ASYMMETRIC 1,3-DIPOLAR CYCLOADDITION REACTIONS OF AZOMETHINE IMINES WITH ACROLEIN CATALYZED BY L-PROLINE AND ITS DERIVATIVES

1,3-Dipolar cycloadditions between acrolein and various N,N'-cyclic azomethine imines in the presence of L-proline and its derivatives as organocatalysts were investigated. Reactions that were catalyzed by (S)-indline-2-carboxylic acid (30 mol%) in CHCl3/MeOH 97:3 (v/v) showed high exo-selectivities (exolendo 91:9 similar to 99:1) and enantioselectivities (75 similar to 98% ee). In contrast, reactions catalyzed by L-proline (30 mol%) under similar conditions favored the endo-cycloadduct (83:27 similar to 99:1) with modest to good enantioselectivities (31 similar to 83% ee). Based on our studies, the diastereoselective mechanism of the L-proline-catalyzed reaction was found to involve the isomerization of the exo- to the endo-cycloadduct in the presence of L-proline.ArticleHETEROCYCLES. 81(7):1669-1688 (2010)journal articl

Inverse electron demand asymmetric cycloadditions of cyclic carbonyl ylides catalyzed by chiral Lewis acids-Scope and limitations of diazo and olefinic substrates

High enantioselectivities (94–96% ee) were obtained for the inverse electron-demand 1,3-dipolar cycloadditions between cyclohexyl vinyl ether and 2-benzopyrylium-4-olate generated via Rh₂(OAc)₄-catalyzed decomposition of o-methoxycarbonyl-α-diazoacetophenone. The reactions were effectively catalyzed by Eu(OTf)₃, Ho(OTf)₃, or Gd(OTf)₃ complexes (10 mol %) of chiral 2,6-bis[(4S,5S)-4,5-diphenyl-2-oxazolinyl]pyridine. The reactions with the other electron-rich dipolarophiles such as allyl alcohol, 2,3-dihydrofuran, and butyl-tert-butyldimethylsilylketene acetal showed moderate enanantioselectivities (60–73% ee). Good to high enantioselectivities (73–97% ee) were also obtained for the cycloadditions between 3-acyl-2-benzopyrylium-4-olates, generated from methyl 2-(2-diazo-1,3-dioxoalkyl)benzoates and butyl or cyclohexyl vinyl ethers, in the presence of binaphthyldiimine (BINIM)–Ni(II) complexes (10 mol %). Under similar conditions, the reaction between methyl 2-(2-diazo-1,3-dioxohexyl)benzoate and 2,3-dihydrofuran was highly endo-selective, and moderately enantioselective (70% ee). For the BINIM–Ni(II)-catalyzed reactions of cyclohexyl vinyl ether, the use of an epoxyindanone as the 3-acyl-2-benzopyrylium-4-olate precursor revealed that the chiral Lewis acid can function as a catalyst for asymmetric induction. The scope of the cyclic carbonyl ylides was extended to those generated from 1-diazo-2,5-pentanedione derivatives, which were reacted with butyl or TBS vinyl ether and catalyzed using the (4S,5S)-Pybox-4,5-Ph₂–Lu(OTf)₃ complex to give good levels of asymmetric inductions (75–84% ee).ArticleTetrahedron. 66(16):3070-3089 (2010)journal articl