Catalytic discrimination between formyl groups in regio- and stereoselective intramolecular cross-aldol reactions

• Published in: Chemical science (Cambridge) Vol. 7; no. 6; pp. 3791 - 3797
• Main Authors: Baba, Tomonori, Yamamoto, Junya, Hayashi, Kazuhiro, Sato, Makoto, Yamanaka, Masahiro, Kawabata, Takeo, Furuta, Takumi
• Format: Journal Article
• Language: English
• Published: England 01-01-2016
• Subjects: Amines; Catalysis; Catalysts; Dials; Discrimination; Isotope effect; Reaction kinetics; Stereoselectivity
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/c5sc04594k

Catalytic discrimination between inequivalent formyl groups was achieved using an aniline-type acid-base catalyst for the regio-, diastereo-, and enantioselective intramolecular cross-aldol reactions of enolizable dials. Although l-proline gave a mixture of the regio- and stereoisomeric products in the presence of an
-containing 1,6-dial, the aniline-type catalyst afforded
-3,4-disubstituted pyrrolidine in high regio-, and stereoselectivity beyond the background reaction, which led to the regioisomeric 2,3-disubstituted products. The mild reactivity of the aniline-type amine facilitated catalytic discrimination between the inequivalent formyl groups. Kinetic isotope effect studies and reductive amination experiments suggested that the regioselectivity was controlled under the enamine-forming steps.