Enantioselective Kinetic Resolution/Desymmetrization of Para‐Quinols: A Case Study in Boronic‐Acid‐Directed Phosphoric Acid Catalysis

Abstract

A chiral phosphoric acid-catalyzed kinetic resolution and desymmetrization of paraquinols operating via oxa-Michael addition was developed and subsequently subjected to mechanistic study. Good to excellent s-factors/enantioselectivities were obtained over a broad range of substrates. Kinetic studies were performed, and DFT studies favor a hydrogen bonding activation mode. The mechanistic studies provide insights to previously reported chiral anion phase transfer reactions involving chiral phosphate catalysts in combination with boronic acids.

Asymmetric synthesis of CF2-functionalized aziridines by combined strong Brønsted acid catalysis

“…Unfortunately, these endeavors resulted in either no conversion or no enantioselectivity at all. As arylboronic acids have been harnessed to enhance the Brønsted acidity in asymmetric organocatalysis in combination with chiral diols or chiral aminoalcohols [40][41][42][43][44], we envisioned that the simultaneous use of arylboronic acids and chiral Brønsted acids may bring about a complementary catalytic platform. Encouragingly, the targeted CF 2 -functionalized aziridine 4a was obtained in up to 51% ee and high diastereoselectivity, albeit in a low yield ( Table 1, entries 1 and 2).…”

Asymmetric Synthesis of CF2-Aziridines Enabled by Combined Strong Brønsted Acid Catalysis

“…Unfortunately, such endeavors resulted in either no conversion or no enantioselectivity at all. As aryl boronic acids have been 4 harnessed to enhance Brønsted acidity in asymmetric organocatalysis in combination with chiral diols or chiral amino-alcohols [40][41][42][43][44], we envisioned that the simultaneous use of aryl boronic acids and chiral Brønsted acid may bring with a complementary catalytic platform. Encouragingly, the targeted CF2-aziridine 4a was obtained in up to 51% ee with high diastereoselectivity, albeit in low yield (Table1, entries 1 and 2).…”

Organocatalytic Enantioselective Intramolecular (Hetero)Michael Additions in Desymmetrization Processes

“…The latest example of desymmetrization via oxa-Michael reactions is a very recent work carried out by Toste and collaborators. [41] The authors developed a phosphoric acidcatalyzed kinetic resolution of 4-hydroxycyclohexadienones 12 through an enantioselective formal oxa-Michael addition of hydroxide, which was actually an enantioselective intramolecular cyclisation of boronic acid followed by the hydrolysis of the monoester intermediate. After screening of different chiral phosphoric acids as well as boronic acids and boroxines, the optimal conditions found for the kinetic resolution of 12 involved the use of BINOL-derived phosphoric acid XXV as catalyst and 1-naphthyl boroxine XXVI as co-catalyst, in toluene at room temperature (Scheme 27).…”