The Suzuki–Miyaura cross-coupling of C(sp3)-hybridised boronic compounds still remains a challenging task, thereby hindering the broad application of alkyl boron substrates in carbon-carbon bond-forming reactions. Herein, we developed an NHC/photoredox...

The diversity of spirocyclic architecture offers a vast chemical space and enormous potential for drug discovery, while the skeletal diversity-oriented synthesis of spiromolecules from simple starting materials remains a challenging task. Here, we report a divergent stereoselective construction of [5,5] and [5,6] spiroheterocycles from identical substrates (vinylethylene carbonates and pyrrolidone-derived enones) through Lewis-acid-assisted and Brønsted-base-assisted palladium catalysis, respectively. With this protocol, a broad spectrum of enantioenriched tetrahydrofuranyl spiroketolactams was achieved via palladium/Al(OiPr) 3 cocatalyzed asymmetric (3 + 2) annulations. A collection of cyclohexenyl spiroketolactams was synthesized through diastereoselective (4 + 2) annulations under a palladium/NaHCO 3 catalytic system. Further synthesis elaboration was performed using both spiroskeletons to showcase the versatility of this methodology. In addition, density functional theory calculations provide a rationale toward the observed different reaction pathways with the divergently cooperative palladium catalysis.

Efficient construction of medium-sized lactones has attracted considerable interest over several decades, but remains a formidable challenge in synthetic chemistry. Here, we describe an unprecedented palladium-catalysed regioselective [5+n] cyclisation (n...

Biosynthesis utilizes kinetic strategies to regulate the chemoselectivity for the transformations of molecules containing multiple active reaction sites. But it is a grand challenge to realize the transformations without protecting group manipulations for chemosynthesis. α-Amino acid esters contain NH2 and α-C-H, two nucleophilic sites. Direct asymmetric α-C-alkylation of NH2-unprotected amino acid esters with alkyl halides represents one of the most straightforward strategies to access chiral quaternary α-amino acids, which are widely present in many pharmaceuticals. However, the transformation is challenging due to the high reactivity of intrinsic N-alkylation. Here, by using chiral pyridoxal 6 having a benzene-pyridine biaryl skeleton as a carbonyl catalyst, we successfully unlock the nucleophilic reactivity of the α-amino C–H bonds of α-amino acid esters toward alkyl halides without protection of the NH2 group, forming a wide range of chiral quaternary α-amino acid esters in up to 99% yield and 99% ee. Like transformations in biological systems, this protocol is featured with no protecting group manipulations and high atom and step efficiencies enabled by a biomimetic organocatalyst.