Highly Enantio‐ and Diastereoselective Inverse Electron Demand Hetero‐Diels–Alder Reaction using 2‐Alkenoylpyridine N‐Oxides as Oxo‐Heterodienes

Abstract

A general catalytic inverse electron demand hetero-Diels Alder reaction for 2-alkenoylpyridine N-oxides is presented. 2-Alkenoylpyridine N-oxides react very efficiently with alkenes in the presence of bisoxazolidine-copper(II) [BOXCu(II)] complexes to give chiral dihydropyrans bearing a pyridine ring at the 6-position with very high yields and excellent diastereo-and enantioselectivity. These heterodienes exhibited higher reactivity and enantioselectivity than the corresponding non-oxidized 2-alkenoylpyridines.

Asymmetric Cycloaddition of β,γ‐Unsaturated α‐Ketoesters with Electron‐Rich Alkenes Catalyzed by a Chiral Er(OTf)3/N,N′‐Dioxide Complex: Highly Enantioselective Synthesis of 3,4‐Dihydro‐2 H‐pyrans

“…[8e, f] Recently, two examples catalyzed by oxazoline/copper(II) complexes were presented. [15,16] However, most of the HDA reactions were performed at extremely low temperatures (generally À78 8C) and with relatively high catalyst loadings (generally 2-10 mol %). There-Abstract: The asymmetric inverse-electron-demand hetero-Diels-Alder (HDA) reactions of b,g-unsaturated aketoesters with electron-rich alkenes were investigated, with an N,N'-dioxide/erbiumA C H T U N G T R E N N U N G (III) complex employed as the catalyst.…”

Enantioselective Addition of Cyclic Enol Silyl Ethers to 2‐Alkenoyl‐Pyridine‐N‐Oxides Catalysed by CuII–Bis(oxazoline) Complexes

“…( E )‐Cinnamoyl‐pyridine‐ N ‐oxides 1 were prepared according to the procedure reported in the literature 9. This preparation includes the oxidation of 2‐acetylpyridine to the corresponding N ‐oxide by meta ‐chloroperoxybenzoic acid ( m CPBA), followed by condensation under basic conditions with the appropriate aromatic aldehyde to give ( E )‐ 1 .…”

“…Later, the enantioselective Friedel–Crafts alkylation with indoles8a and pyrroles8b catalysed by [Cu II –PyBOX] complexes was investigated (Scheme ). Afterwards, the inverse‐electron‐demand hetero Diels–Alder reaction9 with electron‐rich alkenes was explored, as well as the asymmetric 1,3‐dipolar cycloaddition,10 which was further investigated by Barroso et al. (Scheme ) 11.…”

Enantioselectively-Catalyzed Reactions with (E)-2-Alkenoyl-pyridines, TheirN-Oxides, and the Corresponding Chalcones

“…reactions with ethyl thioether 97 (Scheme 42). 71 All reactions occurs through the attack to the β-Si face of both 2 and 1a, to give the opposite stereochemical outcome obtained by using [(4S)-XIX/ Cu(OTf) 2 ] (Scheme 48).…”