Transaminase-Catalyzed Synthesis of ß-Branched Noncanonical Amino Acids Driven by a Lysine Amine Donor.

Transaminases are choice biocatalysts for the synthesis of chiral primary amines, including amino acids bearing contiguous stereocenters. In this study, we employ lysine as a "smart" amine donor in transaminase-catalyzed dynamic kinetic resolution reactions to access ß-branched noncanonical arylalanines. Our mechanistic investigation demonstrates that, upon transamination, the lysine-derived ketone byproduct readily cyclizes to a six-membered imine, driving the equilibrium in the desired direction and thus alleviating the need to load superstoichiometric quantities of the amine donor or deploy a multienzyme cascade. Lysine also shows good overall compatibility with a panel of wild-type transaminases, a promising hint of its application as a smart donor more broadly. Indeed, by this approach, we furnished a broad scope of ß-branched arylalanines, including some bearing hitherto intractable cyclopropyl and isopropyl substituents, with high yields and excellent selectivities.

Oxalohydrazide Ligands for Copper-Catalyzed C-O Coupling Reactions with High Turnover Numbers.

Here, we report a class of ligands based on oxalohydrazide cores and N-amino pyrrole and N-amino indole units that generates long-lived copper catalysts for couplings that form the C-O bonds in biaryl ethers. These Cu-catalyzed coupling of phenols with aryl bromides occurred with turnovers up to 8000, a value which is nearly two orders of magnitude higher than those of prior couplings to form biaryl ethers and nearly an order of magnitude higher than those of any prior copper-catalyzed coupling of aryl bromides and chlorides. This ligand also led to copper systems that catalyze the coupling of aryl chlorides with phenols and the coupling of aryl bromides and iodides with primary benzylic and aliphatic alcohols. A wide variety of functional groups including nitriles, halides, ethers, ketones, amines, esters, amides, vinylarenes, alcohols and boronic acid esters were tolerated, and reactions occurred with aryl bromides in pharmaceutically related structures.

Ruthenium-Catalyzed Aerobic Oxidation of Amines.

Amine oxidation is one of the fundamental reactions in organic synthesis as it leads to a variety of value-added products such as oximes, nitriles, imines, and amides among many others. These products comprise the key N-containing building blocks in the modern chemical industry, and such transformations, when achieved in the presence of molecular oxygen without using stoichiometric oxidants, are much preferred as they circumvent the production of unwanted wastes. In parallel, the versatility of ruthenium catalysts in various oxidative transformations is well-documented. Herein, this review focuses on aerobic oxidation of amines specifically by using ruthenium catalysts and highlights the major achievements in this direction and challenges that still need to be addressed.

Highly Selective Ruthenium-Catalyzed Direct Oxygenation of Amines to Amides.

Reports on aerobic oxidation of amines to amides are rare, and those reported suffer from several limitations like poor yield or selectivity and make use of pure oxygen under elevated pressure. Herein, we report a practical and an efficient ruthenium-catalyzed synthetic protocol that enables selective oxidation of a broad range of primary aliphatic, heterocyclic and benzylic amines to their corresponding amides, using readily available reagents and ambient air as the sole oxidant. Secondary amines instead, yield benzamides selectively as the sole product. Mechanistic investigations reveal intermediacy of nitriles, which undergo hydration to afford amide as the final product.

Ligand controlled switchable selectivity in ruthenium catalyzed aerobic oxidation of primary amines.

A ligand controlled catalytic system for the aerobic oxidation of 1° amines to nitriles and imines has been developed where the varying π-acidic feature of BIAN versus phen in the frameworks of ruthenium catalysts facilitates switchable selectivity.

Electronic Structure and Multicatalytic Features of Redox-Active Bis(arylimino)acenaphthene (BIAN)-Derived Ruthenium Complexes.

