Catalytic Asymmetric Iodocyclization of N-Tosyl Alkenamides using Aminoiminophenoxy Copper Carboxylate: A Concise Synthesis of Chiral 8-Oxa-6-Azabicyclo[3.2.1]octanes

• Published in: Angewandte Chemie International Edition 2015-10, Vol.54 (43), p.12767-12771
• Main Authors: Arai, Takayoshi, Watanabe, Ohji, Yabe, Shinnosuke, Yamanaka, Masahiro
• Format: Article
• Language: English
• Subjects: Amides - chemistry; Anions; asymmetric catalysis; Asymmetry; Carboxylates; Carboxylic Acids - chemistry; Catalysis; Catalysts; Copper; Copper - chemistry; Crystallography, X-Ray; Cyclization; DFT calculations; Halogenation; Hydrogen bonding; Iodine - chemistry; Mathematical analysis; Models, Molecular; Stereoisomerism; Synthesis; Tosyl Compounds - chemistry; Tropanes - chemical synthesis; Tropanes - chemistry
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201505748

A newly developed aminoiminophenoxy copper carboxylate (L7‐Cu‐OAc)‐catalyzed asymmetric iodocyclization of N‐Tosyl alkenamides gave O‐cyclized products in good yields with high enantioselectivity. From the O‐cyclized products, a skeletal transformation was succeeded in the synthesis of biologically important chiral 8‐oxa‐6‐azabicyclo[3.2.1]octanes. DFT calculations suggested that the acetoxy anion of the [L7‐Cu‐OAc] acts as a base to generate the anion of N‐Tosyl alkenamide substrates. The exchanged acetic acid reconstructs a new hydrogen‐bonding network between the catalyst and the substrates to accomplish the highly efficient asymmetric O‐iodocyclization of N‐Tosyl alkenamides. An aminoiminophenoxy copper carboxylate‐catalyzed asymmetric iodocyclization of N‐Tosyl alkenamides gave O‐cyclized products in good yields with high enantioselectivity. Chiral 8‐oxa‐6‐azabicyclo[3.2.1]octanes were synthesized by a sequential reduction/cyclization process from the iodocyclization product. DFT calculations suggested that the N‐tosyl alkenamides are activated by hydrogen bonding with a carboxylate anion on the copper center to allow iodo‐O‐cyclization.