Benzannulation and Hydrocarboxylation Methods for the Synthesis of a Neopentylene-Fused Analogue of Ibuprofen

A C Martin; Jessica A Rogers; Paratchata Batsomboon; Alec E Morrison; Ron R Ramsubhag; Brian V Popp; Gregory B Dudley

doi:10.1021/acsomega.1c04943

Benzannulation and Hydrocarboxylation Methods for the Synthesis of a Neopentylene-Fused Analogue of Ibuprofen

ACS Omega. 2021 Oct 26;6(44):30108-30114. doi: 10.1021/acsomega.1c04943. eCollection 2021 Nov 9.

Authors

A C Martin¹, Jessica A Rogers¹, Paratchata Batsomboon¹, Alec E Morrison², Ron R Ramsubhag², Brian V Popp¹, Gregory B Dudley^{1

2}

Affiliations

¹ C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, West Virginia 26505, United States.
² Department of Chemistry and Biochemistry, Florida State University, Tallahassee, Florida 32306, United States.

Abstract

Neopentylene ring fusions (ring-fused 4,4-dimethylcyclopentane polycycles) are found in many natural products, but they are largely absent from synthetic compound libraries and focused medicinal chemistry research. Here is reported a synthetic approach to one of the few non-natural product-based target compounds from medicinal chemistry that includes a neopentylene ring fusion: an analogue of ibuprofen referred to herein as "neoprofen". The approach features ring-opening fragmentation reactions of dimedone derivatives coupled with transition metal-catalyzed benzannulation and hydrocarboxylation methods.