aggregates are formed, the Mannich-type reaction proceeds inefficiently. A nonlinear effect analysis provided evidence of asymmetric amplification in the present Mannich-type reaction, proving the participation of aggregated species in the reaction pathway. Together, these results highlight the importance of controlling catalyst aggregation as a strategy to optimize the reactivity and selectivity in asymmetric organocatalysis.
Hecht et al. (Tue,) studied this question.