Highly Enantioselective Electrophilic Amination and Michael Addition of Cyclic β-Ketoesters Induced by Lanthanides and (S,S)-ip-pybox:  The Mechanism

Abstract

High enantioselection is obtained in Michael additions of cyclic beta-ketoesters in the presence of lanthanium triflates and (S,S)-ip-pybox. Intermediates based on simultaneous coordination of the lanthanide to both (S,S)-ip-box and beta-ketoester (in keto and enolate forms) are detected by means of ESI mass spectrometry and NMR experiments, and a possible mechanism is proposed through theoretical calculations.

DFT/MM Study on Copper‐Catalyzed Cyclopropanation – Enantioselectivity with No Enthalpy Barrier

“…[31][32][33] The Cu[adam-box] complex performs excellently in cyclopropanation, Diels-Alder, and allylic oxidation processes. [31] In particular, the catalysis of the reaction of ethyl diazoacetate (EDA) with 1,1-diphenylethylene accomplishes cyclopropanation with an enantiomeric excess of over 95 %.…”

Toward the Synthesis of Muironolide A: Synthesis and Structure of Heteroleptic Lanthanide–Terpyridine Complexes with 2‐Oxo Amides

“…In contrast to other Lewis acids investigated [Cu(OTf) 2 , Fe(OAc) 2 , Zr(OiPr) 4 , Sc(OTf) 3 ], several lanthanide triflates substantially increased the rate of the IMDA reaction. The most active catalysts, La(OTf) 3 , Eu(OTf) 3 , Yb(OTf) 3 , and Dy(OTf) 3 effected a complete conversion at 45°C in a range of solvents within 24 h. The diastereoselectivity varied from 4:1 to Ͼ 30:1 depending on the choice of catalysts and solvent, suggesting a possible switch in the reaction pathway between a polar concertedtype and a stepwise double-Michael addition. In general, polar solvents substantially decreased the diastereomer ratios.…”

“…Under optimized conditions, [La(OTf) 3 or Dy(NO 3 ) 3 ; Entries 12, 13, and 15] a high diastereocontrol and conversion of β-oxo amide 5 into isoindolone 6 were observed at 45°C in ethyl acetate as the solvent after 24 h. Our next goal was to evaluate the performance of various chiral ligands in achieving an enantioselective IMDA reaction, initially using additives previously described to be effective in asymmetric catalysis with lanthanide Lewis acids. [3][4][5] The www.eurjoc.orgchiral ligands included in this study are illustrated in Scheme 2.…”

“…[3][4][5] The www.eurjoc.orgchiral ligands included in this study are illustrated in Scheme 2. [12] Although the reaction conditions for each ligand were individually optimized, none of them afforded satisfactory enantioselectivity, with the best, L1, performing substantially better than the rest (40-50 % ee).…”

“…[2] Among the most utilized ligands for asymmetric catalysis with lanthanides are bis(oxazoline) ligands (BOX), [3] 2,6-pyridinebis(oxazoline) compounds (PY-BOX), [4] and heterodimetallic BINOL derivatives. [5] Our interest in lanthanide catalysis has been recently stimulated by a project directed at the total synthesis of the unique tetrachlorinated marine poliketide muironolide A (1) (Scheme 1a).…”