Adducts 3a Research Articles

Osmium(0)-Catalyzed C-C Coupling of Ethylene and α-Olefins with Diols, Ketols, or Hydroxy Esters via Transfer Hydrogenation.

Osmium(0) complexes derived from Os3(CO)12 and XPhos (2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl) catalyze the C-C coupling of α-hydroxy esters 1a-1i, α-ketols 1j-1o, or 1,2-diols dihydro-1j-1o with ethylene 2a to form ethylated tertiary alcohols 3a-3o. As illustrated in couplings of 1-octene 2b with vicinally dioxygenated reactants 1a, 1b, 1i, 1j, 1k, 1m, higher α-olefins are converted to adducts 4a, 4b, 4i, 4j, 4k, 4m with complete levels of branched regioselectivity. Oxidation level independent C-C coupling is demonstrated by the reaction of 1-octene 2b with diol dihydro-1k, α-ketol 1k, and dione dehydro-1k. Functionalized olefins 2c-2f react with ethyl mandelate 1a to furnish adducts 5a-8a as single regioisomers. The collective data, including deuterium labeling studies, are consistent with a catalytic mechanism involving olefin-dione oxidative coupling to form an oxa-osmacyclopentane, which upon reductive cleavage via hydrogen transfer from the secondary alcohol reactant releases the product of carbinol C-alkylation with regeneration of the ketone. Single-crystal X-ray diffraction data of the dinuclear complex Os2(CO)4(O2CR)2(XPhos)2 and the trinuclear complex Os3(CO)11(XPhos) are reported. These studies suggest increased π-backbonding at the stage of the metal-olefin π-complex plays a critical role in facilitating alkene-carbonyl oxidative coupling, as isostructural ruthenium(0) complexes, which are weaker π-donors, do not catalyze the transformations reported herein.

Organocatalytic Enantioselective Synthesis of Tetrahydrofluoren-9-ones via Vinylogous Michael Addition/Henry Reaction Cascade of 1,3-Indandione-Derived Pronucleophiles.

An unprecedented organocatalytic enantioselective vinylogous Michael addition/Henry cyclization cascade is presented for the synthesis of highly substituted tetrahydrofluoren-9-ones 3 employing novel 1,3-indandione-derived pronucleophiles 1a-g and nitroalkenes 2. Following a very simple protocol, a wide range of products were obtained in good to excellent yields and with excellent enantioinduction (43-98% yield, up to 98% ee). The reaction proceeded with excellent diastereocontrol despite the simultaneous generation of four stereogenic centers. Surprisingly, when 2-(1-phenylethylidene)-1H-indandione (1h) was used as a pronucleophile, no cyclization was observed, and only Michael addition adducts 4a-x were furnished in very good yields and excellent enantioselectivities.

Formation of BH3 Adducts with Pyridine-2-Methylaminophosphine ligands: An experimental and computational study

The reaction of pyridine-2-methylaminophosphine [C5H4N-CH2NHPPh2] (1) and pyridine-2-methylphosphinoselenoic amide [C5H4N-CH2NHP(Se)Ph2] (2) with BH3⋅SMe2 yields the corresponding adducts [C5H4N(BH3)-CH2NHP(BH3)Ph2] (1a), and [C5H4N(BH3)-CH2NHP(Se)Ph2] (2a), respectively. The solid state structures of both the compounds were established by single crystal X-ray diffraction analysis. The phosphorus and the pyridine nitrogen atoms are coordinated to the boron atom in the case of 1a whereas only pyridine nitrogen atom is attached to the BH3 group in the case of 2a. To understand the nature of P-B/ N-B bonds and to compare the basicities of pyridine nitrogen, amino nitrogen and phosphorus atoms, density functional theoretical (DFT) calculations were performed on the BH3 adducts 1a and 2a. The results are consistent with the experimental results. Experimental and computational studies have been carried out to demonstrate the Pcoordination and N-coordination of various pyridine-2-methylaminophosphine ligands towards the BH3 group.

