Irradiation at 460 nm of [Mo 3 (μ 3 -S)(μ 2 -S 2 ) 3 (S 2 CNR 2 ) 3 ]I ([2a]I, R = Me; [2b]I, R = Et; [2c]I, R = i Bu; [2d]I, R = CH 2 C 6 H 5 ) in a mixed aqueous−polar organic medium with [Ru(bipy) 3 ] 2+ as photosensitizer and Et 3 N as electron donor leads to H 2 evolution. Maximum activity (300 turnovers, 3 h) is found with R = i Bu in 1:9 H 2 O:MeCN; diminished activity is attributed to deterioration of [Ru(bipy) 3 ] 2+ . Monitoring of the photolysis mixture by mass spectrometry suggests transformation of [Mo 3 (μ 3 -S)(μ 2 -S 2 ) 3 (S 2 CNR 2 ) 3 ] + to [Mo 3 (μ 3 -S)(μ 2 -S) 3 (S 2 CNR 2 ) 3 ] + via extrusion of sulfur on a time scale of minutes without accumulation of the intermediate [Mo 3 S 6 (S 2 CNR 2 ) 3 ] + or [Mo 3 S 5 (S 2 CNR 2 ) 3 ] + species. Deliberate preparation of [Mo 3 S 4 (S 2 CNEt 2 ) 3 ] + ([3] + ) and treatment with Et 2 NCS 2 1− yields [Mo 3 S 4 (S 2 CNEt 2 ) 4 ] ( 4), where the fourth dithiocarbamate ligand bridges one edge of the Mo 3 triangle. Photolysis of 4 leads to H 2 evolution but at ∼25% the level observed for [Mo 3 S 7 (S 2 CNEt 2 ) 3 ] + . Early time monitoring of the photolyses shows that [Mo 3 S 4 (S 2 CNEt 2 ) 4 ] evolves H 2 immediately and at constant rate, while [Mo 3 S 7 (S 2 CNEt 2 ) 3 ] + shows a distinctive incubation prior to a more rapid H 2 evolution rate. This observation implies the operation of catalysts of different identity in the two cases.

The exceptionally π-basic metal fragments {MoTp-(NO)(DMAP)} and {WTp(NO)(PMe 3 )} (Tp = tris(pyrazolyl)borate; DMAP = 4-(N,N-dimethylamino)pyridine) form thermally stable η 2 -coordinated complexes with a variety of electron-deficient arenes. The tolerance of substituted arenes with fluorine-containing electron withdrawing groups (EWG; −F, −CF 3 , −SF 5 ) is examined for both the molybdenum and tungsten systems. When the EWG contains a π bond (nitriles, aldehydes, ketones, ester), η 2 coordination occurs predominantly on the nonaromatic functional group. However, complexation of the tungsten complex with trimethyl orthobenzoate (PhC(OMe) 3 ) followed by hydrolysis allows access to an η 2 -coordinated arene with an ester substituent. In general, the tungsten system tolerates sulfur-based withdrawing groups well (e.g., PhSO 2 Ph, MeSO 2 Ph), and the integration of multiple electron-withdrawing groups on a benzene ring further enhances the π-back-bonding interaction between the metal and aromatic ligand. While the molybdenum system did not form stable η 2 -arene complexes with the sulfones or ortho esters, it was capable of forming rare examples of stable η 2 -coordinated arene complexes with a range of fluorinated benzenes (e.g., fluorobenzene, difluorobenzenes). In contrast to what has been observed for the tungsten system, these complexes formed without interference of C−H or C−F insertion.

IntroductionIn concussion, clinical and physiological recovery are increasingly recognized as diverging definitions. This study investigated whether central microglial activation persisted in participants with concussion after receiving an unrestricted return-to-play (uRTP) designation using [18F]DPA-714 PET, an in vivo marker of microglia activation.MethodsEight (5 M, 3 F) current athletes with concussion (Group 1) and 10 (5 M, 5 F) healthy collegiate students (Group 2) were enrolled. Group 1 completed a pre-injury (Visit1) screen, follow-up Visit2 within 24 h of a concussion diagnosis, and Visit3 at the time of uRTP. Healthy participants only completed assessments at Visit2 and Visit3. At Visit2, all participants completed a multidimensional battery of tests followed by a blood draw to determine genotype and study inclusion. At Visit3, participants completed a clinical battery of tests, brain MRI, and brain PET; no imaging tests were performed outside of Visit3.ResultsFor Group 1, significant differences were observed between Visits 1 and 2 (p < 0.05) in ImPACT, SCAT5 and SOT performance, but not between Visit1 and Visit3 for standard clinical measures (all p > 0.05), reflecting clinical recovery. Despite achieving clinical recovery, PET imaging at Visit3 revealed consistently higher [18F]DPA-714 tracer distribution volume (VT) of Group 1 compared to Group 2 in 10 brain regions (p < 0.001) analyzed from 164 regions of the whole brain, most notably within the limbic system, dorsal striatum, and medial temporal lobe. No notable differences were observed between clinical measures and VT between Group 1 and Group 2 at Visit3.DiscussionOur study is the first to demonstrate persisting microglial activation in active collegiate athletes who were diagnosed with a sport concussion and cleared for uRTP based on a clinical recovery.

Reactions are described for complexes of the form WTp(NO)(PMe3)(η2‐arene) and various amines, where the arene is benzene or benzene with an electron‐withdrawing substituent (CF3, SO2Ph, SO2Me). The arene complex is first protonated to form an η2‐arenium species, which then selectively adds the amine. The resulting η2‐5‐amino‐1,3‐cyclohexadiene complexes can then be subjected to the same sequence with a second nucleophile to form 3‐aminocyclohexene complexes, where up to three stereocenters originate from the arene carbons. Alternatively, 1,3‐cyclohexadiene complexes containing an ester group at the 5 position (also prepared from an arene) can be treated with acid followed by an amine to form trisubstituted 3‐aminocyclohexenes. When the amine is primary, ring closure can occur to form a cis‐fused bicyclic γ‐lactam. Highly functionalized cyclohexenes can be liberated from the tungsten through oxidative decomplexation. The potential utility of this methodology is demonstrated in the synthesis of the alkaloid γ‐lycorane. An enantioenriched synthesis of a lactam precursor to γ‐lycorane is also described. This compound is prepared from an enantioenriched version of the tungsten benzene complex. Regio‐ and stereochemical assignments for the reported compounds are supported by detailed 2D‐NMR analysis and 13 molecular structure determinations (SC‐XRD).

A novel process is described for the synthesis of di-and trisubstituted cyclohexenes from an arene. These compounds are prepared from three independent nucleophilic addition reactions to a phenyl sulfone (PhSO 2 R; R = Me, Ph, and NC 4 H 8 ) dihapto-coordinated to the tungsten complex {WTp(NO)(PMe 3 )}(Tp = trispyrazolylborate). Such a coordination renders the dearomatized aryl ring susceptible to protonation at a carbon ortho to the sulfone group. The resulting arenium species readily reacts with the first nucleophile to form a dihapto-coordinated sulfonylated diene complex. This complex can again be protonated, and the subsequent nucleophilic addition forms a trisubstituted cyclohexene species bearing a sulfonyl group at an allylic position. Loss of the sulfinate anion forms a π-allyl species, to which a third nucleophile can be added. The trisubstituted cyclohexene can then be oxidatively decomplexed, either before or after substitution of the sulfonyl group. Nucleophiles employed include masked enolates, cyanide, amines, amides, and hydride, with all three additions occurring to the same face of the ring, anti to the metal. Of the 12 novel functionalized cyclohexenes prepared as examples of this methodology, nine compounds meet five independent criteria for evaluating drug likeliness. Structural assignments are supported with nine crystal structures, density functional theory studies, and full 2D NMR analysis.