McMurry Coupling Research Articles

Reaction Update: A McMurry Coupling with Silicon

Reaction Update: A McMurry Coupling with Silicon

Unsymmetrical E-Alkenes from the Stereoselective Reductive Coupling of Two Aldehydes.

The unprecedented formation of unsymmetrical alkenes from the intermolecular reductive coupling of two different aldehydes is described. In contrast to the McMurry reaction which affords statistical product mixtures, selectivity in the reported procedure is achieved by a sequential ionic mechanism in which a first aldehyde is reacted with a phosphanylphosphonate to afford a phosphaalkene intermediate which, upon activation by hydroxide, reacts with a second aldehyde to the unsymmetrical E-alkenes. The described reaction is free of transition metals and proceeds under ambient temperature within minutes in good to excellent overall yields. It is a new methodology to use feedstock aldehydes for the direct production of C═C double bond-containing products and may impact how chemists think of multistep synthetic sequences in the future.

A divergent McMurry coupling of the bis-salisaldehyde with methylene linker: The characterization of a key by-product with the possible pathway formation

ABSTRACTThe McMurry coupling of a bis-salisaldehyde 3a with methyl linker as the smallest member of its alkyl series is known to give the remarkably lower yield of the corresponding stilbenophanes. The half part of this molecule, unlike bigger analogues, is a good leaving group which affordsthreo isomer of 4H, 4′H–4,4′-bibenzo[d][1,3]dioxine 4 in high diastereoisomeric ratio (99>). A further study showed that the formation of this key by-product is the reason for formation of other by-products, namely, 5a,10b-dihydrobenzofuro[2,3-b]benzofuran 9 and 2-(2,3-dihydrobenzofuran-2-yl)phenol 10. Two reaction pathways for the formation of by-products have been proposed which are responsible for the unusual activity of dialdehyde 3a.

Unsymmetrical Bipyrrole‐Derived β‐Tetraalkylporphycenes and C–H···Br–C Interaction Induced 2D Arrays of the 2:1 Supramolecular Sandwich Complex of Their cis‐/trans‐Dibromo Isomers

Two novel stable β‐tetraethylporphycenes (TEPos), namely, trans‐TEPo (1T) and its unsymmetrical isomer cis‐TEPo (1C), were synthesized by reductive McMurry coupling of an unsymmetrical bipyrrole dialdehyde and were isolated through recrystallization. Both isomers showed interesting photophysical properties. Their corresponding dibromo derivatives obtained through bromination of a mixture of 1C and 1T, however, could not be separated in pure form. Interestingly, they were found to form an unprecedented 2:1 supramolecular sandwich complex through π–π stacking interactions, and in addition, only strong C–H···Br–C interactions among the oppositely oriented cis isomers led to the formation of 2D arrays in the solid state.

β-Hexaalkylporphycenes: Positional Effect of Alkyl Groups toward Design and Control of Structural and Photophysical Properties in Isomeric Hexaethylporphycenes.

Two novel β-hexaalkylated porphycenes, i.e., 2,3,7,12,13,17- (HOT) and 2,3,6,12,13,16-hexaethylporphycenes (HIT) were introduced for the first time in porphycene chemistry. These were synthesized through McMurry coupling reactions of new isomeric unsymmetrically substituted triethylbipyrrole dialdehydes. The positional effects of alkyl groups could be manifested through significant alteration in structure of porphycene cores and, as a consequence their photophysical properties, not noticed in β-octaethylporphycene. HOT displays significant fluorescence accompanied by reasonable singlet oxygen generation ability.

A Chiron Approach to Diversity-Oriented Synthesis of Aminocyclitols, (-)-Conduramine F-4 and Polyhydroxyaminoazepanes from a Common Precursor.

