Total Synthesis of Acortatarin A Using a Pd(II)-Catalyzed Spiroketalization Strategy

The total synthesis of acortatarin A relying on a Pd­(II)-catalyzed spiroketalization is reported. This strategy allows a single stereocenter in the spiroketalization substrate to produce the target efficiently under mild conditions, installing the necessary oxygenation in the backbone through an allylic transposition. The synthesis also verifies that pollenopyrroside B and acortatarin A are the same compound, and electrochemical studies suggest that the reported bioactivity is not due to simple antioxidant properties

Enantioselective Alkyne Conjugate Addition Enabled by Readily Tuned Atropisomeric <i>P</i>,<i>N</i>‑Ligands

By the nature of its structure, the 5-membered chiral biaryl heterocyclic scaffold represents a departure from 6-membered <i>P</i>,<i>N</i>-ligands that facilitates tuning and enables ligand evolution to address issues of selectivity and reactivity. In this vein, the Cu-catalyzed enantioselective conjugate alkynylation of Meldrum’s acid acceptors is reported using Me-StackPhos. Enabled by this new ligand, the reaction tolerates a wide range of alkynes furnishing the products in high yields and excellent enantioselectivity. The transformation provides access to highly useful chiral β-alkynyl Meldrum’s acid building blocks as demonstrated by an efficient enantioselective synthesis of the preclinical agent OPC 51803

Catalytic Enantioselective Alkyne Addition to Nitrones Enabled by Tunable Axially Chiral Imidazole-Based P,N-Ligands

Although catalytic enantioselective alkyne addition is an established method for the synthesis of chiral propargylic alcohols and amines, addition to nitrones presents unique challenges, and no general chiral catalyst system has been developed. In this manuscript, we report the first Cu-catalyzed enantioselective alkyne addition to nitrones utilizing tunable axially chiral imidazole-based P,N-ligands. Our approach effectively overcomes difficulties in both reactivity and selectivity, resulting in a simple Cu-catalyzed protocol. The reaction accommodates a wide range of nitrones and alkynes, enabling the streamlined synthesis of chiral propargyl N-hydroxylamines via the enantioselective C–C bond formation. A diverse array of optically active nitrogen-containing compounds, including chiral hydroxylamines, can be accessed directly through facile transformations of the reaction products

Diastereoselective Synthesis of Protected 1,3-Diols by Catalytic Diol Relocation

A complementary diastereoselective gold­(I) or bismuth­(III) catalyzed tandem hemiacetalization/dehydrative cyclization of 1,5-monoallylic diols was developed to access 1,3-dioxolanes and dioxanes. This methodology provides rapid access to protected 1,3-diols under mild conditions with high levels of diastereoselectivity

Catalytic Enantioselective Synthesis of Amino Skipped Diynes

The Cu-catalyzed synthesis of nonracemic 3-amino skipped diynes via an enantiodetermining C–C bond formation is described using StackPhos as ligand. Despite challenging issues of reactivity and stereoselectivity inherent to these chiral skipped diynes, the reaction tolerates an extremely broad substrate scope with respect to all components and provides the title compounds in excellent enantiomeric excess. The alkyne moieties are demonstrated here to be useful synthetic handles, and 3-amino skipped diynes are convenient building blocks for enantioselective synthesis

Design, Preparation, and Implementation of an Imidazole-Based Chiral Biaryl P,N-Ligand for Asymmetric Catalysis

A new strategy for increasing the barrier to rotation in biaryls has been developed that allows for the incorporation of 5-membered aromatic heterocycles into chiral atropisomers. Using this concept, an imidazole-based biaryl P,N-ligand has been designed and prepared as a single enantiomer. This ligand performs exceptionally well in the enantioselective A³-coupling, demonstrating the potential of this new design element

Design, Preparation, and Implementation of an Imidazole-Based Chiral Biaryl P,N-Ligand for Asymmetric Catalysis

A new strategy for increasing the barrier to rotation in biaryls has been developed that allows for the incorporation of 5-membered aromatic heterocycles into chiral atropisomers. Using this concept, an imidazole-based biaryl P,N-ligand has been designed and prepared as a single enantiomer. This ligand performs exceptionally well in the enantioselective A³-coupling, demonstrating the potential of this new design element

Incorporation of Axial Chirality into Phosphino-Imidazoline Ligands for Enantioselective Catalysis

A complementary strategy for ligand tuning that enables controlling ligand conformation is described here. The concept is demonstrated with new ligands that are employed in the catalytic enantioselective preparation of the highly important C2-aminoalkyl five-membered heterocycle motif. The alkynylation/cyclization sequence developed here is convergent, highly modular, and allows for a complementary scope to the heteroarylation of imines. This new ligand platform should offer new possibilities for expanding the use of PHIM-type ligands in a large variety of new transformations

Controlling Regiochemistry in the Gold-Catalyzed Synthesis of Unsaturated Spiroketals

A novel gold-catalyzed synthesis of unsaturated spiroketals that addresses regioselectivity issues commonly reported in metal-catalyzed spiroketalization of alkynes is reported. The reaction sequence is regulated by an acetonide protecting group which undergoes extrusion of acetone to deliver the desired spiroketals in good yields and diastereoselectivities. The reaction, which is carried out under very mild conditions employing AuCl as the catalyst, should be widely applicable in the synthesis of a broad range of spiroketals

Design, Preparation, and Implementation of an Imidazole-Based Chiral Biaryl P,N-Ligand for Asymmetric Catalysis

A new strategy for increasing the barrier to rotation in biaryls has been developed that allows for the incorporation of 5-membered aromatic heterocycles into chiral atropisomers. Using this concept, an imidazole-based biaryl P,N-ligand has been designed and prepared as a single enantiomer. This ligand performs exceptionally well in the enantioselective A³-coupling, demonstrating the potential of this new design element