Tsuji–Trost reaction
The Tsuji–Trost reaction is a palladium-catalysed substitution reaction of a nucleophile with a substrate containing a leaving group in an allylic position. The nucleophile can be carbon, nitrogen or oxygen based. Examples are alcohols, enolates, phenols and enamines. The leaving group can for example be a halide or acetate. A base is required for in-situ generation of the nucleophile from a precursor. In the reaction product the nucleophile has replaced the leaving group.[1] The reaction is also known as Trost allylation or allylic alkylation. This organic reaction is named after Jiro Tsuji who first reported the method in 1965 [2] and named after Barry Trost who in 1973 introduced phosphine ligands in the reaction and introduced an asymmetric version.[3][4]
In the procedure reported by Tsuji in 1965 allylpalladium chloride dimer was reacted with the sodium salt of diethyl malonate to form a mixture of monoalkylated and dialkylated product:
Tsuji was building on earlier work by Schmidt who in 1962 published on the reaction of water as a nucleophile on olefin-palladium chloride complexes to form ketones.[5]
In the procedure reported by Trost in 1973 using a different alkene the use of triphenylphosphine was required (The Tsuji procedure did not work)
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[edit] Mechanism
Zerovalent palladium is used or is generated in situ from a palladium(II) source. A phosphine ligand is required such as triphenylphosphine or the Trost ligand or for example dba. The metal coordinates to the alkene forming a η2 π-allyl-Pd0 Π complex. The next step is oxidative addition in which the leaving group is expelled with inversion of configuration and a η3 π-allyl-PdII is created. The nucleophile then adds to the proximus or distal carbon atom of the allyl group regenerating the η2 π-allyl-Pd0 complex. The palladium compound detaches from the alkene in the completion of the reaction and can start again in the catalytic cycle. Chirality stored in a ligand is transferred to the final product in one of the complexes formed.
[edit] Allylic asymmetric substitution
The enantioselective version is called Trost asymmetric allylic alkylation or Trost AAA or allylic asymmetric substitution and used in asymmetric synthesis.[6][7][8] The reaction was originally developed with a catalyst based on palladium supported by the Trost ligand. The nucleophile can be a phenol, a phthalimide or simply water.
[edit] Scope
An AAA example is the synthesis of an intermediate in the combined total synthesis of galanthamine and morphine[9] with 1 mol% [pi-allylpalladium chloride dimer], 3 mol% (S,S) Trost ligand, and triethylamine in dichloromethane solvent at room temperature resulting (−)-enantiomer of the aryl ether in 72% chemical yield and 88% enantiomeric excess.
Ongoing research is taking place into new asymmetric ligands such as one based on biphenyl and fenchol.[10]
The reaction substrate is also extended to allenes and in a specific ring expansion the AAA reaction is accompanied by a Wagner-Meerwein rearrangement[11][12]:
[edit] External links
- Org. Synth. 1989, 67, 105
- Org. Synth. 2009, 86, 47
- example of tsuji-trost reaction in total synthesis see : http://www.biocis.u-psud.fr/IMG/pdf/concise_total_synthesis_of_Minfiensine.pdf the second reaction found on website of the biocis team : http://www.biocis.u-psud.fr/spip.php?article332
[edit] References
- ^ Strategic Applications of Named Reactions in Organic Synthesis (Paperback) by Laszlo Kurti, Barbara Czako ISBN 0-12-429785-4
- ^ Organic syntheses by means of noble metal compounds XVII. Reaction of π-allylpalladium chloride with nucleophiles Tetrahedron Letters, Volume 6, Issue 49, 1965, Pages 4387-4388 Jiro Tsuji, Hidetaka Takahashi, Masanobu Morikawa doi:10.1016/S0040-4039(00)71674-1
- ^ Trost, B. M.; Fullerton, T. J. "New synthetic reactions. Allylic alkylation." J. Am. Chem. Soc. 1973, 95, 292–294. doi:10.1021/ja00782a080.
- ^ Asymmetric Transition Metal-Catalyzed Allylic Alkylations Barry M. Trost David L. Van Vranken Chem. Rev., 1996, 96 (1), pp 395–422 doi:10.1021/cr9409804
- ^ Smidt, J., Hafner, W., Jira, R., Sieber, R., Sedlmeier, J. and Sabel, A. (1962), Olefinoxydation mit Palladiumchlorid-Katalysatoren. Angewandte Chemie, 74: 93–102. doi:10.1002/ange.19620740302
- ^ Trost, B. M.; Dietsch, T. J. "New synthetic reactions. Asymmetric induction in allylic alkylations." J. Am. Chem. Soc. 1973, 95, 8200–8201. doi:10.1021/ja00805a056.
- ^ Trost, B. M.; Strege, P. E. "Asymmetric induction in catalytic allylic alkylation." J. Am. Chem. Soc. 1977, 99, 1649–1651. doi:10.1021/ja00447a064.
- ^ Asymmetric Transition-Metal-Catalyzed Allylic Alkylations:Applications in Total Synthesis Trost, B. M.; Crawley, M. L. Chem. Rev.; (Review); 2003; 103(8); 2921-2944. doi:10.1021/cr020027w
- ^ Trost, B. M.; Tang, W.; Toste, F. D. "Divergent Enantioselective Synthesis of (−)-Galanthamine and (−)-Morphine." J. Am. Chem. Soc. 2005, 127, 14785–14803. doi:10.1021/ja054449+.
- ^ Goldfuss, B.; Löschmann, T.; Kop-Weiershausen, T.; Neudörfl, J.; Rominger, F. "A superior P-H phosphonite: Asymmetric allylic substitutions with fenchol-based palladium catalysts." Beilstein J. Org. Chem. 2006, 2, 7–11. doi:10.1186/1860-5397-2-7.
- ^ Trost, B. M.; Xie, J. "Palladium-Catalyzed Asymmetric Ring Expansion of Allenylcyclobutanols: An Asymmetric Wagner-Meerwein Shift." J. Am. Chem. Soc. 2006, 128, 6044–6045. doi:10.1021/ja0602501.
- ^ The co-catalysts are benzoic acid and triethylamine. Molecular sieves (MS) prevent hydrolysis.