The total syntheses of aminocyclitols, (-)-conduramine F-4, and polyhydroxyaminoazepanes have been achieved from a common precursor derived from tri-O-benzyl-d-glucal through a 'diversity-oriented' approach. Tri-O-benzyl-d-glucal was converted into a protected 1,6-diol through a sequence of steps that include transformation to a 2-tosylamidoglucose derivative, selective deprotection of primary C-6 benzyloxy group, LiAlH4-mediated one-step reduction of acetate groups, and reductive ring opening of the resulting hemiacetal as the key steps. The 1,6-diol served as a common precursor in our diversity oriented approach toward the target molecules. Mesylation of the diol followed by double nucleophilic substitution reaction with primary amines led to the synthesis of amino-substituted polyhydroxyazepanes. On the other hand, dialdehyde obtained from the oxidation of 1,6-diol was found to be a convenient starting material for the synthesis of aminocyclitols and (-)-conduramine F-4. McMurry coupling of the dialdehyde was successfully employed, for the first time, to construct the carbocyclic framework of aminoyclitols, while bis-Wittig olefination of the dialdehyde followed by Grubb's(II)-catalyzed RCM delivered (-)-conduramine F-4. The stereochemistry of newly created chiral centers in aminocyclitols was established through single crystal X-ray crystallography and detailed NOE studies.

Tetraarylethylenes from Diarylmethanones and Hexachlorodisilane: The "Sila-McMurry" Reaction.

Hexachlorodisilane reacts with diarylmethanones (aryl=C6 H5 , 4-MeC6 H4 , 4-tBuC6 H4 , 4-ClC6 H4 , 4-BrC6 H4 ) to furnish the corresponding tetraarylethylenes in good yields. The reductive conversion requires temperatures of about 160 °C and reaction times of 60-72 h. In the initial step, the Lewis-basic carbonyl groups likely generate low-valent [SiCl2 ] as an analogue of [TiCl2 ] in the classical McMurry reaction. The coupling sequence further proceeds via benzopinacolones, which have been isolated as key intermediates.

Regioselective Synthesis of Substituted Cyclopenta[l]phenanthrenes.

A simple and efficient synthesis of cyclopenta[l]phenanthrenes from substituted acetophenones provides access to polycyclic aromatics with a variety of substitution patterns. The synthesis requires only three steps from a silyl enol ether: a Mukaiyama aldol reaction followed by McMurry coupling and then Mallory photocyclooxidation to give the target phenanthrenes. Photocyclization conditions have been found that give regioselective formation of 2,7-phenanthrenes from bis(meta-substituted) stilbenes.

Synthesis, Structures and Conformational Studies of 1,2‐Dimethyl[2.10]metacyclophan‐1‐enes

AbstractA series of 1,2‐dimethyl[2.10]metacyclophan‐1‐enes (MCP‐1‐enes) containing different substituent groups has been synthesized to illustrate their conformational behavior. 4,22‐dimethoxy‐1,2‐dimethyl[2.10]MCP‐1‐ene 3 was synthesized by a Grignard coupling reaction, Friedel‐Crafts acylation reactions and McMurry coupling reaction from 1,10‐dibromodecane. The formation of 4,22‐dihydroxy‐1,2‐dimethyl[2.10]MCP‐1‐ene 4 was carried out by demethylation of compound 3 with boron tribromide at room temperature. The syn type conformation of 4 was characterized by X‐ray diffraction and was found to form both intramolecular and intermolecular hydrogen bonds between the two hydroxyl groups. From this reaction an interesting compound [10]tetrahydrobenzofuranophane 5 was afforded on prolonging the reaction time. 5,21‐diformyl‐4,22‐dihydroxy‐1,2‐dimethyl[2.10]MCP‐1‐ene 6 has been prepared from 4,22‐dihydroxy‐1,2‐dimethyl[2.10]MCP‐1‐ene 4 by using the Duff method in the presence of hexamethylenetetramine. Structural analysis by 1H NMR spectroscopy and X‐ray diffraction confirmed that both the solution and the crystalline state of compound 6 adopts an anti‐conformation which forms an intramolecular hydrogen bond between the formyl group and the hydroxyl group, which is an interesting finding for long carbon chain MCP compounds.

