[reaction: see text] beta-Isocupreidine (beta-ICD)-catalyzed asymmetric Baylis-Hillman reactions of aromatic imines with 1,1,1,3,3,3-hexafluoroisopropyl acrylate (HFIPA) give (S)-enriched N-protected-alpha-methylene-beta-amino acid esters. In contrast to the corresponding aldehydes, imines show the opposite enantioselectivity. A mechanistic proposal governed by hydrogen bonding is presented.
[Structure: see text] Beta-isocupreidine (beta-ICD)-catalyzed Baylis-Hillman reaction of chiral N-Boc-alpha-amino aldehydes and 1,1,1,3,3,3-hexafluoroisopropyl acrylate (HFIPA) takes place without racemization and exhibits the match-mismatch relationship between the substrate and the catalyst. In the case of acyclic amino aldehydes, L-substrates show excellent syn selectivity and high reactivity in contrast to D-substrates. On the other hand, in the case of cyclic amino aldehydes, D-substrates rather than L-substrates show excellent anti selectivity and high reactivity.
Compound 20, a pseudoenantiomer of bisocupreidine (b-ICD), was synthesized from quinine employing a Barton reaction of nitrosyl ester 13 and acid-catalyzed cyclization of carbinol 18 as key steps. The Baylis-Hillman reaction of benzaldehyde, p-nitrobenzaldehyde, and hydrocinnamaldehyde with 1,1,1,3,3,3-hexafluoroisopropyl acrylate (HFIPA) using 20 as a chiral amine catalyst was found to give the corresponding S-enriched adducts in high optical purity ( > 91% ee) in contrast to the b-ICD-catalyzed reaction which affords R-enriched adducts. This result suggests that compound 20 can serve as an enantiocomplementary catalyst of b-ICD in the asymmetric Baylis-Hillman reaction of aldehydes with HFIPA.
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