Synthesis of Chiral 1,2-Amino Alcohol-Containing Compounds Utilizing Ruthenium-Catalyzed Asymmetric Transfer Hydrogenation of Unprotected α-Ketoamines.

Herein, we disclose a facile synthetic strategy to access an important class of drug molecules that contain chiral 1,2-amino alcohol functionality utilizing highly effective ruthenium-catalyzed asymmetric transfer hydrogenation of unprotected α-ketoamines. Recently, the COVID-19 pandemic has caused a crisis of shortage of many important drugs, especially norepinephrine and epinephrine, for the treatment of anaphylaxis and hypotension because of the increased demand. Unfortunately, the existing technologies are not fulfilling the worldwide requirement due to the existing lengthy synthetic protocols that require additional protection and deprotection steps.

Design and Discovery of Water-Soluble Benzooxaphosphole-Based Ligands for Hindered Suzuki-Miyaura Coupling Reactions with Low Catalyst Load.

We report a new class of highly effective, benzooxaphosphole-based, water-soluble ligands in the application of Suzuki-Miyaura cross-coupling reactions for sterically hindered substrates in aqueous media. The catalytic activities of the coupling reactions were greatly enhanced by the addition of catalytic amounts of organic phase transfer reagents, such as tetraglyme and tetrabutylammonium bromide. The optimized general protocol can be conducted with a low catalyst load, thereby providing a practical solution for these reactions.

The Design of "Neutral" Carbanions with Intramolecular Charge Compensation.

Strategies to construct zwitterionic anions from the parent anions are proposed. Two principles are employed; the cationic counterpart is (a) attached as a substituent or (b) inserted as an integral part at a remote location in the assembly. The optimized geometries reveal that a striking similarity exists between the zwitterions and the respective precursor parent anion.

The geometry and electronic topology of higher-order charged Möbius annulenes.

Higher-order aromatic charged Möbius-type annulenes have been L(k) realized computationally. These charged species are based on strips with more than one electronic half-twist, as defined by their linking numbers. The B3LYP/6-311+G(d,p) optimized structures and properties of annulene rings with such multiple half-twists (C(12)H(12)(2+), C(12)H(12)(2-), C(14)H(14), C(18)H(18)(2+), C(18)H(18)(2-), C(21)H(21)(+), C(24)H(24)(2-), C(28)H(28)(2+), and C(28)H(28)(2-)) have the nearly equal C-C bond lengths, small dihedral angles around the circuits, stabilization energies, and nucleus-independent chemical shift values associated with aromaticity.

4n pi electrons but stable: N,N-dihydrodiazapentacenes.

Despite having 4n pi electrons, dihydrodiazapentacenes are more viable than their 4n+2 pi azapentacene counterparts. Ab inito valence bond block-localized wave function (BLW) computations reveal that despite having 4n pi electrons, dihydrodiazapentacenes are stabilized and benefit substantially from four dihydropyrazine ethenamine (enamine) conjugations. Almost all of these dihydrodiazapentacenes have large negative overall nucleus independent chemical shifts NICS(0)(pizz) values even though their dihydropyrazine rings (e.

A neutral Ga(6) octahedron: synthesis, structure, and aromaticity.

Potassium graphite reduction of L:Ga(Mes)Cl(2) [L: = :C{(i-Pr)NC(Me)}(2), Mes = 2,4,6-Me(3)C(6)H(2)] (1) in hexane yields the organogallium dimer L:(Mes)(Cl)Ga-Ga(Cl)(Mes):L (2), while potassium reduction of 1 in toluene affords the neutral aromatic Ga(6) octahedron L:Ga[Ga(4)Mes(4)]Ga:L (3).

Pi and sigma-phenylethynyl radicals and their isomers o-, m-, and p-ethynylphenyl: structures, energetics, and electron affinities.

Molecular structures, energetics, vibrational frequencies, and electron affinities are predicted for the phenylethynyl radical and its isomers. Electron affinities are computed using density functional theory, -namely, the BHLYP, BLYP, B3LYP, BP86, BPW91, and B3PW91 functionals-, employing the double-zeta plus polarization DZP++ basis set; this level of theory is known to perform well for the computation of electron affinities. Furthermore, ab initio computations employing perturbation theory, coupled cluster with single and double excitations [CCSD], and the inclusion of perturbative triples [CCSD(T)] are performed to determine the relative energies of the isomers.

The concept of protobranching and its many paradigm shifting implications for energy evaluations.

Branched alkanes like isobutane and neopentane are more stable than their straight chain isomers, n-butane and n-pentane (by 2 and 5 kcal mol(-1), respectively). Electron correlation is largely responsible. Branched alkanes have a greater number of net attractive 1,3-alkyl-alkyl group interactions, there are three such stabilizing 1,3 "protobranching" dispositions in isobutane, but only two in n-butane.

The existence of secondary orbital interactions.

B3LYP/6-311+G** (and MP2/6-311+G**) computations, performed for a series of Diels-Alder (DA) reactions, confirm that the endo transition states (TS) and the related Cope-TSs are favored energetically over the respective exo-TSs. Likewise, the computed magnetic properties (nucleus-independent chemical shifts and magnetic susceptibililties) of the endo- (as well as the Cope) TS's reveal their greater electron delocalization and greater aromaticity than the exo-TS's. However, Woodward and Hoffmann's original example is an exception: their endo-TS model, involving the DA reaction of a syn- with an anti-butadiene (BD), actually is disfavored energetically over the corresponding exo-TS; magnetic criteria also do not indicate the existence of SOI delocalization in either case.