Self-assembly in solvates of 2,4-diamino-6-(4-methyl- phenyl)-1,3,5-triazine and in its molecular adducts with some aliphatic dicarboxylic acids

Solid state structures of 2,4-diamino-6-(4-methylphenyl)-1,3,5-triazine, 1, in the form of methanol and dimethylsulfoxide (DMSO) solvates, as well as supramolecular assemblies of 1 with various aliphatic dicarboxylic acids, oxalic (a), malonic (b), succinic (c), glutaric (d) and adipic (e) have been reported. Analysis of the assemblies has been carried out by single crystal X-ray diffraction and thermal methods. Triazine 1 yields anhydrous molecular adducts with acids a–d, upon co-crystallization either from CH3OH and DMSO solvents. However acid e gives anhydrous adduct from DMSO solvent, while it gives a methanol adduct from CH3OH. Structure determination reveals that molecular adducts 1a, 1d and 1e are in a 2:1 ratio of 1 and the corresponding acid. However the ratio is 1:1, in 1b, perhaps due to the involvement of one of the acid groups in the intramolecular hydrogen bonding and in adduct 1c the ratio observed is 3:2. Structural features in all these assemblies have been rationalised in terms of various recognition patterns formed between the acceptor and donor groups. A noteworthy feature is that –COOH groups in acid a establish interaction with 1 through amino groups, while such interactions are observed to be through hetero -N atoms in case of the acids b–e.

Carbocation Lewis Acid Catalyzed Redox-Neutral α-C(sp3)H Arylation of Amines

The α-substituted nitrogen-containing heterocycles (N-heterocycles) like tetrahydroisoquinolines (THIQs) and piperidines are common in nature and are present as the key functional group in bioactive and pharmacologically active compounds. The two traditional approaches for the synthesis of α-substituted N-heterocycles are Pictet-Spengler condensa- tion and hydrogenation of the α-substituted cyclic imines. Recently, direct C(sp 3 )-H functionalization of N-heterocycles with various nucleophiles catalyzed by transition metal complex under the oxidants presents an atom-economic protocol without prior installation of activating group. However, new catalytic strategy or catalysts are still desirable in order to further address the use of excess oxidants and expensive transition metal complex. Stable carbocations, such as tritylium ions, have been widely used as organic Lewis acid catalysts and reagents in organic synthesis. In our studies, it was found that tritylium salts (Ph3C)(BArF) (10 mol%) in situ generated by Ph3CBr (0.02 mmol) and NaBArF (0.02 mmol) could promote the three com- ponent redox-neutral α-arylation of amines reaction with tetrahydroisoquinoline 2 (0.3 mmol), aldehyde 3 (0.2 mmol) and indole 4 (0.3 mmol) in toluene (1.0 mL) to afford the desired α-substituted N-heterocyclic compounds 5 in good yields (up to 99% yield) at ambient temperature to 50 ℃. To our satisfaction, a variety of differently substituted indoles 4a~4i could work well with tetrahydroisoquinoline 2 and 2,6-dichlorobenzaldehyde 3a to provide the corresponding α-substituted N-heterocyclic compounds 5a~5i in good to excellent yields at room temperature. When other substituted benzaldehydes 3b~3f were used, the reactions could also proceed smoothly to give the compounds 5j~5o with moderate yield (up to 66% yield) at 50 ℃. Moreover, we have also developed redox-neutral α-arylation of tetrahydroisoquinoline 2 with other aromatic nucleophile such as substituted phenol, β-naphthol and pyrrole under the optimal reaction conditions. Importantly, the model reaction, conducted in the presence of Na2CO3(1.0 equiv.) or 2,6-bis(tert-butyl) pyridine (0.5 equiv.) at room temperature in toluene also proceeded smoothly to give the desired adduct 5a with comparable yields (82% and 92% yield, respectively), which could exclude the possibility of free acid catalysis in this reaction.

Reactions of m-chloroperoxybenzoic acid with dimeric cyclopalladated complexes derived from 2-phenyl-2-oxazolines

