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 Tsuij in 1965 allylpalladium chloride dimer was reacted with the sodium salt of diethyl malonate to form a mixture of monoalkylated and dialkylated product:

Tsuij 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 Tsuij procedure did not work)

Contents

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.

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.

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]:

External links

References

  1. ^ Strategic Applications of Named Reactions in Organic Synthesis (Paperback) by Laszlo Kurti, Barbara Czako ISBN 0-12-429785-4
  2. ^ 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
  3. ^ Trost, B. M.; Fullerton, T. J. "New synthetic reactions. Allylic alkylation." J. Am. Chem. Soc. 1973, 95, 292–294. doi:10.1021/ja00782a080.
  4. ^ 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
  5. ^ 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
  6. ^ 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.
  7. ^ Trost, B. M.; Strege, P. E. "Asymmetric induction in catalytic allylic alkylation." J. Am. Chem. Soc. 1977, 99, 1649–1651. doi:10.1021/ja00447a064.
  8. ^ 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
  9. ^ 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+.
  10. ^ 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.
  11. ^ 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.
  12. ^ The co-catalysts are benzoic acid and triethylamine. Molecular sieves (MS) prevent hydrolysis.