Event Information

Mark C. Kohler (Duke University)
Proximity Accelerated Organocatalytic Soft Enolization of Carboxylate Derivatives: Development of a Biomimetic Asymmetric Addition Reaction
Abstract:

We have developed the first organocatalytic Mannich reaction based on proximity-accelerated intramolecular soft enolization of thioesters. This approach employs a cooperative mode of enolization, which allows thioesters over a range of acidity to react efficiently, and is not restricted to only the most acidic. The functional pKa barrier associated with this method has been estimated to be ≥ 21 units, strongly suggesting its potential in terms of developing a general enolization-based organocatalytic strategy applicable to simple monocarboxylic acid derivatives. Here we present the application of this method to the syntheses of a variety of -amino thioesters with good to moderate enantioselectivity. A mechanistic model is proposed to explain the basis for enantioselectivity. NMR studies were conducted that confirm the beneficial role of proximity-accelerated activation and deprotonation in this mode of organocatalysis.

Preliminary Examination Seminar

Wednesday, March 25, 2009, 2:00pm
Student Exams Seminar