Cyclopalladated complexes (CPCs) (S,S)-di-μ-Cl(κ2-C,N)2Pd2 (1a,b) and (S,S)-di-μ-OAc(κ2-C,N)2Pd2 (7a,b) obtained from (S)-4-t-butyl-(a) and (S)-4-ethyl-2-phenyl-2-oxazoline (b) were reacted with m-chloroperoxybenzoic acid (m-CPBA) at room temperature in methylene chloride, ethyl acetate or acetonitrile followed by workup with lithium chloride. Oxidation products formed in these reactions include dinuclear complexes (S,S)-di-μ-Cl(κ2-N,O)2Pd2 (2a), (S,S)-di-μ-oxo(κ2-N,O)2Pd2Cl2 (2b), and (S,S)-di-μ-(m-Cl-C6H4CO2)(κ2-N,O)2Pd2 (3a,b), mononuclear derivatives (S,S)-bis(κ2-N,O)Pd (4a,b) and dinuclear monooxidation complexes (S,S)-di-μ-Cl(κ2-N,O)(κ2-C,N)Pd2 (5a,b). Each complex was isolated in low yield (6–46 %) with the combined yield of oxidation products reaching up to 64 %. The best selectivity in product distribution was observed for the reactions of μ-OAc–CPCs 7a,b with 2.7 equiv. of m-CPBA in acetonitrile, in which oxygen-insertion adducts 2a and 4b were isolated in 44 and 46 % yields, respectively. The structures of all complexes were supported by spectroscopic methods. An X-ray crystallographic study of compound 4a was performed, confirming its mononuclear structure and revealing an unusual bent geometry.

Molecular structure investigation and biological evaluation of Michael adducts derived from dimedone

Trimolecular salt Michael adducts 2a–c were synthesized in excellent yields up to 92 % via one-pot multicomponent reactions in an aqueous medium. The chemical structures of compounds 2a–c were characterized by X-ray single-crystal diffraction techniques. Calculations of the density functional theory for the synthesized compound were performed. The stability of the products was deduced by TGA analysis. Compounds 2a–c were screened in vitro for different bio-assays such as thymidine phosphorylase inhibition assay, urease inhibition assay, β-glucuronidase inhibition assays and cytotoxicity against PC-3 and HeLa cell lines.

Vinyl ruthenium-modified biphenyl and 2,2'-bipyridines.

We report here on ruthenium alkenyl complexes 2 and 3 derived from 2,2'-bipyridine and their Re(CO)3X adducts 4a,b and 5. Detailed electrochemical studies on these complexes and spectroscopic characterization of their oxidized forms by IR, UV/vis/NIR, and electron paramagnetic resonance spectroscopies as well as quantum chemical studies reveal sizable (bridging) ligand contributions to the redox orbitals. Engagement of the free bipy functions of complexes 2 and 3 in binding to the electron-withdrawing fac-Re(CO)3X (X = Br, Cl) moiety enhances the metal-to-ligand charge-transfer character of the optical excitations, causes sizable anodic shifts of the redox potentials, and decreases the number of observable anodic redox waves by one when compared to complexes 2 and 3. Despite the decreasing electron density at the terminal or bridging alkenyl bipyridine ligand, the anodic redox processes still maintain appreciable ligand character as is seen by the shifts of the Ru(CO) and Re(CO)3 stretching frequencies on oxidation. Binding of the fac-Re(CO)3X moiety also attenuates the degree of ground-state delocalization in the mixed-valent states.

New, Homochiral Synthons Obtained through Simple Manipulations of Enzymatically Derived 3-Halo-cis-1,2-dihydrocatechols

The bromoepoxide 5a, which is obtained from the homochiral and enzymatically derived cis-1,2-dihydrocatechol 1a, is readily and efficiently transformed into either isomer 8a or the corresponding methoxymethyl-ether 2a. Though both of these products can be fully characterized, they are somewhat unstable, with the former being converted into the crystalline enone 3a on standing and the latter readily participating in a Diels–Alder cycloaddition reaction with the potent dienophile N-phenyl-1,2,4-triazoline-3,5-dione to give adduct 7a. The single-crystal X-ray structures of compounds 3a and 7a are reported. Using the related chemistry the chloro-analogue, 3b, of enone 3a can be obtained.

