Rapid C–H Transformation: Addition of Diarylmethanes to Imines in Seconds by Catalytic Use of Base

Abstract

The addition of diarylmethanes or methylarenes via activation of benzylic C(sp 3 )−H bonds to N-aryl imines proceeds under catalysis by alkali hexamethyldisilazide (HMDS) base to give N-(1,2,2-triarylethyl)anilines or N-(1,2-diarylethyl)anilines, respectively. In the presence of 10 mol % of LiHMDS at room temperature, the diarylmethane addition equilibrates within 20−30 s and is driven to near completion by cooling the reaction mixture to −25 °C, providing N-(1,2,2-triarylethyl)aniline in a >90% yield.

Synthesis of Indolines via Base‐Mediated C−H Activation and Defluorinative C−N Coupling, with no Need for Transition‐Metals

“…Fluorine‐containing products 3 apa and 3 aea displayed lower yields due to side reactions. Likewise, ring‐methylated ( 2 ba – 2 da ), ‐halogenated ( 2 qa , 2 ra ), or heterocyclic imines suffered from base‐induced self‐polymerization [18] and gave the respective products 3 xa in low yield ( cf . Scheme S1) [39]…”

“…[38] We have recently described base-catalyzed additions of diarylmethanes to imines and found that methylarenes likewise add to imines after suitable modification of the reaction conditions (Scheme 1c). [18] This led us to propose a synthesis of indolines by a transition-metal-free, but base-mediated process by combining the Mao/Walsh approach of benzylic C(sp 3 )À H bond activation in ortho-fluorinated methylarenes with 1,2addition to imines, with an ensuing defluorinative S N Arcyclization of an alkali amide intermediate (Scheme 1d). A related precedent by García Ruano et al condensed orthoalkyl(4-tolylsulfinyl)benzenes with perfluoroalkyl imines (Scheme 1e), but was limited by the fairly specific reaction partners.…”

“…[8,9] An approach with many recent examples relies on the specific activation of allylic [10][11][12][13][14][15][16][17] or benzylic C(sp 3 )À H bonds. [18][19][20][21][22][23][24][25][26][27][28][29][30] Catalytic syntheses of indoles have profited from this strategy through recent work of Mao and Walsh et al, who have obtained indoles by condensation of 2fluoro-1-methylarenes and nitriles via 1,2-addition and subsequent cyclization in the presence of the base LiHMDS (lithium hexamethyldisilazide) and a cesium salt additive (Scheme 1a). [20] Kang et al have presented a related base-mediated and copper-catalyzed condensation of 2-halogen-1-methylarenes with nitriles (Scheme 1b).…”

“…Solutions to the problem include the choice of intramolecular reaction paths, a reliance on the presence of directing groups, or the harnessing of variations in the steric hindrance or acidity of C−H bonds [8,9] . An approach with many recent examples relies on the specific activation of allylic [10–17] or benzylic C(sp 3 )−H bonds [18–30] . Catalytic syntheses of indoles have profited from this strategy through recent work of Mao and Walsh et al ., who have obtained indoles by condensation of 2‐fluoro‐1‐methylarenes and nitriles via 1,2‐addition and subsequent cyclization in the presence of the base LiHMDS (lithium hexamethyldisilazide) and a cesium salt additive (Scheme 1a) [20] .…”

Masters of Mediation: MN(SiMe3)2 in Functionalization of C(sp3)−H Latent Nucleophiles

“…With these advantages very recently, Hintermann and co-workers disclosed the synthesis of N-(1,2-diarylethyl) aniline 5 mediated by KN(SiMe 3 ) 2 or NaN(SiMe 3 ) 2 (Scheme 5). [27] Unlike the above-mentioned reports, here Hintermann and co-workers directly employed the imines instead of aldehydes (in situ generated aldimines under MN(SiMe 3 ) 2 conditions). They observed that the KN(SiMe 3 ) 2 with bigger cation K + mediated the reaction with 1 equiv.…”