Tsuji–Trost Reaction of Non‐Derivatized Allylic Alcohols

Abstract

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 -BiPhePhos][η -C H ] was observed. When ClPd[κ -BiPhePhos][η -C H ] (complex I) was used as catalyst, non-reproducible results were obtained. Study of the complex by X-ray crystallography, 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 -BiPhePhosphite-phosphate][η -C H ] species (complex II). When the chloride was exchanged to the weaker coordinating OTf counter ion the more stable Pd[κ -BiPhePhos][η -C H ] +[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 Diastereoselective Synthesis of (Z)‐Conjugated Enynyl Homoallylic Alcohols

“…Partial redox transmetalation in which additional Pd 0 L n species attack η 3 -allylpalladium intermediate A may occur. [28] Scheme 4 shows a plausible reaction mechanism that is based on the above results; this mechanism is similar to that of our previously reported palladium-catalyzed three-component reaction. [5] η 3 -Allylpalladium intermediate A is formed through the oxidative addition of allylic benzoate (R)-2 a to a Pd 0 species.…”

Catalytic, Enantioselective Syn-Diamination of Alkenes

“…The 1 H NMR spectra matched those in the literature. 28 Data for 12: 7), 1.39 (d,J = 6.3 Hz,3 H,HC(8)).…”

“…[22][23][24] The catalytic, enantioselective, oxidative diamination of olefins is perhaps the most conceptually straightforward approach to the preparation of enantioenriched vicinal diamines, however alternative methods involving (reductive) carbon-carbon bond formation have also been described. 25,26 Alkene diamination has more recently been achieved in large part with palladium and copper catalysts, [27][28][29][30] by N-N bond activation of hydrazine derivatives to oxidize the catalytic metal species and to generate the nucleophile ( Figure 2). These methods, limited by the need for high-energy reagents, have been expanded to engage more common N-H nucleophiles.…”

Highly Efficient and Selective N-Alkylation of Amines with Alcohols Catalyzed by in Situ Rehydrated Titanium Hydroxide

“…Also various of heterogeneous catalysts [27,28,29,30,31,32,33,34] have been used. (ii) Tsuji-Trost type reactions for allylic alcohols using Pd [35] or Ni [36] complexes. (iii) Lewis-acid catalyzed reactions using a variety of salts and ligands [37,38].…”