The role of achiral pyrazolidinone templates in enantioselective Diels-Alder reactions: scope, limitations, and conformational insights.
We have evaluated the role of achiral pyrazolidinone templates in conjunction with chiral Lewis acids in room temperature, enantioselective Diels-Alder cycloadditions. The role of the fluxional N(1) substituent was examined, with the bulky 1-naphthylmethyl group providing enantioselectivities up to 99% ee, while templates with smaller fluxional groups gave lower selectivities. High selectivities were also observed in reactions of 7d with chiral Lewis acids derived from relatively small chiral ligands, suggesting the pyrazolidinone templates are capable of relaying stereochemical information from the ligand to the reaction center. Lewis acids capable of adapting square planar geometries, such as Cu(OTf)2, Cu(ClO4)2, and Pd(ClO4)2, were found to be particularly effective at providing high selectivities. Additionally, substitution at the C-5 position of the pyrazolidinone templates has been shown to be critical for optimal selectivity. Reactions of the optimal pyrazolidinone appended with a number of common dienophiles and various dienes demonstrate the utility of this achiral template. Furthermore, catalytic loadings could be lowered to 2.5 mol % with essentially no loss in selectivity. Pi-Pi interactions were evaluated as a means to explain the unusually high selectivity observed at room temperature. Finally, non-C2-symmetric ligands were employed as a test to determine if chiral relay was operative.
Sibi
Mukund P
MP
Department of Chemistry and Molecular Biology, North Dakota State University, Fargo, North Dakota 58105, USA. mukund.sibi@ndsu.edu
Stanley
Levi M
LM
Nie
Xiaoping
X
Venkatraman
Lakshmanan
L
Liu
Mei
M
Jasperse
Craig P
CP
D002384:Catalysis; D018360:Crystallography, X-Ray; D003500:Cyclization; D007659:Ketones / Q000138:chemical synthesis* / Q000737:chemistry; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D019216:Metals, Heavy / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*; D011720:Pyrazoles / Q000737:chemistry*; D012680:Sensitivity and Specificity; D013237:Stereoisomerism
D007659:Ketones; D008024:Ligands; D019216:Metals, Heavy; D009942:Organometallic Compounds; D011720:Pyrazoles