Synthesis, aggregation-induced emission, and electroluminescence properties of a novel emitter comprising tetraphenylethene and carbazole moieties

In this paper, a new tetraphenylethene-based molecule with two carbazole-containing moieties, 1,2-bis(4-(9H-carbazol-9-yl)phenyl)-1,2-diphenylethylene (BCPD), has been successfully prepared by the McMurry coupling reaction of (4-(9H-carbazol-9-yl)phenyl)(phenyl)methanone (1). The structure of BCPD was fully characterized by elemental analysis, mass spectrometry, NMR spectroscopy and infrared spectroscopy. Its optical properties in both solution and solid-state were investigated systematically. The results show that BCPD has almost no emission in solution but is highly emissive in the aggregated form, demonstrating a typical aggregation-induced emission phenomenon. An extensive investigation of its thermal properties verifies that BCPD enjoys excellent thermal and morphological stabilities with Td of 335°C and Tg of 105°C. Eventually, non-doped electroluminescence device by utilizing BCPD as emitting layer was fabricated. The device exhibits sky blue light with the maximum luminance and the maximum luminescent efficiency reaching 8624cdm−2 and 4.243cdA−1, respectively.

Synthesis and biological evaluation of novel tamoxifen-1,2,4-triazole conjugates.

A new class of compounds, structurally related to the breast cancer drug tamoxifen, was designed and synthesized. The McMurry coupling reaction was used as the key synthetic step in the preparation of these analogs, and the structural assignments were made on the basis of [Formula: see text] NMR, [Formula: see text] NMR, and HRMS studies. The absolute stereochemistry of E and Z isomers was unambiguously confirmed by a single-crystal X-ray diffraction analysis. Water was found to be an inexpensive nontoxic and effective medium for the C-N bond formation. Utilizing this protocol, various tamoxifen derivatives were synthesized in good yields. Environmental acceptability, low cost, and high yields are the important features of this protocol. These compounds were evaluated for their antiproliferative activity on five human tumor cell lines. Compound 4p ([Formula: see text]) showed improved antiproliferative activity against breast cancer cell line (MDA-MB-231) compared to tamoxifen ([Formula: see text]), while the compound 4o ([Formula: see text]) exhibited similar activity against SiHa compared to the reference drug, tamoxifen ([Formula: see text]). In addition, these analogs were investigated for their antibacterial activity against six bacterial strains. Preliminary results indicate that some of the newly synthesized title compounds exhibited promising antibacterial activity compared with the standard drug, vancomycin. A new class of compounds were designed rationally by the replacement of a ethyl group in tamoxifen with a methylene (1H-1,2,4-triazole) group. The absolute stereochemistry of E and Z isomers were unambiguously confirmed by a single-crystal X-ray diffraction analysis. The title compounds were evaluated for their antiproliferative and antibacterial activities.

Synthetic Reactions Using Low-valent Titanium Reagents Derived from Ti(OR)4 or CpTiX3 (X = O-i-Pr or Cl) in the Presence of Me3SiCl and Mg.

In the presence of Me3SiCl, Ti(OR)4 or CpTiX3 (X = O-i-Pr or Cl) is reduced by Mg powder in THF to gradually generate a specific low-valent titanium (LVT) species that mediates several synthetic reactions. The LVT-catalyzed C-O bond-cleaving reactions of allyl and propargyl ethers and esters generate parent alcohols and carboxylic acids, respectively. O-allyl and propargyl carbamates are also readily deprotected by the LVT to afford parent amines. In addition, the respective reductive N-S or O-S bond cleavage of sulfonamides or sulfonyl esters mediated by the LVT was developed as a novel facile deprotection method. The reagent catalyzes intra- and intermolecular alkyne or alkyne/nitrile cycloaddition to produce substituted benzenes and pyridines, while epoxides and oxetanes are reduced to alcohols via an LVT-mediated homolytic ring opening. The McMurry coupling of aryl aldehydes and ketones proceeds with the LVT under homogeneous and mild reaction conditions and is effective for the polymerization of aromatic dialdehydes, generating conjugated polymers. Finally, imino-pinacol coupling of imines is mediated by the LVT to provide 1,2-diamines.

