How Understanding the Role of an Additive Can Lead to an Improved Synthetic Protocol without an Additive: Organocatalytic Synthesis of Chiral Diarylmethyl Alkynes

The use of additives for organic synthesis has become a common tactic to improve the outcome of organic reactions. Herein, by using an organocatalytic process for the synthesis of chiral diarylmethyl alkynes as a platform, we describe how an additive is involved in the improvement of the process. The evolution of an excellent synthetic protocol has been achieved in three stages, from 1) initially no catalyst turnover, to 2) good conversion and enantioselectivity with a superior additive, and eventually 3) even better efficiency and selectivity without an additive. This study is an important and rare demonstration that understanding the role of additive can be so beneficial as to obviate the need for the additive. Addition and subtraction: On the basis of an organocatalytic process, it is shown how a reaction can be evolved from an initial stage without catalyst turnover to a highly efficient and enantioselective transformation in the presence of an additive, and eventually without the additive (see picture). Thus, by understanding the role of an additive, it was possible to redesign and significantly improve the synthetic protocol.