An Enantioselective Synthesis of Cis Perhydroisoquinoline LY235959

Autor:	Harkness Allen Robert, Barry C. Peterson, Vien V. Khau, Jerry W. Misner, Marvin M. Hansen, Carl Franklin Indianapolis Bertsch, Michael E. LeTourneau, John Allan Rieck, D. R. Hutchison, Kevin A. Sullivan, Ian G. Wright, Michael J. Martinelli, Huff Bret Eugene
Rok vydání:	1998
Předmět:	chemistry.chemical_compound Chiral auxiliary Bicyclic molecule Chemistry Stereochemistry Yield (chemistry) Organic Chemistry Imine Enantioselective synthesis Epimer Alkylation Phosphonate
Zdroj:	The Journal of Organic Chemistry. 63:775-785
ISSN:	1520-6904 0022-3263
DOI:	10.1021/jo9717649
Popis:	A novel synthesis of NMDA receptor antagonist LY235959 (1) has been achieved in 13% overall yield and 17 steps from (R)-pantolactone (7). Highlights of the synthesis include (a) use of a chiral auxiliary controlled asymmetric Diels-Alder reaction to provide the desired absolute and relative stereochemistry at C-4a, C-6, and C-8a, (b) an efficient alkylation of hindered iodide 13 using a novel amide benzophenone imine, (c) oxidative ring opening of the [2.2.2] bicyclic system to simultaneously functionalize the molecule for intramolecular cyclization and phosphonate introduction, and (d) an increased understanding of how the C-3 stereochemistry may be controlled by thermodynamic equilibration. Synthesis of epimer 20 in high overall yield makes this synthetic route attractive for future development efforts.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ee14790b74cfd25ce5698b7dcb5a24fa https://doi.org/10.1021/jo9717649 Zobrazit plný text záznamu