Experimental procedure
You will be assigned (master experiment assignment board) your own combination of
aldehyde and amino acid (ie different from your lab partner(s)). Make sure you use the
assigned combination!
Dissolve your assigned aromatic aldehyde (10 mmol), amino acid (10 mmol) and dimethyl
fumarate (10 mmol) in methanol (70 ml) containing a few drops of glacial acetic acid. Add a few
anti-bumping granules and heat the mixture to a gentle reflux overnight. Allow the mixture to cool
to room temperature. A white precipitate should form (this may form before cooling - don't worry
about this unless you have lost some of the solvent during the reflux); filter this off at the water
pump, keeping both this solid (a fraction rich in the first diastereomer) and the filtrate. Evaporate
the filtrate under reduced pressure, and triturate the residue with small portions of dichloromethane
(up to 50 ml total) to afford a fraction enriched in the other diastereomer. Purify both fractions by
crystallisation from hot methanol (the addition of SMALL amounts of water may be necessary to
aid dissolution). Record the yield, m.p., IR and NMR spectra (d6-DMSO) of both compounds.
Note: You should be able to recrystallise your compounds to isomeric purity, but if the samples
ARE contaminated with some of the other diastereomer, use the integral in the NMR to help you
calculate the overall isomeric ratio.
Write Up
The write up should conform to a J. Chem. Soc., Perkin Trans. I, style (Title, Abstract,
Introduction, Results and Discussion, Experimental, References). Your introduction must include
discussion of the following points:
1.The mechanism for the formation of your products, together with representations of the
transition states leading to the two diastereoisomeric products;
2.Three recent (1993 or later) examples from the primary literature of multi-component
syntheses;
3.Three other recent (1993 or later) examples from the primary literature of the use of
azomethine ylide cycloadditions in synthesis;
4.Your reaction produces two diastereoisomers: what techniques might you use to assign
the correct relative stereochemistry of each isomer?
References and Notes
1."The Logic of Chemical Synthesis", E. J. Corey and X.-M. Cheng, John Wiley and
Sons, Chichester, 1989; "Classics in Total Synthesis", K. C. Nicolaou and E. J.
Sorensen, VCH, Cambridge, 1996.
2."Combinatorial Peptide and Non-Peptide Libraries - A Handbook", ed. G. Jung, VCH,
Weinheim. 1996
3.A. Domling, E. Herdtweck, I. Ugi, Acta Chem. Scand. 1998, 52, 107
4.M. F. Aly, M. I. Younes, S. A. M. Metwally, Tetrahedron, 1994, 50, 3159
Steve Marsden, 28/9/98
