Bifunctional Squaramide Organocatalysts for the Asymmetric Addition of Formaldehyde tert‐Butylhydrazone to Simple Aldehydes

• Published in: Chemistry : a European journal Vol. 24; no. 26; pp. 6854 - 6860
• Main Authors: Matador, Esteban, de Gracia Retamosa, María, Monge, David, Iglesias‐Sigüenza, Javier, Fernández, Rosario, Lassaletta, José M.
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 07-05-2018
• Subjects: Alcohol; Alcohols; Aldehydes; Carbonyls; Chemistry; Enantiomers; Formaldehyde; hydrazones; hydrogen bonds; organocatalysis; Oxazolidinones; solvent effects; squaramides; organocatalysis; squaramides; solvent effects; hydrogen bonds; hydrazones
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201801052

The nucleophilic addition of formaldehyde tert‐butylhydrazone to simple aldehydes (a formal hetero‐carbonyl–ene reaction) can be performed with good reactivity and excellent enantioselectivity by virtue of the dual hydrogen‐bonding activation exerted by amide–squaramide organocatalysts. The resulting hydroxydiazenes (azo alcohols) were isolated in high yields as enantiomerically enriched azoxy compounds after a regioselective azo‐to‐azoxy transformation. Subsequent derivatization provides an entry to relevant amino alcohols, oxazolidinones, and derivatives thereof.
Two heads are better than one: Bifunctional amide–squaramide catalysts enabled the highly enantioselective addition of formaldehyde tert‐butylhydrazone to simple aldehydes (see scheme; MMPP=magnesium monoperoxyphthalate). Subsequent derivatizations provide an entry to relevant amino alcohols, oxazolidinones, and derivatives thereof.