Catalytic Arene-forming Aldol Condensation: Stereoselective Synthesis of Rotationally Restricted Aromatic Compounds

Fäseke, Vincent C.; Witzig, Reto M.; Link, Achim; Lotter, Dominik; Sparr, Christof

doi:10.2533/chimia.2017.596

Cited by 5 publications

(5 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our previous efforts were engaged in polyketide cyclizations of artificial aldehyde substrates with pre‐organizing aromatic moieties . The mild substrate preparation and the observed control over increasingly complex substrates thereby indicated the feasibility of small‐molecule catalyzed, divergent cyclizations of native polyketides, if the reactivity and selectivity requirements are met.…”

Section: Methodsmentioning

confidence: 99%

Catalyst‐Controlled Transannular Polyketide Cyclization Cascades: Selective Folding of Macrocyclic Polyketides

et al. 2020

Self Cite

View full text Add to dashboard Cite

The biomimetic synthesis of aromatic polyketides from macrocyclic substrates by means of catalyst-controlled transannular cyclization cascades is described. The macrocyclic substrates, which feature increased stability and fewer conformational states, were thereby transformed into several distinct polyketide scaffolds. The catalyst-controlled transannular cyclizations selectively led to aromatic polyketides with a defined folding and oxygenation pattern, thus emulating bketo-processing steps of polyketide biosynthesis.

show abstract

Section: Methodsmentioning

confidence: 99%

Catalyst‐Controlled Transannular Polyketide Cyclization Cascades: Selective Folding of Macrocyclic Polyketides

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…Our group focused on the development of atroposelective areneforming aldol condensations, which were inspired by the biosynthesis of aromatic polyketides. [44,45] The amine catalyzed aldol methodology was found to be broadly applicable permitting the preparation of binaphthalene carbaldehydes, [46] configurationally stable oligo-1,2-naphthylenes [47] , axially chiral amides [48] and the stereodivergent synthesis of atropisomeric multi-axis systems. [49]…”

Section: Stereoselective Synthesis Of Atropisomersmentioning

confidence: 99%

“…These cyclization studies [44][45][46][47][48][49] revealed the ability of smallmolecule catalysts to trigger polyketide-type cyclizations and suggested that also noncanonical polyketide cyclizations, that are related to the conversion of poly-β-carbonyl compounds by the polyketide synthase machineries, could be feasible. of substrates to examine this hypothesis involved the preparation of cinnamyl biindene precursors which were accessed through an oxidative dimerization or a Suzuki crosscoupling strategy.…”

Section: Synthesis Of Enantioenriched Tetra-ortho-33'-substituted Bimentioning

confidence: 99%

Synthesis of Enantioenriched Tetra-ortho-3,3′-substituted Biaryls by Small-Molecule-Catalyzed Noncanonical Polyketide Cyclizations

Witzig¹,

Sparr²

2019

Synlett

Self Cite

View full text Add to dashboard Cite

The arene-forming aldol condensation is a fundamental reaction in the biosynthesis of aromatic polyketides. Precisely controlled by the polyketide synthases, the highly reactive poly-β-carbonyl substrates are diverged into numerous aromatic natural products by selective cyclization reactions; a fascinating biosynthetic strategy that sparked our interest to investigate atroposelective aldol condensations. In this Account, we contextualize and highlight the ability of small-molecule catalysts to selectively convert noncanonical hexacarbonyl substrates in a double arene-forming aldol condensation resulting in the atroposelective synthesis of tetra-ortho-3,3′-substituted biaryls. The hexacarbonyl substrates were obtained by a fourfold ozonolysis enabling a late-stage introduction of all carbonyl functions in one step. Secondary amine catalysts capable of forming an extended hydrogen-bonding network triggered the noncanonical polyketide cyclization in order to form valuable biaryls in high yields and with stereocontrol of up to 98:2 er.1 Biosynthesis of Aromatic Polyketides2 Rotationally Restricted Aromatic Polyketides3 3,3′-Substituted Binaphthalenes in Catalysis4 Stereoselective Synthesis of Atropisomers5 Synthesis of Enantioenriched Tetra-ortho-3,3′-Substituted Biaryls by the Atroposelective Arene-Forming Aldol Condensation6 Conclusion

show abstract

“…However, although the enantioselective and diastereoselective aldol reactions have been developed significantly, the atroposelective versions of them are rare . The Sparr group performed atroposelective arene-forming aldol reactions using proline-driven organocatalysts and further used them elegantly in some natural products − and axially chiral amide syntheses . Here, we report atroposelective aldol reactions of axially chiral thiohydantoin derivatives using a different approach.…”

Section: Introductionmentioning

confidence: 99%

Aldol Reactions of Conformationally Stable Axially Chiral Thiohydantoin Derivatives

2021

View full text Add to dashboard Cite

Two novel axially chiral ortho-trifluoromethylphenyl thiohydantoin derivatives have been prepared atroposelectively from the reaction of R and S alanine methyl ester HCl salts with ortho-trifluoromethylphenyl isothiocyanate in the presence of triethyl amine. It was found that after purification of the crude product by simple recrystallization, the R amino acid esters yielded thiohydantoins having solely M axial chirality whereas the S ones returned the P isomers only. This result prompted us to perform sterically controlled aldol reactions on M and P thiohydantoin atropisomers. It was found that during the aldol reaction of 3-o-trifluoromethyl-5methylthiohydantoins, the o-trifluoromethyl group of the M isomers efficiently shielded the Si face of the intermediate and in this way, enabled the selective formation of only the R configured aldol products at C5 of the heterocyclic ring. The P thiohydantoins, on the other hand, yielded only the S C5 configured aldol products as a result of the Re face shielding of the orthotrifluoromethyl group of intermediate enolates. A noteworthy face selectivity of the benzaldehyde molecule was not observed (anti/ syn only 3/2) during the aldolization of trifluoromethylphenyl derivatives of thiohydantoins. Aldol reactions were also done using the previously synthesized axially chiral thiohydantoins with ortho-Cl, Br, and I phenyl substituents which had predominantly P conformations (P/M ratios > 95%), and the stereochemical outcomes were compared with those of the ortho-trifluoromethyl substituted ones. 80−90% face selectivity of the benzaldehyde molecule was observed for the axially chiral o-halophenyl substituted thiohydantoins. The syntheses done with axially chiral 3-ortho-trifluoromethylphenyl-and 3-ortho-iodophenyl-5-methyl thiohydantoins enabled stereoselective formation of quaternized chiral carbon centers at C5 of the thiohydantoin ring.

show abstract

Catalytic Arene-forming Aldol Condensation: Stereoselective Synthesis of Rotationally Restricted Aromatic Compounds

Cited by 5 publications

References 12 publications

Catalyst‐Controlled Transannular Polyketide Cyclization Cascades: Selective Folding of Macrocyclic Polyketides

Catalyst‐Controlled Transannular Polyketide Cyclization Cascades: Selective Folding of Macrocyclic Polyketides

Synthesis of Enantioenriched Tetra-ortho-3,3′-substituted Biaryls by Small-Molecule-Catalyzed Noncanonical Polyketide Cyclizations

Aldol Reactions of Conformationally Stable Axially Chiral Thiohydantoin Derivatives

Contact Info

Product

Resources

About