Enantioselective Michael Addition: An Experimental Introduction to Asymmetric Synthesis

Abstract

Nuclear Magnetic Resonance spectra were acquired on 300 MHz or 400 MHz Bruker Avance III spectrometers fitted with BBFO probeheads (300 or 400 MHz, and 75 or 100 MHz for 1H and 13C, respectively). Chemical shifts were reported in parts per million relative to the solvent residual peak (1 H) or to the central peak of the solvent signal (13 C). The spectra were processed on Bruker Topspin 4.0.7. Note about process parameters in 1 H NMR: All 1 H NMR spectra without Eu(hfc) 3 were obtain with exponential line broadening of FID signal (command "efp"), with Line Broadening parameter set at 0.3 Hz (command "lb" set to 0.3). It improved signal-to-nose ratio, but to the detriment of the resolution. To determine enantiomeric ratio of 3 with Eu(hfc) 3 , it was needed to improve resolution of the spectra : they were obtain with Gaussian broadening of FID signal (command "gfp") with Line Broadening parameter set to-1 Hz (command "lb" set to-1), and Gaussian maximum position set to 0.3 (command "gb" set to 0.3). It explains distortions in figure S7 and figure S10. FTIR spectra (ATR) were performed on samples using a AGILENT Cary 630 FTIR Spectrometer Optical rotation were performed on POLARTRONIC E polarimeter, using chloroform as solvent and a 10-cm long polarimeter tube. All reagents were used as received, without further purification. Anhydrous THF and LiAlH 4 solution 1M in THF were purchased from Sigma-Aldrich ans and were used as received by students. Flash column chromatography separations were achieved on silica gel (Merck-Geduran Si 60, 63-200 μm).m). download file view on ChemRxiv SI Michael Addition ChemEdu Tiano.pdf (1.55 MiB) Enantioselective Michael addition : an experimental introduction to asymmetric synthesis

Updating Dimedone─The Humble Hero of the Organic Laboratory

“…The first of the two named reactions, the Michael addition, remains widely used, 16 and it develops a good understanding of electrophilicity of reagents 17,18 and principles of regioselectivity 19 and furthermore has been adapted into a stereoselective process by the incorporation of chiral catalysts. 20 The subsequent Dieckmann ring closure, hydrolysis, and decarboxylation steps all offer good "curly arrow" mechanism practice. 19 Ideally students will also have been introduced to the retrosynthetic concept in order to gain a fuller educational value from this reaction.…”

“…This experiment must run after students have been taught enolate chemistry in the classroom. The first of the two named reactions, the Michael addition, remains widely used, and it develops a good understanding of electrophilicity of reagents , and principles of regioselectivity and furthermore has been adapted into a stereoselective process by the incorporation of chiral catalysts . The subsequent Dieckmann ring closure, hydrolysis, and decarboxylation steps all offer good “curly arrow” mechanism practice …”