Ivo Starý

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.

Rapid Access to Dibenzohelicenes and their Functionalized Derivatives

Spiraling up: Easy access to dibenzo[5]-, dibenzo[6]-, and dibenzo[7]helicenes as well as their functionalized derivatives includes Sonogashira and Suzuki-Miyaura couplings, desilylation, and [2+2+2] alkyne cycloisomerization. The simplicity of this non-photochemical approach combined with the potential for helicity control favors dibenzohelicenes over the parent helicenes for practical applications.

On the origin of diastereoselectivity in [2 + 2 + 2] cycloisomerization of chiral triynes: controlling helicity of helicene-like compounds by thermodynamic factors.

Diastereoselective CoI-mediated [2 + 2 + 2] cycloisomerization of CH(3)O-substituted optically pure aromatic triynes to obtain nonracemic functionalized helicene-like compounds (comprising a penta-, hexa-, and heptacyclic helical scaffold) was studied. The stereochemical outcome of the reaction at 140 degrees C using CpCo(CO)(2) was controlled by thermodynamic factors yielding diastereomeric ratios up to 91:9. Using CpCo(ethylene)(2) at room temperature, a kinetic control took place leading to the loss of stereoselectivity. Barriers to epimerization for selected helicene-like compounds were measured indicating their lower configurational stability in comparison to the parent carbohelicenes. Free energy differences between corresponding pairs of diastereomers (calculated at the DFT B3LYP/TZV+P level) were in excellent agreement with the experimental data and allowed for the prediction of the stereochemical outcome of the reaction. An optically pure hexacyclic helicene-like alcohol was prepared on a multigram scale. Its X-ray structure confirmed the previous helicity assignments being based on (1)H-(1)H correlations in ROESY (1)H NMR spectra.

Evaluation of the intramolecular basis set superposition error in the calculations of larger molecules: [n]helicenes and Phe-Gly-Phe tripeptide

Correlated ab initio calculations on large systems, such as the popular MP2 (or RI‐MP2) method, suffer from the intramolecular basis set superposition error (BSSE). This error is typically manifested in molecules with folded structures, characterized by intramolecular dispersion interactions. It can dramatically affect the energy differences between various conformers as well as intramolecular stabilities, and it can even impair the accuracy of the predictions of the equilibrium molecular structures. In this study, we will present two extreme cases of intramolecular BSSE, the internal stability of [n]helicene molecules and the relative energies of various conformers of phenylalanyl‐glycyl‐phenylalanine tripeptide (Phe‐Gly‐Phe), and compare the calculated data with benchmark values (experimental or high‐level theoretical data). As a practical and cheap solution to the accurate treatment of the systems with large anticipated value of intramolecular BSSE, the recently developed density functional method augmented with an empirical dispersion term (DFT‐D) is proposed and shown to provide very good results in both of the above described representative cases.

Allylic alcohols as substrates for the palladium(0)-catalyzed allylic substitution

Abstract A new method has been developed which allows palladium(0)-catalyzed allylic substitution to occur between allylic alcohols and anionic C-nucleophiles:

Stereochemistry of the palladium-catalyzed allylic substitution: the syn-anti dichotomy in the formation of (π-allyl)palladium complexes and their equilibration☆

Abstract The mechanism of palladium(0)-catalyzed allylic substitution has been investigated with the aim of finding whether or not the intermediate (π-allyl)palladium complexes can arise in a syn fashion as an alternative to the well known anti-mechanism. Using (diphenylphosphino)acetate as a leaving group and stereochemically biased substrates 30b and 35b evidence for the syn stereochemistry has been acquired (30b → 31 and 35b → 36). This reversal of stereochemistry is facilitated by severe steric congestion in the starting allylic esters (which impairs the ordinary anti-mechanism) and is boosted by the pre-coordination of the Pd(0) reagent to the leaving group. The latter effect apparently lowers the activation entropy. With cyclohexene derivatives 10b, 18b, and 19b and acyclic substrate 25b, where steric hindrance does not operate, the anti-mechanism producing η3-complexes dominates even for (diphenylphosphino)acetates. At elevated temperature, rapid equilibration of η3-complexes (13 ⇄ 14 and 20 ⇄ 21) has been observed prior to the reaction with a nucleophile. This effect has been attributed to the presence of (diphenylphosphino)acetate ion acting as a ligand for palladium.

