Oxidants Controlled C-H Bond Functionalization of N-Aryltetrahydroisoquinolines: The Construction of the Quaternary Carbon Center and Cleavage of the C-N Bond.

Initiated by triarylamine radical cation salt (TBPA), the direct C-H bond functionalization of α-N-aryltetrahydroisoquinoline esters was smoothly realized, giving a series of α-hydroxylated derivatives with a quaternary carbon center in good yields. Differently, in the presence of tert-butyl nitrite (TBN), the C-N single bond was cleaved to keto esters. The mechanistic study revealed that these reactions were mediated by a similar mechanism, in which the N-nitrosation might provide a driving force to the C-N bond cleavage.

CBr4 as a Mild Oxidant-Enabled Oxidation of a sp3 C-H Bond: A Facile Synthesis of the Persistent Iminium Salts of Tetrahydroisoquinolines.

Using CBr4 as a mild oxidant, the direct C-H bond oxidation of N-aryltetrahydroisoquinolines was achieved, giving a series of the corresponding iminium salts in high yields under metal- and photo-free reaction conditions. This reaction is superior in high yields and good functional group tolerance, and the late-stage derivatization showed that these iminium salts can readily be applied to the synthesis of the functionalized THIQs.

Single-Electron Reduction of "Push-Pull" C-C Single Bond and Decyanation Using Tertiary Amines as the Organic Electron Donor.

Using commercially available tertiary amines as an organic electron donor (OED), the reduction of "push-pull" C-C single bond and reductive decyanation of tetrahydroisoquinolines were realized. These reactions exhibited higher reaction efficiency and better functional group tolerance compared with those of metallic reductants, and the mechanistic study indicated that a radical intermediate was involved in the reduction of the C-C single bond, which provides a new way to the OED-enabled mild reduction.

C-H Bond Activation Relay (CHAR) of Proline Ester Derivatives Promoted by In Situ Triarylamine Radical Cation: Selective Synthesis of 4-Bromopyrrole Derivatives.

Using the in situ generated triarylamine radical cation as an initiator, the sp3 C-H bond of proline esters was smoothly oxidized and brominated through C-H activation relay (CHAR), giving a series of 4-bromopyrroles in good yields with high regioselectivity. The mechanistic study revealed that the oxidation of the active C-H bond initiated the followed 1,5-HAT and bromination, which provides a new method to realize the functionalization of the remote C-H bond.

Halogen Bond (XB) Promoted α-Tribromomethylation of N-Aryltetrahydroisoquinolines and Further Cyclization to 5,6-Dihydroindolo[2,1-a]isoquinolines.

Using CBr4 as a halogen bond donor and the source of tribromomethyl group, a halogen bond promoted tribromomethylation of N-aryltetrahydroisoquinolines was achieved. This reaction was also extended to the construction of the dibenzopyrrocoline alkaloid skeleton through a one-pot process. The mechanistic study confirmed the existence of the halogen bond.

Tris(4-bromophenyl)aminium Hexachloroantimonate as a "Waste-Utilized"-Type Initiator-Promoted C-H Chlorination via C-H Activation Relay: Synthesis of Chlorinated Pyrroles.

Using tris(4-bromophenyl)aminium hexachloroantimonate as a "waste-utilized"-type initiator, the aerobic oxidation of the sp3 C-H bond of proline esters was realized via C-H activation relay, giving a series of halogenated pyrroles in high yields. The mechanistic study revealed that the counterion, SbCl6-, was involved in the radical chlorination process, which provides a new way to understand the role of the counterions.

Tert-Butyl Nitrite-initiated C-N Bond Cleavage of 1-Nitromethyl-N-aryltetrahydroisoquinolines: Synthesis of Furoxans with N-NO Skeleton.

A series of furoxan derivatives with N-nitroso groups were synthesized in good yields by TBN initiated radical sp3 C-N bond cleavage of 1-nitromethyl-N-aryltetrahydroisoquinolines. This reaction grafts the biologically important furoxan skeleton and N-nitroso group into on molecule, greatly improving the molecular complexity in one step transformation. The mechanistic study shows that this reaction is mediated by the in situ generated α-carbonyl nitrile oxide, which is afforded by TBN promoted C-N bond cleavage.

