Rhodium‐Catalyzed Enantioselective Intramolecular [4+2] Cycloaddition using a Chiral Phosphine‐Phosphite Ligand: Importance of Microwave‐Assisted Catalyst Conditioning

Abstract

AbstractThe use of modular α,α,α′,α′‐tetraaryl‐1,3‐dioxolane‐4,5‐dimethanol (TADDOL)‐ and 1,1′‐bi‐2‐naphthol (BINOL)‐derived phosphine‐phosphite ligands (L2*) in the asymmetric rhodium‐catalyzed intramolecular [4+2] cycloaddition (“neutral” Diels–Alder reaction) of (E,E)‐1,6,8‐decatriene derivatives (including a 4‐oxa and a 4‐aza analogue) was investigated. Initial screening of a small ligand library led to the identification of a most promising, TADDOL‐derived ligand bearing a phenyl group adjacent to the phosphite moiety at the arene backbone. In the course of further optimization studies, the formation of a new, more selective catalyst species during the reaction time was observed. By irradiating the pre‐catalyst with microwaves prior to substrate addition high enantioselectivities (up to 93% ee) were achieved. The new cyclization protocol was successfully applied to all three substrates investigated to give the bicyclic products in good yield and selectivity. 31P NMR and ESI‐MS measurements indicated the formation of a [Rh(L2*)2]+ species as the more selective (pre‐) catalyst.