Halogen Bond-Catalyzed Friedel–Crafts Reactions of Aldehydes and Ketones Using a Bidentate Halogen Bond Donor Catalyst: Synthesis of Symmetrical Bis(indolyl)methanes

Abstract

The use of a halogen bond donor to catalyze Friedel–Crafts reactions of indoles with a range of aldehydes and ketones to directly produce bis­(indolyl)­methanes, including the natural products arsindoline A, arundine, trisindoline, and vibrindole A, is reported. The bidentate catalyst used in these reactions proved to be more effective than a monondentate analogue, a thiourea commonly used as an organocatalyst, and even a trityl cation that has been used previously in the synthesis of bis­(indolyl)­methanes.

A robust and tunable halogen bond organocatalyzed 2-deoxyglycosylation involving quantum tunneling

“…A comparison of the kinetic profiles between XB and thiourea catalysts illuminated superior XB catalytic performance. An extension of the same activation concept was exemplified by Toy et al, wherein they demonstrated substantially improved effectiveness of a bidentate XB catalyst over thiourea catalysis in a bis-Friedel-Crafts-type reaction of indoles on ketones 41 .…”

“…In recent years, despite the development of excellent proof-ofconcept XB-catalyzed reactions by multiple research groups [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] , protocols whereby XB catalysis shows clear catalytic advantages in over conventional thiourea catalysis is lacking 21 . Moreover, a conceivable configurational advantage pertaining to XB catalysis would involve the ease of σ-hole tunability via halogen swapping to accommodate challenging substrates-an advantage not well adoptable in thiourea catalysis due to strict requirements of hydrogen atoms for dual HB activation.…”

Halogen Bond‐Catalyzed Friedel−Crafts Reactions of Furans Using a 2,2’‐Bipyridine‐Based Catalyst

“…In the field of halogen bond catalysis, we previously reported the use of an achiral bidentate bis(benzimidazolium iodide) salt to catalyze Friedel−Crafts reactions of aldehyde and ketone electrophiles and indole nucleophiles to form bis(indolyl)methanes, [27] and Povarov reactions between imines and electron‐rich dienophiles, [28] that were similar to reactions reported by others using different halogen bond‐donating catalysts [29,30] . As we considered the possibility of performing the later reactions enantioselectively and surveyed the state of the art, we realized that organic halide halogen bond donors with an axis of chirality, as in the anion of 5 , have not been examined as catalysts, even though chiral compounds such as those based on a 1,1’‐binapthyl skeleton have been wildly successful as catalysts and ligands in asymmetric catalysis [31] .…”

Humic acid: A Biodegradable Organocatalyst for Solvent‐free Synthesis of Bis(indolyl)methanes, Bis(pyrazolyl)methanes, Bis‐coumarins and Bis‐lawsones

“…A few protocols are reported in literature using various catalyst and solvent such as enzymes, [21] meglumine, [22] thiamine hydrochloride, [23] graphene oxide, [24] ethyl lactate, [25] sulphated polyborate, [26] Lewis acids, [27–32] Brønsted acids, [33] heteropoly acids, [34–36] solid acids, [37–42] ionic liquids, [43] metal complexes, [44–46] 4‐sulfophthalic acid [47] and Iodine/tert‐Butyl Hydroperoxide [48] . Recently, a number of methodologies have been developed in this field [49–68] . A generalize scheme for the different processes so far reported in literature are drawn in Scheme 1.…”