Asymmetric Synthesis of -Borylated Amines via Rhodium-Catalyzed Hydroboration of Allylamine Derivatives

The Takacs group has explored different dimensions of Catalytic Asymmetric Hydroboration (CAHB) reaction mainly focusing on variety of amide, oxime ether and phosphonate directing groups. Inspired by the results obtained with BINOL- and TADDOL- derived chiral catalysts along with pinacolborane, we explored the potential of acyclic N-acyl allylamines as substrates for direct-hydroboration to prepare chiral amine derivatives bearing g-boronic ester functionality, yields up to 90% with 98:2 enantioselectivity. The major enantiomer obtained is independent of starting alkene geometry, revealing that rhodium-catalyzed cis/trans-alkene isomerization occurs prior to hydroboration. In this poster, we will discuss the generation of active catalysts starting from different pre-catalysts. We find that the counterion (e.g., BF4-, BArF-) plays an important role in the reaction. Furthermore, we find that the addition of an external fluoride source (e.g., tetrabutylammonium difluorotriphenylsilicate (TBAT)) significantly impacts the reaction rate. These and other observations lead us to consider a novel catalytic cycle initiated by a rhodium(I)-hydride complex. Finally, the stereospecific transformations of the newly generated C–B bond to access drug candidates will be highlighted to demonstrate the utility of these chiral synthons

Tracking the Expression of Excitatory and Inhibitory Neurotransmission-Related Proteins and Neuroplasticity Markers after Noise Induced Hearing Loss

Excessive exposure to loud noise can damage the cochlea and create a hearing loss. These pathologies coincide with a range of CNS changes including reorganisation of frequency representation, alterations in the pattern of spontaneous activity and changed expression of excitatory and inhibitory neurotransmitters. Moreover, damage to the cochlea is often accompanied by acoustic disorders such as hyperacusis and tinnitus, suggesting that one or more of these neuronal changes may be involved in these disorders, although the mechanisms remain unknown. We tested the hypothesis that excessive noise exposure increases expression of markers of excitation and plasticity, and decreases expression of inhibitory markers over a 32-day recovery period. Adult rats (n = 25) were monaurally exposed to a loud noise (16 kHz, 1/10th octave band pass (115 dB SPL)) for 1-hour, or left as non-exposed controls (n = 5). Animals were euthanased at either 0, 4, 8, 16 or 32 days following acoustic trauma. We used Western Blots to quantify protein levels of GABAA receptor subunit α1 (GABAAα1), Glutamic-Acid Decarboxylase-67 (GAD-67), N-Methyl-D-Aspartate receptor subunit 2A (NR2A), Calbindin (Calb1) and Growth Associated Protein 43 (GAP-43) in the Auditory Cortex (AC), Inferior Colliculus (IC) and Dorsal Cochlear Nucleus (DCN). Compared to sham-exposed controls, noise-exposed animals had significantly (p<0.05): lower levels of GABAAα1 in the contralateral AC at day-16 and day-32, lower levels of GAD-67 in the ipsilateral DCN at day-4, lower levels of Calb1 in the ipsilateral DCN at day-0, lower levels of GABAAα1 in the ipsilateral AC at day-4 and day-32. GAP-43 was reduced in the ipsilateral AC for the duration of the experiment. These complex fluctuations in protein expression suggests that for at least a month following acoustic trauma the auditory system is adapting to a new pattern of sensory input

Ag(I)-Catalyzed Indolization/C3-Functionalization Cascade of 2‑Ethynylanilines via Ring Opening of Donor–Acceptor Cyclopropanes

A AgSbF₆-catalyzed cascade involving the ring opening of donor–acceptor cyclopropanes (DACs) preceded by the cyclization of <i>N</i>-protected 2-ethynylaniline is described. The method discloses a step-economy route to 2,3-disubstituted indole, where a Ag catalyst is found to trigger the cascade by activating both alkyne and DACs. Various functionalities at different ends of both substrates offer rapid access to 2,3-disubstituted indole derivatives in one pot in good to excellent yields. Elaboration of the cascade product to useful intermediates is also depicted