The article examines the newly designed and structurally characterized redox-active BIAN-derived [Ru(trpy)(R-BIAN)Cl]ClO4 ([1a]ClO4-[1c]ClO4), [Ru(trpy)(R-BIAN)(H2O)](ClO4)2 ([3a](ClO4)2-[3c](ClO4)2), and BIAO-derived [Ru(trpy)(BIAO)Cl]ClO4 ([2a]ClO4) (trpy = 2,2':6',2''-terpyridine, R-BIAN = bis(arylimino)acenaphthene (R = H (1a(+), 3a(2+)), 4-OMe (1b(+), 3b(2+)), 4-NO2 (1c(+), 3c(2+)), BIAO = [N-(phenyl)imino]acenapthenone). The experimental (X-ray, (1)H NMR, spectroelectrochemistry, EPR) and DFT/TD-DFT calculations of 1a(n)-1c(n) or 2a(n) collectively establish {Ru(II)-BIAN(0)} or {Ru(II)-BIAO(0)} configuration in the native state, metal-based oxidation to {Ru(III)-BIAN(0)} or {Ru(III)-BIAO(0)}, and successive electron uptake processes by the α-diimine fragment, followed by trpy and naphthalene π-system of BIAN or BIAO, respectively. The impact of the electron-withdrawing NO2 function in the BIAN moiety in 1c(+) has been reflected in the five nearby reduction steps within the accessible potential limit of -2 V versus SCE, leading to a fully reduced BIAN(4-) state in [1c](4-). The aqua derivatives ({Ru(II)-OH2}, 3a(2+)-3c(2+)) undergo simultaneous 2e(-)/2H(+) transfer to the corresponding {Ru(IV)═O} state and the catalytic current associated with the Ru(IV)/Ru(V) response probably implies its involvement in the electrocatalytic water oxidation. The aqua derivatives (3a(2+)-3c(2+)) are efficient and selective precatalysts in transforming a wide variety of alkenes to corresponding epoxides in the presence of PhI(OAc)2 as an oxidant in CH2Cl2 at 298 K as well as oxidation of primary, secondary, and heterocyclic alcohols with a large substrate scope with H2O2 as the stoichiometric oxidant in CH3CN at 343 K. The involvement of the {Ru(IV)═O} intermediate as the active catalyst in both the oxidation processes has been ascertained via a sequence of experimental evidence.

Simple and Efficient Ruthenium-Catalyzed Oxidation of Primary Alcohols with Molecular Oxygen.

Oxidative transformations utilizing molecular oxygen (O2 ) as the stoichiometric oxidant are of paramount importance in organic synthesis from ecological and economical perspectives. Alcohol oxidation reactions that employ O2 are scarce in homogeneous catalysis and the efficacy of such systems has been constrained by limited substrate scope (most involve secondary alcohol oxidation) or practical factors, such as the need for an excess of base or an additive. Catalytic systems employing O2 as the "primary" oxidant, in the absence of any additive, are rare. A solution to this longstanding issue is offered by the development of an efficient ruthenium-catalyzed oxidation protocol, which enables smooth oxidation of a wide variety of primary, as well as secondary benzylic, allylic, heterocyclic, and aliphatic, alcohols with molecular oxygen as the primary oxidant and without any base or hydrogen- or electron-transfer agents. Most importantly, a high degree of selectivity during alcohol oxidation has been predicted for complex settings. Preliminary mechanistic studies including (18) O labeling established the in situ formation of an oxo-ruthenium intermediate as the active catalytic species in the cycle and involvement of a two-electron hydride transfer in the rate-limiting step.

Tunable Electrochemical and Catalytic Features of BIAN- and BIAO-Derived Ruthenium Complexes.

