Efficient access to sp3-rich tricyclic amine scaffolds through Diels–Alder reactions of azide-containing silyloxydienes. Issue 26 (30th June 2016)

• Record Type: Journal Article
• Authors: McLeod, Michael C.; Aubé, Jeffrey
• Is Part Of: Tetrahedron. Volume 72:Issue 26(2016)
• Page Start: 3766
• Page End: 3774
• Publication Date: 2016-06-30
• Subjects: Parallel synthesis -- Diels–Alder cycloaddition -- Polycyclic heterocycles; PTSA para-toluenesulfonic acid -- NP natural product -- Fsp3 fraction sp3 -- HBD hydrogen bond donors -- HBA hydrogen bond acceptors -- tPSA topological polar surface area -- rotB rotatable bonds; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tet.2016.03.016
• Languages: English
• ISSNs: 0040-4020

Abstract

Abstract: The preparation of sp 3 -rich scaffolds to obtain more natural product–like libraries for incorporation into screening decks is challenging. Here, we describe the use of a Diels–Alder reaction between an enone and an azide-containing silyloxydiene to gain efficient access to complex tricyclic amine scaffolds. Derivatization of these scaffolds provided a library of 80 amines, amides, sulfonamides, quinolines and indolenines, all in >20 mg quantities and >90% purities. These library compounds displayed properties more similar to alkaloid natural products than to drugs and commercial drug-like libraries, as shown by a high proportion of sp 3 carbon centers. Graphical abstract: