Nickel-catalyzed reductive cross-coupling reactions have emerged as powerful methods to join two electrophiles. These reactions have proven particularly useful for the coupling of sec-alkyl electrophiles to form stereogenic centers; however, the development of enantioselective variants remains challenging. In this Perspective, we summarize the progress that has been made toward Ni-catalyzed enantioselective reductive cross-coupling reactions.

Cancer stem cells (CSCs) are progenitor cells that contribute to treatment-resistant phenotypes during relapse. CSCs exist in specific tissue microenvironments that cell cultures and more complex models cannot mimic. Therefore, the development of new approaches that can detect CSCs and report on specific properties (e.g., stem cell plasticity) in their native environment have profound implications for studying CSC biology. Herein, we present AlDeSense, a turn-on fluorescent probe for aldehyde dehydrogenase 1A1 (ALDH1A1) and Ctrl-AlDeSense, a matching nonresponsive reagent. Although ALDH1A1 contributes to the detoxification of reactive aldehydes, it is also associated with stemness and is highly elevated in CSCs. AlDeSense exhibits a 20-fold fluorescent enhancement when treated with ALDH1A1. Moreover, we established that AlDeSense is selective against a panel of common ALDH isoforms and exhibits exquisite chemostability against a collection of biologically relevant species. Through the application of surface marker antibody staining, tumorsphere assays, and assessment of tumorigenicity, we demonstrate that cells exhibiting high AlDeSense signal intensity have properties of CSCs. Using these probes in tandem, we have identified CSCs at the cellular level via flow cytometry and confocal imaging, as well as monitored their states in animal models.

A Ni-catalyzed enantioselective reductive cross-coupling of α-chloroesters and (hetero)aryl iodides is reported. A MLR model was developed to quantitatively relate the influence of the α-chloroester substrate and ligand on enantioselectivity.

Scheme 2. Total Synthesis of (−)-Longikaurin E (3) and (−)-Trichorabdal A (2) Accounts of Chemical Research pubs.acs.org/accounts Article

The synthesis of densely functionalized trisubstituted and tetrasubstituted furans via a novel Ru(II)-catalyzed intramolecular cyclization of vinyl diazoesters is reported. The synthetic utility of these furans is further demonstrated through a simple acid-mediated reaction to access highly substituted Δα,β-butenolides.