Synthesis and Property of New Propeller Shaped Emitting Materials for Organic Light-Emitting Devices.

New propeller type emitting compound, namely 3,6-di-anthracen-9-yl-9,10-bis-(4-anthracen-9-yi-phenyl)-phenanthrene[TAnDAP] and 3,6-bis-(10-phenyl-anthracen-9-yl)-9,10-bis-[4-(10-phenyl-anthracen-9-yl)-phenyl]-phenanthrene [TAnPDAP] were synthesized through Suzuki and McMurry reactions. We investigated their physical properties such as optical, electrochemical, and electroluminescent properties. The two compounds were used as an emitting layer in OLED devices: ITO/2-TNATA (60 nm)/NPB (15 nm)/non-doped: TAnDAP or TAnPDAP (35 nm)/Alq3 (20 nm)/LiF (1 nm)/Al (200 nm). The TAnDAP OLED device showed C.I.E. value of (0.28, 0.41) and luminance efficiency of 3.81 cd/A at 10 mA/cm2. The TAnPDAP device showed C.I.E. value of (0.20, 0.27) and high luminance efficiency of 5.40 cd/A at 10 mA/cm2. TAnPDAP was found to show better luminance efficiency and C.I.E. value than TAnDAP because it has a bulky 9-phenylanthracene.

Ferrocenyl analogues of bisacodyl: Synthesis and antimicrobial activity

The antibacterial activity of bisacodyl, a drug used in therapeutic as laxative is described herein for the first time. Ten original ferrocenyl analogues have been synthesized via an efficient synthetic procedure using the McMurry coupling reaction. The antibacterial activity was investigated against Gram-positive and Gram-negative foodborne pathogens including Listeria monocytogenes, Escherichia coli, Enterococcus faecalis, Salmonella enterica, Micrococcus luteus and Staphylococcus aureus. The results showed that most of these compounds exhibit an excellent antimicrobial activity, and the bisacodyl analogues seemed to be more bactericides than bacteriostatic.

ChemInform Abstract: SnCl4—Zn: A Novel Reductive System for Deoxygenative Coupling of Aliphatic, Aromatic, Chalcone Epoxide, and Indanone Carbonyl Compounds to Olefins.

AbstractA novel, efficient, and economical tin‐reagent for the reductive cross‐coupling reaction of carbonyl compounds under McMurry coupling with aliphatic and aromatic ketones, aldehydes, chalcone epoxides, and indanones is developed.

Toward an Understanding of Diamond sp(2)-Defects with Unsaturated Diamondoid Oligomer Models.

Nanometer-sized doubly bonded diamondoid dimers and trimers, which may be viewed as models of diamond with surface sp(2)-defects, were prepared from corresponding ketones via a McMurry coupling and were characterized by spectroscopic and crystallographic methods. The neutral hydrocarbons and their radical cations were studied utilizing density functional theory (DFT) and ab initio (MP2) methods, which reproduce the experimental geometries and ionization potentials well. The van der Waals complexes of the oligomers with their radical cations that are models for the self-assembly of diamondoids, form highly delocalized and symmetric electron-deficient structures. This implies a rather high degree of σ-delocalization within the hydrocarbons, not too dissimilar to delocalized π-systems. As a consequence, sp(2)-defects are thus also expected to be nonlocal, thereby leading to the observed high surface charge mobilities of diamond-like materials. In order to be able to use the diamondoid oligomers for subsequent surface attachment and modification, their C-H-bond functionalizations were studied, and these provided halogen and hydroxy derivatives with conservation of unsaturation.

Crossed McMurry Coupling Reactions for Porphycenic Macrocycles: Non-Statistical Selectivity and Rationalisation.

