Filip Teplý

Transition metal catalysed synthesis of tetrahydro derivatives of [5]-, [6]- and [7]helicene

Abstract Tetrahydro analogues of [5]-, [6]- and [7]helicene have been easily prepared by intramolecular [2+2+2] cycloisomerization of appropriate triynes under CpCo(CO) 2 /PPh 3 or Ni(cod) 2 /PPh 3 catalysis. This nonphotochemical methodology allows enantioselective synthesis of a helical skeleton employing the Ni(cod) 2 /(S)-(−)-MOP catalytic system. On reaction with DDQ, tetrahydro[5]helicene was transformed to [5]helicene.

Helquats: A Facile, Modular, Scalable Route to Novel Helical Dications

The synthesis and properties of helical extended diquat (helquat), and derivatives that bear resemblance to diquat and azoniahelicene, was reported. Triyne with elongated tethers connecting the heterocyclic moiety with the pendant alkyne functionalities undergoing cycloisomerization give helquat featuring two seven-membered rings. The seven helquats reported are accessed uniformly in three steps from commercially available starting materials, entailing a Sonogashira coupling, bisquaternization, cycloisomerization, and 2+2+2 cycloisomerization. The evidence for the reversible electrochemical Weiz-type manifold and regular columnar stacks in crystal structures suggest the potential of helquats as electroactive functional elements.

Intense Chiroptical Switching in a Dicationic Helicene-Like Derivative: Exploration of a Viologen-Type Redox Manifold of a Non-Racemic Helquat

Two-step redox switching in enantiopure helquat system [P-1](2+) ⇌ [P-1](•+) ⇌ [P-1](0) is demonstrated. The viologen-type electroactive unit embedded directly in the helical scaffold of 1 is responsible for the prominent chiroptical switching at 264 nm. This process is associated with a marked sign-reversal of Cotton effect ramping between Δε = +35 M(-1) cm(-1) for [P-1](2+) and Δε = -100 M(-1) cm(-1) for [P-1](0). This helically chiral system features the most intense chiroptical switch response documented in the field of helicenoids.

Helicity control in the synthesis of helicenes and related compounds

Asymmetric synthesis of helicenes and their congeners has been demonstrated to rely either on enantioselective Ni0/PR3*-catalyzed [2+2+2] cycloisomerization of triynes or on diastereoselective CoI-catalyzed [2+2+2] cycloisomerization of chiral triynes. The former approach providing tetrahydrohelicenes in a nonracemic form requires further development as moderate enantioselectivities (up to 54 % ee) have so far been achieved under kinetic control. The latter approach affording helicene-like structures in a diastereomerically enriched form allows for reaching good to excellent diastereoselectivities (up to 100:0) under thermodynamic control.

Chiral analysis of helquats by capillary electrophoresis: resolution of helical N-heteroaromatic dications using randomly sulfated cyclodextrins.

Enantiomers of helical N‐heteroaromatic dications, helquats, were separated by CE. An acidic 22/35 mM sodium/phosphate background electrolyte, pH 2.4, with addition of randomly sulfated α‐, β‐ and γ‐ cyclodextrins allowed enantioresolution of a series of helquats, which comprised 5, 6 and 7 fused rings participating in the helical backbone. In general, at least one of the chiral selectors was found to provide baseline separation for 22 out of 24 helquats and partial separation for the remaining two. Individually, the sulfated γ‐cyclodextrin turned out to separate 79% of the helquats, followed by the β‐ and α‐congeners with 54 and 42% of the resolved compounds, respectively. Migration order of enantiomers was inspected for selected helquats and a relation of molecular size of the analytes to a cavity of the cyclodextrin selectors is discussed.

