Computational Studies of Reactions of 1,2,4,5-Tetrazines with Enamines in MeOH and HFIP.

The reaction between 1,2,4,5-tetrazines and alkenes in polar solvents proceeds through a Diels-Alder cycloaddition along the C-C axis (C3/C6 cycloaddition) of the tetrazine, followed by dinitrogen loss. By contrast, the reactions of 1,2,4,5-tetrazines with enamines in hexafluoroisopropanol (HFIP) give 1,2,4-triazine products stemming from a formal Diels-Alder addition across the N-N axis (N1/N4 cycloaddition). We explored the mechanism of this interesting solvent effect through DFT calculations in detail and revealed a novel reaction pathway characterized by C-N bond formation, deprotonation, and a 3,3-sigmatropic rearrangement.

Acyclic and Heterocyclic Azadiene Diels-Alder Reactions Promoted by Perfluoroalcohol Solvent Hydrogen Bonding: Comprehensive Examination of Scope.

Herein, the first use of perfluoroalcohol H-bonding in accelerating acyclic azadiene inverse electron demand cycloaddition reactions is described, and its use in the promotion of heterocyclic azadiene cycloaddition reactions is generalized through examination of a complete range of azadienes. The scope of dienophiles was comprehensively explored; relative reactivity trends and solvent compatibilities were established with respect to the dienophile as well as azadiene; H-bonding solvent effects that lead to rate enhancements, yield improvements, and their impact on regioselectivity and mode of cycloaddition are defined; new viable diene/dienophile reaction partners in the cycloaddition reactions are disclosed; and key comparison rate constants are reported. The perfluoroalcohol effectiveness at accelerating an inverse electron demand Diels-Alder cycloaddition is directly correlated with its H-bond potential (p).

N1/N4 1,4-Cycloaddition of 1,2,4,5-Tetrazines with Enamines Promoted by the Lewis Acid ZnCl.

The second example of selective N1/N4 1,4-cycloaddition (vs C3/C6 1,4-cycloaddition) of 1,2,4,5-tetrazines with preformed or in situ generated enamines now promoted by the Lewis acid ZnCl and with an expanded scope is described. The reaction constitutes a formal [4 + 2] cycloaddition across two nitrogen atoms (N1/N4 vs C3/C6) of a 1,2,4,5-tetrazine followed by retro [4 + 2] cycloaddition loss of a nitrile and aromatization to provide 1,2,4-triazines. Optimization of reaction parameters, simplification of its implementation through in situ enamine generation from ketones, definition of the enamine reaction scope for 3,6-bis(thiomethyl)-1,2,4,5-tetrazine, exploration of the 1,2,4,5-tetrazine scope, and representative applications of the product 1,2,4-triazines are detailed.

Parallel Manipulation and Flexible Assembly of Micro-Spiral Optoelectronic Tweezers.

Micro-spiral has a wide range of applications in smart materials, such as drug delivery, deformable materials, and micro-scale electronic devices by utilizing the manipulation of electric fields, magnetic fields, and flow fields. However, it is incredibly challenging to achieve a massively parallel manipulation of the micro-spiral to form a particular microstructure in these conventional methods. Here, a simple method is reported for assembling micro-spirals into various microstructures optoelectronic tweezers (OETs), which can accurately manipulate the micro-/bio-particles by projecting light patterns.

Selective N1/N4 1,4-Cycloaddition of 1,2,4,5-Tetrazines Enabled by Solvent Hydrogen Bonding.

An unprecedented 1,4-cycloaddition (vs 3,6-cycloaddition) of 1,2,4,5-tetrazines is described with preformed or in situ generated aryl-conjugated enamines promoted by the solvent hydrogen bonding of hexafluoroisopropanol (HFIP) that is conducted under mild reaction conditions (0.1 M HFIP, 25 °C, 12 h). The reaction constitutes a formal [4 + 2] cycloaddition across the two nitrogen atoms (N1/N4) of the 1,2,4,5-tetrazine followed by a formal retro [4 + 2] cycloaddition loss of a nitrile and aromatization to generate a 1,2,4-triazine derivative.

Accelerating the Drug Delivery Pipeline for Acute and Chronic Pancreatitis: Summary of the Working Group on Drug Development and Trials in Chronic Pancreatitis at the National Institute of Diabetes and Digestive and Kidney Diseases Workshop.

The lack of effective therapeutic agents specifically tailored for chronic pancreatitis (CP) has hampered clinical care and negatively impacted patients' lives. New mechanistic insights now point to novel therapies, which involve both recently developed and/or repurposed agents. This working group focused on 2 main outcomes for CP: pain and progression of disease.

Cobalt-Catalyzed Intramolecular Alkyne/Benzocyclobutenone Coupling: C-C Bond Cleavage via a Tetrahedral Dicobalt Intermediate.

A Co(0)-catalyzed intramolecular alkyne/benzocyclobutenone coupling through C-C cleavage of benzocyclobutenones is described. Co(CO)/P[3, 5-(CF)CH] was discovered to be an effective metal/ligand combination, which exhibits complementary catalytic activity to the previously established rhodium catalyst. In particular, the C8-substituted substrates failed in the Rh system, but succeeded with the Co catalysis.

Palladium-Catalyzed Enantioselective Synthesis of 2-Aryl Cyclohex-2-enone Atropisomers: Platform Molecules for the Divergent Synthesis of Axially Chiral Biaryl Compounds.

The palladium-catalyzed asymmetric synthesis of enone-based atropisomers from 2-iodo-3-methylcyclohex-2-enones and aryl boronic acid is reported. BoPhoz-type phosphine-aminophosphine ligands showed superior enantioselectivity over other ligands. These cyclohexenone-based atropisomers are useful compounds for further elaboration.

Physiological mechanisms contributing to the increased water-use efficiency in winter wheat under deficit irrigation.

Deficit irrigation in winter wheat has been practiced in the areas with limited irrigation water resources. The objectives of this study were to (i) understand the physiological basis for determinations of grain yield and water-use efficiency in grain yield (WUE) under deficit irrigation; and (ii) investigate the effect of deficit irrigation on dry matter accumulation and remobilization of pre-anthesis carbon reserves during grain filling. A field experiment was conducted in the Southern High Plains of the USA and winter wheat (cv.