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

The use of modular a,a,a',a'-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 DielsAlder 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.