaving group (3-position; Scheme 11b). In mono-substituted arenes, no aryne formation is observed at the 2,3-position. Scheme 10. Calculated reaction landscape for aryne formation from 1b-TT and 1m-IMes. a a Intermediates and transition states were optimized at M06-2x/Def2-tzvpp with SMD solvation in toluene using Gaussian09. In 1,2-disubstituted arenes the major site of aryne formation is at the 3,4-position. This selectivity is again initiated by high para-selectivity (4-position) for installation of thianthrenium and iodonium groups; this is followed by generally high selectivity for deprotonation at the 3position (Scheme 11b). In a few cases, we have observed a minor product from deprotonation at the 5-position (i.e., 1r-IMes and 1t-IMes, Scheme 3), but an aryne is not formed at the 5,6-position for 1,2-substituted arenes; this numbering scheme is predicated on the strongest paradirector at the 1-position. In 1,3-substituted arenes, the site of iodination may be impacted by the relative steric effects of the EDG and the R-group at the 3-position (Scheme 11b). When the R-group is a chloride as in 1u we observed preference (8:1) for installation of the iodonium at the 4-position over the 6-position (Scheme 11b). Subsequently, because the 3-position is blocked, deprotonation occurs at the 5-position. The minor aryne adduct arises from iodination at the 6-position and deprotonation at the 5-position (Scheme 11b). There is only one site for aryne formation to occur with 1,4-substituted arynes and it is at the 2,3-position (Scheme 11b). However, in this case it is important to point out that the aryne is flanked by two substituents and in these cases we have shown that the nature of the two substituents impacts the selectivity of nucleophilic addition to the aryne; that is, the site of thianthrenation is not necessarily the site of nucleophilic addition. It should also be noted that higher substitution patterns can be treated as an extension of disubstituted arenes. That is, 1,2,3-substituted arene react similarly to 1,2-substituted arenes (cf. 3ha and 3da, Scheme 2) and 1,2,4-substituted arenes react similarly to 1,4-substituted arenes (cf. 3ia and 3aa, Scheme 2).