One-pot formation and derivatization of di- and triynes based on the Fritsch-Buttenberg-Wiechell rearrangement

A divergent, one-pot synthesis of functionalized polyynes has been developed. Beginning with the appropriately substituted dibromoolefinic precursor, a carbenoid Fritsch-Buttenberg-Wiechell (FBW) rearrangement is used to generate the lithium acetylide of a conjugated polyyne framework, and subsequent trapping with carbon-based electrophiles provides for in situ formation of a wide range of di- and triynes. The lithium acetylide formed from the FBW reaction can also undergo transmetalation to provide the corresponding zinc, copper, tin, or platinum acetylides, leading to the divergent formation of symmetrical and unsymmetrical conjugated acetylenes, as well as ynones.     

Alkyne migration in alkylidene carbenoid species: a new method of polyyne synthesis

The synthesis of conjugated polyyne structures via a modification of the Fritsch-Buttenberg-Wiechell (FBW) rearrangement is reported. Our adaptation provides for the 1,2-migration of an alkyne in a carbene/carbenoid intermediate that is conveniently effected via lithium-halogen exchange with the appropriate dibromo-olefinic precursor. This rearrangement is quite rapidly accomplished under mild conditions (hexane solution, -78 degrees C), and the seemingly high migratory aptitude of the alkynyl moiety provides for efficient rearrangement. This, in turn, allows for multiple rearrangements in a single molecule, greatly facilitating the construction of highly unsaturated substrates. This procedure is exploited for the rapid synthesis of symmetrical and unsymmetrical 1,3,5-hexatriynes, extended polyynes, and aryl polyyne building blocks. Most significantly, many of these structures have been or would be difficult to access via more traditional transition metal catalyzed homo- or cross-coupling techniques.     

A one-pot synthesis and functionalization of polyynes

[reaction: see text] A one-pot synthesis and derivatization of diynes and triynes is reported. The polyyne framework is formed from a dibromoolefin precursor based on a carbenoid rearrangement, and the resulting Li-acetylide is then trapped in situ with an electrophile to provide functionalized di- and triynes. Alternatively, transmetalation of the Li-acetylide intermediate provides either the Zn- or Sn-acetylide, which then allows for the divergent preparation of diaryl polyynes or aryl ynones via palladium-catalyzed cross-coupling reactions.     

Synthesis of unsymmetrically substituted 1,3-butadiynes and 1,3,5-hexatriynes via alkylidene carbenoid rearrangements

Unsymmetrically substituted 1,3-butadiynes and 1,3,5-hexatriynes are synthesized in four steps from commercially available aldehydes or carboxylic acids. The key step in this process involves a Fritsch-Buttenberg-Wiechell rearrangement, in which an alkylidene carbenoid intermediate subsequently rearranges to the desired polyyne. This rearrangement proceeds under mild conditions, and it is tolerant of a range of functionalities. In general, the procedurally facile formation of the dibromoolefinic precursors, in combination with the effectiveness of the rearrangement step, makes this procedure an attractive alternative to traditional methods for di- and triyne synthesis that utilize palladium or copper catalysis.     

Polyynes and cyanopolyynes synthesis from the submerged electric arc: about the role played by the electrodes and solvents in polyynes formation

The products of the electric arc between graphite electrodes have been investigated by high performance liquid chromatography-diode-array detector (HPLC-DAD) analysis in various media: distilled water, liquid nitrogen, methanol, ethanol, n-hexane and benzene. In distilled water, hydrogen capped polyynes H-(CC)_n-H were the unique products demonstrating that carbon is supplied by the graphite electrodes while hydrogen is supplied by the solvent plasmalysis (in this case water plasmalysis). Arcing graphite electrodes in liquid nitrogen produces cyanopolyynes: NC-(CC)_n-CN demonstrating that in this case the end groups of the polyyne chains are supplied by molecular nitrogen plasmalysis caused by the electric arc. Graphite arcing in methanol and ethanol produces very clean solutions (by-products negligible or absent) of hydrogen-capped polyynes with C₈H₂ as the main product accounting for more than 70 mol percent of the total polyyne concentration. By replacing graphite electrodes with titanium electrodes in methanol or in ethanol, polyynes are not formed at all; only trace amounts of polycyclic aromatic hydrocarbons (PAHs) were detected. When arcing with graphite electrodes is conducted in n-hexane or in benzene, polyyne formation is accompanied by a significant production of PAH, especially in benzene. These results have been rationalized in terms of carbonization or coking tendency of a given solvent. The effect of using titanium electrodes in place of graphite electrodes has been investigated also in n-hexane and in benzene as well as the effects of very high electric current intensity employed to ignite and sustain the submerged electric arc.     