Resolution of a configurationally stable [5]helquat: enantiocomposition analysis of a helicene congener by capillary electrophoresis

Racemic [5]helquat as a triflate salt has been synthesized using a robust, three-step procedure. Subsequent exchange of triflate anions for inexpensive (R,R)-dibenzoyltartrate anions via an ion exchange resin afforded two diastereoisomeric salts. Crystallization led to the resolution of the helquat (ee > 98%). This is the first time that a non-racemic helquat has been obtained; its helicity having been assigned and its racemization barrier determined. Capillary electrophoresis with a sulfated β-cyclodextrin chiral selector is introduced for the first time as a straightforward method to analyze the enantiocomposition of charged, helicene-like species.

COUPLING REACTIONS OF ORTHO-SUBSTITUTED ARYL HALIDES WITH ALKYNES. THE SYNTHESIS OF FUNCTIONALIZED 1-NAPHTHYL-, 1-(1-NAPHTHYL)-2-PHENYL-, AND 1,2-BIS( 1-NAPHTHYL))ACETYLENES

Abstract Coupling of 2-functionalized 1-naphthyl halides with gaseous acetylene, (trialkylsilyl)acetylenes, and aryl acetylenes under Pd(PPh3)4 or Pd(PPh 3 ) 4 CuI catalysis has been investigated to prepare 1-naphthyl-, 1-(1-naphthyl)-2-phenyl-, and 1,2-bis(1-naphthyl)acetylenes with various ortho substituents, i.e., the -CH3, -CH2OH, -CO2Me, and -CH2OCH2CCCH3 groups. The reaction conditions have been optimized (yields up to 96 %) by changing halogen atom in aryl halides, solvent, alkyl in (trialkylsilyl)acetylenes, and catalyst (Pd(O) vs. Pd(O) Cu(I) ). In case of 1-naphthyl iodide with a tethered alkyne unit, coupling has been observed to compete with a cascade of intramolecular Heck-type reactions. The mechanism of β-elimination of a hydridopalladium species has been discussed. 1-Naphthyl bromide bearing the -CO2Me group has been found to be susceptible to nucleophilic aromatic substitution with a solvent. The successful synthesis of an unsymmetrical 1-(1-naphthyl)-2-phenylacetylene derivative has been shown to depend critically on combination of aryl halide/aryl acetylene.

[6]Saddlequat: a [6]helquat captured on its racemization pathway

A dicationic [6]helicene congener captured on the racemization pathway in its saddle-shaped geometry is introduced. Synthesis, structure, resolution, and dynamic properties of this chiral [6]saddlequat in-between and its highly stereocontrolled transformation into enantiopure [6]helquat are discussed and demonstrated. The dynamic aspects established by experiment and supported by detailed DFT-D calculations are presented visually in the form of a movie (electronic table-of-contents and electronic supplementary information). The title [6]saddlequat was found to be an isolable chiral species on the entirely chiral enantiomerization pathway of a [6]helquat that is discussed as an example of Mislows “rubber glove” molecule.

Transition metal control in the reaction of alkyne-substituted phenyl iodides with terminal alkynes: Sonogashira coupling vs cyclic carbopalladation

Abstract Reaction between terminal alkynes and phenyl iodides bearing a tethered alkyne unit can be effectively controlled by the nature of a transition metal catalyst. Whereas the use of Pd(0)/Cu(I) promotes the expected Sonogashira coupling to give phenyl alkynes, the absence of the copper co-catalyst triggers a palladium-mediated cyclisation providing 1,2-dihydroacenaphthylene, 1H,3H-benzo[de]isochromene, (1Z)-1-(2-propynylidene)-2,3-dihydro-1H-indene and (4E)-4-(2-propynylidene)-3,4-dihydro-1H-isochromene derivatives. In the latter Pd-catalysed two-component process, the product distribution depends on the structure of alkyne-substituted phenyl iodides, terminal alkynes and secondary amines used as solvents. The proposed reaction mechanism reflects a competitive formation of intermediary σ-(acetylide) vs π-alkyne Pd(II) complexes.

