Highly selective conjugate additions of Grignard reagents to cyclic and linear enones catalyzed by recyclable heterogeneous polysaccharide/nanocopper catalysts are disclosed. The method also allows the synthesis of ketones with an all-carbon quaternary center. When integrated with catalytic asymmetric tandem reactions using enals and β-ketoesters, it yields chiral β,δ-disubstituted ketones with high stereoselectivity.

Herein, we present a highly efficient allylic substitution of carbonates with Grignard reagents using a reusable cellulose-supported nanocopper catalyst. This approach highlights the first instance of heterogeneous catalysis for the cross-coupling of allylic alcohol substrates with Grignard reagents. The method features high yields, excellent regioselectivity, and complete chirality transfer.

Direct cross-coupling reactions between two similar unactivated partners are challenging but constitute a powerful strategy for the creation of new carbon-carbon bonds in organic synthesis. [4]Dendralenes are a class of acyclic branched conjugated oligoenes with great synthetic potential for the rapid generation of structural complexity, yet the chemistry of [4]dendralenes remains an unexplored field due to their limited accessibility. Herein, we report a highly selective palladium-catalyzed oxidative cross-coupling of two allenes with the presence of a directing olefin in one of the allenes, enabling the facile synthesis of a broad range of functionalized [4]dendralenes in a convergent modular manner. Specifically, the selective allenic C-H activation of an allene with an allyl substituent as the assisting group gives rise to a vinylpalladium intermediate, which reacts with a less substituted allene in a carbopalladation, followed by a β-hydride elimination. The reaction sequence leads to a new C(sp2)-C(sp2) bond between two diene units. Remarkably, this protocol provides an unconventional strategy for the site-selective and stereoselective construction of C(vinyl)-C(vinyl) bonds without using any halogenated and organometallics olefin precursors. Furthermore, the practical transformations of the synthesized [4]dendralenes and late-stage modifications of biorelevant molecules demonstrate their potential in the total synthesis of natural products and drug discovery.

Nature efficiently produces a myriad of structurally diverse carbon ring frameworks from common linear precursors via cyclization reactions at specific olefinic sites in dienes or polyenes. In contrast, achieving the site-selective functionalization of diene or polyene substrates remains a formidable challenge in chemical synthesis. Herein, we report a pair of highly site-selective, regiodivergent carbocyclization reactions of dienallenes and trienallenes, enabling the efficient synthesis of cis-1,4-disubstituted cyclohexenes and trans-1,2-disubstituted cyclobutenes from a common precursor with high diastereoselectivity. Remarkably, simple achiral organophosphoric acids and amines are identified as powerful ligands for controlling these palladium-catalyzed regiodivergent carbocyclizations. This approach represents the first example of site-selective regiodivergent carbocyclization, providing a practical method for the stereospecific synthesis of thermodynamically disfavored cis-1,4-disubstituted cyclohexenes and fully substituted trans-1,2-cyclobutenes. Additionally, the methodology developed offers general insights into the development of metal-catalyzed site-selective, regiodivergent carbocyclizations of diene and polyene precursors, mimicking natural carbocyclization processes.

Chemoenzymatic dynamic kinetic resolution (DKR), combining a metal racemization catalyst with an enzyme, has emerged as an elegant solution to transform racemic substrates into enantiopure products, while compatibility of dual catalysis is the key issue. Conventional solutions have utilized presynthesized metal complexes with a fixed and bulky ligand to protect the metal from the enzyme system; however, this has been generally limited to anionic ligands. Herein, we report our strategy to solve the compatibility issue by employing a reliable ligand that firmly coordinates in situ to the metal. Such a reliable ligand offers π* orbitals, allowing additional metal-to-ligand d−π* back-donation, which can significantly enhance coordination effects between the ligand and metal. Therefore, we developed an efficient DKR method to access chiral BINOLs from racemic derivatives under dual copper and enzyme catalysis. In cooperation with lipase LPL-311-Celite, the DKR of BINOLs was successfully realized with a copper catalyst via in situ coordination of BCP (L8) to CuCl. A series of functionalized C2- and C1-symmetric chiral biaryls could be synthesized in high yields with good enantioselectivity. The racemization mechanism was proposed to involve a radical-anion intermediate, which allows the axial rotation with a dramatic decrease of the rotation barrier.

A highly efficient dehydrogenative carbonylative esterification of allenoic acids using Pd-catalysis was developed, providing a novel approach to synthesizing esterified γ-butyrolactone derivatives with consistently good to excellent results demonstrated across over 50 examples. Additionally, we used a heterogeneous catalyst known as Pd-AmP-MCF and harnessed biomimetic-aerobic-oxidation conditions to facilitate the practical execution of this reaction. Furthermore, our detailed study of γ-butyrolactone products highlighted their potential in synthesizing bioactive compounds.

Here we report an efficient route for synthesizing strigolactones (SLs) and their derivatives. Our method relies on a palladium-catalyzed oxidative carbonylation/carbocyclization/carbonylation/alkoxylation cascade reaction, which involves the formation of three new C–C bonds and a new C–O bond while cleaving one C(sp³)–H bond in a single step. With our versatile synthetic strategy, both naturally occurring and artificial SLs were prepared.

A novel and sustainable tandem-catalysis system for asymmetric synthesis is disclosed, which is fabricated by bio-inspired self-assembly of artificial arthropod exoskeletons (AAEs) or artificial fungi cell walls (AFCWs) containing two different types of catalysts (enzyme and metal nanoparticles). The heterogeneous integrated enzyme/metal nanoparticle AAE/AFCW systems, which contain chitosan as the main structural component, co-catalyze dynamic kinetic resolution of primary amines via a tandem racemization/enantioselective amidation reaction process to give the corresponding amides in high yields and excellent ee. The heterogeneous AAE/AFCW systems display successful heterogeneous synergistic catalysis at the surfaces since they can catalyze multiple reaction cycles without metal leaching. The use of natural-based and biocompatible structural components makes the AAE/AFCW systems fully biodegradable and renewable, thus fulfilling important green chemistry requirements. 

Herein, we describe efficient nanogold-catalyzed cycloisomerization reactions of alkynoic acids and allenynamides to enol lactones and dihydropyrroles, respectively (the latter via an Alder-ene reaction). The gold nanoparticles were immobilized on thiol-functionalized microcrystalline cellulose and characterized by electron microscopy (HAADF-STEM) and by XPS. The thiol-stabilized gold nanoparticles (Au-0) were obtained in the size range 1.5-6 nm at the cellulose surface. The robust and sustainable cellulose-supported gold nanocatalyst can be recycled for multiple cycles without losing activity.

Classical Crabbé type S_N2' substitutions of propargylic substrates has served as one of the standard methods for the synthesis of allenes. However, the stereospecific version of this transformation often requires either stoichiometric amounts of organocopper reagents or special functional groups on the substrates, and the chirality transfer efficiency is also capricious. Herein, we report a sustainable methodology for the synthesis of diverse 1,3-di and tri-substituted allenes by using a simple and cheap cellulose supported heterogeneous nanocopper catalyst (MCC-Amp-Cu(I/II)). This approach represents the first example of heterogeneous catalysis for the synthesis of chiral allenes. High yields and excellent enantiospecificity (up to 97 % yield, 99 % ee) were achieved for a wide range of di- and tri-substituted allenes bearing various functional groups. It is worth noting that the applied heterogeneous catalyst could be recycled at least 5 times without any reduced reactivity. To demonstrate the synthetic utility of the developed protocol, we have applied it to the total synthesis of several chiral allenic natural products.