Enantioselectivity in Ruthenium-Catalyzed Propargylic Substitution Reactions of Propargylic Alcohols with Acetone: A DFT Study

The enantioselectivity in the propargylic substitution reactions of propargylic alcohols with acetone catalyzed by optically active thiolate-bridged diruthenium complexes was examined via ωB97X-D level DFT calculations. Some structures with intramolecular dispersion interactions between ligands were found for the ruthenium-allenylidene complex, which is the key intermediate in the catalytic reaction, and it was determined that the structure corresponding to the X-ray crystal structure, which had provided the transition state model for the enantioselectivity in previous studies, was not the most stable among the obtained structures. Then, a variety of transition-state structures for the nucleophilic attack of prop-1-ene-2-ol, which is the enol isomer of acetone, on the γ-carbon of the ruthenium-allenylidene complex were explored. Among the transition-state structures with lower energies, the number of structures leading to the major (R) product was found to be larger than that of structures leading to the minor (S) product, providing enantioselectivity in terms of probability distributions. The introduction of a phenyl group in the thiolate ligand was suggested to increase the selectivity. Thus, we propose the novel transition state model for the asymmetric catalytic reaction system.     

Cooperative Catalytic Reactions Using Distinct Transition‐Metal Catalysts: Ruthenium‐ and Copper‐Catalyzed Enantioselective Propargylic Alkylation

The enantioselective propargylic alkylation of propargylic alcohols with β‐ketoesters in the presence of a thiolate‐bridged diruthenium complex and a copper complex as co‐catalyst affords the corresponding propargylic alkylated products in excellent yields as a mixture of two diastereoisomers with high enantioselectivity (up to 95 % enantiomeric excess (ee)). The findings reported herein not only open up a new type of enantioselective propargylic substitution reaction, but also a new aspect of cooperative catalytic reactions using distinct transition metals to realize a useful transformation that cannot be achieved by a single catalyst.     

New and Efficient Synthesis of 1,3-Dienylphosphonates by Palladium-Catalyzed Substitution of Propargylic Esters to Diethyl Phosphite

An efficient route to the synthesis of 1,3-dienylphosphonates (1) has been developed for the first time by the substitution of propargylic esters (2) to the diethyl phosphite (3) nucleophile in the presence of Pd₂(dba)₃ · CHCl₃ (2 mol %) and 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (4 mol%). Both the alkyl and aryl 1,3-dienylphosphonates can be prepared from this transformation.

Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file.     

Computational Study of the Mechanism and Selectivity of Palladium‐Catalyzed Propargylic Substitution with Phosphorus Nucleophiles

The mechanism and sources of selectivity in the palladium‐catalyzed propargylic substitution reaction that involves phosphorus nucleophiles, and which yields predominantly allenylphosphonates and related compounds, have been studied computationally by means of density functional theory. Full free‐energy profiles are computed for both H‐phosphonate and H‐phosphonothioate substrates. The calculations show that the special behavior of H‐phosphonates among other heteroatom nucleophiles is indeed reflected in higher energy barriers for the attack on the central carbon atom of the allenyl/propargyl ligand relative to the ligand‐exchange pathway, which leads to the experimentally observed products. It is argued that, to explain the preference of allenyl‐ versus propargyl‐phosphonate/phosphonothioate formation in reactions that involve H‐phosphonates and H‐phosphonothioates, analysis of the complete free‐energy surfaces is necessary, because the product ratio is determined by different transition states in the respective branches of the catalytic cycle. In addition, these transition states change in going from a H‐phosphonate to a H‐phosphonothioate nucleophile.     

Switch in Selectivity for Formal Hydroalkylation of 1,3‐Dienes and Enynes with Simple Hydrazones

Controlling reaction selectivity is a permanent pursuit for chemists. Regioselective catalysis, which exploits and/or overcomes innate steric and electronic bias to deliver diverse regio‐enriched products from the same starting materials, represents a powerful tool for divergent synthesis. Recently, the 1,2‐Markovnikov hydroalkylation of 1,3‐dienes with simple hydrazones was reported to generate branched allylic compounds when a nickel catalyst was used. As part of the effort, shown here is that a complete switch of Markovnikov to anti‐Markovnikov addition is obtained by changing to a ruthenium catalyst, thus providing direct and efficient access to homoallylic products exclusively. Isotopic substitution experiments indicate that no reversible hydro‐metallation across the metal‐π‐allyl system occurred under ruthenium catalysis. Moreover, this protocol is applicable to the regiospecific hydroalkylation of the distal C=C bond of 1,3‐enynes.     