This article deals with a class of ruthenium-BIAN-derived complexes, [Ru(II)(tpm)(R-BIAN)Cl]ClO4 (tpm = tris(1-pyrazolyl)methane, R-BIAN = bis(arylimino)acenaphthene, R = 4-OMe ([1a]ClO4), 4-F ([1b]ClO4), 4-Cl ([1c]ClO4), 4-NO2 ([1d]ClO4)) and [Ru(II)(tpm)(OMe-BIAN)H2O](2+) ([3a](ClO4)2). The R-BIAN framework with R = H, however, leads to the selective formation of partially hydrolyzed BIAO ([N-(phenyl)imino]acenapthenone)-derived complex [Ru(II)(tpm)(BIAO)Cl]ClO4 ([2]ClO4). The redox-sensitive bond parameters involving -N═C-C═N- or -N═C-C═O of BIAN or BIAO in the crystals of representative [1a]ClO4, [3a](PF6)2, or [2]ClO4 establish its unreduced form. The chloro derivatives 1a(+)-1d(+) and 2(+) exhibit one oxidation and successive reduction processes in CH3CN within the potential limit of ±2.0 V versus SCE, and the redox potentials follow the order 1a(+) < 1b(+) < 1c(+) < 1d(+) ≈ 2(+). The electronic structural aspects of 1a(n)-1d(n) and 2(n) (n = +2, +1, 0, -1, -2, -3) have been assessed by UV-vis and EPR spectroelectrochemistry, DFT-calculated MO compositions, and Mulliken spin density distributions in paramagnetic intermediate states which reveal metal-based (Ru(II) → Ru(III)) oxidation and primarily BIAN- or BIAO-based successive reduction processes. The aqua complex 3a(2+) undergoes two proton-coupled redox processes at 0.56 and 0.85 V versus SCE in phosphate buffer (pH 7) corresponding to {Ru(II)-H2O}/{Ru(III)-OH} and {Ru(III)-OH}/{Ru(IV)═O}, respectively. The chloro (1a(+)-1d(+)) and aqua (3a(2+)) derivatives are found to be equally active in functioning as efficient precatalysts toward the epoxidation of a wide variety of alkenes in the presence of PhI(OAc)2 as oxidant in CH2Cl2 at 298 K, though the analogous 2(+) remains virtually inactive. The detailed experimental analysis with the representative precatalyst 1a(+) suggests the involvement of the active {Ru(IV)═O} species in the catalytic cycle, and the reaction proceeds through the radical mechanism, as also supported by the DFT calculations.

Revelation of varying bonding motif of alloxazine, a flavin analogue, in selected ruthenium(II/III) frameworks.

The reaction of alloxazine (L) and Ru(II)(acac)2(CH3CN)2 (acac(-) = acetylacetonate) in refluxing methanol leads to the simultaneous formation of Ru(II)(acac)2(L) (1 = bluish-green) and Ru(III)(acac)2(L(-)) (2 = red) encompassing a usual neutral α-iminoketo chelating form of L and an unprecedented monodeprotonated α-iminoenolato chelating form of L(-), respectively. The crystal structure of 2 establishes that N5,O4(-) donors of L(-) result in a nearly planar five-membered chelate with the {Ru(III)(acac)2(+)} metal fragment. The packing diagram of 2 further reveals its hydrogen-bonded dimeric form as well as π-π interactions between the nearly planar tricyclic rings of coordinated alloxazine ligands in nearby molecules. The paramagnetic 2 and one-electron-oxidized 1(+) display ruthenium(III)-based anisotropic axial EPR in CH3CN at 77 K with ⟨g⟩/Δg of 2.136/0.488 and 2.084/0.364, respectively (⟨g⟩ = {1/3(g1(2) + g2(2) + g3(2))}(1/2) and Δg = g1 - g3). The multiple electron-transfer processes of 1 and 2 in CH3CN have been analyzed by DFT-calculated MO compositions and Mulliken spin density distributions at the paramagnetic states, which suggest successive two-electron uptake by the π-system of the heterocyclic ring of L (L → L(•-) → L(2-)) or L(-) (L(-) → L(•2-) → L(3-)) besides metal-based (Ru(II)/Ru(III)) redox process. The origin of the ligand as well as mixed metal-ligand-based multiple electronic transitions of 1(n) (n = +1, 0, -1, -2) and 2(n) (n = 0, -1, -2) in the UV and visible regions, respectively, has been assessed by TD-DFT calculations in each redox state. The pKa values of 1 and 2 incorporating two and one NH protons of 6.5 (N3H, pKa1)/8.16 (N1H, pKa2) and 8.43 (N1H, pKa1), respectively, are estimated by monitoring their spectral changes as a function of pH in CH3CN-H2O (1:1). 1 and 2 in CH3CN also participate in proton-driven internal reorganizations involving the coordinated alloxazine moiety, i.e., transformation of an α-iminoketo chelating form to an α-iminoenolato chelating form and the reverse process without any electron-transfer step: Ru(II)(acac)2(L) (1) → Ru(II)(acac)2(L(-)) (2(-)) and Ru(III)(acac)2(L(-)) (2) → Ru(III)(acac)2(L) (1(+)).

