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Site‐selective transition‐metal‐catalyzed mono‐deboronative cross‐couplings of 1,2‐bis‐boronic esters are valuable methods for the synthesis of functionalized organoboron compounds. However, such cross‐couplings are limited to reaction of the sterically less hindered primary boronic ester. Herein, we report a nickel/photoredox‐catalyzed mono‐deboronative arylation of 1,2‐bis‐boronic esters that is selective for coupling of the more sterically hindered secondary/tertiary position. This is achieved by taking advantage of a 1,2‐boron shift of primary β‐boryl radicals to the thermodynamically favored secondary/tertiary radicals, which are subsequently intercepted by the nickel catalyst to enable arylation. The mild conditions are amenable to a broad range of aryl halides to give β‐aryl boronic ester products in good yields and with high regioselectivity. This method also allows stereodivergent coupling of cyclic cis‐1,2‐bis‐boronic esters to give trans‐substituted products. [ABSTRACT FROM AUTHOR]

Site‐selective transition‐metal‐catalyzed mono‐deboronative cross‐couplings of 1,2‐bis‐boronic esters are valuable methods for the synthesis of functionalized organoboron compounds. However, such cross‐couplings are limited to reaction of the sterically less hindered primary boronic ester. Herein, we report a nickel/photoredox‐catalyzed mono‐deboronative arylation of 1,2‐bis‐boronic esters that is selective for coupling of the more sterically hindered secondary/tertiary position. This is achieved by taking advantage of a 1,2‐boron shift of primary β‐boryl radicals to the thermodynamically favored secondary/tertiary radicals, which are subsequently intercepted by the nickel catalyst to enable arylation. The mild conditions are amenable to a broad range of aryl halides to give β‐aryl boronic ester products in good yields and with high regioselectivity. This method also allows stereodivergent coupling of cyclic cis‐1,2‐bis‐boronic esters to give trans‐substituted products. [ABSTRACT FROM AUTHOR]

Due to unknown pathogenesis and unidentified drug target, no drug for the treatment of osteosarcoma (OS) has been launched to the market. Herein, thiazolidinone 1a was discovered as a hit compound by phenotypic screening with an in-house patrimonial collection of structural diversity. The following SAR (Structure-Activity Relationship) study affords the final water-soluble lead compound (R)- 8i as a potential inhibitor for the proliferation of OS cells by the modulation of solubility of the compounds with remarkable cellular potency (IC 50 = 21.9 nM for MNNG/HOS cells) and in vivo efficacy (52.9% inhibition OS growth in mice), as well as pharmacokinetic properties. (R)- 8i also significantly suppresses OS cell migration in vitro and showed to be well-tolerated. Our preliminary investigation shows that the effects of (R)- 8i are not dependent on p53 and myoferlin (MYOF). These results suggest that (R)- 8i might be a potential drug candidate for OS treatment. [Display omitted] • Thiazolidinones were discovered for treating osteosarcoma by phenotypic screening. • The screening used an in-house patrimonial collection of structural diversity. • Lead compound (R)- 8i selectively inhibit osteosarcoma cell in vitro and in vivo. • (R)- 8i also significantly suppresses osteosarcoma cell migration in vitro. • (R)- 8i presents a considerable bioavailability and a low toxicity. [ABSTRACT FROM AUTHOR]