10.1021/ja030196d.s008
Tomasz Fekner
Tomasz
Fekner
Judith Gallucci
Judith
Gallucci
Michael K. Chan
Michael K.
Chan
Ruffling-Induced Chirality: Synthesis, Metalation, and Optical
Resolution of Highly Nonplanar, Cyclic, Benzimidazole-Based
Ligands
American Chemical Society
2004
parent amide 5 racemizes
chiral
Ni
racemization
phase HPLC
complex
2004-01-14 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Ruffling_Induced_Chirality_Synthesis_Metalation_and_Optical_Resolution_of_Highly_Nonplanar_Cyclic_Benzimidazole_Based_Ligands/3353230
Expedient five-step syntheses of a cyclic bis(benzimidazole)-based amide <b>5 </b>and two sterically
more hindered analogues <b>23</b>−<b>24</b> have been developed. These amides are chiral due to the inherent ruffling
of the macrocyclic plane. Racemization of the optical antipodes of these compounds has been studied
using dynamic chiral stationary phase HPLC. These studies reveal that, while the parent amide <b>5</b> racemizes
rapidly, for the sterically more hindered amides <b>23</b>−<b>24</b>, the rate of racemization is significantly reduced.
Bis(benzimidazole)-based amides <b>5 </b>and<b> 23</b>−<b>24</b> form stable Ni(II) complexes <b>25</b>−<b>27</b>, respectively. Like
their parent ligands, complexes <b>25</b>−<b>27</b> are chiral due to their highly ruffled geometry. Studies of these
complexes by chiral stationary phase HPLC reveal that metalation leads to a much lower rate of racemization.
Incorporation of a strap can slow racemization even further. A series of strapped cyclic amides <b>54</b>−<b>57</b>,
along with their corresponding dimers <b>58</b>−<b>61</b>, have been prepared. The rate of racemization for amides
<b>54</b>−<b>57</b> is strongly dependent on the length of the strap. X-ray single-crystal structure analysis of the Ni(II)
complex of strapped amide <b>54</b> reveals that the bis(benzimidazole) core retains its highly ruffled shape,
with the two phenyl rings of the macrocycle located anti to the strap. Chiral separation of strapped ligands
<b>54</b>−<b>57</b> and their corresponding Ni(II) complexes is shown to be facile by chiral stationary phase HPLC.