Dearomative intermolecular [2 + 2] photocycloaddition for construction of C(sp<sup>3</sup>)-rich heterospirocycles on-DNA
Longbo Li, Bianca T. Matsuo, Guillaume Levitre, Edward J. McClain, Eric A. Voight, Erika A. Crane, Gary A. Molander
Abstract
-methylenecyclobutane substrates were prepared from easily accessible alkyl iodides and styrene derivatives. Broad reactivity with many other DNA-conjugated alkene substrates was observed, including unactivated and activated alkenes, and the process is tolerant of various heterocycles. The cycloaddition was successfully scaled from 10 to 100 nmol without diminished yield, indicative of this reaction's suitability for DNA-encoded library production. Evaluation of DNA compatibility with the developed reaction in a mock-library format showed that the DNA barcode was maintained with high fidelity, with <1% mutated sequences and >99% amplifiable DNA from quantitative polymerase chain reaction (PCR) and next generation sequencing (NGS).