Diastereoselective Synthesis of N-Alkylated Octahydroacridines via a Catalyst-Free SNAr Approach

Autor:	Richard A. Bunce, Nagendra Prasad Muddala, Baskar Nammalwar, Subhashini Selvaraju
Rok vydání:	2015
Předmět:	Steric effects Chemistry Stereochemistry Organic Chemistry Imine Substituent Cyclohexanone Alkylation Ring (chemistry) Medicinal chemistry Catalysis chemistry.chemical_compound Nucleophilic aromatic substitution Nitration
Zdroj:	Synthesis. 47:3198-3206
ISSN:	1437-210X 0039-7881
Popis:	A three-step diastereoselective synthesis of N-alkylated octahydroacridines has been developed from inexpensive starting materials. Alkylation of cyclohexanone with 2-fluorobenzyl bromide, followed by nitration para to the aromatic fluoro substituent provided the cyclization substrate in 61% yield. Finally, a tandem reductive amination-SNAr cyclization with NaCNBH3 furnished the target compounds in 74–92% yields. X-ray and 1H NMR studies permitted assignment of the stereochemistry of the B–C ring junction. The 3:1–10:1 preference for the cis-isomer was rationalized in terms of steric interactions in the imine reduction and a chair-like conformation for the cyclization. Hydride would be delivered to the molecular face opposite the fluoronitrobenzyl substituent at C-2 of the cyclohexanimine intermediate and the resulting amine would be positioned for addition to the SNAr acceptor ring via a chair-like conformation.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::aa05799894740140ab08d86efd7897e2 https://doi.org/10.1055/s-0034-1381033 Zobrazit plný text záznamu