End-cap stabilized oligoynes: model compounds for the linear sp carbon allotrope carbyne

Three series of differently 3,5-disubstituted alpha,omega-diphenylpolyynes Ar-(C[triple bond]C)n-Ar (n=2, 4, 6, 8, 10) were synthesized under optimized Cadiot-Chodkiewicz conditions, isolated and completely characterized. These compounds can be considered as model substances for the hypothetical one-dimensional carbon allotrope carbyne Cx. The longest sp-carbon chain contains 20 atoms and is therefore the longest, purely organic polyyne studied with NMR techniques. Extinction coefficients over 600,000 M(-1) cm(-1) represent the highest measured quantitative values for that compound class so far. Comparisons with previous investigations and electrochemical studies allow the assignment of absorption for both wavelength regions structuring the UV/Vis spectra. Based on the trends in the spectroscopic behaviour of those molecules with increasing chain length, electronic as well as the NMR properties of carbyne are predicted, in line with our previously reported results. The observed stability properties promise the synthesis of even longer polyynes.     

Synthesis and stability of a homologous series of triynol natural products and their analogues

A series of polyyne natural products 1, 13, and 31 and analogues 14, 21, and 22 are synthesized in six steps. The key step is a Fritsch-Buttenberg-Wiechell rearrangement in which a triyne framework is formed from the appropriate dibromoolefin precursor. Terminal conjugated triynes 13 and 14 are obtained as highly unstable products that rapidly decompose under ambient conditions. The stability of triynols increases via either the addition of methylene units (i.e., 6 --> 31 --> 1) or addition of terminal substituents (i.e., 13 --> 21 or 31).     

Polyynes as a model for carbyne: synthesis, physical properties, and nonlinear optical response

With the Fritsch-Buttenberg-Wiechell rearrangement as a primary synthetic route, a series of conjugated, triisopropylsilyl end-capped polyynes containing 2-10 acetylene units has been assembled. In a few steps, significant quantities of the polyynes are made available, which allow for a thorough analysis of their structural, physical, and optical properties. Molecules in the series have been characterized in detail using (13)C NMR spectroscopy, differential scanning calorimetry, mass spectrometry, and, for four derivatives including octayne 6, X-ray crystallography. UV-vis spectroscopy of the polyynes 1-7 shows a consistent lowering of the HOMO-LUMO gap (E(g)) as a function of the number of acetylene units (n), fitting a power-law relationship of E(g) approximately n(-)(0.379)(+/-)(0.002). The third-order nonlinear optical (NLO) properties of the polyyne series have been examined, and the nonresonant molecular second hyperpolarizabilities (gamma) increase as a function of length according to the power-law gamma approximately n(4.28)(+/-)(0.13). This result exhibits an exponent that is larger than theoretically predicted for polyynes and higher than is observed for polyenes and polyenynes. The combined linear and nonlinear optical results confirm recent theoretical studies that suggest polyynes as model 1-D conjugated systems. On the basis of UV-vis spectroscopic analysis, the effective conjugation length for this series of polyynes is estimated to be ca. n = 32, providing insight into characteristics of carbyne.     

Synthesis of naturally occurring polyynes

Over the past fifty years, hundreds of polyyne compounds have been isolated from nature. These often unstable molecules are found in sources as common as garden vegetables and as obscure as bacterial cultures. Naturally occurring polyynes feature a wide range of structural diversity and display an equally broad array of biological properties. Early synthetic efforts relied primarily on Cu-catalyzed, oxidative acetylenic homo- and heterocoupling reactions to assemble the polyyne framework. The past 25 years, however, have witnessed a renaissance in the field of polyyne natural product synthesis: transition-metal-catalyzed alkynylation reactions and asymmetric transformations have combined to substantially expand access to natural polyynes. This Review recounts these synthetic achievements and also highlights both the natural source(s) and biological relevance for many of these compounds.     

The Molecular Basis of Conjugated Polyyne Biosynthesis in Phytopathogenic Bacteria

Polyynes (polyacetylenes), which are produced by a variety of organisms, play important roles in ecology. Whereas alkyne biosynthesis in plants, fungi, and insects has been studied, the biogenetic origin of highly unstable bacterial polyynes has remained a riddle. Transposon mutagenesis and genome sequencing unveiled the caryoynencin (cay) biosynthesis gene cluster in the plant pathogen B. caryophylli, and homologous gene clusters were found in various other bacteria by comparative genomics. Gene inactivation and phylogenetic analyses revealed that novel desaturase/acetylenase genes mediate bacterial polyyne assembly. A cytochrome P450 monooxygenase is involved in the formation of the allylic alcohol moiety, as evidenced by analysis of a fragile intermediate, which was stabilized by an in situ click reaction. This work not only grants first insight into bacterial polyyne biosynthesis but also demonstrates that the click reaction can be employed to trap fragile polyynes from crude mixtures.     