Efficient and simple approaches towards direct oxidative esterification of alcohols.

The present article describes novel oxidative protocols for direct esterification of alcohols. The protocols involve successful demonstrations of both "cross" and "self" esterification of a wide variety of alcohols. The cross-esterification proceeds under a simple transition-metal-free condition, containing catalytic amounts of TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxy)/TBAB (tetra-n-butylammonium bromide) in combination with oxone (potassium peroxo monosulfate) as the oxidant, whereas the self-esterification is achieved through simple induction of Fe(OAc)2 /dipic (dipic=2,6-pyridinedicarboxylic acid) as the active catalyst under an identical oxidizing environment.

Revelation of varying coordination modes and noninnocence of deprotonated 2,2'-bipyridine-3,3'-diol in {Os(bpy)2} frameworks.

The reaction of 2,2'-bipyridine-3,3'-diol (H2L) and cis-Os(II)(bpy)2Cl2 (bpy = 2,2'-bipyridine) results in isomeric forms of [Os(II)(bpy)2(HL(-))]ClO4, [1]ClO4 and [2]ClO4, because of the varying binding modes of partially deprotonated HL(-). The identities of isomeric [1]ClO4 and [2]ClO4 have been authenticated by their single crystal X-ray structures. The ambidentate HL(-) in [2]ClO4 develops the usual N,N bonded five-membered chelate with a strong O-H···O hydrogen bonded situation (O-H···O angle: 160.78°) at its back face. The isomer [1]ClO4 however represents the monoanionic O(-),N coordinating mode of HL(-), leading to a six-membered chelate with the moderately strong O-H···N hydrogen bonding interaction (O-H···N angle: 148.87°) at its backbone. The isomeric [1]ClO4 and [2]ClO4 also exhibit distinctive spectral, electrochemical, electronic structural, and hydrogen bonding features. The pKa values for [1]ClO4 and [2]ClO4 have been estimated to be 0.73 and <0.2, respectively, thereby revealing the varying hydrogen bonding interaction profiles of O-H···N and O-H···O involving the coordinated HL(-). The O-H···O group of HL(-) in 2(+) remains invariant in the basic region (pH 7-12), while deprotonation of O-H···N group of HL(-) in 1(+) estimates the pKb value of 11.55. This indeed has facilitated the activation of the exposed O-H···N function in [1]ClO4 by the second {Os(II)(bpy)2} unit to yield the L(2-) bridged [(bpy)2Os(II)(µ-L(2-))Os(II)(bpy)2](ClO4)2 ([3](ClO4)2). However, the O-H···O function in [2]ClO4 fails to react with {Os(II)(bpy)2}. The crystal structure of [3](ClO4)2 establishes the symmetric N,O(-)/O(-),N bridging mode of L(2-). On the other hand, the doubly deprotonated L'(2-) (H2L' = 2,2'-biphenol) generates structurally characterized twisted seven-membered O(-),O(-) bonded chelate (torsion angle >50°) in paramagnetic [Os(III)(bpy)2(L'(2-))]ClO4 ([4]ClO4). The electronic structural aspects of the complexes reveal the noninnocent potential of the coordinated HL(-), L(2-), and L'(2-). The Kc value of 49 for 3(3+) reveals a class I mixed-valent Os(II)Os(III) state.

