Presentation Title

Chiral Bisphosphorylimides as Organocatalysts for Asymmetric Friedel–Crafts Reactions

Faculty Mentor

Robert Iafe

Start Date

17-11-2018 12:30 PM

End Date

17-11-2018 2:30 PM

Location

CREVELING 101

Session

POSTER 2

Type of Presentation

Poster

Subject Area

physical_mathematical_sciences

Abstract

As a growing number of complex bioactive molecules flood the pharmaceutical industry, the demand for powerful enantioselective reactions and purification methods for these compounds becomes essential. Asymmetric organocatalysis is a field in organic chemistry that has emerged as a valuable synthetic tool complementary to traditional metal-catalyzed transformations. A type of organocatalyst that has been gaining notoriety is the bisphosphorylimide, which is a stronger acid and is more sterically hindered than chiral BINOL-derived phosphoric acids. This upsurge can be attributed to the simple preparation and functionalization of bisphosphorylimides. An enantioselective Friedel-Crafts reaction of electron-rich aromatic groups with Boc-protected aldimine electrophiles has been successfully accomplished using a chiral bisphosphorylimide organocatalyst. The chemical scaffold of bisphosphorylimides, which mimics the active site of an enzyme, enables the bisphosphorylimide organocatalyst to afford enantioenriched products. The use of triethyl amine as an additive was found to speed up the reaction and prevent product decomposition, resulting in excellent yields and regioselectivity. An improved synthesis of the bisphosphorylimide has also been developed using catalytic hydrogenation in a flow reactor. In addition, another bisphosphorylimide with a diphenyl modification was successfully synthesized, which generated an enantiomeric excess. The progress of catalyst development studies and planned catalyst investigations will be presented.

Summary of research results to be presented

The model bisphosphorylimide was synthesized in a series of four synthetic steps in a 55% overall yield. The investigation of the model bisphosphorylimide upon the Friedel–Crafts reaction between sesamol and benzylidenecarbamates yielded optimized reaction conditions of 5 mol % catalyst loading and 2.5 mol % triethyl amine additive at 0 ˚C, resulted in a 97% yield in 3 hours. Enantiomeric excess was determined by high performance liquid chromatography (HPLC). With these results, new efforts were focused on synthesizing bisphosphorylimides with various modifications. One bisphosphorylimide with a diphenyl modification was successfully synthesized in 8 steps in an 18% overall yield. An enantiomeric excess of 20% was obtained using this modified catalyst as confirmed by HPLC. Furthermore, progress toward the preparation of the bistrimethylsilyl modified organocatalyst will be presented. Future studies upon this catalyst and other planned bisphosphorylimide syntheses are currently in progress.

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Nov 17th, 12:30 PM Nov 17th, 2:30 PM

Chiral Bisphosphorylimides as Organocatalysts for Asymmetric Friedel–Crafts Reactions

CREVELING 101

As a growing number of complex bioactive molecules flood the pharmaceutical industry, the demand for powerful enantioselective reactions and purification methods for these compounds becomes essential. Asymmetric organocatalysis is a field in organic chemistry that has emerged as a valuable synthetic tool complementary to traditional metal-catalyzed transformations. A type of organocatalyst that has been gaining notoriety is the bisphosphorylimide, which is a stronger acid and is more sterically hindered than chiral BINOL-derived phosphoric acids. This upsurge can be attributed to the simple preparation and functionalization of bisphosphorylimides. An enantioselective Friedel-Crafts reaction of electron-rich aromatic groups with Boc-protected aldimine electrophiles has been successfully accomplished using a chiral bisphosphorylimide organocatalyst. The chemical scaffold of bisphosphorylimides, which mimics the active site of an enzyme, enables the bisphosphorylimide organocatalyst to afford enantioenriched products. The use of triethyl amine as an additive was found to speed up the reaction and prevent product decomposition, resulting in excellent yields and regioselectivity. An improved synthesis of the bisphosphorylimide has also been developed using catalytic hydrogenation in a flow reactor. In addition, another bisphosphorylimide with a diphenyl modification was successfully synthesized, which generated an enantiomeric excess. The progress of catalyst development studies and planned catalyst investigations will be presented.