Multifunctional Organocatalysts ‐ Singly‐Linked and Macrocyclic Bisphosphoric Acids for Asymmetric Phase‐Transfer and Brønsted‐Acid Catalysis

Abstract

The linking of phosphoric acids via covalent or mechanical bonds has proven to be a successful strategy for the design of novel organocatalysts. Here, we present the first systematic investigation of singly‐linked and macrocyclic bisphosphoric acids, including their synthesis and their application in phase‐transfer and Brønsted acid catalysis. We found that the novel bisphosphoric acids show dramatically increased enantioselectivities in comparison to their monophosphoric acid analogues. However, the nature, length and number of linkers has a profound influence on the enantioselectivities. In the asymmetric dearomative fluorination via phase‐transfer catalysis, bisphosphoric acids with a single, rigid bisalkyne‐linker give the best results with moderate to good enantiomeric excesses. In contrast, bisphosphoric acids with flexible linkers give excellent enantioselectivities in the transfer‐hydrogenation of quinolines via cooperative Brønsted acid catalysis. In the latter case, sufficiently long linkers are needed for high stereoselectivities, as found experimentally and supported by DFT calculations.

Chiral Bis‐phosphate Macrocycles for Catalytic, Efficient, and Enantioselective Electrophilic Fluorination

“…Chiral phosphoric acids (CPAs) are one kind of the most well‐known and versatile organocatalysts, which can catalyze various enantioselective transformations [6] . Following the above strategy, direct incorporation of this privileged catalytic scaffold into a macrocyclic skeleton, e. g. through 3,3′‐connection of two BINOL‐derived phosphoric acid moieties, will build up one kind of chiral bis‐phosphate macrocycles [7] (Figure 1). By using different linkers, two CPA units can be placed with tunable distances to afford different status of CPA‐CPA cooperation at demand.…”

Asymmetric Fluorofunctionalizations with Carboxylate‐Based Phase‐Transfer Catalysts

“…With fluorine being a bioisostere of the hydroxyl group, we became interested in dearomative fluorination of hydroxyarenes for an alternative preparation of α‐hydroxy ketone substructure. However, when we started this project, there had been only one report of the catalytic asymmetric fluorination of phenols [31] and no report in the case of naphthol derivatives [32] …”

para-Selective dearomatization of phenols by I(i)/I(iii) catalysis-based fluorination

“…Inspired by the hydroxylation-based dearomatization by Maruoka and co-workers (Scheme 1B), 12 and the C4 selective fluorination of bicyclic phenols by Toste and co-workers using Selectfluor® under phase-transfer catalysis conditions (Scheme 1C) 13,15 we initiated a study to explore the causative factors that orchestrate enantioinduction (Scheme 1D).…”