N‐Aryl Groups Are Ubiquitous in Cross‐Dehydrogenative Couplings Because They Stabilize Reactive Intermediates

Abstract

The mechanism of cross-dehydrogenative coupling (CDC) reactions has been examined by experimental and computational methods. We provide a rationale for the ubiquity of the N-aryl group in these reactions. The aryl substituent stabilizes two intermediates and the high-energy transition state that connects them, which together represent the rate-determining step. This knowledge has enabled us to predict whether new CDC substrates will react either well or poorly.

Toward Rational Understandings of α-C–H Functionalization: Energetic Studies of Representative Tertiary Amines

“…Also, it is worth noting that the effects of changing the ring size (6e vs. 11 and 12) or aromaticity (7a vs. 14) are quite significant. One can find that the hydricity of serial 6 determined here correlates well with the previously observed kinetic trend of THIQ oxidation by DDQ (Tsang et al, 2017). Besides, the gradual increase of DH H -D for N-Ph (6e), N-(1-Naph) (7h), and N-Cbz (7g) is also found to agree with the descending reaction rates of their oxidation by DDQ (Tsang et al, 2017).…”

“…The combined scale reveals that amines (colored bars, ranging 60-92 kcal mol À1 ) are generally weaker hydride donors than biomimetic donors such as 1,3-dimethyl-2,3-dihydro-1H-benzimidazole (DMBI, 54.1 kcal mol À1 ), 1-benzyl-1,4-dihydropyridine-3-carboxamide (BNAH, 64.2 kcal mol À1 ), and diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate (HEH, 69.3 kcal mol À1 ). Indeed, strong oxidants with -DH H -A values greater than 100 kcal mol À1 (e.g., DDQ, Ph 3 C + , AcNH-TEMPO + ) were experimentally observed to be capable of splitting the a-C-H bonds of all N-alkyl/aryl-THIQs in a few minutes at room temperature (de Costa et al, 1992;Tsang et al, 2017). This also explains the need of a longer reaction time (2h) reported for N-Cbz-THIQ (Yan et al, 2015) and the loss of its reactivity with a weaker oxidant, tropylium (T + ,-DH H -A = 85 kcal mol À1 ) (Oss et al, 2018).…”

Gold Catalyzed Photoredox C1‐Alkynylation of N‐Alkyl‐1,2,3,4‐tetrahydroisoquinolines by 1‐Bromoalkynes with UVA LED Light

“…On the basis of the above results, a tentative mechanism for the present dimeric Au(I)‐catalyzed photoredox C1‐alkynylation of THIQs with alkynyl bromides under UVA LED light is outlined in Scheme ,. With the reaction of substrates 1 a and 2 a as a representative example, this could initially involve the exciplex species V of the dinuclear gold(I) complex being generated as it absorbs the UVA LED light .…”

“…[8][9][10]16] With the reaction of substrates 1 a and 2 a as a representative example, this could initially involve the exciplex species V of the dinuclear gold(I) complex being generated as it absorbs the UVA LED light. [8][9][10]16] With the reaction of substrates 1 a and 2 a as a representative example, this could initially involve the exciplex species V of the dinuclear gold(I) complex being generated as it absorbs the UVA LED light.…”

Cross‐Dehydrogenative Coupling of Tetrahydroisoquinolines and 2‐Fluoro‐1,3‐benzodithiole‐1,1,3,3‐tetraoxide: A New Synthetic Approach to α‐Monofluoromethyl Tertiary Amines

“…Product 2 a was obtained in a moderate yield (Table 1, entry 5). [13] Finally, CuBr/TBHP was found to be the best combination. An excellent yield was obtained in acetonitrile (Table 1, entry 6).…”