A General Approach to Optically Pure [5]-, [6]-, and [7]Heterohelicenes†

The lack of a general method for the effective synthesis of nonracemic helicenes and their analogues has been a major hurdle that has limited a wider exploitation of these helically chiral aromatic systems in enantioselective catalysis, molecular recognition, self-assembly, surface science, chiral materials, and other branches of science. Ideally, a practical asymmetric synthesis would be independent of both the length of the helical backbone and the presence of functional groups. Since the pioneering studies by Martin et al. and Katz et al. , who successfully used diastereoselective photodehydrocyclization of stilbene-type precursors, various concepts of the asymmetric synthesis of helicenes have been explored but no general procedure for obtaining optically pure helicenes or their analogues with a wide structural diversity has yet been reported. Recently, we demonstrated diastereoselective [2+2+2] cycloisomerization of centrally chiral triynes to receive nonracemic helicene-like compounds with incorporated dihydrooxepine or dihydroazepine ring(s). This promising approach, however, has not yet reached the merit of being general and practical. Herein, we present fundamental progress in this endeavor to receive optically pure and functionalized [5]-, [6]-, and [7]heterohelicenes by means of asymmetric synthesis. With the aim of keeping the molecular shape of the helicene analogues as close as possible to that of the parent helicenes, such as 1 (Figure 1), we proposed embedding two

An Ultimate Stereocontrol in Asymmetric Synthesis of Optically Pure Fully Aromatic Helicenes.

The role of the helicity of small molecules in enantioselective catalysis, molecular recognition, self-assembly, material science, biology, and nanoscience is much less understood than that of point-, axial-, or planar-chiral molecules. To uncover the envisaged potential of helically chiral polyaromatics represented by iconic helicenes, their availability in an optically pure form through asymmetric synthesis is urgently needed. We provide a solution to this problem present since the birth of helicene chemistry in 1956 by developing a general synthetic methodology for the preparation of uniformly enantiopure fully aromatic [5]-, [6]-, and [7]helicenes and their functionalized derivatives. [2 + 2 + 2] Cycloisomerization of chiral triynes combined with asymmetric transformation of the first kind (ultimately controlled by the 1,3-allylic-type strain) is central to this endeavor. The point-to-helical chirality transfer utilizing a traceless chiral auxiliary features a remarkable resistance to diverse structural perturbations.

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.

Tailored formation of N-doped nanoarchitectures by diffusion-controlled on-surface (cyclo)dehydrogenation of heteroaromatics.

Surface-assisted cyclodehydrogenation and dehydrogenative polymerization of polycyclic (hetero)aromatic hydrocarbons (PAH) are among the most important strategies for bottom-up assembly of new nanostructures from their molecular building blocks. Although diverse compounds have been formed in recent years using this methodology, a limited knowledge on the molecular machinery operating at the nanoscale has prevented a rational control of the reaction outcome. We show that the strength of the PAH-substrate interaction rules the competitive reaction pathways (cyclodehydrogenation versus dehydrogenative polymerization). By controlling the diffusion of N-heteroaromatic precursors, the on-surface dehydrogenation can lead to monomolecular triazafullerenes and diazahexabenzocoronenes (N-doped nanographene), to N-doped oligomeric or polymeric networks, or to carbonaceous monolayers. Governing the on-surface dehydrogenation process is a step forward toward the tailored fabrication of molecular 2D nanoarchitectures distinct from graphene and exhibiting new properties of fundamental and technological interest.