CAREER: The Interplay of Photochromism and C-H Functionalization for Spatial Controlled Difunctionalization

With the support of the Chemical Synthesis (SYN) program in the Division of Chemistry Professor Marvin Parasram of New York University is studying the development of spatially controlled C–H functionalization reactions empowered by photochromic directing groups. The ability to functionalize strong and prevalent C–H bonds is a contemporary challenge in synthetic chemistry. Scientific advances in the area of transition metal (TM) catalyzed directed C–H functionalization reactions are limited to mono-functionalization using difficult-to-remove directing groups (DG). Moreover, the planarity of the employed DGs does not allow for spatial control, and functionalization is limited to predisposed C–H bonds based on favorable organometallic cycles. The research team will investigate the merger of photochromism and TM–catalyzed C–H functionalization to empower directional control of DGs to enable last-stage C–H difunctionalization at different spatial sites of the molecule. The ability to utilize photochromic DGs for positional controlled C–H functionalization has the potential to expedite the synthesis of important synthetic cores in a highly selective and diverse manner, thereby solving a prominent challenge in synthesis. The education and outreach activities will focus on increasing STEM interest through the development of research-based STEM laboratory classes for undergraduate and high-school students. For graduate students, a non-technical seminar focusing on a speaker’s career journey toward achieving their scientific career goals will be carried out. Lastly, a social/networking triannual symposium with the organic divisions of local New York City universities will be created to promote scientific interactions with graduate students and postdocs. In this work, Dr. Parasram leverages the interplay between photochromism and TM-catalyzed directed C–H functionalization to enable spatial selective C–H difunctionalization of organic molecules. The PI seeks to overcome the inherent limitations of state-of-the-art methodologies by 1) employing easy-to-remove photochromic DGs, 2) allowing directionality control of the directing group using different wavelengths of light, and 3) employing unsymmetrical electrophiles to generate unsymmetrical difunctionalized products. Objective 1 explores the use of innate functional groups as photoswitchable DGs to facilitate two separate and spatially different C–H functionalization events, allowing for the multivectorization of organic motifs in a highly selective and efficient manner. Methods to carry out this approach asymmetrically using chiral ligands, and applications to access molecular scaffolds of biological interest including natural products will be explored. Objective 2 investigates the use of designer photochromic DGs for the difunctionalization of heterocyclic motifs. The directionality control of the photochromic DGs can enable the functionalization of unconventional C–H sites on heterocycles, thus, solving a longstanding problem in the field. . This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.