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Chelated Enolates of Amino Acid Esters − New and Efficient Nucleophiles for Isomerization‐Free, Stereoselective Palladium‐Catalyzed Allylic Substitutions
Author(s) -
Kazmaier Uli,
Zumpe Franz L.
Publication year - 2001
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/1099-0690(200111)2001:21<4067::aid-ejoc4067>3.0.co;2-4
Subject(s) - nucleophile , chemistry , allylic rearrangement , isomerization , tsuji–trost reaction , palladium , stereoselectivity , claisen rearrangement , medicinal chemistry , catalysis , chirality (physics) , chelation , stereochemistry , organic chemistry , chiral symmetry breaking , physics , quantum mechanics , nambu–jona lasinio model , quark
Chelated amino acid ester enolates were found to be suitable nucleophiles for palladium‐catalyzed allylic alkylations. Unlike stabilized soft nucleophiles, the chelated enolates react under very mild reaction conditions, even at −78 °C. If TFA‐protected amino acid tert ‐butyl esters are used as nucleophiles, the anti ‐configured products are obtained in a highly diastereoselective fashion. This protocol is therefore a good supplement to the chelate enolate Claisen rearrangement, which gives rise to the corresponding syn products. Especially good results are obtained with allylic carbonates as substrates, as these are readily able to form the required π‐allylpalladium complexes at temperatures as low as −78 °C. In this temperature range, π−σ−π isomerization of the π‐allyl intermediates does not play a significant role, and so application of the highly reactive chelated enolates allows the use of C‐nucleophiles in allylic alkylation of ( Z )‐allyl substrates with complete conservation of the olefin geometry for the first time. With ( Z )‐allyl carbonates bearing two identical substituents at the allyl termini, the attack of the nucleophile on the intermediate π‐allylpalladium complex occurs exclusively at the anti position, giving rise to the ( E )‐configured substitution product. If optically active allyl carbonates are used, complete transfer of the chirality to the product is observed. These examples clearly indicate that the π−σ−π isomerization is completely suppressed under the reaction conditions used. This opens up new synthetic applications, which will be evaluated in the near future.