Triarylmethanes and their Medium‐Ring Analogues by Unactivated Truce–Smiles Rearrangement of Benzanilides

Abstract

Intramolecular nucleophilic aromatic substitution (Truce-Smiles rearrangement) of the anions of 2-benzyl benzanilides leads to triarylmethanes in an operationally simple manner. The reaction succeeds even without electronic activation of the ring that plays the role of electrophile in the S N Ar reaction, being accelerated instead by the preferred conformation imposed by the tertiary amide tether. The amide substituent of the product may be removed or transformed into alternative functional groups. A ring-expanding variant (n to n + 4) of the reaction provided a route to doubly benzo-fused medium ring lactams of 10 or 11 members. Hammett analysis returned a 1 value consistent with the operation of a partially concerted reaction mechanism.

Radical and Ionic Mechanisms in Rearrangements of o-Tolyl Aryl Ethers and Amines Initiated by the Grubbs–Stoltz Reagent, Et3SiH/KOtBu

“…Generally, Smiles and Truce-Smiles rearrangements proceed through the formation of a spiro intermediate, which subsequently undergoes a ring-opening to yield the product [6,17]. Mechanisms featuring a spiro transition state rather than a spiro intermediate have been proposed [7], with several examples being identified by Clayden et al for the Smiles and Truce-Smiles rearrangements [56][57][58][59][60][61][62]. Concerted reaction pathways have also been identified for other Smiles-type rearrangements [63][64][65].…”

C(sp3)-Arylation by Conformationally Accelerated Intramolecular Nucleophilic Aromatic Substitution (SNAr)

“…Amide tethers as conformational controllers 72 , 73 also hold promise for the assembly of benzylic stereocenters. 74 , 75 In addition, we are using the conformational preference of anilide congeners to develop other types of intramolecular transition metal-free couplings, including C-alkenylations. 76 − 79 …”

Recent Advances in the Smiles Rearrangement: New Opportunities for Arylation

“…11), the reaction gave products containing medium sized lactam rings (12), negating the need for a more traditional entropically disfavored cyclisation reaction. [27] The efficiency of the reaction was attributed to the conformational preference of the starting materials. The authors commented that amide 7 prefers to adopt an E-conformation whereby the N-aryl substituent lies opposite to the carbonyl, allowing for spatial proximity to the nucleophilic benzylic position.…”

“…The group then showed how the products of the reaction could be diversified in Heck reactions to give bulky, tetrasubstituted enol ethers. [34] Scheme 6 Jiang and co-workers' desulfonylative Smiles rearrangement A further example of the polar Smiles rearrangement mediated by anionic heteroatoms is exemplified by Yoshida who showed that by using o-sulfanylanilines (27) under basic conditions, a nitrogen-based Smiles rearrangement could be achieved, followed by a subsequent SNAr reaction to give the Narylphenothiazine product 28 (scheme 7). [35,36] The researchers noted that owing to the lack of activation of either of the participating aromatic rings, both processes operate through a concerted mechanism.…”

“…Furthermore, by tethering the N-substituent to the migrating arene, the reaction gave products containing medium-sized lactam rings (e.g., 11 → 12), negating the need for a more traditional entropically disfavored cyclization reaction. 27 The efficiency of the reaction was attributed to the conformational preference of the starting materials; amide 7 prefers to adopt an E-conformation whereby the N-aryl substituent lies opposite to the carbonyl, allowing for spatial proximity to the nucleophilic benzylic position. 28 Scheme 2 Triarylmethane synthesis via a Truce-Smiles rearrangement using benzanilides (Clayden group)…”