The influence of ligand bite angle on the enantioselectivity of copper(II)-catalysed Diels–Alder reactions

Abstract

Novel spirobis(oxazo1ines) provide excellent levels of stereocontrol in copper-catalysed Diels-Alder reactions; the larger the ligand bite angle the higher the enantioselection (up to 98.4% ee).

Studies on the Bisoxazoline‐ and (−)‐Sparteine‐Mediated Enantioselective Addition of Organolithium Reagents to Imines

“…Furthermore, none of the conformations placed the carbon-nitrogen double bonds of the molecule in a coplanar or nearly coplanar orientation as predicted by Davies calculations. [38] Examining the numerous low energy conformations that did contain coplanar arrangements of the C=N bonds also provided a series of angles that did not conform to the expected trend (Table 17, …”

“…[37] Of greater relevance is the study by Davies on the enantioselectivity of a copper(II) catalyzed Diels-Alder reaction that was significantly influenced by changing the bridging angle, Φ, of an indanol-based bisoxazoline. [38] By evaluating a series of spirocyclic bisoxazolines, Davies discovered that increasing Φ improved both the endo/exo selectivity and enantioselectivity (Scheme 7). Finally, we have carried out a computational analysis of possible complexes and transition structures in an attempt to rationalize the structural effects on selectivity.…”

“…[38] The conformational searches produced a large number of energy minima for each ligand. As a first approximation, it was expected that as ring size increased the bridge angle would decrease.…”

Highly Enantioselective Friedel–Crafts Reaction of Indole with Alkylidenemalonates Catalyzed by Heteroarylidene Malonate‐Derived Bis(oxazoline) Copper(II) Complexes

“…1n 1996, Davis reported the copper(II) complex of BOX ligand I containing different spirorings catalyzed Diels-Alder reactions. [8] A conclusive trend has been obtained: the larger the value of F (hence the ligand bite angle V), the higher the observed enantioselectivity. As the spiroring size decreased, the bridge angle F correspondingly increased, then the highest ee value (96%) was afforded by the copper complex of BOX ligand I bearing a cyclopropyl group at the bridge carbon.…”

The Influence of Ligand Side Chain on the Enantioselectivity of Lewis Acid Catalyzed Diels-Alder Reactions.

“…[4][5][6][7][8][9] Recently, a non-C 2 -symmetric box bearing a meso backbone 10) and a non-C 2 -symmetric mono-(oxazoline) (mox) such as pyridyloxazoline 11) or pyosphinoaryloxazoline [12][13][14][15] have also been shown to be effective ligands in the enantioselective catalytic Diels-Alder reaction. In previous paper we have reported 16,17) that the magnesiumcatalyzed Diels-Alder reaction of ethyl 2-benzoylacrylate and 1-phenyl-2-methylenebutane-1,3-dione gave the adduct enantioselectively with N-[(1R)-2-chloro-1-phenylethyl]-2-ethyl-2-[(4R)-4-phenyl-4,5-dihydrooxazol-2-yl]butyramide 2, a non-C 2 -symmetric mox, as a chiral ligand.…”