A new alternative to Stryker's reagent in hydrosilylation: synthesis, structure, and reactivity of a well-defined carbene-copper(II) acetate complex

A new, air stable and well-defined carbene-copper(II) complex has been prepared, which is an efficient precatalyst for the 1,2- and 1,4-reduction of carbonyl compounds under hydrosilylation conditions.     

Diastereo‐ and Enantioselective Iridium Catalyzed Carbonyl (α‐Cyclopropyl)allylation via Transfer Hydrogenation

The first examples of diastereo‐ and enantioselective carbonyl α‐(cyclopropyl)allylation are reported. Under the conditions of iridium catalyzed transfer hydrogenation using the chiral precatalyst (R)‐Ir‐ I modified by SEGPHOS, carbonyl α‐(cyclopropyl)allylation may be achieved with equal facility from alcohol or aldehyde oxidation levels. This methodology provides a conduit to hitherto inaccessible inaccessible enantiomerically enriched cyclopropane‐containing architectures.     

Synthesis of 2-oxazolidinones by salen-Co-complexes catalyzed oxidative carbonylation of β-amino alcohols

2-Oxazolidinones are synthesized in high yield by oxidative carbonylation of β-amino alcohols using salen-Co(II)/NaI or salen-Co(III)-I as a catalyst and using CO as the carbonyl source. Studies of functional group compatibility using a series of substituted salen-Co(II) or salen-Co(III)-I complexes demonstrate a broad tolerance of functionality during the carbonylation reaction.     

Diastereoselective nickel-catalyzed reductive aldol cyclizations using diethylzinc as the stoichiometric reductant: scope and mechanistic insight

In the presence of diethylzinc as a stoichiometric reductant, Ni(acac) 2 functions as an efficient precatalyst for the reductive aldol cyclization of alpha,beta-unsaturated carbonyl compounds tethered to a ketone electrophile through an amide or an ester linkage. The reactions are tolerant of a wide range of substitution at both alpha,beta-unsaturated carbonyl and ketone components and proceed smoothly to furnish beta-hydroxylactams and beta-hydroxylactones with generally high diastereoselectivities. A series of experiments, including deuterium-labeling studies, was carried out in an attempt to gain some insight into the possible reaction mechanisms that might be operative.     

Origin of syn/anti diastereoselectivity in aldehyde and ketone crotylation reactions: a combined theoretical and experimental study

We report on experimentally determined and computationally predicted diastereoselectivities of (a) multicomponent crotylation (MCC) reactions of simple aliphatic aldehydes and ketones and (b) of acetal substitution (AS) reactions of aldehyde dimethyl acetals with E- and Z-configurated crotyl trimethylsilane to give homoallylic methyl ethers bearing two newly formed stereogenic centers. We found that corresponding MCC and AS reactions give nearly equal syn/anti ratios. While the crotylations of acetaldehyde and propionaldehyde mainly result in the syn product for E-configurated silane and in the anti product for Z-configurated silane, the syn product is found as main product for the crotylation of pivaldehyde regardless of substrate double bond geometry. Using butanone as substrate, the anti product is found as main product in both cases. By computational investigation employing the B3LYP/6-31+G(d) level of theory in dichloromethane solution (PCM/UAKS), we found that the attack of O-methyl-substituted carboxenium ions by crotyl silane explains the experimentally observed selectivities, indicating that these crotylations in fact proceed in an S(N)1-type reaction via this ionic intermediate. Comparison of relevant open transition-state structures leads to a rationalization of the observed selectivities. For all systems studied, three transition-state conformations are necessary and sufficient to determine the selectivity. This has been confirmed by studying the MCC reactions of isobutyraldehyde. Activation energies for the stereogenic step have been determined by calculation of the transition state and substrate structures in dichloromethane solution at the B3LYP/6-311+G(2d,p)//B3LYP/6-31+G(d) level of theory in dichloromethane solution. The possibility to predict simple diastereoselectivity in general Lewis acid-mediated crotylations of aldehydes and ketones is discussed.     

