Enantioselective Hydroarylation of Bridged [3.2.1] Heterocycles: An Efficient Entry into the Homoepibatidine Skeleton

Achiral [3.2.1] bridged heterocycles containing a bridging amide can undergo enantioselective hydroarylation reactions under rhodium(I) catalysis. These reactions proceed in high yield and enantioselectivity in most cases, under mild reaction conditions and using commercially available Josiphos ligands. The phosphine ligand structure and the protecting group on the nitrogen both have significant effects on the selectivity and yield of the reactions

Enantioselective Hydroarylation of Bridged [3.2.1] Heterocycles: An Efficient Entry into the Homoepibatidine Skeleton

Achiral [3.2.1] bridged heterocycles containing a bridging amide can undergo enantioselective hydroarylation reactions under rhodium(I) catalysis. These reactions proceed in high yield and enantioselectivity in most cases, under mild reaction conditions and using commercially available Josiphos ligands. The phosphine ligand structure and the protecting group on the nitrogen both have significant effects on the selectivity and yield of the reactions

An Efficient Synthesis of Bridged Heterocycles from an Ir(I) Bis-Amination/Ring-Closing Metathesis Sequence

The amination of bis-allylic imidates using an Iridium(I) catalyst leads to the efficient formation of 2,6-divinyl heterocycles. Careful screening of amines, solvents, and conditions has led to the discovery of a system that favors formation of the desired <i>cis</i> products with synthetically useful levels of diastereoselectivity, and these results are further explained by computer based transition state energy calculations. Exposure of the heterocycles to ring-closing metathesis catalysts leads to the desired bridged heterocyclic systems

Enantioselective Hydroarylation of Bridged [3.2.1] Heterocycles: An Efficient Entry into the Homoepibatidine Skeleton

Achiral [3.2.1] bridged heterocycles containing a bridging amide can undergo enantioselective hydroarylation reactions under rhodium(I) catalysis. These reactions proceed in high yield and enantioselectivity in most cases, under mild reaction conditions and using commercially available Josiphos ligands. The phosphine ligand structure and the protecting group on the nitrogen both have significant effects on the selectivity and yield of the reactions

An Efficient Synthesis of Bridged Heterocycles from an Ir(I) Bis-Amination/Ring-Closing Metathesis Sequence

The amination of bis-allylic imidates using an Iridium(I) catalyst leads to the efficient formation of 2,6-divinyl heterocycles. Careful screening of amines, solvents, and conditions has led to the discovery of a system that favors formation of the desired <i>cis</i> products with synthetically useful levels of diastereoselectivity, and these results are further explained by computer based transition state energy calculations. Exposure of the heterocycles to ring-closing metathesis catalysts leads to the desired bridged heterocyclic systems

An Efficient Synthesis of Bridged Heterocycles from an Ir(I) Bis-Amination/Ring-Closing Metathesis Sequence

The amination of bis-allylic imidates using an Iridium(I) catalyst leads to the efficient formation of 2,6-divinyl heterocycles. Careful screening of amines, solvents, and conditions has led to the discovery of a system that favors formation of the desired <i>cis</i> products with synthetically useful levels of diastereoselectivity, and these results are further explained by computer based transition state energy calculations. Exposure of the heterocycles to ring-closing metathesis catalysts leads to the desired bridged heterocyclic systems

An Efficient Synthesis of Bridged Heterocycles from an Ir(I) Bis-Amination/Ring-Closing Metathesis Sequence

The amination of bis-allylic imidates using an Iridium(I) catalyst leads to the efficient formation of 2,6-divinyl heterocycles. Careful screening of amines, solvents, and conditions has led to the discovery of a system that favors formation of the desired <i>cis</i> products with synthetically useful levels of diastereoselectivity, and these results are further explained by computer based transition state energy calculations. Exposure of the heterocycles to ring-closing metathesis catalysts leads to the desired bridged heterocyclic systems

An Efficient Synthesis of Bridged Heterocycles from an Ir(I) Bis-Amination/Ring-Closing Metathesis Sequence

The amination of bis-allylic imidates using an Iridium(I) catalyst leads to the efficient formation of 2,6-divinyl heterocycles. Careful screening of amines, solvents, and conditions has led to the discovery of a system that favors formation of the desired <i>cis</i> products with synthetically useful levels of diastereoselectivity, and these results are further explained by computer based transition state energy calculations. Exposure of the heterocycles to ring-closing metathesis catalysts leads to the desired bridged heterocyclic systems

Enantioselective Hydroarylation of Bridged [3.2.1] Heterocycles: An Efficient Entry into the Homoepibatidine Skeleton

Achiral [3.2.1] bridged heterocycles containing a bridging amide can undergo enantioselective hydroarylation reactions under rhodium(I) catalysis. These reactions proceed in high yield and enantioselectivity in most cases, under mild reaction conditions and using commercially available Josiphos ligands. The phosphine ligand structure and the protecting group on the nitrogen both have significant effects on the selectivity and yield of the reactions

Use of 3D Properties to Characterize Beyond Rule-of-5 Property Space for Passive Permeation

The application of conformationally dependent measures of size and polarity to characterize beyond rule-of-5 (Ro5) space for passive permeation was investigated. Specifically, radius of gyration, an alternative to molecular weight, and three-dimensional polar surface area and the generalized Born/surface area dehydration free energy, alternatives to hydrogen-bond donor and acceptor counts, were computed on models of the permeating conformations of over 35 000 molecules. The resulting guidelines for size and polarity, described by the 3D properties, should aid the design of Ro5 violators with passive permeability