Metal‐coordinating directing groups have seen extensive use in the field of transition‐metal‐catalyzed alkene functionalization; however, their waste‐generating installation and removal steps limit the efficiency and practicality of reactions that rely on their use. Inspired by developments in asymmetric organocatalysis, where reactions rely on reversible covalent interactions between an organic substrate and a chiral mediator, we have developed a transient‐directing‐group approach to reductive Heck hydroarylation of alkenyl benzaldehyde substrates that proceeds under mild conditions. Highly stereoselective migratory insertion is facilitated by in situ formation of an imine from catalytic amounts of a commercially available amino acid additive. Computational studies reveal an unusual mode of enantioinduction by the remote chiral center in the transient directing group.
Metal‐coordinating directing groups have seen extensive use in the field of transition‐metal‐catalyzed alkene functionalization; however, their waste‐generating installation and removal steps limit the efficiency and practicality of reactions that rely on their use. Inspired by developments in asymmetric organocatalysis, where reactions rely on reversible covalent interactions between an organic substrate and a chiral mediator, we have developed a transient‐directing‐group approach to reductive Heck hydroarylation of alkenyl benzaldehyde substrates that proceeds under mild conditions. Highly stereoselective migratory insertion is facilitated by in situ formation of an imine from catalytic amounts of a commercially available amino acid additive. Computational studies reveal an unusual mode of enantioinduction by the remote chiral center in the transient directing group.
more » « less- PAR ID:
- 10143400
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Angewandte Chemie International Edition
- Volume:
- 59
- Issue:
- 23
- ISSN:
- 1433-7851
- Page Range / eLocation ID:
- p. 8885-8890
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
more » « less
Abstract -
more » « less
Abstract Carbazole alkaloids hold great potential in pharmaceutical and material sciences. However, the current approaches for C1 functionalization of carbazoles rely on the use of a pre‐installed directing group, severely limiting their applicability and hindering their overall efficiency. Herein, we report for the first time the development of direct Pd‐catalyzed C−H alkylation and acylation of carbazoles assisted by norbornene (NBE) as a transient directing mediator. Notably, the involvement of a six‐membered palladacycle intermediate was suggested in this case, representing the first example of such intermediacy within the extensively studied Pd/norbornene reactions realm.
-
more » « less
Abstract Carbazole alkaloids hold great potential in pharmaceutical and material sciences. However, the current approaches for C1 functionalization of carbazoles rely on the use of a pre‐installed directing group, severely limiting their applicability and hindering their overall efficiency. Herein, we report for the first time the development of direct Pd‐catalyzed C−H alkylation and acylation of carbazoles assisted by norbornene (NBE) as a transient directing mediator. Notably, the involvement of a six‐membered palladacycle intermediate was suggested in this case, representing the first example of such intermediacy within the extensively studied Pd/norbornene reactions realm.
-
more » « less
2-Pyridone ligand-facilitated palladium-catalyzed direct C–H bond functionalization via the transient directing group strategy has become an attractive topic. Here, we report a Pd-catalyzed direct β-C(sp3)–H arylation reaction of tertiary aliphatic aldehydes by using an α-amino acid as a transient directing group in combination with a 2-pyridone ligand.
-
more » « less
Abstract Enantioselective substrate directed Heck reactions are desirable for the stereoselective synthesis of complex molecules. However, due to the coordination requirements of both chiral ligands and directing groups, such methodologies are underdeveloped. We report herein the desymmetrization of
meso (1R ,2S )‐cyclohex‐4‐ene‐1,2‐diol in an enantioselective and substrate directed fashion. The method provides allcis substituted highly functionalized chiral allylic alcohols in a complementary fashion to other Heck protocols.The products were obtained in high enantioselectivities (higher than 95% ee) and moderate to high yields (38–87%). The noncovalent interactions responsible for the directing effect were elucidated through computational examination of relevant minima and transition structures.magnified image