Features of the Diels-Alder reaction between 9,10-diphenylanthracene and 4-phenyl-1,2,4-triazoline-3,5-dione

The Diels-Alder reaction between substituted anthracenes 1a−1j and 4-phenyl-1,2,4-triazoline-3,5 (2) is studied. In all cases except one, the reaction proceeds on the most active 9,10-atoms of substituted anthracenes. The orthogonality of the two phenyl groups at the 9,10-position of diene 1a is found to shield 9,10-reactive centers. No dienophiles with C=C bonds are shown to participate in the Diels-Alder reaction with 1a; however, the reaction 1a + 2 proceeds with the very active dienophile 2,4-phenyl-1,2,4-triazoline-3,5-dione. It is shown that attachment occurs on the less active but sterically accessible 1,4-reactive center of diene 1a. The structure of adduct 3a is proved by 1H and 13C NMR spectroscopy and X-ray diffraction analysis. The following parameters are obtained for reaction 1a + 2 ⇆ 3a in toluene at 25°C: K eq = 2120 M−1, ΔH f ≠ = 58.6 kJ/mol, ΔS f ≠ = −97 J/(mol K), ΔV f ≠ = −17.2 cm3/mol, ΔH b ≠ = 108.8 kJ/mol, ΔS b ≠ = 7.3 J/(mol K), ΔV b ≠ = −0.8 cm3/mol, ΔH r-n = −50.2 kJ/mol, ΔS r-n = −104.3 J/(mol K), ΔV r-n = −15.6 cm3/mol. It is concluded that the values of equilibrium constants of the reactions 1a−1j + 2 ⇆ 3a−3j vary within 4 × 101−1011 M−1.

Synthesis, structure, and reactivity of C-isopropyl-ortho-carborane organoboron derivatives

A reaction of isopropyl-ortho-carborane with n-butyllithium, followed by treatment of the lithium derivative formed with boron trichloride, chlorodimethoxyborane, or chloropinacolatoborane furnished C-boryl-ortho-carboranes 1a-c. Further functionalization of 1-Cl2B-2-Pri-1,2-C2B10H10 (1a) with pentafluorophenylmagnesium bromide or pentafluorophenol led to 1-(C6F5)2B-2-Pri-1,2-C2B10H10 (2) and (1-(C6F5O)B-2-Pri-1,2-C2B10H10)2O (3), respectively. A reaction of 1-(MeO)2B-2-Pri-1,2-C2B10H10 (1b) with the complexes of BH3 with THF and dimethyl sulfide gave rise to carboranylborane adducts 4a,b. The use of the complex of 1-H2B-2-Pri-1,2-C2B10H10 with dimethyl sulfide 4b as a hydroboration agent in the reactions with hex-1-ene and phenylacetylene allowed us to obtain dialkyl- and di(phenylolefin)-containing C-isopropyl-ortho-carboranylboranes, respectively. The reaction of C-isopropyl-ortho-carboranyldimethoxyborane with triallylborane led to the substitution of only one of two MeO groups with the allyl one, which is explained by the steric effects of bulky carboranyl substituent in the precursor. Compounds obtained are characterized by X-ray diffraction analysis.

Asymmetric Evans syn‐Aldol Reactions of Terpene‐Derived Enals: Scope and Limitations

AbstractThe (E)‐ and (Z)‐terpene‐based aldehydes 6b and 6c with a silyl ether function in the γ‐position were prepared and investigated in boron‐mediated asymmetric Evans aldol reactions. Screening experiments of chiral N‐acylated oxazolidinones 7, which are conveniently accessible from 5‐methyl‐5‐hexenoic acid and Evans oxazolidinone auxiliaries, with various boron triflates and terpenoid neral (Z)‐6a as aldehyde component, provided conditions in which highly selective formation of syn‐aldol adduct 5a occurred and competing C=C double bond isomerization to 10 was completely suppressed. Applying the optimized conditions to O‐silylated aldehydes 6b and 6c and N‐acyloxazolidinone derivative (R)‐7a confirmed the syn‐selectivity and gave the appropriate products syn‐5b,c and syn‐21b,c in good yields. In the case of neral‐derived syn adduct 5a, the configuration of the new stereogenic centers C‐2/C‐3 could be assigned as (2R,3S).

Primary-tertiary diamine-catalyzed Michael addition of ketones to isatylidenemalononitrile derivatives.

Simple primary-tertiary diamines easily derived from natural primary amino acids were used to catalyze the Michael addition of ketones with isatylidenemalononitrile derivatives. Diamine 1a in combination with D-CSA as an additive provided Michael adducts in high yield (up to 94%) and excellent enantioselectivity (up to 99%). The catalyst 1a was successfully used to catalyze the three-component version of the reaction by a domino Knoevenagel–Michael sequence. The Michael adduct 4a was transformed into spirooxindole 6 by a reduction with sodium borohydride in a highly enantioselective manner.

