Asymmetric Synthesis of Tetrahydroquinolines via Saegusa‐type Oxidative Enamine Catalysis/1,5‐Hydride Transfer/Cyclization Sequences

Abstract

Enantioselective organocatalytic synthesis of tetrahydroquinolines has been achieved via Saegusa‐type oxidative enamine catalysis/1,5‐hydride transfer/cyclization sequences. The feature of this research is a one‐pot transformation of 3‐aryl aldehydes into tetrahydroquinolines by using environmentally benign catalytic Saegusa oxidation and highly efficient internal redox reactions. The synthetically useful ring‐fused tetrahydroquinoline derivatives were obtained in moderate yields and high levels of enantioselectivity.

Progress in the Chemistry of Tetrahydroquinolines

“…They generated the conjugated CC double bond in situ using a catalytic Saegusa oxidation, and in this case, following precedent from their own laboratory, 116 they employed the Hayashi−Jørgensen catalyst 1023 to promote the enantioselective hydride transfer/cyclization step to access the chiral THQs 1022 (Scheme 270). 432 In a related procedure, they also reported the use of IBX under acidic conditions as an oxidant to generate the required enal moiety. 433 Finally, as yet another alternative, the same group showed that the enal function could be generated in situ by oxidation of an allylic alcohol 1024 with a catalytic amount of the Ley−Griffith TPAP catalyst in the presence of oxygen to regenerate the perruthenate species (Scheme 271).…”

Visible Light Photocatalytic Trifluoromethylation/SET Oxidation/Cycloaddition Sequences of 2‐Vinyl Phenols: Multicomponent Synthesis of 4H‐Chromenes

“…[11] Although these pioneering results have been achieved by this system, the development of multicomponent reaction of the in situ generation of o-QMs with various dipoles is highly desired. Therefore, we envisioned that in situ formed o-QMs, which are generated from vinyl phenols by visible-light mediated radical trifluoromethylation and single electron transfer (SET) oxidation, could react with malononitrile as 1,2-dipole (Scheme 1c).In connection with our ongoing research program related to the synthesis of heterocyclic compounds, [12] we reported the synthesis of benzopyran derivatives via the alkylation of β-keto acids to o-QMs intermediates, followed by sequential cyclization. [13] Herein, we present the visible light photocatalytic trifluoromethyl radical-mediated generation of o-QMs from 2vinyl phenols for the multicomponent synthesis of 4H-chromenes.To determine suitable reaction conditions for the photocatalytic trifluoromethylation/SET oxidation and cycloaddition cascades of vinyl phenols, we examined the reaction of 2-vinyl phenol (1 a), Umemoto's reagent 2 a, and malononitrile 3 in dichloromethane in the presence of 2 mol% photocatalyst with blue LEDs (5 W, λ max = 455 nm).…”

“…In connection with our ongoing research program related to the synthesis of heterocyclic compounds, [12] we reported the synthesis of benzopyran derivatives via the alkylation of β-keto acids to o-QMs intermediates, followed by sequential cyclization. [13] Herein, we present the visible light photocatalytic trifluoromethyl radical-mediated generation of o-QMs from 2vinyl phenols for the multicomponent synthesis of 4H-chromenes.…”

Aerobic Asymmetric Dehydrogenative Cross‐Coupling between Two CH Groups Catalyzed by a Chiral‐at‐Metal Rhodium Complex

“…Firstly,current methods rely too often on oxidation reagents which produce undesired waste, whereas molecular oxygen as the ideal "green" oxidant suffers from poor reactivity. [5] With respect to the coupling of two C sp 3 À Hg roups,C ui, Jiao,a nd co-workers introduced the a-alkylation of aldehydes using combined enamine and acid catalysis (Figure 1a), [5a] Xu and co-workers disclosed the b-alkylation of aldehydes using combined oxidative enamine and palladium catalysis (Figure 1b), [5c] and Kim and co-workers reported the combination of oxidative enamine chemistry with an intramolecular 1,5hydride shift (Figure 1c). [4] In one of the most attractive scenarios,t wo C À Hg roups are coupled in acatalytic and asymmetric fashion by the formation of anew CÀCb ond, including at least one stereocenter,w hile molecular oxygen serves as the oxidant (Figure 1).…”