Crossed McMurry reactions of bifuran- or bithiophenedicarbaldehydes with bipyrroledicarbaldehydes have been studied for the first time. Only those porphycenic macrocycles derived from homocoupled McMurry products were formed. The results are explained by using both density functional theory and electron propagator computations to model the electron affinity of the dialdehyde starting materials. It was predicted that bifuran\\bithiophene cross-coupling would indeed occur, and this was demonstrated by the first synthesis of a novel dioxa,dithio hetero-porphycenoid annulene. This approach will allow the prior identification of viable substrates for related crossed McMurry reactions.

ChemInform Abstract: Total Synthesis of (‐)‐Haouamine B Pentaacetate and Structural Revision of Haouamine B.

The enantiocontrolled total synthesis of (−)-haouamine B pentaacetate was accomplished via an optically active indane-fused β-lactam, which was prepared by a newly developed Friedel–Crafts reaction. Subsequent cleavage of the β-lactam and an intramolecular McMurry coupling reaction provided the core indane-fused tetrahydropyridine, which led to the elucidation of the structure, as proposed by Trauner and Zubia.

Attempts to prepare an all-carbon indigoid system.

First attempts are described to prepare a precursor for an all-carbon analog of indigo, the tetracyclic triene 4. Starting from indan-2-one (9) the α-methylene ketone 13 was prepared. Upon subjecting this compound to a McMurry coupling reaction, it dimerized to the bis-indene derivative 17, rather than providing the tetramethyl derivative of 4, the hydrocarbon 14. In a second approach, indan-1-one (18) was dimerized to the conjugated enedione 21 through the bis-1-indene dimer 19. All attempts to methylenate 21 failed, however. When 19 was treated with the Tebbe reagent, the dimer 23 was produced, presumably through a Cope reaction of the intermediately generated isomer 22. The bis-indene derivative 23 can be alkylated with 1,2-dibromoethane to produce a 1:1 mixture of the spiro compounds 24 and 25. Although 9 could be reductively dimerized to 30, the conversion of this olefin to 14 failed.

Synthesis, structures, and photophysical properties of π-expanded oligothiophene 8-mers and their Saturn-like C₆₀ complexes.

Two isomers of a multifunctional π-expanded macrocyclic oligothiophene 8-mer, E,E-1 and Z,Z-1, were synthesized using a McMurry coupling of a dialdehyde composed of four 2,5-thienylene and three ethynylene units under high dilution conditions. On the other hand, cyclo[8](2,5-thienylene-ethynylene) 2 was synthesized by intramolecular Sonogashira cyclization of ethynyl bromide 5. From STM measurements, both E,E-1 and Z,Z-1 formed self-assembled monolayers at the solid-liquid interface to produce porous networks, and from X-ray analyses of E,E-1 and 2, both compounds had a round shape with a honeycomb stacked structure. E,E-1 formed various fibrous polymorphs due to nanophase separation of the macrorings. E,E-1 and Z,Z-1 in solution exhibited photochromism upon irradiation with visible and UV light, respectively, and this photoisomerization was confirmed by using STM. Furthermore, amorphous films of Z,Z-1 and E,E-1 showed photoisomerization, although single crystals, fibers, and square tubes of E,E-1 remained unchanged under similar conditions. E,E-1 with a 12.5-14.7 Å inner cavity incorporated fullerene C60 in the cavity in solution and the solid state to produce a Saturn-like complex, whose structure was determined by X-ray analysis. 2 also formed a Saturn-like complex with C60 in the solid state. These Saturn-like complexes are stabilized by van der Waals interactions between the sulfur atoms of 8-mer and C60. The complexes exhibited charge-transfer interactions in the solid state. Like E,E-1, Saturn-like complex E,E-1⊃C60 formed small cube and fiber structures depending on the solvent used, whereas those of Saturn-like complex 2⊃C60 were limited due to the rigidity of the macroring of 2.