Tsuji–Trost Reaction of Non‐Derivatized Allylic Alcohols

• Published in: Chemistry : a European journal Vol. 24; no. 14; pp. 3488 - 3498
• Main Authors: Akkarasamiyo, Sunisa, Sawadjoon, Supaporn, Orthaber, Andreas, Samec, Joseph S. M.
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 07.03.2018; Wiley Subscription Services, Inc
• Subjects: Alcohol; Alcohols; Alkaloids - chemical synthesis; Alkaloids - chemistry; asymmetric catalysis; Catalysis; Chemical synthesis; Chemistry; Chemistry, Multidisciplinary; Crystallography; Crystallography, X-Ray; cuspareine; Hydroxyl groups; Ligands; Magnetic resonance spectroscopy; Molecular Structure; NMR spectroscopy; Nucleophiles; OH activation; Palladium; Palladium - chemistry; Phosphates; Phosphites - chemistry; Physical Sciences; Propanols - chemistry; Quinolines - chemical synthesis; Quinolines - chemistry; Reaction mechanisms; Science & Technology; Substitution reactions; Tsuji-Trost reaction; Water; XPD protein; Tsuji-Trost reaction; O BOND-CLEAVAGE; ENANTIOSELECTIVE SYNTHESIS; asymmetric catalysis; CHIRAL PHOSPHORIC-ACID; SUBSTITUTION-REACTIONS; 1,3-CHIRALITY TRANSFER; HETEROAROMATIC-COMPOUNDS; DEHYDRATIVE ALLYLATION; PALLADIUM-CATALYZED AMINATION; ASYMMETRIC ALPHA-ALLYLATION; cuspareine; (PI-ALLYL)PALLADIUM COMPLEXES; palladium; OH activation
• ISSN: 0947-6539; 1521-3765; 1521-3765
• DOI: 10.1002/chem.201705164

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[κ2‐BiPhePhos][η3‐C3H5] was observed. When ClPd[κ2‐BiPhePhos][η3‐C3H5] (complex I) was used as catalyst, non‐reproducible results were obtained. Study of the complex by X‐ray crystallography, 31P NMR spectroscopy, and ESI‐MS showed that a decomposition occurred where one of the phosphite ligands was oxidized to the corresponding phosphate, generating ClPd[κ1‐BiPhePhosphite‐phosphate][η3‐C3H5] species (complex II). When the chloride was exchanged to the weaker coordinating OTf− counter ion the more stable Pd[κ2‐BiPhePhos][η3‐C3H5]++[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. Palladium‐catalyzed enantiospecific allylic substitution of non‐derivatized allylic alcohols with a variety of uncharged N‐, S‐, C‐ and O‐centered nucleophiles using a bidentate BiPhePhos ligand is described. The desired products were obtained in good to excellent yields and enantiospecificity for both inter‐ and intramolecular substitution reactions with only water generated as a by‐product. A remarkable effect of the counter ion (X) of the XPd[BiPhePhos][allyl] was observed, whereby weaker coordinating counter ions gave a more stable complex that performed better and gave higher enantiospecificity in substitution reactions. The efficiency of this catalyst was further demonstrated in the 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.