Enantioselective Total Synthesis of (-)-Vinigrol: The Evolution of a Transannular Diels-Alder Strategy.

Vinigrol is a structurally and stereochemically complex diterpenoid that displays various potent pharmacological activities. Two generations of synthetic routes were designed and pursued based on a transannular Diels-Alder (TADA) cycloaddition strategy. An intramolecular [2 + 2]photocycloaddition in the presence of the chelating Lewis acid (MgBr2·Et2O) was first discovered to enable the reaction of sterically challenging substrates, which was followed by [2 + 2]cycloreversion to provide α-pyrones fused with a 10-membered ring. Eventually, a new and scalable synthetic route toward (-)-vinigrol was developed and provided over 600 mg materials, manifesting the power of macrocyclic stereocontrol and TADA reaction.

Scalable Total Synthesis of (-)-Vinigrol.

Vinigrol is a structurally and stereochemically complex natural product that displays various potent pharmacological activities, including the capability to modulate TNF-α. A new and efficient synthetic route toward this natural product has been developed to complete the asymmetric synthesis of (-)-vinigrol and provide over 600 mg of material, manifesting the power of macrocyclic stereocontrol and transannular Diels-Alder reaction.

Surface-confined alternating copolymerization with molecular precision by stoichiometric control.

Keen desires for artificial mimicry of biological polymers and property improvement of synthesized ones have triggered intensive explorations for sequence-controlled copolymerization. However, conventional synthesis faces great challenges to achieve this goal due to the strict requirements on reaction kinetics of comonomer pairs and tedious synthetic processes. Here, sequence-controlled alternating copolymerization with molecular precision is realized on surface. The stoichiometric control serves as a thermodynamic strategy to steer the polymerization selectivity, which enables the selective alternating organometallic copolymerization via intermolecular metalation of 4,4"-dibromo-p-terphenyl (P-Br) and 2,5-diethynyl-1,4-bis(phenylethynyl)benzene (A-H) with Ag adatoms on Ag(111) at P-Br: A-H = 2, as verified by scanning tunneling microscopy and density functional theory studies. In contrast, homopolymerization yield increases as the stoichiometric ratio deviates from 2. The microscopic characterizations rationalize the mechanism, providing a delicate explanation of the stoichiometry-dependent polymerization. These findings pave a way to actualizing an efficient sequence control of copolymerization by surface chemistry.

Lattice-Directed Formation of Covalent and Organometallic Molecular Wires by Terminal Alkynes on Ag Surfaces.

Surface reactions of 2,5-diethynyl-1,4-bis(phenylethynyl)benzene on Ag(111), Ag(110), and Ag(100) were systematically explored and scrutinized by scanning tunneling microscopy, molecular mechanics simulations, and density functional theory calculations. On Ag(111), Glaser coupling reaction became dominant, yielding one-dimensional molecular wires formed by covalent bonds. On Ag(110) and Ag(100), however, the terminal alkynes reacted with surface metal atoms, leading to one-dimensional organometallic nanostructures. Detailed experimental and theoretical analyses revealed that such a lattice dependence of the terminal alkyne reaction at surfaces originated from the matching degree between the periodicities of the produced molecular wires and the substrate lattice structures.