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Tsuji–Trost Reaction of Non‐Derivatized Allylic Alcohols
Author(s) -
Akkarasamiyo Sunisa,
Sawadjoon Supaporn,
Orthaber Andreas,
Samec Joseph S. M.
Publication year - 2018
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201705164
Subject(s) - allylic rearrangement , chemistry , palladium , tsuji–trost reaction , stereocenter , medicinal chemistry , denticity , substitution reaction , ligand (biochemistry) , catalysis , nucleophile , hydride , reaction mechanism , stereochemistry , organic chemistry , enantioselective synthesis , crystal structure , metal , biochemistry , receptor
Palladium‐catalyzed allylic substitution of non‐derivatized enantioenriched allylic alcohols with a variety of uncharged N‐, S‐, C‐ and O‐centered nucleophiles using a bidentate BiPhePhos ligand is described. A remarkable effect of the counter ion (X) of the XPd[κ 2 ‐BiPhePhos][η 3 ‐C 3 H 5 ] was observed. When ClPd[κ 2 ‐BiPhePhos][η 3 ‐C 3 H 5 ] (complex I ) was used as catalyst, non‐reproducible results were obtained. Study of the complex by X‐ray crystallography, 31 P NMR spectroscopy, and ESI‐MS showed that a decomposition occurred where one of the phosphite ligands was oxidized to the corresponding phosphate, generating ClPd[κ 1 ‐BiPhePhosphite‐phosphate][η 3 ‐C 3 H 5 ] species (complex II ). When the chloride was exchanged to the weaker coordinating OTf − counter ion the more stable Pd[κ 2 ‐BiPhePhos][η 3 ‐C 3 H 5 ] + +[OTf] − (complex III ) was formed. Complex III performed better and gave higher enantiospecificities in the substitution reactions. Complex III was evaluated in Tsuji–Trost reactions of stereogenic non‐derivatized allylic alcohols. The desired products were obtained in good to excellent yields (71–98 %) and enantiospecificities (73–99 %) for both inter‐ and intramolecular substitution reactions with only water generated as a by‐product. The methodology was applied to key steps in total synthesis of ( S )‐cuspareine and (+)‐lentiginosine. A reaction mechanism involving a palladium hydride as a key intermediate in the activation of the hydroxyl group is proposed in the overall transformation.