Catalyst control over three- and fourfold stereogenicity

Schmidt, Tanno. Catalyst control over three- and fourfold stereogenicity. 2023, Doctoral Thesis, University of Basel, Faculty of Science.

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Molecules with higher-order stereogenicity exist in the form of more than two stereoisomers emerging from a single irreducible stereogenic unit. Although some of these systems are known for a long time, their stereoselective synthesis under catalyst control, requiring the realization of both enantio- and diastereoselectivity, remained elusive until recently. Herein, the catalyst stereocontrol over molecular systems with three- and fourfold stereogenicity – namely overcrowded alkenes, six-coordinate stereocenters and C–S atropisomers – is described.
Because of their unique stereochemical features, anti-folded overcrowded alkenes find applications as functional units in molecular nanoscience. Here, the induced stereodynamics enable the controlled motion of molecular switches and motors while a high configurational stability prevents the undesired isomeric scrambling. The congested molecules are expeditiously prepared by the versatile Barton–Kellogg olefination, the usually uncatalyzed coupling between a thioketone and a diazo compound which is followed by a reduction of the resulting thiirane to the alkene. Despite their widespread use, the catalyst-controlled stereoselective synthesis of overcrowded alkenes in a broadly applicable manner remained elusive. Now, catalyst stereocontrol was achieved in the Barton–Kellogg olefination through a stereoselective diazo–thioketone coupling in the presence of a chiral dirhodium tetracarboxylate catalyst. The product of this unprecedented enantio- and diastereoselective thiiranation was reduced to yield one out of four overcrowded alkene stereoisomers, with its stereoisomerism arising from the double bond geometry (E, Z) and the molecule’s helicity (P, M). Moreover, full stereodivergence was accomplished by the combination of the catalyst-controlled thiiranation with distinct thiirane reductions to selectively provide all four stereoisomers from the same starting materials. This strategy is envisaged to enable the synthesis of topologically unique overcrowded alkenes for various applications ranging from catalysis to bioactive compounds.
The stereoisomerism of six-coordinate metal centers is known since the days of Alfred Werner, yet catalytic methods to control the configuration of octahedral metal stereocenters are scarce. Auxiliary-assisted Ru(II)/2,2'-bipyridine complexes have been employed as photocatalysts in the deracemization of cobalt(III) acetylacetonate, making use of the transient stereodynamics of the intermediate cobalt(II) complex. When the β-diketonate ligands are unsymmetrically substituted, the homoleptic cobalt(III) β-diketonates exist in the form of two diastereomeric pairs (mer, fac) of enantiomers (Λ, Δ). Employing the photocatalytic deracemization on these fourfold stereogenic cobalt(III) complexes, e.r.’s of up to 88:12 were obtained under diastereomerization of the cobalt stereocenter. Interestingly, it could be shown that the d.r. in the photostationary state can differ from the d.r. in the thermal equilibrium, thus exerting both enantio- and diastereocontrol in the photostereoisomerization. Besides, the diastereomerization of racemic cobalt(III) β-diketonates under blue light by means of cooperative tertiary amine/acridinium photocatalysis was explored.
Atropisomers with more than two stereoisomeric states arising from a single stereogenic axis were pioneered by Michinori Ōki and his coworkers since the 1970s, but their stereoselective synthesis was not accomplished until recently. Triptycyl sulfones exist as three configurationally stable conformers, namely the enantiomeric (±sc)- and the achiral (ap)-isomers, resulting from an atropisomeric C–S bond. By employing an enantioselective oxidation of rotationally dynamic thioethers to sulfoxides, which were subsequently oxidized to the (sc)-sulfones, the stereoselective synthesis of various Ōki triptycyl sulfones with threefold stereogenicity was realized under catalyst control. While a chiral phosphoric acid catalyst defined the configuration of the intermediary sulfoxide stereocenter, VO(On-Pr)3 in combination with cumene hydroperoxide rendered their subsequent oxidation a highly enantiospecific and diastereoselective process. This way, the atropisomeric sulfones were obtained in high degrees of stereoisomeric enrichment with selectivities of up to 94:6:<1 (–sc)/(+sc)/(ap), representing the first example of catalyst control over C–S atropisomerism and threefold stereogenicity. By choosing distinct reaction conditions, the diastereoselectivity of the second oxidation step could be diverted to the achiral (ap)-isomer, rendering all three stereoisomeric states selectively addressable under catalyst control. This could enable the future application of these scaffolds as catalytically encoded angle-adjustment modules in molecular nanotechnology.
Advisors:Sparr, Christof
Committee Members:Baudoin, Olivier and Cramer, Nicolai
Faculties and Departments:05 Faculty of Science > Departement Chemie > Chemie > Organische Chemie (Sparr)
05 Faculty of Science > Departement Chemie > Chemie > Synthetische Chemie (Baudoin)
UniBasel Contributors:Sparr, Christof and Baudoin, Olivier
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:15146
Thesis status:Complete
Number of Pages:IX, 500
Identification Number:
  • urn: urn:nbn:ch:bel-bau-diss151464
edoc DOI:
Last Modified:27 Oct 2023 04:30
Deposited On:26 Oct 2023 12:13

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