Intramolecular hydroamination of unactived olefins with Ti(NMe2)4 as a precatalyst

Commercially available Ti(NMe(2))(4) has been used effectively as a precatalyst in a facile protocol for the intramolecular hydroamination of aminoalkenes to yield pyrrolidine and piperidine heterocyclic products with isolated yields up to 92%. Geminally substituted substrates display the highest reactivity. This precatalyst is also effective for the hydroamination of activated internal alkenes, providing access to more complex heterocyclic target molecules.     

The carbonyl group as homoconjugated electron donating substituent. Ab initio sto 3G mo calculations.

ab initio STO 3g calculations on 2,3-episulfonionorbornanes and 2-norbornyl cations substituted at C(5) or C(6) suggest that homoconjugated carbonyl group and related (-M, -I) functions can be remote electron-donors.     

Hydrogenation versus transfer hydrogenation of ketones: two established ruthenium systems catalyze both

The established standard ketone hydrogenation (abbreviated HY herein) precatalyst [Ru(Cl)(2)((S)-tolbinap)[(S,S)-dpen]] ((S),(S,S)-1) has turned out also to be a precatalyst for ketone transfer hydrogenation (abbreviated TRHY herein) as tested on the substrate acetophenone (3) in iPrOH under standard conditions (45 degrees C, 45 bar H(2) or Ar at atmospheric pressure). HY works at a substrate catalyst ratio (s:c) of up to 10(6) and TRHY at s:c<10(4). Both produce (R)-1-phenylethan-1-ol ((R)-4), but the ee in HY are much higher (78-83 %) than in TRHY (4-62 %). In both modes, iPrOK is needed to generate the active catalysts, and the more there is (1-4500 equiv), the faster the catalytic reactions. The ee is about constant in HY and diminishes in TRHY as more iPrOK is added. The ketone TRHY precatalyst [Ru(Cl)(2)((S,S)-cyP(2)(NH)(2))] ((S,S)-2), established at s:c=200, has also turned out to be a ketone HY precatalyst at up to s:c=10(6), again as tested on 3 in iPrOH under standard conditions. The enantioselectivity is opposite in the two modes and only high in TRHY: with (S,S)-2, one obtains (R)-4 in up to 98 % ee in TRHY as reported and (S)-4 in 20-25 % ee in HY. iPrOK is again required to generate the active catalysts in both modes, and again, the more there is, the faster the catalytic reactions. The ee in TRHY are only high when 0.5-1 equivalents iPrOK are used and diminish when more is added, while the (low) ee is again about constant in HY as more iPrOK is added (0-4500 equiv). The new [Ru(H)(Cl)((S,S)-cyP(2)(NH)(2))] isomers (S,S)-9 A and (S,S)-9 B (mixture, exact structures unknown) are also precatalysts for the TRHY and HY of 3 under the same conditions, and (R)-4 is again produced in TRHY and (S)-4 in HY, but the lower ee shows that in TRHY (S,S)-9 A/(S,S)-9 B do not lead to the same catalysts as (S,S)-2. In contrast, the ee are in accord with (S,S)-9 A/(S,S)-9 B leading to the same catalysts as (S,S)-2 in HY. The kinetic rate law for the HY of 3 in iPrOH and in benzene using (S,S)-9 A/(S,S)-9 B/iPrOK or (S,S)-9 A/(S,S)-9 B/tBuOK is consistent with a fast, reversible addition of 3 to a five-coordinate amidohydride (S,S)-11 to give an (S,S)-11-substrate complex, in competition with the rate-determining addition of H(2) to (S,S)-11 to give a dihydride [Ru(H)(2)((S,S)-cyP(2)(NH)(2))] (S,S)-10, which in turn reacts rapidly with 3 to generate (S)-4 and (S,S)-11. The established achiral ketone TRHY precatalyst [Ru(Cl)(2)(ethP(2)(NH)(2))] (12) has turned out to be also a powerful precatalyst for the HY of 3 in iPrOH at s:c=10(6) and of some other substrates. Response to the presence of iPrOK is as before, except that 12 already functions well without it at up to s:c=10(6).     

