Trost asymmetric allylic alkylation

From Wikipedia, the free encyclopedia

The Trost asymmetric allylic alkylation or Trost AAA or allylic asymmetric substitution is an organic reaction used in asymmetric synthesis ^{[1] [2] [3]}.

In the reaction an allylic leaving group in an organic compound is displaced by a nucleophile while at the same time palladium is coordinated to the allyl double bond as a Π complex. A typical substrate in this reaction is an allylic compound with a good leaving group such as an acetate group. The reaction was originally developed with a catalyst based on palladium supported the Trost ligand. The nucleophile can be a phenol, a phthalimide or simply water.

Contents 1 reaction mechanism 2 Scope 2.1 AAA-Wagner-Meerwein shift 3 External links 4 References

[edit] reaction mechanism

Zerovalent palladium is generated in situ from a palladium(II) source and a phosphine ligand such as the Trost ligand. 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-Pd^II 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. The chirality stored in the ligand is transferred to the final product in one of the complexes formed.

[edit] Scope

An AAA example is the synthesis of an intermediate in the combined total synthesis of galanthamine and morphine ^[4] with 2.5 mol% Pd₂dba₃ tris(dibenzylideneacetone)dipalladium(0)) 7.5 mol% (S,S) Trost ligand, triethylamine, dichloromethane at room temperature resulting in 64% chemical yield and (-) 77% enantiomeric excess.

Ongoing research is taking place into new asymmetric ligands such as one based on biphenyl and fenchol ^[5].

[edit] AAA-Wagner-Meerwein shift

The reaction substrate is also extended to allenes and in a specific ring expansion the AAA reaction is accompanied by a Wagner-Meerwein rearrangement ^[6] in scheme 3 ^[7]:

[edit] External links

• catalyst supplier
• Asymmetric allylic substitution: mechanism and recent advances using palladium and molybdenum Kyle D. Bodine Review

[edit] References

1. ^ New synthetic reactions. Allylic alkylation Barry M. Trost and Terry J. Fullerton J. Am. Chem. Soc.; 1973; 95(1) pp 292 - 294; DOI: 10.1021/ja00782a080 Abstract
2. ^ New synthetic reactions. Asymmetric induction in allylic alkylations Barry M. Trost and Thomas J. Dietsch J. Am. Chem. Soc.; 1973; 95(24) pp 8200 - 8201; DOI: 10.1021/ja00805a056 Abstract
3. ^ Asymmetric induction in catalytic allylic alkylation Barry M. Trost and Paul E. Strege J. Am. Chem. Soc.; 1977; 99(5) pp 1649 - 1651; DOI: 10.1021/ja00447a064 Abstract
4. ^ Divergent Enantioselective Synthesis of (-)-Galanthamine and (-)-Morphine Barry M. Trost, Weiping Tang, and F. Dean Toste J. Am. Chem. Soc.; 2005; 127(42) pp 14785 - 14803; (Article) DOI: 10.1021/ja054449+ Abstract
5. ^ Bernd Goldfuss et al. Beilstein Journal of Organic Chemistry 2006, 2:7 Abstract + Article
6. ^ Palladium-Catalyzed Asymmetric Ring Expansion of Allenylcyclobutanols: An Asymmetric Wagner-Meerwein Shift Barry M. Trost and Jia Xie J. Am. Chem. Soc.; 2006; 128(18) pp 6044 - 6045; Abstract
7. ^ The co-catalysts are benzoic acid and triethylamine. Molecular sieves (MS) prevent hydrolysis