Bislactime ether process

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The bislactimether process , also known as the Schöllkopf method or Schöllkopf-Hartwig reaction , describes a method of synthesis of optically active amino acids in organic chemistry . The method was developed in 1981 by the German chemist Ulrich Schöllkopf .

Reaction mechanism

Reaction mechanism of the Schöllkopf method

Glycine and valine are converted to a cyclic dipeptide (dioxopiperazine), which is converted into the bislactime ether by double methylation . This can e.g. B. be accomplished using trimethyloxonium tetrafluoroborate . One of the prochiral protons derived from glycine can be abstracted from this with butyllithium . The following step is decisive for the stereoselectivity : The carbanion formed is sterically hindered on the upper side by the isopropyl radical of the valine and can only be attacked from below. Trapping the anion with an alkyl iodidetherefore always delivers the enantiomer produced by attack on the back . Finally, the dipeptide is split into the two amino acid methyl esters by acid hydrolysis , which are then separated from one another.

With valine, Schöllkopf chose the natural, proteinogenic amino acids with the largest aliphatic , non-reactive, non-chiral residue in order to achieve the highest possible stereoselectivity. As a rule, enantiomeric excesses of about 95% ( ee ) can be achieved.

Possibilities and limits

The Schöllkopf method can be used to produce all amino acids for which a suitable capture reagent (RI) can be found that leads to the desired product under the reaction conditions. The radical R is not restricted to alkyl, but can also have a more complex structure. The bislactime ether process is used exclusively as a laboratory process for the synthesis of small amounts of exotic amino acids. An industrial application of the process is not known because its atom economy is limited.

Individual evidence

  1. ^ Leo A. Paquette: Chiral Reagents for Asymmetric Synthesis . Wiley and Sons, 2003, ISBN 0-47085625-4 , pp. 220-223.
  2. a b Jan Bülle, Aloys Hüttermann: The basic knowledge of organic chemistry: The most important organic reactions in the laboratory and in nature . Wiley-VCH, 2000, ISBN 3-52730847-4 , pp. 310/311.
  3. U. Schöllkopf, T. Tiller, J. Bardenhagen: Tetrahedron 1988, 44, 5293.