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Pd-PEPPSI type complexes are widely used as precatalyst in a variety of organic reactions, including the Negishi, Kumada and Suzuki-Miyaura cross-coupling reactions. The aim of this research is to determine potential proposed reaction pathways 1, 2, or 2′ (See Schemes 1 and S1–S4 ) for Pd-PEPPSI precatalyst activation in the presence of ethylene glycol as a solvent also in the gas phase at Cam-B3LYP-D3 method nominated among eight DFT methods examined. There is also investigation into the impact of promoter bases (NaOEt, NaOⁱPr, NaO^tBu) on precatalyst activation of Pd-PEPPSI. Eventually, the most favorable proposed reaction pathway and promoter base for reducing Pd(II) to Pd(0) are predicted computationally. Notably, our findings are consistent with the organ Pd-PEPPSI type complexes that offer increased catalytic activity and provide basic information in the presence of solvents designing the monoligated Pd(0)-solvent.     

Catalytic diboration of aldehydes via insertion into the copper-boron bond

Mesitaldehyde reacts cleanly with (IPr)CuB(pin) [IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene); pin = 2,3-dimethyl-2,3-butanediolate] to afford the product complex 1, the first well-defined product of carbonyl group insertion into a metal-boron bond. Analysis of 1 by NMR spectroscopy and single-crystal X-ray diffraction indicates the formation of a copper-carbon and a boron-oxygen bond. A copper(I) precatalyst supported by the less sterically demanding ligand ICy (1,3-dicyclohexylimidazol-2-ylidene) achieves the efficient 1,2-diboration of aryl-, heteroaryl-, and alkyl-substituted aldehydes at room temperature.     

Solid-supported cross metathesis and the role of the homodimerization of the non-immobilized olefin

We have prepared immobilized olefins as models for the cross metathesis using different olefin partners in the presence of second generation Grubbs and Hoveyda-Grubbs precatalysts. We have demonstrated that solid-phase cross metathesis is strongly dependent on the degree of homodimerization of the non-immobilized olefin and the reactivity of such a homodimer. As in the homogeneous phase, the Hoveyda-Grubbs precatalyst was better for immobilized alpha,beta-unsaturated carbonyl compounds.     

Enantioselective pinacol coupling of aryl aldehydes catalyzed by chiral Salan-Mo(IV) complexes

Reported herein is the asymmetric pinacol coupling of aromatic aldehydes with chiral Salan-Mo(VI) dioxo complex as an effective precatalyst. Chiral diols were obtained with high diastereoselectivity and enantioselectivity up to 92/8 and 95%, respectively. The possible mechanism of the pinacol coupling reaction with the catalytic system was investigated. The X-ray crystal structure of the precatalyst Mo(L3)O2 was determined and the oxidation state of the intermediate C was confirmed as +4 with X-ray photoelectron spectroscopy study. The proposed mechanism speculated the stereochemical outcome of the reaction, and a working model for the radical coupling of E was proposed, which explained the absolute configuration of the favored (S,S)-enantiomer of the dl isomer.     

Chiral sulfoxides as neutral coordinate-organocatalysts in asymmetric allylation of N-acylhydrazones using allyltrichlorosilanes

Sulfoxides were first introduced to the allylation of N-acylhydrazones with allyltrichlorosilanes as effective neutral coordinate-organocatalysts (NCOs). Both high diastereo- and enantioselectivity were attained when optically active chiral sulfoxides were used. Asymmetric crotylations using (Z)- and (E)-crotyltrichlorosilanes showed a high level of stereospecificity (Z --> anti and E --> syn) with high enantioselectivity.     

Catalytic conjugate additions of carbonyl anions under neutral aqueous conditions

The conjugate addition of carbonyl anions catalyzed by thiazolium salts that is fully operative under neutral aqueous conditions has been accomplished. The combination of alpha-keto carboxylates and thiazolium-derived zwitterions produces reactive carbonyl anions in a buffered protic environment that readily undergo conjugate additions to substituted alpha,beta-unsaturated 2-acyl imidazoles. The scope of the reaction has been examined and found to accommodate various alpha-keto carboxylates and beta-aryl substituted unsaturated 2-acyl imidazoles. The optimal precatalyst for this process is the commercially available thiazolium salt 5, a simple analogue of thiamin diphosphate. In this process, no benzoin products from carbonyl anion dimerization are observed. The corresponding 1,4-dicarbonyl compounds can be efficiently converted into esters and amides by way of activation of the N-methylimidazole ring via alkylation.     

