gem‐Difluoromethylene Alkyne‐Enabled Diverse C−H Functionalization and Application to the on‐DNA Synthesis of Difluorinated Isocoumarins

Abstract

Using gem-difluoromethylene alkynes as effectors, unprecedented diverse CÀHa ctivation/[4+ +2] annulations of simple benzoica cids are reported. The chemodivergent reaction outcomes are well-tuned by Rh/Ir-catalyzed system; in the Rh III catalysis,3-alkenyl-1H-isochromen-1-one and 3,4dialkylideneisochroman-1-one skeletons are afforded in asolvent-dependent manner whereas difluoromethylene-substituted 1H-isochromen-1-ones are generated under the Ir III-catalyzed system. Mechanistic studies revealed that unusually double b-F eliminations and fluorine effect-induced regioselective reductive elimination are independently involved to enable distinct reaction modes for divergent product formations.B esides,s ynthetic application in both the derivatization of obtained diene products and the on-DNAsynthesis of DNAtagged difluorinated isocoumarin have been demonstrated, which manifested great potential for synthetic utility of the developed protocols.

Bioinspired Selenium‐Nitrogen Exchange (SeNEx) Click Chemistry Suitable for Nanomole‐Scale Medicinal Chemistry and Bioconjugation

“…However, this task is generally of big challenge due to the intractable contradiction that the highly functionalized DNA barcodes are water‐soluble and very sensitive, but their integrity must be maintained during the reaction process [63,64] . Despite this, the mild conditions, high yields and the suitability for nanomole‐scale parallel synthesis of this SeNEx click chemistry, as well as the successful experience of our group in the synthesis of DEL, [65–70] especially Se‐containing DNA‐encoded library ( Se DEL), [22,36,37,71] have prompted us to convert this newly developed reaction into on‐DNA synthesis.…”

Bioinspired Selenium‐Nitrogen Exchange (SeNEx) Click Chemistry Suitable for Nanomole‐Scale Medicinal Chemistry and Bioconjugation

“…However, this task is generally of big challenge due to the intractable contradiction that the highly functionalized DNA barcodes are water‐soluble and very sensitive, but their integrity must be maintained during the reaction process [63,64] . Despite this, the mild conditions, high yields and the suitability for nanomole‐scale parallel synthesis of this SeNEx click chemistry, as well as the successful experience of our group in the synthesis of DEL, [65–70] especially Se‐containing DNA‐encoded library ( Se DEL), [22,36,37,71] have prompted us to convert this newly developed reaction into on‐DNA synthesis.…”

Selenylation Chemistry Suitable for On‐Plate Parallel and On‐DNA Library Synthesis Enabling High‐Throughput Medicinal Chemistry

“…Typically, building blocks (BBs) and DNA barcodes are assembled by 3 to 4 cycles of interactive enzymatic encoding and DNA compatible reactions to efficiently generate the corresponding DEL. Therefore, the development of DNA compatible reactions is one of the key issues in DEL research field [53‐66] …”