Enantioselective Hydrophosphonylation of <i>in Situ</i> Generated <i>N</i>‑Acyl Ketimines Catalyzed by BINOL-Derived Phosphoric Acid

An efficient route to pharmacologically interesting isoindolinone-based α-amino phosphonates is described via asymmetric hydrophosphonylation of <i>in situ</i> generated ketimines catalyzed by BINOL-derived phosphoric acid. The reaction proceeds smoothly at ambient temperature affording a variety of α-amino phosphonates with a quaternary stereogenic center embedded in isoindolinone motif in high yields with excellent enantiomeric ratios (up to 98.5:1.5 er). Several interesting transformations of the products into valuable synthetic intermediates are also depicted

Approach to Isoindolinones, Isoquinolinones, and THIQs via Lewis Acid-Catalyzed Domino Strecker-Lactamization/Alkylations

A one-pot, three-component synthesis of widely substituted isoindolinones and isoquinolinones, featuring a Lewis acid-catalyzed efficient Strecker reaction and lactamization sequence, affording products in good to high yields is reported. The method has also been extended to the synthesis of tetrahydroisoquinolines (THIQs) in high yields

Ni(II)-Catalyzed Highly Stereo- and Regioselective Syntheses of Isoindolinones and Isoquinolinones from <i>in Situ</i> Prepared Aldimines Triggered by Homoallylation/Lactamization Cascade

An efficient route to isoindolinones and isoquinolinones has been achieved via a domino Ni-catalyzed homoallylation/lactamization from <i>in situ</i> prepared imines, derived from <i>o</i>-formyl benzoates and <i>o</i>-formyl arylacetates, with conjugated dienes promoted by diethylzinc. The reaction proceeds smoothly at room temperature for a variety of aldehydes, amines, and dienes. The method involves one C–C and two C–N bond forming events under operationally simple conditions

Unified Approach to Isoindolinones and THIQs via Lewis Acid Catalyzed Domino Mukaiyama–Mannich Lactamization/Alkylations: Application in the Synthesis of (±)-Homolaudanosine

A novel and efficient synthesis of a variety of isoindolinones and tetrahydroisoquinolines via a Lewis acid catalyzed domino Mukaiyama–Mannich lactamization/alkylation is achieved. This transformation comprises a sequential formation of three new bonds through a one-pot, three-component procedure to afford product in moderate to high yields. A concise synthesis of (±)-homolaudanosine (<b>2b</b>) has been achieved using this method

An Efficient Entry to <i>syn</i>- and <i>anti</i>-Selective Isoindolinones via an Organocatalytic Direct Mannich/Lactamization Sequence

An organocatalytic direct Mannich–lactamization sequence for the syntheses of pharmacologically important enantioenriched isoindolinones is reported. The method utilizes simple α-amino acids to deliver <i>syn-</i> and <i>anti</i>- selective isoindolinones with remarkably high enantioselectivity (up to >99% ee) in good to excellent yields and diastereomeric ratios. The overall sequence involves one C–C and two C–N bond forming events in one pot starting from inexpensive starting material

An Efficient Entry to <i>syn</i>- and <i>anti</i>-Selective Isoindolinones via an Organocatalytic Direct Mannich/Lactamization Sequence

An organocatalytic direct Mannich–lactamization sequence for the syntheses of pharmacologically important enantioenriched isoindolinones is reported. The method utilizes simple α-amino acids to deliver <i>syn-</i> and <i>anti</i>- selective isoindolinones with remarkably high enantioselectivity (up to >99% ee) in good to excellent yields and diastereomeric ratios. The overall sequence involves one C–C and two C–N bond forming events in one pot starting from inexpensive starting material

A General Catalytic Route to Isoindolinones and Tetrahydroisoquinolines: Application in the Synthesis of (±)-Crispine A

An unprecedented highly efficient Lewis acid catalyzed one-pot cascade has been demonstrated as a general catalytic system for the synthesis of diversely substituted isoindolinones and tetrahydroisoquinolines. The cascade effects one C–C and two C–N bond-forming events in one pot. Several interesting transformations of the products into valuable synthetic intermediates are featured with the successful total synthesis of (±)-crispine A