Asymmetric Organocatalytic Synthesis of Fluorinated β‐Hydroxy Diazenes. Issue 1 (4th December 2018)

• Record Type: Journal Article
• Authors: Matador, Esteban; de Gracia Retamosa, María; Jiménez‐Sánchez, Antonio; Monge, David; Fernández, Rosario; Lassaletta, José M.
• Is Part Of: European journal of organic chemistry. Issue 1(2019)
• Page Start: 130
• Page End: 138
• Publication Date: 2018-12-04
• Subjects: Hydrazones -- Fluorinated ketones -- H‐bonding organocatalysis -- Azoxy compounds -- Amino alcohols -- Oximes; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.201801477
• Languages: English
• ISSNs: 1434-193X

Abstract

Abstract : The nucleophilic addition of formaldehyde tert ‐butyl hydrazone to fluoromethyl ketones provides a valuable tool for the synthesis of highly functionalized β‐hydroxy β‐tri‐ and difluoromethyl diazenes. Excellent reactivities and moderate to good enantioselectivities (up to 90 % ee ) were achieved by H ‐bonding activation exerted by tert ‐Leucine derived H ‐bonding (squaramide or thiourea) organocatalysts. Subsequent derivatizations in one‐pot fashion provide synthetically useful intermediates for target‐oriented synthesis: tri‐ and di‐fluoromethylated azoxy compounds, β‐amino alcohols, α‐hydroxy aldoximes and derivatives thereof. Abstract : A formylation strategy: tert ‐Leucine derived organocatalysts promote the enantioselective 1, 2‐addition ofFTBH to fluorinated ketones to afford quaternary β‐hydroxy β‐fluoromethyl diazenes in excellent yields and moderate‐to‐good enantioselectivities. Subsequent high‐yielding and racemization‐free transformations provide an expedient entry to enantioenriched azoxy compounds, aldehydes and derivatives thereof.