Uncommon cis configuration of a metal-metal bridging noninnocent Nindigo ligand.

In contrast to several reported coordination compounds of trans-Nindigo ligands [Nindigo = indigo-bis(N-arylimine) = LH2] with one or two six-membered chelate rings involving one indole N and one extracyclic N for metal binding, the new diruthenium complex ion [(acac)2Ru(µ,η(2):η(2)-L)Ru(bpy)2](2+) = 2(2+) exhibits edge-sharing five- and seven-membered chelate rings in the first documented case of asymmetric bridging by a Nindigo ligand in the cis configuration [L(2-) = indigo-bis(N-phenylimine)dianion]. The dication in compound [2](ClO4)2 displays one Ru(α-diimine)3 site and one ruthenium center with three negatively charged chelate ligands. Compound [2](ClO4)2 is obtained from the [Ru(bpy)2](2+)-containing cis precursor [(LH)Ru(bpy)2]ClO4 = [1]ClO4, which exhibits intramolecular H-bonding in the cation. Four accessible oxidation states each were characterized for the 1(n) and 2(n) redox series with respect to metal- or ligand-centered electron transfer, based on X-ray structures, electron paramagnetic resonance, and ultraviolet-visible-near-infrared spectroelectrochemistry in conjunction with density functional theory calculation results. The structural asymmetry in the Ru(III)/Ru(II) system 2(2+) is reflected by the electronic asymmetry (class I mixed-valence situation), leaving the noninnocent Nindigo bridge as the main redox-active site.

Sensitivity of the valence structure in diruthenium complexes as a function of terminal and bridging ligands.

The compounds [(acac)2Ru(III)(µ-H2L(2-))Ru(III)(acac)2] (rac, 1, and meso, 1') and [(bpy)2Ru(II)(µ-H2L(•-))Ru(II)(bpy)2](ClO4)3 (meso, [2](ClO4)3) have been structurally, magnetically, spectroelectrochemically, and computationally characterized (acac(-) = acetylacetonate, bpy = 2,2'-bipyridine, and H4L = 1,4-diamino-9,10-anthraquinone). The N,O;N',O'-coordinated µ-H2L(n-) forms two ß-ketiminato-type chelate rings, and 1 or 1' are connected via NH···O hydrogen bridges in the crystals. 1 exhibits a complex magnetic behavior, while [2](ClO4)3 is a radical species with mixed ligand/metal-based spin. The combination of redox noninnocent bridge (H2L(0) → → → →H2L(4-)) and {(acac)2Ru(II)} → →{(acac)2Ru(IV)} or {(bpy)2Ru(II)} → {(bpy)2Ru(III)} in 1/1' or 2 generates alternatives regarding the oxidation state formulations for the accessible redox states (1(n) and 2(n)), which have been assessed by UV-vis-NIR, EPR, and DFT/TD-DFT calculations. The experimental and theoretical studies suggest variable mixing of the frontier orbitals of the metals and the bridge, leading to the following most appropriate oxidation state combinations: [(acac)2Ru(III)(µ-H2L(•-))Ru(III)(acac)2](+) (1(+)) → [(acac)2Ru(III)(µ-H2L(2-))Ru(III)(acac)2] (1) → [(acac)2Ru(III)(µ-H2L(•3-))Ru(III)(acac)2](-)/[(acac)2Ru(III)(µ-H2L(2-))Ru(II)(acac)2](-) (1(-)) → [(acac)2Ru(III)(µ-H2L(4-))Ru(III)(acac)2](2-)/[(acac)2Ru(II)(µ-H2L(2-))Ru(II)(acac)2](2-) (1(2-)) and [(bpy)2Ru(III)(µ-H2L(•-))Ru(II)(bpy)2](4+) (2(4+)) → [(bpy)2Ru(II)(µ-H2L(•-))Ru(II)(bpy)2](3+)/[(bpy)2Ru(II)(µ-H2L(2-))Ru(III)(bpy)2](3+) (2(3+)) → [(bpy)2Ru(II)(µ-H2L(2-))Ru(II)(bpy)2](2+) (2(2+)). The favoring of Ru(III) by σ-donating acac(-) and of Ru(II) by the π-accepting bpy coligands shifts the conceivable valence alternatives accordingly. Similarly, the introduction of the NH donor function in H2L(n) as compared to O causes a cathodic shift of redox potentials with corresponding consequences for the valence structure.

