Enantioselective Synthesis of Caprolactam and Enone Precursors to the Heterocyclic DEFG Ring System of Zoanthenol. Issue 12 (19th April 2016)

• Record Type: Journal Article
• Authors: Bagdanoff, Jeffrey T.; Behenna, Douglas C.; Stockdill, Jennifer L.; Stoltz, Brian M.
• Is Part Of: European journal of organic chemistry. Issue 12(2016)
• Page Start: 2101
• Page End: 2104
• Publication Date: 2016-04-19
• Subjects: Zoanthamines -- Zoanthenol -- Enantioselectivity -- Hetero‐Diels–Alder reaction -- Allylation; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.201600223
• Languages: English
• ISSNs: 1434-193X

Abstract

Abstract: The enantioselective synthesis of both caprolactam and enone synthons for the DEFG ring system of zoanthenol are described. The evolution of this approach proceeds first through a synthesis using the chiral pool as a starting point. Challenges in protecting‐group strategy led to the modification of this approach beginning with (±)‐glycidol. Ultimately, an efficient approach was developed by employing an asymmetric hetero‐Diels–Alder reaction. The caprolactam building block can be converted by an interesting selective Grignard addition into the corresponding enone synthon. Addition of a model alkyne provides support for the late‐stage addition of a hindered alkyne to the caprolactam building block. Abstract : The syntheses of two synthons for the heterocyclic core of the marine alkaloid zoanthenol are described. These fragments can be generated in a divergent manner from the product of an enantioselective hetero‐Diels–Alder reaction. Judicious selection of protecting groups allows control of a key Grignard reaction to form the enone synthon. The feasibility of the caprolactam as a synthon is validated.