Enantioselective Synthesis of Cyclopentenes by (3+2) Annulation via a 2-Carbon Phosphonium.

Herein we report a catalytic enantioselective (3+2) annulation, in which a vinyl phosphonium intermediate serves as the 2-carbon component. The reaction involves an α-umpolung ß-umpolung coupling sequence, enabled by ß-haloacrylates and chiral enantioenriched phosphepine catalysts. The reaction shows good generality, providing access to an array of cyclopentenes, with mechanistic studies supporting stereospecific formation of the vinyl phosphonium intermediate which, then undergoes annulation with turn over limiting catalyst elimination. Beyond defining a new approach to cyclopentenes, these studies demonstrate that ß-haloacrylates can replace ynoates in reaction designs that require exclusive umpolung coupling at the α- and ß-positions.

Multifaceted View on the Mechanism of a Photochemical Deracemization Reaction.

Upon irradiation in the presence of a chiral benzophenone catalyst (5 mol %), a racemic mixture of a given chiral imidazolidine-2,4-dione (hydantoin) can be converted almost quantitatively into the same compound with high enantiomeric excess (80-99% ee). The mechanism of this photochemical deracemization reaction was elucidated by a suite of mechanistic experiments. It was corroborated by nuclear magnetic resonance titration that the catalyst binds the two enantiomers by two-point hydrogen bonding. In one of the diastereomeric complexes, the hydrogen atom at the stereogenic carbon atom is ideally positioned for hydrogen atom transfer (HAT) to the photoexcited benzophenone. Detection of the protonated ketyl radical by transient absorption revealed hydrogen abstraction to occur from only one but not from the other hydantoin enantiomer. Quantum chemical calculations allowed us to visualize the HAT within this complex and, more importantly, showed that the back HAT does not occur to the carbon atom of the hydantoin radical but to its oxygen atom. The achiral enol formed in this process could be directly monitored by its characteristic transient absorption signal at λ ≅ 330 nm. Subsequent tautomerization leads to both hydantoin enantiomers, but only one of them returns to the catalytic cycle, thus leading to an enrichment of the other enantiomer. The data are fully consistent with deuterium labeling experiments and deliver a detailed picture of a synthetically useful photochemical deracemization reaction.

Radical Coupling Initiated by Organophosphine Addition to Ynoates.

Dual nucleophilic phosphine photoredox catalysis is yet to be developed due to facile oxidation of the phosphine organocatalyst to the phosphoranyl radical cation. Herein, we report a reaction design that avoids this event and exploits traditional nucleophilic phosphine organocatalysis with photoredox catalysis to allow the Giese coupling with ynoates. The approach has good generality, while its mechanism is supported by cyclic voltametric, Stern-Volmer quenching, and interception studies.

Photochemical Deracemization at sp3-Hybridized Carbon Centers via a Reversible Hydrogen Atom Transfer.

A photochemical deracemization of 5-substituted 3-phenylimidazolidine-2,4-diones (hydantoins) is reported (27 examples, 69%-quant., 80-99% ee). The reaction is catalyzed by a chiral diarylketone which displays a two-point hydrogen bonding site. Mechanistic evidence (DFT calculations, radical clock experiments, H/D labeling) suggests the reaction to occur by selective hydrogen atom transfer (HAT). Upon hydrogen binding, one substrate enantiomer displays the hydrogen atom at the stereogenic center to the photoexcited catalyst allowing for a HAT from the substrate and eventually for its conversion into the product enantiomer. The product enantiomer is not processed by the catalyst and is thus enriched in the photostationary state.

Enantioselective Synthesis of Cyclopentanes by Phosphine-Catalyzed ß,γ-Annulation of Allenoates.

Herein, we report the enantioselective phosphine-catalyzed ß,γ-annulation of electron-poor allenes with bifunctional malonates. The reaction exploits a 2C phosphonium synthon that when accessed using (R)-SITCP gives 23 cyclopentanes with high stereoselectivity (most >95:5 er and >9:1 dr) and yield. In addition to the (3+2) annulation, a one-pot three-component variant to give the same cyclopentanes and a (3+2) annulation/Dieckmann cyclization cascade, along with mechanistic studies, are reported.

Bi- and poly(carbyne) functionalised polycyclic aromatics.

Complexes where a central polyaromatic ring system is substituted with one to four tungsten carbynes have been prepared by Pd0/AuI-mediated coupling between a tungsten stannylcarbyne and aryl halides. This strategy enables preparation of complexes with one to three carbynes substituted onto a single phenyl ring, the first anthracenyl mono- and bis-carbynes, and a tetra(carbyne) complex constructed about a central pyrene ring system.

Decision-making dysregulation in first-episode schizophrenia.

Studies with chronic schizophrenia patients have demonstrated that patients fluctuate between rigid and unpredictable responses in decision-making situations, a phenomenon which has been called dysregulation. The aim of this study was to investigate whether schizophrenia patients already display dysregulated behavior at the beginning of their illness. Thirty-two first-episode schizophrenia or schizophreniform patients and 30 healthy controls performed the two-choice prediction task. The decision-making behavior of first-episode patients was shown to be characterized by a high degree of dysregulation accompanied by low metric entropy and a tendency towards increased mutual information. These results indicate that behavioral abnormalities during the two-choice prediction task are already present during the early stages of the illness.

The acoustic startle reflex and its modulation: effects of age and gender in humans.

The acoustic startle reflex and its modulation by prepulse inhibition (PPI) and habituation are used in many studies in different fields of neuropsychiatric research. The aim of this study was to examine the effects of age and gender on PPI, startle magnitude, and habituation in healthy human volunteers. Twenty-seven male and 28 female participants of four different age groups (range: 20-60 years) were investigated in an acoustic startle paradigm using a startle stimulus of 115 dB and a prepulse of 86 dB (16 dB over the white noise background) with five different lead intervals (30, 60, 120, 240, and 2000 ms). Seventeen males and 16 female participants were tested three times at monthly intervals. Aged participants showed significantly lower startle magnitude and significantly more habituation than younger participants, but there was no effect of age on PPI or prepulse facilitation. Moreover, there were no effects of gender on startle magnitude, PPI, prepulse facilitation, or habituation measures. Healthy males and females exhibited stable startle magnitudes and PPI across sessions. The results demonstrated that PPI and startle are reliable measures of sensory information processing in both genders and that startle magnitude and habituation are age-dependent measures.