Ligand Substitution Reactions on Aquapentachloro‐ and Hexachloroplatinic Acid — Synthesis and Characterization of Tetrachloroplatinum(IV) Complexes with Heterocyclic N,N Donors

Reactions of aquapentachloroplatinic acid, (H₃O)[PtCl₅(H₂O)]·2(18C6)·6H₂O ( 1 ) (18C6 = 18‐crown‐6), and H₂[PtCl₆]·6H₂O ( 2 ) with heterocyclic N, N donors (2, 2′‐bipyridine, bpy; 4, 4′‐di‐tert‐butyl‐2, 2′‐bipyridine, tBu₂bpy; 1, 10‐phenanthroline, phen; 4, 7‐diphenyl‐1, 10‐phenanthroline, Ph₂phen; 2, 2′‐bipyrimidine, bpym) afforded with ligand substitution platinum(IV) complexes [PtCl₄(N∩N)] (N∩N = bpy, 3a ; tBu₂bpy, 3b ; Ph₂phen, 5 ; bpym, 7 ) and/or with protonation of N, N donor yielding (R₂phenH)₂[PtCl₆] (R = H, 4a ; Ph, 4b ) and (bpymH)⁺ ( 8 ). With UV irradiation Ph₂phen and bpym reacted with reduction yielding platinum(II) complexes [PtCl₂(N∩N)] (N∩N = Ph₂phen, 6 ; bpym, 9 ). Identities of all complexes were established by microanalysis as well as by NMR (¹H, ¹³C, ¹⁹⁵Pt) and IR spectroscopic investigations. Molecular structures of [PtCl₄(bpym)]·MeOH ( 7 ) and [PtCl₂(Ph₂phen)] ( 6 ) were determined by X‐ray diffraction analyses. Differences in reactivity of bpy/bpym and phen ligands are discussed in terms of calculated structures of complexes [PtCl₅(N∩N)]^— with monodentately bound N, N ligands (N∩N = bpy, 10a ; phen, 10b ; bpym, 10c ).     

Synthesis of Branched Hydrazones by Reaction of N-(2,3-Epoxypropyl) Derivatives of Hydrazones with Benzenediols

A series of branched hydrazones have been prepared by reaction of N-(2,3-epoxypropyl) derivatives of 9-ethyl-3-carbazolecarbaldehyde and 4-diethylamino-benzcarbaldehyde phenylhydrazones with 1,2-, 1,3-, and 1,4-benzenediols. It was found that the reaction rate depends on the polarity of solvents.     

Copper-Catalyzed Ring-Opening Reactions of Alkyl Aziridines with B2pin2: Experimental and Computational Studies

The possibility to form new C–B bonds with aziridines using diboron derivatives continues to be a particularly challenging field in view of the direct preparation of functionalized β-aminoboronates, which are important compounds in drug discovery, being a bioisostere of β-aminoacids. We now report experimental and computational data that allows the individuation of the structural requisites and of reaction conditions necessary to open alkyl aziridines using bis(pinacolate)diboron (B₂pin₂) in a regioselective nucleophilic addition reaction under copper catalysis.     

Radical Silyl- and Germylzincation of Propargylic Alcohols

The silyl- and germylzincation of terminal or internal propargylic alcohols by reaction with (Me₃Si)₃SiH/Et₂Zn, [(Me₃Si)₃Si]₂Zn/Et₂Zn or Ph₃GeH/Et₂Zn is examined. These reactions proceed through the addition of silicon- or germanium-centered radicals across the carbon≡carbon triple bond followed by the trapping by diethylzinc of the produced vinyl radical through homolytic substitution at the zinc atom. The influence of the hydroxy unit on the regio- and stereoselectivity of these reactions is discussed and compared to its role played in radical hydrosilylation and hydrogermylation reactions. Protocols developed to achieve the β-regioselective silylzincation of propargyl alcohol and the α-regioselective germylzincation of internal propargylic alcohols are particularly important, as they occur with trans stereoselectivity. For both procedures the C(sp²)−Zn bond remains available for subsequent in-situ electrophilic substitution leading overall to net alkyne trans difunctionalization.     

Structural and Spectroscopic Properties of Benzoylpyridine-Based Hydrazones

Photochromic hydrazones are attracting the attention in the field of photochromic systems especially due to their P-type character. To understand the structural features and their correlation with the spectroscopic data, UV-Vis, vibrational and ellipsometry spectroscopic techniques are employed with the support of density functional theory (DFT) calculations to three hydrazone derivatives based on benzoylpyridine. Interestingly, analysis of the structure shows the presence of two distinct rotamers around the pyridine ring with different energy and the well-defined conjugation path that changes due to E to Z isomerization especially in the hydrazone −C=N−NH part of the skeleton. IR and Raman spectra are analyzed, showing a higher selectivity in the Z form; moreover, the comparison with the normal modes proves the effect of the reaction on the backbone structure. The experimental results are in good agreement with the theoretical predictions, especially in the case of the Raman spectrum. The molecular polarization also changes from E to Z forms as predicted by DFT calculations. Spectroscopic ellipsometry on thin films of TOPAS doped with 10 %wt of the dimethylamino hydrazone derivative is used to prove such change at the molecular level. A modulation of the refractive index is observed, and it is correlated with the concentration of the active moiety and the calculated electronic polarizabilities.