Planar tetracoordinate carbon atoms centered in bare four-membered rings of late transition metals.

Planar tetracoordinate carbons (ptC's) can be stabilized by four-membered ring perimeters composed of four bare transition metal atoms. DFT analyses of the molecular orbitals, electronic structures, energies, and magnetic properties of these CM4 species (where M represents isoelectronic combinations of Cu, Ni, Ag, and Pd) reveal striking similarities with main group metal ptC analogues (e.g.

Which NICS aromaticity index for planar pi rings is best?

Five increasingly sophisticated aromaticity indexes, based on nucleus-independent chemical shifts (NICS), were evaluated against a uniform set of aromatic stabilization energies (ASE) for 75 mono- and polyheterocyclic five-membered rings. While acceptable statistical correlations were given by all of the NICS methods, the most fundamentally grounded index, NICS(0)pizz (based on the pi contribution to the out-of-plane zz tensor component), performed best statistically (cc=0.980) and in practice.

Octahedral and tetrahedral coinage metal clusters: is three-dimensional d-orbital aromaticity viable?

The first quantitative evidence for the viability of three-dimensional aromatic clusters involving d-orbitals in pseudo-octahedral coinage metal cages M(6)Li(2) (M = Cu, Ag, Au) as well as in tetrahedral coinage metal cages M'(4)Li(4) (M' = Cu, Ag) was obtained computationally. These cages exhibit many features similar to those of their square planar M(4)Li(2) analogues. The large negative nucleus-independent chemical shifts (NICS) at the cage centers indicate three-dimensional delocalization.

The peculiar trend of cyclic perfluoroalkane electron affinities with increasing ring size.

The adiabatic electron affinities (AEAs), vertical electron affinities (VEAs), and vertical detachment energies (VDEs) of cyclic perfluoroalkanes, c-C(n)F(2n) (n = 3-7), and their monotrifluoromethyl derivatives were computed using various pure and hybrid density functionals with DZP++ (polarization and diffuse function augmented double-zeta) basis sets. The theoretical AEA of c-C(4)F(8) at KMLYP/DZP++ is 0.70 eV, which exhibits satisfactory agreement with the 0.

Effects of fluorine on the structures and energetics of the propynyl and propargyl radicals and their anions.

[reaction: see text] The adiabatic electron affinity (EA(ad)) of the CH(3)-C[triple bond]C(*) radical [experiment = 2.718 +/- 0.008 eV] and the gas-phase basicity of the CH(3)-C[triple bond]C:(-) anion [experiment = 373.

A metallocene-complexed dibismuthene: Cp2Zr(BiR)2 (Cp = C5H5; R = C6H3-2,6-Mes2).

The zirconocene-complexed dibismuthene, Cp2Zr(BiR)2 (Cp = C5H5; R = C6H3-2,6-Mes2), was prepared by the reaction of sodium metal with Cp2ZrCl2 and RBiCl2. The air- and moisture-sensitive dark reddish/brown compound is the first organometallic compound containing Bi-Zr bonds and the only example of a ZrBi2 ring. Moreover, our computations on associated model systems offer insight into the nature of the interaction of the heaviest dipnictene with a metallocene center.

Evidence for d orbital aromaticity in square planar coinage metal clusters.

Quantitative evidence for the existence of aromaticity involving the d orbitals of transition metals is provided for the first time. The doubly bridged square planar (D(4)(h)()) coinage metal clusters (M(4)Li(2), M = Cu (1), Ag (2), and Au (3)) are characterized as aromatic by their substantial nucleus independent chemical shifts (NICS) values in the centers (-14.5, -14.

Downfield proton chemical shifts are not reliable aromaticity indicators.

[structure: see text] The downfield chemical shifts of arene hydrogens (delta (1)H) are due only in part to the pi ring current contribution [sigma(//)(pi)]; local framework effects are equally important. Neither proton chemical shifts nor even sigma(||)(pi) tensor elements, per se, are reliable aromaticity indicators. Unsaturated polycyclic hydrocarbons with nonaromatic quinoid structures have delta (1)H and sigma(//)(pi) values in the "aromatic range".

Investigation of a putative mobius aromatic hydrocarbon. The effect of benzannelation on mobius [4n]annulene aromaticity.

The first experimental example of a [4n]annulene derivative with one Mobius twist, 1, was synthesized recently [Ajami, D.; Oeckler, O.; Simon, A.

On the stability of large [4n]annulenes.

[reaction: see text] The stabilization energies (B3LYP/6-31G) of planar [4n]annulenes, evaluated by a new indene-isoindene isomerization method (see Abstract graphic), reveal that all 4n pi-electron rings larger than the energetically unfavorable cyclobutadiene are only slightly destabilized by the pi-electron interactions. Cyclooctatetraene prefers the "tub" conformation because of strain effects. Generally, the antiaromatic character of the larger systems with 4n pi-electrons is revealed best by their magnetic properties rather than by their energies.