Enantioselective Synthesis and Postsynthetic Functionalization of Thiahelicenes and their Oxa-analogues

by Wei Fu
Doctoral thesis
Date of Examination:2024-12-05
Date of issue:2025-01-30
Advisor:Prof. Dr. Manuel Alcarazo
Referee:Prof. Dr. Manuel Alcarazo
Referee:Prof. Dr. Konrad Koszinowski
Persistent Address: http://dx.doi.org/10.53846/goediss-11053

 

 

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Abstract

English

Based on the Alcarazo group’s experience in enantioselective Au(I)-catalyzed synthesis of (hetero)helicenes employing alkyne hydroaryration reactions, the gold precatalyst 188c, combining a chiral BINOL-derived backbone decorated with biphenyl substituents and a cationic imidazolium unit, has demonstrated its versatility in assembling a variety of configurationally stable thia-, and oxahelicenes. Due to the length of biphenyl substituents, this precatalyst is distinguished by a chiral cavity that clearly extends the chiral information beyond the central gold atom, which might also enable a potential π-π stacking interaction with the polyaromatic substrates for precise stereocontrol. In collaboration with Dr. Valentina Pelliccioli and Dr. Pablo Redero, a general catalytic and enantioselective route for the synthesis of non-symmetric thia[5]helicenes and thia[6]helicenes with different substitution patterns is established. Single-crystal X-ray analyses (performed by Dr. Christopher Golz) unambiguously confirmed the connectivity of the new structures obtained and established their absolute configuration, in good agreement with ECD-measurements, to be P. Preliminary studies on the post-synthetic functionalization of these thiahelicenes and their transformation into azahelicenes are also presented. In addition, by treatment of thia[6]helicenes with acid, the annulation between their two arms has been achieved, resulting in bowl-shaped pleiadene derivatives with complete helical-to-point chirality transfer. Encouraged by the results, the highly regio- and enantioselective syntheses of three different families of furan-containing oxa[5]-, oxa[6]-, and dioxa[6]helicenes and their skeletal transformations into pyridine-containing aza-oxa[7]helicene were developed, also in collaboration with Dr. Valentina Pelliccioli. Comparison of the inversion barriers and chiroptical properties of oxahelicenes with those reported for thia- or carbohelicenes sharing an otherwise identical helical framework enables the establishment of comprehensive correlations between the nature of the embedded (hetero)atom(s) and the magnitude of these properties. The first enantioselective synthesis of DTT-embedded thia[5]helicenes has also proved to be viable using sequential Au(I)-catalyzed intramolecular hydroarylation of diynes. The twofold bromination of helicenes obtained has taken place regioselectively in good isolated yield, which opens up a range of possibilities for its subsequent transformation. Under Pd-catalyzed conditions, ring-opening arylation of the core was obtained exclusively with complete helicalto-axial chirality transfer.
Keywords: thiahelicenes; oxahelicenes; Au-catalysis; enantioselective synthesis; racemization dynamics; postsynthetic functionalization
 
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