The mechanism of efficient asymmetric transfer hydrogenation of acetophenone using an iron(II) complex containing an (S,S)-Ph2PCH2CH═NCHPhCHPhN═CHCH2PPh2 ligand: partial ligand reduction is the key

On the basis of a kinetic study and other evidence, we propose a mechanism of activation and operation of a highly active system generated from the precatalyst trans-[Fe(CO)(Br)(Ph(2)PCH(2)CH═N-((S,S)-C(Ph)H-C(Ph)H)-N═CHCH(2)PPh(2))][BPh(4)] (2) for the asymmetric transfer hydrogenation of acetophenone in basic isopropanol. An induction period for catalyst activation is observed before the catalytic production of 1-phenethanol. The activation step is proposed to involve a rapid reaction of 2 with excess base to give an ene-amido complex [Fe(CO)(Ph(2)PCH(2)CH═N-((S,S)-C(Ph)H-C(Ph)H)-NCH═CHPPh(2))](+) (Fe(p)) and a bis(enamido) complex Fe(CO)(Ph(2)PCH═CH-N-(S,S-CH(Ph)CH(Ph))-N-CH═CHPPh(2)) (5); 5 was partially characterized. The slow step in the catalyst activation is thought to be the reaction of Fe(p) with isopropoxide to give the catalytically active amido-(ene-amido) complex Fe(a) with a half-reduced, deprotonated PNNP ligand. This can be trapped by reaction with HCl in ether to give, after isolation with NaBPh(4), [Fe(CO)(Cl)(Ph(2)PCH(2)CH(2)N(H)-((S,S)-CH(Ph)CH(Ph))-N═CHCH(2)PPh(2))][BPh(4)] (7) which was characterized using multinuclear NMR and high-resolution mass spectrometry. When compound 7 is treated with base, it directly enters the catalytic cycle with no induction period. A precatalyst with the fully reduced P-NH-NH-P ligand was prepared and characterized by single crystal X-ray diffraction. It was found to be much less active than 2 or 7. Reaction profiles obtained by varying the initial concentrations of acetophenone, precatalyst, base, and acetone and by varying the temperature were fit to the kinetic model corresponding to the proposed mechanism by numerical simulation to obtain a unique set of rate constants and thermodynamic parameters.     

Synthesis of (3S,5R)-cis- and (3S,5S)-trans-3,5-Dimethylvalerolactones and Their Conversion to Biotransformation Products of (S)-5-Ethyl-5-(2′-pentyl)barbituric Acid

(R,S)-5-Ethyl-5-(2′-pentyl)barbituric acid (I)^1,2 is metabolized in vivo to give all four possible optical isomers of 5-ethyl-5-(3′-hydroxy-1′-methylbutyl)barbituric acid (II). ^3,4 From metabolism studies of pure (1′S)- I and (1′3)-I, Palmer and co-workers^4,5 were able to determine the relative amounts of each of the four isomers formed. These studies showed that (1′S)-I gave mainly one enantiomer of (1′S)-II, whereas (1′R)-I gave approximately equal amounts of both (1′R)-II enantiomers.     

Suzuki–Miyaura coupling reactions of aryl chlorides catalyzed by a new nickel(II) σ‐aryl complex

A new nickel(II) σ‐aryl complex, trans‐chloro(9‐phenanthrenyl)bis(triphenylphosphine)nickel(II), was used as a precatalyst for the Suzuki–Miyaura coupling reactions of aryl chlorides. The catalytic conditions were optimized by investigating the cross‐coupling of p‐chloroanisole with phenylboronic acid. The results show that this complex is efficient for both electron‐rich and electron‐deficient aryl chlorides, though it gives better yields for activated arylboronic acids than deactivated ones. All isolated cross‐coupled biaryl products have been characterized by ¹H and ¹³C NMR, and their spectral data are consistent with those reported. Side products from the coupling of arylboronic acid with the precatalyst complex have also been isolated and characterized, which is helpful for understanding the coupling mechanism. Copyright © 2013 John Wiley & Sons, Ltd.     

