A competition study comparing the reactivity of 5 , 6 , and 8 toward ynamine 22a (1.2 equiv, 22 °C, CHCl 3 , 30 min) defined a clear trend ( 6 > 5 > 8 ) where the now complementary C4 and C6 disubstitution (CO 2 Et) electronically enhances the reactivity of 6 relative to 5 bearing a single electron-withdrawing group (CO 2 Me), and the C5 methyl substitution of 8 sterically slows the cycloaddition relative to not only 6 but also 5 , despite the C4/C6 disubstitution activation of 8 (Figure 6 ).
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