Significant influence of coligands toward varying coordination modes of 2,2'-bipyridine-3,3'-diol in ruthenium complexes.

The varying coordination modes of the ambidentate ligand 2,2'-bipyridine-3,3'-diol (H2L) in a set of ruthenium complexes were demonstrated with special reference to the electronic features of the coligands, including σ-donating acac(-) (= acetylacetonate) in Ru(III)(acac)2(HL(-)) (1), strongly π-accepting pap (= 2-phenylazopyridine) in Ru(II)(pap)2(L(2-)) (2)/[(pap)2Ru(II)(µ-L(2-))Ru(II)(pap)2](ClO4)2 ([4](ClO4)2), and reported moderately π-accepting bpy (= 2,2'-bypiridine) in [Ru(II)(bpy)2(HL(-))]PF6 ([5]PF6)/[(bpy)2Ru(µ-L(2-))Ru(bpy)2](PF6)2 ([7](PF6)2). The single-crystal X-ray structures reveal that, in paramagnetic and electron paramagnetic resonance active 1 and reported diamagnetic [5]PF6, nearly planar monoanionic HL(-) coordinates to the metal ion via the N,N donors forming a five-membered chelate ring with hydrogen-bonded O-H···O function at the backbone of the ligand framework, as has also been reported in other metal complexes. However, structurally characterized diamagnetic 2 represents O(-),O(-) bonded seven-membered chelate of fully deprotonated but twisted L(2-). The nonplanarity of the coordinated L(2-) in 2 does not permit the second metal fragment {Ru(pap)2} or {Ru(bpy)2} or {Ru(acac)2} to bind with the available N,N donors at the back face of L(2-). Further, the deprotonated form of the model ligand 2,2'-biphenol (H2L') yields Ru(II)(pap)2(L'(2-)) (3); its crystal structure establishes the expected O(-),O(-) bonded seven-membered chelate of nonplanar L'(2-) as in reported Ru(II)(bpy)2(L'(2-)) (6), although {Ru(acac)2} metal precursor altogether fails to react with H2L'. All attempts to make diruthenium complex from {Ru(acac)2} and H2L failed; however, the corresponding {Ru(pap)2(2+)} derived dimeric [4](ClO4)2 was structurally characterized. It establishes the symmetric N,O(-)/N,O(-) bridging mode of nonplanar L(2-) as in reported [7](PF6)2. Besides structural and spectroscopic characterization of the newly developed complexes, the ligand (HL(-), L(2-), L'(2-), pap)-, metal-, or mixed metal-ligand-based accessible redox processes in 1(n) (n = +2, +1, 0, -1), 2(n)/3(n) (n = +2, +1, 0, -1, -2), and 4(n) (n = +4, +3, +2, +1, 0, -1) were analyzed in conjunction with density functional theory calculations.

Iron catalysed nitrosation of olefins to oximes.

Fe(BF4)2·6H2O/2,6-pyridinedicarboxylic acid catalysed nitrosation of a wide variety of substituted styrenes has been developed in the presence of t-BuONO/NaBH4 under H2 pressure (10 bar) in MeOH-H2O (5 : 1) to afford corresponding oximes in good to excellent yields.

An iron catalyzed regioselective oxidation of terminal alkenes to aldehydes.

Fe(BF(4))(2)·6H(2)O with pyridine-2,6-dicarboxylic acid and PhIO can efficiently catalyze the regioselective oxidation of terminal alkene derivatives to aldehydes under mild and benign reaction conditions.