Enantioselective Intermolecular C-H Functionalization of Primary Benzylic C-H Bonds Using ((Aryl)(diazo)methyl)phosphonates.

Catalyst-controlled C-H functionalization using donor/acceptor carbenes has been shown to be an efficient process capable of high levels of site control and stereocontrol. This study demonstrated that the scope of the donor/acceptor carbene C-H functionalization can be extended to systems where the acceptor group is a phosphonate. When using the optimized dirhodium catalyst, Rh(-(4-Br)TPPTTL), ((aryl)(diazo)methyl)phosphonates undergo highly enantioselective (84-99% ee) and site-selective (>30:1 r.

On-DNA hydroalkylation of -vinyl heterocycles photoinduced EDA-complex activation.

The emergence of DNA-encoded library (DEL) technology has provided a considerable advantage to the pharmaceutical industry in the pursuit of discovering novel therapeutic candidates for their drug development initiatives. This combinatorial technique not only offers a more economical, spatially efficient, and time-saving alternative to the existing ligand discovery methods, but also enables the exploration of additional chemical space by utilizing novel DNA-compatible synthetic transformations to leverage multifunctional building blocks from readily available substructures. In this report, a decarboxylative-based hydroalkylation of DNA-conjugated -vinyl heterocycles enabled by single-electron transfer (SET) and subsequent hydrogen atom transfer through electron-donor/electron-acceptor (EDA) complex activation is detailed.

Diversifying chemical space of DNA-encoded libraries: synthesis of 2-oxa-1-azaspiro(bicyclo[3.2.0])heptanes on-DNA visible light-mediated energy transfer catalysis.

Azaspiro[3.3]heptanes are valuable synthetic targets for drug discovery programs. The challenges associated with the preparation and diversification of this moiety as compared to other small, saturated rings have led to limited applications of compounds containing this spirocycle.

Dearomative intermolecular [2 + 2] photocycloaddition for construction of C(sp)-rich heterospirocycles on-DNA.

DNA-encoded library (DEL) screens have significantly impacted new lead compound identification efforts within drug discovery. An advantage of DELs compared to traditional screening methods is that an exponentially broader chemical space can be effectively screened using only nmol quantities of billions of DNA-tagged, drug-like molecules. The synthesis of DELs containing diverse, sp-rich spirocycles, an important class of molecules in drug discovery, has not been previously reported.