Short Enantioselective Total Synthesis of Tatanan A and 3‐epi‐Tatanan A Using Assembly‐Line Synthesis. Issue 51 (16th November 2016)

• Record Type: Journal Article
• Authors: Noble, Adam; Roesner, Stefan; Aggarwal, Varinder K.
• Is Part Of: Angewandte Chemie international edition. Volume 55:Issue 51(2016)
• Page Start: 15920
• Page End: 15924
• Publication Date: 2016-11-16
• Subjects: alkynylation -- lithiation–borylation -- Matteson homologation -- tatanan A -- total synthesis; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201609598
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: Short and highly stereoselective total syntheses of the sesquilignan natural product tatanan A and its C3 epimer are described. An assembly‐line synthesis approach, using iterative lithiation–borylation reactions, was applied to install the three contiguous stereocenters with high enantio‐ and diastereoselectivity. One of the stereocenters was installed using a configurationally labile lithiated primary benzyl benzoate, resulting in high levels of substrate‐controlled (undesired) diastereoselectivity. However, reversal of selectivity was achieved by using a novel diastereoselective Matteson homologation. Stereospecific alkynylation of a hindered secondary benzylic boronic ester enabled completion of the synthesis in a total of eight steps. Abstract : An assembly‐line synthesis involving iterative lithiation‐borylations enabled a short, highly enantio‐ and diastereoselective synthesis of tatanan A, and its C3 epimer. High substrate‐controlled diastereoselectivity with a lithiated primary benzyl benzoate furnished the C3 epimer. A complete switch in selectivity was achieved using a novel substrate‐controlled diastereoselective Matteson homologation to provide access to the natural product in only eight steps.