Straightforward and Facile Synthesis of a Bioactive Component from Zingiber cassumunar Roxb.

Straightforward and facile synthesis of a bioactive component A from Zingiber cassumunarRoxb. is described. The phenylbutenoid dimer A was reported to possess anti-inflammatory and cytotoxic activities. The optically active cyclohexene ring fragment was obtained via the highly diastereo- and enantioselective Diels–Alder reaction of chiral acryloyloxazolidinones (1a and 1b) and 1-(4-hydroxy-3-methoxyphenyl)butadiene (2). The enantiomeric excess of Diels–Alder adducts 3a and 3bwere determined via high-performance liquid chromatotography of the corresponding bis-acetate (6). The greatest enantiomeric excess (99.9% ee) was obtained when the 4-phenyloxazolidin-2-one (1a) chiral auxiliary was used in combination with TiCl4. The optically pure bioactive compound A was prepared from the optically active Diels–Alder adduct (3a) in two additional steps.

S-[3-Cyano-2-oxo-3-(triphenyl-λ5-phosphanylidene)propyl] O-ethyl Carbonodithioate: A Novel Xanthate Reagent for the Synthesis of α-keto (cyanomethylene)triphenylphosphorane Ylides from Olefins

Since the first report of phosphorane ylide-based synthetic route for α-keto amide/ester units by Wasserman’s group in 1994, it has widely been used in the synthesis of numerous complex compounds including peptides due to its mild reaction conditions and outstanding convergence. This route, however, has the limitation that α-keto (cyanomethylene)triphenylphosphorane ylides 2, the key intermediates in Wasserman’s route, can be prepared only from carboxylic acids or acid chlorides (Scheme 1). In a series of papers recently published by us, we have developed new synthetic approaches to α-keto cyanophosphorane ylides from readily available chemicals using specially designed new reagents to overcome such limitation. For example, α-keto cyanophosphorane ylides have been prepared from carbonyl compounds using a new Horner-Wadsworth-Emmons (HWE) reagent, from alkyl bromides using a new phenylsulfinyl reagent through alkylation-sulfoxide elimination sequence, and from alkyl halides using a new phenylsulfonyl reagent via sequential alkylation-reductive desulfonylation protocol. In continuation of our interest in this field of chemistry, we envision that a novel xanthate reagent 4 having α-oxo cyanophosphorane subunit could undergo group transfer addition to olefins 5 under radical conditions and subsequent reduction of 6 would afford a-keto cyanophosphorane ylides 2' in a concise manner (Scheme 2). The realization of the new synthetic approach requires the successful synthesis of requisite xanthate 4, which has been prepared from the intermediate 8 and potassium O-ethyl xanthate in acetone in 95% yield as a stable solid (Scheme 3). By using 4 as the key reagent, radical addition of 4 to various olefins were undertaken and the representative results are summarized in Table 1. To obtain the information regarding the optimized reaction conditions, xanthate 4 and 1-octene 5a were attempted first by using catalytic amount of dilauroyl peroxide (DLP) in 1,2-dichloroethane (DCE) under reflux conditions. When DLP (0.1 eq) was added every hour to the mixture of 4 and 5a (2.0 eq) in DCE for 3 h, 4 was completely consumed affording xanthate adduct 6a along with reduced adduct 2'a in 72% and 4%, respectively (run 1). The structure of 6a was unambiguously corroborated by H-NMR in which the proton peak at the chiral center appears at 3.97 ppm (m) and methylene and methyl peaks of xanthate subunit appear at

Synthesis and Reactivity of the CO2 Adducts of Amine/Bis(2,4,6-tris(trifluoromethyl)phenyl)borane Pairs

Frustrated Lewis pairs (FLPs) comprised of bis(2,4,6-tris(trifluoromethyl)phenyl)borane (1) and a secondary amine (such as HNiPr2 or HNEt2) readily react with CO2 at room temperature to afford ammonium carbamatoborate salts 2. When the reaction was carried out at 80 °C, carbamate boryl esters 3 were obtained with release of 1 equiv of H2. The iPr-substituted carbamate boryl ester 3a can function as an intramolecular FLP to activate H2, affording ammonium borylformate salt 4a and formamide adduct 5a. Two reaction pathways leading to the formation of 4a and 5a are proposed.

