Asymmetric Total Synthesis of Sarpagine and Koumine Alkaloids.

We report here a concise, collective, and asymmetric total synthesis of sarpagine alkaloids and biogenetically related koumine alkaloids, which structurally feature a rigid cage scaffold, with L-tryptophan as the starting material. Two key bridged skeleton-forming reactions, namely tandem sequential oxidative cyclopropanol ring-opening cyclization and ketone α-allenylation, ensure concurrent assembly of the caged sarpagine scaffold and installation of requisite derivative handles. With a common caged intermediate as the branch point, by taking advantage of ketone and allene groups therein, total synthesis of five sarpagine alkaloids (affinisine, normacusine B, trinervine, N -methyl-16-epipericyclivine, and vellosimine) with various substituents and three koumine alkaloids (koumine, koumimine, and N-demethylkoumine) with more complex cage scaffolds has been accomplished.

Lewis acid-catalyzed domino generation/[2,3]-sigmatropic rearrangement of ammonium ylides to access chiral azabicycles.

[2,3]-Sigmatropic rearrangement of ammonium ylides represents a fundamental reaction for stereoselective synthesis of nitrogenous compounds. However, its applicability is limited by the scarcity of efficient, catalytic, and mild methods for generating ammonium ylides. Here, we report silver-catalyzed domino generation/[2,3]-sigmatropic rearrangement of ammonium ylides, furnishing chiral azabicycles with bridgehead quaternary stereogenic centers in high enantiomeric purity (up to 99% ).

Enantioselective Alkynylation of Isatins: A Combination of Metal Catalysis and Organocatalysis.

An efficient and catalytic asymmetric alkynylation of isatins has been developed using a bifunctional amidophosphine-urea/AgBF complex as the catalyst. By a combination of metal catalysis and organocatalysis, excellent enantioselectivities (up to 99 % ee) and good yields are achieved. A wide range of both terminal alkynes and isatins are tolerated by this new catalyst system, providing access to structurally diverse propargylic alcohols with tetrasubstituted stereogenic centers in high efficiency.

Enantioselective Mannich Reaction of Glycine Iminoesters with -Phosphinoyl Imines: A Bifunctional Approach.

A bifunctional catalytic approach for the asymmetric Mannich reaction of glycine iminoesters with -phosphinoyl imines has been developed. By the combination of metal catalysis and organocatalysis, the vicinal two stereogenic centers were efficiently constructed, affording a wide range of -diamino esters in high yields with excellent enantio- and diastereoselectivities (up to >99:1 dr, 99% ee).

Copper-Catalyzed Aerobic Oxidative Cyclization Cascade to Construct Bridged Skeletons: Total Synthesis of (-)-Suaveoline.

Based on the discovery of copper-catalyzed cyclopropanol ring-opening addition to iminium ions, an unprecedented catalytic aerobic C-H oxidation/cyclopropanol cyclization cascade using CuCl as the multifunctional catalyst and air as the oxidant was developed to construct the azabicyclo[3.3.1]nonane skeleton, which is widespread in natural products and medicines.

Neighboring Hydroxyl Group-Assisted Allylboration and Lewis Acid-Mediated Carbonyl-Ene Reaction for Access to a Hapalindole Cyclohexane Core with Multiple Contiguous Stereogenic Centers.

A neighboring hydroxyl group-assisted allylboration of 3-indolyl ketones with γ,γ-disubstituted allylboronic acids is reported, affording various 3-indolyl-substituted homoallylic alcohols in good yields with excellent diastereoselectivies (up to >20:1 dr). The hydroxyl group not only played a vital role in the challenging allylboration but was elaborated for the subsequent construction of a hapalindole cyclohexane core by a highly diastereoselective Lewis acid-catalyzed carbonyl-ene reaction. In the overall process, four contiguous stereogenic centers including two quaternary stereogenic centers were installed.

Well-Designed Phosphine-Urea Ligand for Highly Diastereo- and Enantioselective 1,3-Dipolar Cycloaddition of Methacrylonitrile: A Combined Experimental and Theoretical Study.

A novel chiral phosphine-urea bifunctional ligand has been developed for Cu-catalyzed asymmetric 1,3-dipolar cycloaddition of iminoesters with methacrylonitrile, a long-standing challenging substrate in asymmetric catalysis. Distortion-interaction energy analysis based on density functional theory (DFT) calculations reveals that the distortion energy plays an important role in the observed enantioselectivity, which can be attributed to the steric effect between the phosphine ligand and the dipole reactant. DFT calculations also indicate that nucleophilic addition is the enantioselectivity-determining step and hydrogen bonding between the urea moiety and methacrylonitrile assists in control of the diastereo- and enantioselectivity.

Chiral Amino Alcohol Accelerated and Stereocontrolled Allylboration of Iminoisatins: Highly Efficient Construction of Adjacent Quaternary Stereogenic Centers.

We have developed a highly efficient asymmetric allylboration of ketimines with nonchiral γ,γ-disubstituted allylboronic acids by using a chiral amino alcohol as the directing group, which is otherwise challenging. The amino alcohol not only serves as a cheap source of nitrogen and chirality, but also dramatically enhances the reactivity. The versatility of this method was demonstrated by its ability to access all four stereoisomers with adjacent quaternary carbon centers.