exo-Selective Catalysts for 1,3-Dipolar Nitrone Cycloaddition

Key words

exo-selective cycloaddition - bis(oxazolines) - magnesium(II) - cobalt(II) - nickel(II) - zinc(II)

Significance

There are numerous methods for endo-selective cycloaddition reactions; however, few examples addressing exo-selectivity can be found. 1,3-Dipolar nitrone cycloadditions serve as templates for developing selective catalysts, as regio-, diastereo- and enantioselectivity must all be addressed. Using Ph-BOX ligands and Lewis acids such as Mg(II), Co(II), Ni(II) and Zn(II), selectivity can be tuned for the 1,3-dipolar cycloaddition between acryloyloxazolidinone and diphenyl nitrone. Under the optimal exo-selective conditions, >98:2 regioselectivity, 10:90 endo/exo selectivity and 99% ee _exo was obtained with trans-diphenyl-BOX ligand and Ni(ClO₄)₂ as Lewis acid.

Comment

All of the Lewis acid catalysts used produce quantitative conversion of the cycloaddition products. Addition of 4Å molecular sieves tends to favor formation of the exo-adduct, as well as the use of trans-disubstituted BOX ligands. One exception is the use of Zn(II), which showed reversed selectivity with the trans-ligands. In the absence of substituents on the 5-position of the BOX ligand, all cases show endo-selectivity. Overall, Ni(II) and Mg(II) performed the best, allowing access to the elusive exo-adduct.