UV-Polarizing Linear Polyyne Molecules Aligned in PVA

Electronic absorption bands of conjugated linear carbon chain molecules, namely polyynes H(C≡C)_nH (n=5-7), are exploited to devise light-polarizing films applicable to the UV. Laser ablated polyynes are separated in size and dispersed in a film of polyvinyl alcohol (PVA), which is stretched to align the trapped linear polyyne molecules inside. As a nature of the structural anisotropy, transition dipole of the UV absorption for polyyne molecules is in parallel with the molecular axis and the absorption occurs only for the electromagnetic wave having the amplitude of its electric vector along the molecular axis. Aligned and fixed orientationally in the solid PVA film, polyyne molecules act as selective absorbers of one of the polarization components of incident light at particular wavelength. Using a light source of linearly polarized UV light, whose direction of polarization is rotatable, angular dependence of the absorption intensity is investigated for the stretched PVA film containingaligned polyyne molecules and analyzed in terms of an order parameter in the theory of linear dichroism.     

Gas Phase Formation of the Interstellar Molecule Methyltriacetylene

Methyltriacetylene – the largest methylated polyacetylene detected in deep space – has been synthesized in the gas phase via the bimolecular reaction of the 1-propynyl radical with diacetylene under single-collision conditions. The barrier-less route to methyltriacetylene represents a prototype of a polyyne chain extension through a radical substitution mechanism and provides a novel low temperature route, in which the propynyl radical piggybacks a methyl group to be incorporated into methylated polyynes. This mechanism overcomes a key obstacle in previously postulated reactions of methyl radicals with unsaturated hydrocarbon, which fail the inclusion of methyl groups into hydrocarbons due to insurmountable entrance barriers thus providing a fundamental understanding on the electronic structure, chemical bonding, and formation of methyl-capped polyacetylenes. These species are key reactive intermediates leading to carbonaceous nanostructures in molecular clouds like TMC-1.     

Conformational study of C24 cyclic polyyne clusters

Polyynes were first synthesized before the year 1900, and isolated and characterized after 2000. Cyclic polyynes are of particular interest since possess a high order of symmetry. Furthermore, some studies reported special mechanical properties of the condensed polyyne bulks. The optimal size of polyynes to form rings has been previously investigated and was found to be 24 with a stable cluster of crossing four C₂₄ cyclic polyynes. We investigated in this study the conformation of clusters of polyynes (nC₂₄) by the pattern previously identified to stabilize the cluster. Clusters of 4C₂₄, 10C₂₄, 22C₂₄, 46C₂₄, and 94C₂₄ were designed and subjected to energy minimization. The main finding is the preservation of the symmetry for the nC₂₄ cluster with the increase of its size. The study revealed that 4C₂₄, 10C₂₄, and 22C₂₄ preserve a high symmetry and the calculations suggest an excellent increasing of the cluster stability with the increase of the number of polyyne rings. A 22C₂₄ derived cluster namely 28C₂₄ was found as the one likely to limit the growth of the polyyne clusters.     

Synthetic Applications of Carbonyl Ylides Generated via the Tandem Cyclization Cycloaddition Reaction of Rhodium Carbenoids

The author's chemical studies dealing with the generation of carbonyl ylides via the rhodium(II) induced cyclization of α-diazo alkanediones are summarized, Dipole formation occurs by reaction of a transient rhodium carbenoid intermediate with a neighboring carbonyl group. These cyclizations are performed under extremely mild conditions, typically at room temperature in a neutral organic solvent. Since these cycloadditions involve carbonyl ylides, the resulting products are oxabicycles of varying ring size. When the dipolarophile is intramolecularly tethered to the dipole, the subsequent cycloaddition affords complex oxapolycyclic systems with three (or more) component rings.     

The rearrangement and solvolysis of furfuryl arenesulfinates

Furfuryl benzenesulfinate, furfuryl p-toluenesulfinate and 5-nitrofurfuryl benzenesulfinate were synthesized, and their behaviour under various conditions was investigated. The first two esters were found to undergo readily rearrangement to sulfone. In nonhydroxylic solvents, a mixture of furfuryl aryl sulfone and 2-methyl-3-furyl aryl sulfone is obtained. The ratio between the two sulfones changes with the polarity of the solvent. In hydroxylic solvents, only rearrangement to the furfuryl aryl sulfone takes place, and this is accompanied by solvolysis of the ester. A kinetic study of the reaction in ethanol and aqueous ethanol solvents indicated an ionization mechanism. It is suggested that under these conditions the sulfone is formed by recombination of ion pairs. A kinetic study of the rearrangement under nonsolvolytic conditions was also performed in order to obtain the effect of the solvent and the effect of added salts on the rate of rearrangement. This study has shown that the rate of rearrangement is sensitive to the ionizing power of the solvent. The addition of perchlorate was found to have a stronger effect on the formation of the furfuryl sulfone than on the 2-methyl-3-furyl sulfone. In this case an ionic mechanism is also suggested, and the two sulfones may arise by recombination from two different species of ion pairs.     