The Utility of Carbon Disulphide and Lawesson's Reagent for Synthesis of Different Fused Heterocycles for Antimicrobial Evaluation

Hexahydroquinolines 1a, 1b reacted with carbon disulphide in different conditions to yield the corresponding adducts 2a, 2b and 3a, 3b. Carrying out the same reactions in acetone as solvent produced the modified new products 4a, 4b. The interaction of pyrazolopyridine derivatives 5a, 5b, 5c, 5d with carbon disulphide under the same previous conditions furnished the isolated products 6a, 6b, 6c, 6d, 7a, 7b, 7c, 7d, and 8a, 8b, 8c, 8d. Studying the behavior of 1a, 1b or 5a, 5b, 5c, 5d toward Lawesson's reagent (LR) formed the final adducts 11a, 11b or 12a, 12b, 12c, 12d. The structure of synthesized compounds was confirmed with the spectroscopic and microanalytical data. The biological activities of 2a, 4a, 4b, 7a, 7c, 8d, 11a, 11b, 12b, and 12c were tested for antimicrobial evaluation.

Redox Reaction between Main‐Group Elements (Te, Sn, Bi) and N‐Heterocyclic‐Carbene‐Derived Selenium Halides: A Facile Method for the Preparation of Monomeric Halides

AbstractThe synthesis and characterization of substituted benzimidazolin‐2‐selones (4c–4d) and ‐tellone (4i) are reported. Upon reaction with halogens (I2, Br2, and Cl2), these selones and tellone yield dihaloselones/tellone (5c–5i). The reaction of dihaloselones with elemental tellurium/tin/bismuth leads to the formation of selone‐coordinated monomeric tellurium tetrahalides, tellurium dibromide (8), tin tetrahalides, and bismuth triiodide adducts (7a–7g), respectively. The structures of the tellurium tetrahalide (7a, 7d, and 7g), tellurium dibromide (8), tin tetrahalide, and bismuth triiodide adducts have been established by single‐crystal X‐ray analysis. The bismuth triiodide adduct is the first neutral tetrameric structure with selones. The bismuth adduct has been used as a single‐source precursor for the synthesis of bismuth selenide (Bi2Se3) nanoparticles, which were characterized by powder XRD patterns. The TEM images show the hexagonal shape of the nanoparticles.

Simple Route to Adducts of (Amino)(aryl)carbene with Phosphorus Pentafluoride

AbstractThe tetramethyl ester of (hydroxy)(phenyl)methylenebis(phosphonic acid) reacts with morpholinosulfur trifluoride (MOST) to provide, along with the expected product of the substitution of a hydroxy group by fluorine, the adduct of (morpholino)(phenyl)carbene with PF5, compound 3a. Fluorination of dimethyl α‐aroylphosphonates with MOST yields adducts of (amino)(aryl)carbene with PF5 (p‐XC6H4)(Morph)C:→PF5 [3a–f, where Morph is morpholyl, X = H (a), Me (b), OEt (c), F (d), Cl (e), CF3 (f)] as the major reaction products. The reaction mechanism proposed is based on experimental data and DFT calculations. The structure of adduct 3a was determined by X‐ray studies. Hydrolysis of compounds 3e and 3f, bearing substituents Cl and CF3 on the phenyl ring, respectively, yields previously unknown benzoylpentafluorophosphates [p‐XC6H4–C(=O)PF5]–MorphH+.

KHSO4-Assisted Michael Addition–Elimination Reactions of Indole with 3-Dimethylamino-1-phenylprop-2-en-1-ones in Water: An Environmentally Friendly Synthesis of Novel 3-Indolylchalcones

KHSO4-assisted Michael addition–elimination reactions of 2-methylindoles and 1,2-dimethylindoles with 3-dimethylamino-1-phenylprop-2-en-1-ones (2) in water, leading to the formation of 3-(2-methyl-1H-indol-3-yl)-1-arylpropenones (3a–e) and 3-(1,2-dimethy-1H-lindol-3-yl)-1-arylpropenones (3f–j) respectively in good to excellent yields have been reported. However, cyclodehydration of adducts 3a–f to give carbazoles 4 failed to take place under the reaction conditions. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file.