Can Hindered Intramolecular Vibrational Energy Redistribution Lead to Non-Ergodic Behavior of Medium-Sized Ion Pairs?†

Ergodicity, that is, the ability to predict the behavior of an ensemble from the behavior of its components, is a key concept in various areas of science, while in daily life nonergodic behavior is quite common. In chemistry, ergodicity is typically associated with energy partitioning at a molecular level. Given the selective excitation of a certain rovibrational mode, for example, it is generally assumed that intramolecular vibrational energy redistribution (IVR) is much faster than interactions with the environment. Chemical systems are hence generally assumed to behave ergodically, that is, their properties and in particular their reactivities do not depend on the way of activation, but only on the total energy content, irrespective of the initial state. In turn, nonergodic behavior refers to chemical systems in which the outcome of a reaction is determined by the initial conditions. Most known examples for non-ergodic behavior in chemistry involve systems containing very few atoms, and even systems only slightly larger (e.g. ionized acetone) typically behave ergodically. In recent years, however, electron-capture induced dissociation (ECID) of biomolecules, that is, the recombination of an electron with a multiply charged cation, has been proposed to involve highly excited states of the charged-reduced species, whose dissociations are fast and may not follow ergodicity. Similar arguments have been put forward for highly exothermic electron-transfer reactions between dications and neutral molecules or rapid dissociation/abstraction reactions. However, for thermal reactions of medium-sized molecules, not only associated with the cleavage of existing, but also with the formation of new chemical bonds, many chemists (including ourselves) would generally deny a non-ergodic behavior. In the context of possible correlations between gaseous ions and condensed-phase properties, we recently identified a case which challenges the general assumption of ergodic behavior. Specifically, we investigated the noncovalent ion pairs of a triflate ion (TfO =CF3SO3 ) with a bispyridinium ion that exists in two separable conformers (see structures in Figure 1), which have been termed as helquat (h-1) and saddlequat (s-1), respectively. Amongst a series of other mass spectrometric studies, we have recorded the infrared-multiphoton dissociation (IRMPD) spectra of the mass-selected ion pairs [h1·TfO ] and [s-1·TfO ] . The exclusive fragmentation in IRMPD is a loss of triflic acid through a kinetically controlled Hofmann elimination and is thus associated with the formation of an O H bond. Surprisingly, the IRMPD spectra do not agree with either the experimental IR spectra of the solid salts [h-1·2TfO ] and [s-1·2TfO ], respectively, or the computed IR spectra of the singly charged, binary ion pairs [h-1·TfO ] and [s-1·TfO ] (Figure 1). Favorable agreement is obtained, however, if only the S=O stretching modes (scaling factor 1.0325) are allowed to be active in IRMPD. In this respect it is important to realize that IRMPD is an action spectroscopy, in which the infrared absorption of a gaseous ion is monitored through the amount of fragmentation induced. While this may lead to significant discrimination of certain modes, a situation as profound as in Figure 1, that is, the practical absence of all modes other than certain heteronuclear stretches, has not been addressed before. One possible explanation for the exclusive response of the S=O modes to the infrared irradiation in the IRMPD experiments is a non-ergodic behavior of the ion pairs [h1·TfO ] and [s-1·TfO ]. Thus, the hypothesis is that the S= O bands experience limited intramolecular vibrational energy redistribution (IVR) with the other modes of the molecule such that the triflate unit “overheats”, until proton abstraction becomes kinetically feasible. In turn, adsorption of IR photons in the organic backbone is associated with rapid IVR and hence dissipation of the excess energy across the molecule. While the argument involving non-ergodicity appears fascinating, a problem is that—much like with other [*] Dr. C. J. Shaffer, Dr. . R v sz, Dr. D. Schrcder, Ing. L. Severa, Dr. F. Teplý Institute of Organic Chemistry and Biochemistry Academy of Sciences of the Czech Republic Flemingovo n m. 2, 16610 Prague 6 (Czech Republic) E-mail: schroeder@uochb.cas.cz