D04 Chelating Auxiliary
Chelating Auxiliary:
As discussed in the nitrone reactions, MS 4A works as powerful
dehydrating agent. In the absence of water, we propose that the nitrone
cycloaddition takes place through the transition structure including a trigonal
bipyramid complex. When water is present in the reaction system, an octahedral
complex becomes more stable by coordination of water to the metal center
so that the reaction cite becomes more open. This is the reason that the
endo- and enantioselectivities are both lowered.
The aqua complex derived from DBFOX/Ph and Ni(ClO4)2´6H2O is stable against water. To utilize this advantage, the nitrone synthesis and cycloaddition sequence in one flask was examined. Reaction of N-benzylhydroxylamine with aldehydes in the presence of the aqua complex and 3-crotonoyl-2-oxazolidinone was performed. The product obtained in high yields was 2-benzyl-3-methyl-5-isoxazolidinone, the addition/condensation product. This indicates that the conjugate addition is catalyzed by DBFOX/Ph´Ni(ClO4)2´3H2O and is faster than the condensation leading to nitrone formation. However, enantioselectivity was not satisfactory.
As easily anticipated, nitrones are activated by complexiation to the DBFOX/Ph complex catalyst so that water adds to the C=N bond of activated nitrones. When a sufficient amount of water is present, hydrolysis of nitrones takes place to give N-substituted hydroxylamines. Then, a small amount of the above 5-isoxazolidinone is formed.