Practical Organocatalytic Synthesis of Functionalized Non‐C2‐Symmetrical Atropisomeric Biaryls

An organic acid catalyzed direct arylation of aromatic C(sp²)? H bonds in phenols and naphthols for the preparation of 1,1′‐linked functionalized biaryls was developed. The products are non‐C₂‐symmetrical, atropoisomeric, and represent previously untapped chemical space. Overall this transformation is operationally simple, does not require an external oxidant, is readily scaled up (up to 98 mmol), and the structurally diverse 2,2′‐dihydroxy biaryl (i.e., BINOL‐type), as well as 2‐amino‐2′‐hydroxy products (i.e., NOBIN‐type) are formed with complete regioselectivity. Density‐functional calculations suggest that the quinone and imino‐quinone monoacetal coupling partners are exclusively arylated at their α‐position by an asynchronous [3,3]‐sigmatropic rearrangement of a mixed acetal species which is formed in situ under the reaction conditions.     

Synthesis of novel alpha-substituted and alpha,alpha-disubstituted amino acids by rearrangement of ammonium ylides generated from metal carbenoids

[reaction: see text] A new and general four-step synthesis of protected alpha-substituted and alpha,alpha-disubstituted amino acids has been developed. The key step involves intramolecular ammonium ylide generation from a copper carbenoid with concomitant [2,3] rearrangement. The aromatic template serves as a tether, protecting group, and activating group for peptide coupling. The ylide rearrangement products can be converted into protected cyclic amino acids by ring-closing metathesis.     

Synthesis of Long,Palladium End‐Capped Polyynes through the Use of Asymmetric 1‐Iodopolyynes

The synthesis of a unique series of long, asymmetric 1‐iodopolyynes ( 1 ‐C_nI and 2 ‐C_nI) with the sp‐hybridized carbon chain up to a decapentayne is reported. These compounds were then used as substrates in reactions with Pd(PPh₃)₄ leading to another series of palladium end‐capped polyynes, which were unstable in solution. Organometallic octatetraynes 1 ‐C₈[Pd]I, 2 ‐C₈[Pd]I, and decapentayne 1 ‐C₁₀[Pd]I are palladium end‐capped polyyne compounds with the longest carbon chains reported so far. All the complexes as well as their organic precursors were fully characterized by NMR, HRMS(ESI), IR, TGA‐DTA, and UV/Vis techniques, and the X‐ray crystal structures of two silyl‐protected precursors and one palladium complex are presented. The synthetic approach for palladium species is envisioned as a general route for the synthesis of labile organometallic polyynes.     

Generation of Nucleophilic Chromium Acetylides from gem-Trichloroalkanes and Chromium Chloride: Synthesis of Propargyl Alcohols

Nucleophilic mixed chromium(II) and chromium(III) acetylides are generated from the smooth reduction of primary 1,1,1-trichloroalkanes with chromium(II) chloride in the presence of an excess amount of triethylamine at room temperature. These species arise from chromium(III) vinylidene carbenoids. It has been demonstrated that uncommon low-valent Cr(II) acetylides are formed by C-H insertion of Cr(II)Cl(2) into terminal alkynes, formed in situ through the Fritsch- Buttenberg-Wiechell (FBW) rearrangement, whereas Cr(III) acetylides are concomitantly generated by HCl elimination from the chromium(III) vinylidene carbenoid. Both divergent pathways result, overall, in the formation of nucleophilic acetylides. In situ trapping with electrophilic aldehydes afforded propargyl alcohols. Furthermore, deuteration experiments and the use of deuterium labeled 1,1,1-trichloroalkane substrates demonstrated the prevalence of low-valent Cr(II) acetylides, potentially useful, yet highly elusive synthetic intermediates.     

Submerged electric arc between graphite electrodes: a one-pot tool for the synthesis of long-chain polyynes in solution

Polyynes, a class of molecules described by the general formula H-(CC)_mH (where m is an integer) can be synthesized using an electric arc between graphite electrodes submerged in an organic solvent such as methanol, n-hexane, n-dodecane, decahydronaphthalene or acetonitrile. When the electric arc is used in acetonitrile at −40 °C, polyyne chains of up to 18 carbon atoms (m=9) have been produced together with monocyanopolyyne as by-product. The polyynes can be reduced to ene-ynes by shaking a hexane solution of them with Zn/HCl.