A highly enantioselective 1,3-dipolar cycloaddition reaction in alcoholic media: Ni(II)-pybox-tipsom catalyst

From the viewpoint of environmentally friendly reaction conditions, catalytic asymmetric nitrone 1,3-dipolar cycloaddition (DC) reactions in protic media have been investigated. DC reaction of nitrones with alkenoyl oxazolidinone and pyrrolidinone derivatives in t-BuOH in the presence of sterically tuned bis(oxazolinyl)pyridine (pybox-tipsom 1d) and Ni(II) complex as a chiral Lewis acid catalyst proceeded smoothly to give the corresponding cycloadducts ranging from 90:10 to >99:1 of endo/exo ratio and ranging from 90 to 98% ee for the endo adduct. The use of sterically hindered alcohols such as t-BuOH and s-BuOH as a non-halogenated solvent was shown to effect rate acceleration for the DC reaction compare to CH2Cl2 at the same temperature. Furthermore, no solvolysis products of nitrones and cycloadducts were observed in these protic media despite the possible formation of Brønsted acid. [Copyright &y& Elsevier]