SbCl3 Initiated Aerobic Phosphorylation of sp3 C-H Bond: A Facile Approach to α-Phosphorylated Tetrahydroisoquinolines.

An aerobic phosphorylation of N-aryltetrahydroisoquinolines was realized by SbCl3 initiated sp3 C-H bond functionalization, providing a series of α-aminophosphonates in high yields. This work reveals that SbCl3 /O2 is an efficient and facile catalyst system to enable the aerobic C-H functionalization, and antimony containing reagents might be potentially applied to more general transformations.

SbCl3 initiated conjunctive C-H bond functionalization and carbochlorination between glycine esters and methylenecyclopropanes (MCPs).

In the presence of dioxygen, an antimony trichloride enabled conjunctive sp3 C-H bond functionalization and carbochlorination of glycines was realized, providing a series of chlorinated quinolines in high yields. The mechanistic study shows that the antimony(V) species might be involved in the oxidation of the sp3 C-H bond and is followed by carbochlorination through a radical intermediate.

Oxidation of the inert sp3 C-H bonds of tetrahydroisoquinolines through C-H activation relay (CHAR): construction of functionalized isoquinolin-1-ones.

A TBN/O2-initiated oxidation of the relatively inert 3,4-C-H bonds of THIQs was accomplished, in which the existence of an α-phosphoric ester group is crucial to enable dioxygen trapping and intramolecular HAT (C-H activation relay, CHAR), realizing the synthesis of a series of isoquinolin-1-ones in high yields. The mechanistic study confirmed that the formation of the 3,4-double bond is mediated by the CHAR process. This work provides a new strategy to achieve remote C-H bond activation.

Tris(4-bromophenyl)aminium Hexachloroantimonate-Initiated Oxidative Povarov-Type Reaction between Glycine Esters and (Cyclopropylidenemethyl)benzenes Using the Counterion as a Chlorine Donor.

A tris(4-bromophenyl)aminium hexachloroantimonate-initiated oxidative Povarov-type reaction between glycines and methylenecyclopropanes was realized in the presence of dioxygen, in which the counterion, SbCl6-, served as a chlorine atom donor, enabling the synthesis of a series of chlorinated quinolines in high yields. The mechanistic study showed that the chlorination step might be related to antimony chloride via a radical chlorine atom transfer.

Visual cortical activations on fMRI upon stimulation of the vision-implicated acupoints.

We used fMRI to reveal the visual cortical activations during conventional or electro-acupuncture over four vision-implicated acupoints in 18 healthy volunteers and compared the results with those obtained during direct visual stimulation. Positive activations were seen over the visual cortex during visual stimulation in all subjects, and similar activations were observed in 10 subjects during conventional acupuncture as well as in eight and seven subjects during electro-acupuncture at 2 and 20 Hz, respectively. Negative activations were also seen over the occipital lobes, temporal gyri and frontal gyri bilaterally in 13 subjects during conventional acupuncture. Thus, acupuncture may modulate the activity of relevant brain sites. Our results also suggest that electro-acupuncture is useful in future studies.

An fMRI study comparing brain activation between word generation and electrical stimulation of language-implicated acupoints.

We compared the brain activation on functional magnetic resonance imaging (MRI) during word generation with the activation during electrical stimulation of two language-implicated acupoints in 17 healthy, Mandarin-speaking, Chinese male volunteers (age 19-26 years). All subjects were strongly right handed according to a handedness inventory. Using a standard functional MRI procedure and a word-generation paradigm, significant activation was seen in the left and right inferior frontal gyri (BA 44, 45) as well as the left superior temporal gyrus (BA 22, 42). Stronger activation with a larger volume was seen in the left hemisphere. Electrical stimulation of either one of the two language-implicated acupoints, SJ 8 (11 subjects) and Du 15 (6 subjects), without the word-generation paradigm in the same cohort, produced significant activation in the right inferior frontal gyrus (BA 44, 46) and in the left and right superior temporal gyri (BA 22, 42), respectively. Nevertheless, no activation was seen in the left inferior frontal gyrus. In addition, electrical stimulation of the adjacent non-acupoints did not produce any significant brain activation. Although our results support the notion of acupoint-brain activation, applying acupuncture at SJ 8 or Du 15 does not activate the typical language areas in the left inferior frontal cortex.