Chapter 12
Amino Acid-Based Phosphorous(III) Ligands
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D. Jayasinghe and H. B. Kraatz Department of Chemistry, University of Saskatchewan, 110 Science Place, Saskatoon, Saskatchewan S7N 5C9, Canada
The synthesis of chiral ligands using naturally occurring and renewable sources of chirality has become an important area of research. Chiral phosphorous ligands based on amino acids can be readily synthesized in a few steps giving useful components to catalytic systems. Here we provide a brief overview of current ligands and applications.
© 2004 American Chemical Society In Methodologies in Asymmetric Catalysis; Malhotra, S.; ACS Symposium Series; American Chemical Society: Washington, DC, 2004.
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176 Phosphorous-based ligands have attracted tremendous attention and are among the most important ligands in organometallic chemistry with a wide range of steric and electronic properties. In particular, for asymmetric transformations these chiral phosphine ligands have found wide-spread applications! 1-3]. However, their synthesis often involves multistep reactions. Chiral biomolecules on the other hand, such as amino acids, peptide and carbohydrates, offer a particularly convenient starting point for the synthetis of chiral phosphorous ligands and are readily available in an enantiopure form. In addition, they are ready accessible, renewable and often of low cost. Carbohydrates, have been exploited as chiral starting materials for the synthesis of phosphinites, making use of the rich array of stereochemical and functional group diversity[4-9]. These have found applications in catalysis[4,6]. However, in some cases, the desired enantiomer for a particular reaction leading to a specific enantiopure product may not be available from natural sources and thus maybe very costly. Amino acids, on the other hand, are readily available in both enantiomeric forms (L-phenylalanine CA$ 1.25/g; D-phenylalanine CA$ 6.75/g; Aldrich-2003/2004) when compared to that of sugars, (aD-glucose CA$ 0.98/g; L-glucose CA$ 106.8/g; Aldrich- 2003/2004) and may facilitate the synthesis of both enantiomers of the intended product. Amino acids and their derivatives have also found widespread applications. In particular, proline-derived aminoalcohols have been popularized by Mortreux and coworkers for the synthesis of chelating aminophosphine-phosphinite ligands [10-13]. More recently, amino acid and peptide-based phosphines and phosphinites have been reported in the literature. Here we wish to summarize recent results on the synthetic aspects of amino acid and peptide-based phosphinite (R P(OR)) and phosphine (R2PR) ligands and highlight some of their applications. 2
Phosphinites Phosphinites provide different chemical, electronic and structural properties compared to phosphines. As was shown by RajanBabu and others, phosphinites are versatile ligands which allow effective catalytic asymmetric transformations. The metal-phosphorous bond is often stronger in phosphinites compared to the related phosphines due to the presence of the electron-withdrawing P-OR group. In addition, the empty a*-orbital of the phosphinite, P(OR)R is stabilized and thus a better acceptor. The synthesis of phosphinites is conveniently achieved by reacting alcohols with dialkyl or diarylphosphinechlorides in the presence of a base. Using this approach, Mortreux was able to synthesize chiral amino alcohol based aminophosphine-phosphinite (AMPP) ligands. He proposed two parallel synthetic pathways to generate chiral AMPP ligands from amino acids, either by direct synthesis from amino alcohols (Scheme 1), or by the reduction of formyl esters of α-amino acids followed by coupling with PPh Cl (Scheme 2) [12]. 2
2
In Methodologies in Asymmetric Catalysis; Malhotra, S.; ACS Symposium Series; American Chemical Society: Washington, DC, 2004.
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OPPb,
PPh Cl
Ν I
2
NEt,
PPh
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Scheme 1: Synthesis of a prolinol-based aminophosphine-phosphinite (AMPP) ligands
In contrast to this, recent work from our group has shown the use of protected hydroxyl-containing amino acids to form phosphinites and even peptido-phosphinites. R
