A Straightforward Route to Helically Chiral N‐Heteroaromatic Compounds: Practical Synthesis of Racemic 1,14‐Diaza[5]helicene and Optically Pure 1‐ and 2‐Aza[6]helicenes

Abstract

Helicenes have attracted attention as unique inherently chiral three-dimensional aromatic compounds for several decades. Despite significant recent progress in the synthesis and applications of carbohelicenes and thiaheterohelicenes, [1] the potential of the aza analogues with a pyridine unit (pyridohelicenes) have not been explored. [2,3] There are only scattered examples of the preparation of pyridohelicenes, [4] but with no general synthetic methodology, since the photochemical approach can fail with pyridohelicenes [4b,c,e] while non-photochemical alternatives can be difficult to adapt to the synthesis of N-heteroaromatic compounds. The properties and chemical behavior of pyridohelicenes are practically unknown apart from their basicities [4e,g] and the self-assembly [5] of certain derivatives. Nevertheless, promising applications of pyridohelicenes in various branches of chemistry and material science might be envisaged and, therefore, further research in the field is required.Recently, we observed remarkably high proton affinities of pyridohelicene derivatives, as measured by mass spectrometric techniques.[6] In the gas phase, helically chiral 1-aza[6]helicene (2, Scheme 1), for example, exhibits a comparable proton affinity (1000 kJ mol À1 ) to 4-(dimethylamino)-pyridine (DMAP, 997 kJ mol À1 ). Herein, we report the practical syntheses of 1,14-diaza[5]helicene (1), [7] 1-aza[6]helicene (2), [8] and 2-aza[6]helicene (3).[9] Moreover, we have succeeded in resolving racemates of 2 and 3 into their enantiomers, assigning their absolute configuration, determining the energy barriers to racemization, and obtaining Xray structures of their corresponding silver complexes. The strategy for the preparation of 1-3 relies on a [2+2+2] cyclotrimerization of an aromatic triyne in the presence of a Co I catalyst to build the helical scaffold. We have already proven that such a methodology is robust and reliable for the preparation of helicenes and their analogues.[10] Thus, the straightforward synthesis of 1 started from the readily accessible bromopyridine 4, [11] which was treated with lithiated 1-(triisopropylsilyl)-1-propyne to yield 5 which contained an attached alkyne side arm (Scheme 2). Sonoga-

Helicene-Based Chiral Auxiliaries and Chirogenesis

“…The preparation of helicenes 81 and 82 [60] involves the [2 + 2 + 2] cyclotrimerization of regioisomeric aromatic triynes 83 and 84 using a Co(I)-catalyzed reaction as the major synthetic step to obtain tetrahydrohelicenes 85 (82%) and 86 (89%), respectively (Scheme 13). Finally, the MnO 2 -based oxidation resulted in rac aza [6]helicene 81 (65%) and 82 (53%).…”

“…Finally, the MnO2-based oxidation resulted in rac aza [6]helicene 81 (65%) and 82 (53%). The optical resolution of helicene 81 was carried out through the diastereomeric salt formation with optically pure (+)-O,O′-dibenzoyl-D-tartaric acid, whereas enantiopure 82 was obtained by separation of the corresponding racemic mixture with chiral HPLC (Scheme 13) [60].…”

A Scalable and Expedient Route to 1-Aza[6]helicene Derivatives and Its Subsequent Application to a Chiral-Relay Asymmetric Strategy

“…31 We believe this is the first example of axial to helical chiral relay using such cycloisomerization chemistry. The apparent loss of stereochemical information is likely within error of the measurement, since product racemization, 14 would not be significant under these conditions (see Supporting Information). The high fidelity transfer of stereochemical information from biaryl 6 to helicene 4 opens up the possibility of an enantioselective synthesis of azahelicenes using this strategy in the future, via enantioselective synthesis of biaryl 6.…”

“…1 These chiral aromatics have promise to have wide-ranging impact, with preliminary studies already reported in the fields of catalysis, 2-7 non-linear optics, 8 electrooptical switches 9 and molecular recognition 10-13 amongst others. Azahelicenes (such as 4) have been a particularly exciting target class of helicenes recently for chemical synthesis, [1][2][3]14 exhibiting fascinating coordination chemistry, [13][14][15][16] self-assembly potential 17 and interesting photophysics. 18 We have recently demonstrated the high potential of this class in materials science, using enantiopure dopant quantities of 1-aza [6]helicene (4) to induce circularly polarized (CP) electroluminescence from an achiral light emitting polymer, 19 and fabricating organic phototransistors based on 4 that can reversibly detect CP light.…”

“…For example, the Takenaka route 2a,b involves 7 linear steps to assemble three fragments, all of which are non-commercially available, and it uses significant amounts of hexamethylditin to mediate two aryl-aryl bond formation steps. Alternatively, the route developed by Starý, Stará, and co-workers, 14 comprises of 8 linear steps starting from two non-commercial fragments, and requires 30 equivalents of MnO 2 in a final oxidation step. In both cases, the enantiopure products were obtained by semipreparative chiral HPLC or crystallisation of diastereomeric salts.…”