Efficient N-arylation catalyzed by a copper(I) pyrazolyl-nicotinic acid system

Catalyst 6-(1H-pyrazol-1-yl)nicotinic acid L-CuCl behaves as a very active promoter of the N-arylation reactions, as it has been demonstrated with varieties of substrates under mild reaction conditions. A Cu(I) complex based on L of precatalyst has been isolated by a hydrothermal method and structurally characterized.     

Statistical and theoretical investigations on the directionality of nonbonded S...O interactions. Implications for molecular design and protein engineering

Weak nonbonded interactions between a divalent sulfur (S) atom and a main-chain carbonyl oxygen (O) atom have recently been characterized in proteins. However, they have shown distinctly different directional propensities around the O atom from the S...O interactions in small organic compounds, although the linearity of the C-S...O or S-S...O atomic alignment was commonly observed. To elucidate the observed discrepancy, a comprehensive search for nonbonded S.O interactions in the Cambridge Structural Database (CSD) and MP2 calculations on the model complexes between dimethyl disulfide (CH(3)SSCH(3)) and various carbonyl compounds were performed. It was found that the O atom showed a strong intrinsic tendency to approach the S atom from the backside of the S-C or S-S bond (in the sigma(S) direction). On the other hand, the S atom had both possibilities of approach to the carbonyl O atom within the same plane (in the n(O) direction) and out of the plane (in the pi(O) direction). In the case of S...O(amide) interactions, the pi(O) direction was significantly preferred as observed in proteins. Thus, structural features of S...O interactions depend on the type of carbonyl groups involved. The results suggested that S.O interactions may control protein structures to some extent and that the unique directional properties of S...O interactions could be applied to molecular design.     

The unusual role of CO transfer in molybdenum-catalyzed asymmetric alkylations

Spectroscopic and crystallographic studies were undertaken to gain insight into the mechanism of the highly regio- and enantioselective allylic aklylation reaction catalyzed by molybdenum. The chiral ligand (L*) consisting of the mixed benzamide/picolinamide of (S,S,)-trans-1,2-diaminocyclohexane reacts with a typical Mo precatalyst, (norbornadiene)Mo(CO)4, to give a neutral complex L*Mo(CO)4 in which the ligand binds to the metal in a bidentate fashion through the pyridine and adjacent amide group. Reaction of this complex with the methyl carbonate of cinnamyl alcohol gives the corresponding pi-allyl complex L*(CO)2Mo(eta3-CH2=CH-CHPh). NMR and X-ray crystallographic characterization of this complex reveal the ligand binds in a facially capping tridentate fashion via the pyridine nitrogen, the nitrogen of the adjacent amide group, which has now been deprotonated, and the carbonyl oxygen of the remote amide. Surprisingly, the face of the allyl group open to attack with nucleophiles is that which would lead to the sense of stereochemistry opposite to that which is observed in catalytic reactions. Furthermore, the allyl complex in its isolated form is unreactive toward sodium dimethyl malonate. However, in the presence of a source of carbon monoxide (either Mo(CO)6 or gaseous CO), the allyl complex reacts with malonate to give the typically observed branched alkylated product in high yield and enantiomeric excess. The metal-containing product of this reaction is the molybdate complex [L*Mo(CO)4]-Na+. Reaction of the molybdate complex with linear or branched allylic carbonates regenerates the allyl complex, thus closing the catalytic cycle. Both the allyl complex and the molybdate complex are the only metal-containing species observed by NMR in typical catalytic reactions and thus appear to be catalyst resting states. Turnover of the catalytic cycle therefore involves shuttling of carbon monoxide between the two catalyst resting states. Coordination of CO appears to be necessary to activate the allyl complex toward nucleophilic attack, in effect stabilizing the molybdenum fragment as a leaving group.