Chlorination Aldol

Highlighted Works:

  • Kang, B., et al. 'Development of a Concise and General Enantioselective Approach to 2,5-Disubstituted-3-hydroxytetrahydrofurans.' Org. Lett., 2009
  • Draper, J. and Britton, R. 'A Concise and Stereoselective Synthesis of Hydroxypyrrolidines: Rapid Synthesis of Preussin' Org. Lett., 2010
  • Halperin, S.,  et al. 'Lithium Aldol Reactions of α-Chloroaldehydes Provide Versatile Building Blocks for Natural Product Synthesis' Synthesis, 2011
  • Bergeron-Brlek, M., et al. 'A tandem organocatalytic α-chlorination-aldol reaction that proceeds with dynamic kinetic resolution: A powerful tool for carbohydrate synthesis' Org. Lett., 2013
  • Bergeron-Brlek, M., et al. 'Direct synthesis of imino-C-nucleoside analogues and other biologically active iminosugars' Nat. Commun., 2015
  • Michael Meanwell, Mathew Sutherland and Robert Britton. 'Application of Sequential Proline-catalyzed α-chlorination and Aldol Reactions in the Total Synthesis of 1-deoxygalactonojirimycin' Can. J. Chem., 2017
  • Ren W., et al. 'Revealing the mechanism for covalent inhibition of glycoside hydrolases by carbasugars at an atomic level' Nat. Commun., 2018
  • Meanwell, M., et al. 'Diversity-oriented synthesis of glycomimetics' Commun. Chem., 2021

The stereoselective synthesis of heterocyclic compounds is a longstanding synthetic challenge. In recent years we have made several advances in this area by exploiting α-chloroaldehydes as versatile building blocks for the synthesis of tetrahydrofuran, tetrahydropyran, and pyrrolidine-containing natural products and therapeutic leads (including carbohydrate analogues, iminosugars). These efforts rely on highly diastereoselective aldol reactions of α-chloroaldehydes, affording β-ketochlorohydrins that can be rapidly converted into stereochemically rich heterocycles and natural products. We have also reported a one-pot organocatalytic aldehyde α-chlorination/aldol reaction that proceeds with dynamic kinetic resolution and provides direct entry to a new class of carbohydrate building blocks.