Synthetic Method for 2,2'‐Disubstituted Fluorinated Binaphthyl Derivatives and Application as Chiral Source in Design of Chiral Mono‐Phosphoric Acid Catalyst

Abstract

A practical synthetic method for 2,2'-disubstituted fluorinated binaphthyl derivatives was achieved using magnesium bis(2,2,6,6-tetramethylpiperamide) [Mg(TMP)(2)], prepared from LiTMP (2 equiv) and MgBr(2) (1 equiv), which allows for access to a variety of fluorinated binaphthyl compounds. The utility of the fluorinated binaphthyl backbone was evaluated in F10 BINOL derived chiral mono-phosphoric acid (R)- as the chiral Brønsted acid catalyst. The catalyst (R)- performs exceptionally well in the catalytic enantioselective imino-ene reaction, demonstrating the potential of a fluorinated binaphthyl framework.

B(C6F5)3/Chiral Phosphoric Acid Catalyzed Ketimine–Ene Reaction of 2‐Aryl‐3H‐indol‐3‐ones and α‐Methylstyrenes

“…We speculated that enhancing the acidity of the catalytic system would solve the problem. However, the reported strong Brønsted acid catalytic systems for ene reaction, such as List's imidodiphosphate (IDP) Brønsted acids and Terada's F 10 BINOL‐derived chiral phosphoric acids, require complex synthetic routes. More readily available strongly acid catalytic systems were then considered .…”

“…Second, the catalyst must be capable of overcoming significant steric hindrance for the formation of tetrasubstituted carbon stereocenters. Previously reported Brønsted acid catalytic systems for asymmetric ene reactions are limited to carbonyls and aldimines, leading to the formation of hydroxy or amino tertiary carbon stereocenters. Third, an appropriate chiral environment is required to facilitate the stereo‐inducement process.…”

Perfluorinated Aryls in the Design of Chiral Brønsted Acid Catalysts: Catalysis of Enantioselective [4 + 2] Cycloadditions and Ene Reactions of Imines with Alkenes by Chiral Mono-Phosphoric Acids with Perfluoroaryls

“…In the context of the imino–ene reaction, an N -tosyl-α-iminoester has been used as the chelating and highly electrophilic component in all previous reports of chiral Lewis acid catalysis. − Our initial study suggested that the imino–ene reaction proceeds when the benzaldehyde-derived N -Fmoc imine 4 was used as an electrophile (Table , entries 5 and 6) . We expected that relatively stronger chiral Brønsted acids, such as 1a , 1c , and 2a , might generate N -Fmoc aldimines directly from the condensation of the aldehydes and a 9-fluorenylmethyl carbamate (FmocNH 2 ) .…”

“…Their electronic and steric alterations lead to notable changes in the chemical yields and the stereoselectivities of reactions involving these catalysts. , Unfortunately, the full potential of perfluorinated aryls has not been exploited in the development of chiral Brønsted acid catalysts . We have previously reported the monophosphoric acids 1a and 2a , which incorporate perfluorinated aryls, as stronger chiral Brønsted acid catalysts than the chiral monophosphoric acid 3 (Figure ). In 1a and 2a , the electron-withdrawing nature of the perfluoroaryl groups leads to higher Brønsted acidity, and 1a is a robust catalyst in the Hosomi–Sakurai reaction of N -acyl imines .…”

“…In 1a and 2a , the electron-withdrawing nature of the perfluoroaryl groups leads to higher Brønsted acidity, and 1a is a robust catalyst in the Hosomi–Sakurai reaction of N -acyl imines . Notably, 1a initiated this reaction even when less nucleophilic allyl- and crotyl trimethylsilanes, which do not possess a hydrogen bond donor site (Figure a upper reaction scheme), were used. , Based on previous results, we decided to explore whether the chiral monophosphoric acids incorporating perfluoroaryls, which are stronger chiral Brønsted acid catalysts, − can be used in reactions with other less reactive alkenes (Figure a lower reaction scheme) …”