Double stereoselective coordination of chiral N,S ligands: Synthesis, coordination chemistry and utilization in Pd‐catalyzed allylic alkylation

Abstract

A series of chiral pentane‐2,4‐diyl‐based thioether‐amine ligands [4 and 5; (R,S)‐ and (S,S)‐R1SCH(CH3)CH2CH(CH3)NHR2, respectively, where 4a R1 = iPr, R2 = Ph; 4b R1 = tBu, R2 = Ph; 4c R1 = 1‐Ad, R2 = Ph; 5a R1 = iPr, R2 = Ph; 5b R1 = tBu, R2 = Ph; 5c R1 = 1‐Ad, R2 = Ph; 5d R1 = iPr, R2 = 4‐MeOC6H4; 5e R1 = iPr, R2 = 4‐MeC6H4; 5f R1 = iPr, R2 = 3,5‐Me2C6H3] with stereogenic S‐ and N‐donor atoms has been prepared starting from cyclic sulfates via optically pure γ‐aminoalcohol or 2,4‐dimethylazetidine intermediates. The synthesis of the novel diastereomerically related ligand sets 4 and 5 was accomplished starting from the same source of chirality. The modular ligand structure and the novel synthetic strategies developed for their synthesis allowed the easy modification of the ligands’ (i) S‐ and (ii) N‐substituents, as well as (iii) the relative stereochemistry within the ligand backbone. Six‐membered [Pd(N,S)Cl2]‐type chelate complexes of the diastereomerically related ligands 4a and 5a were synthesized and characterized by X‐ray crystallography in the solid phase, by density functional theory calculations and in solution by NMR spectroscopy. The coordination of 5a resulted in the formation of a single chair conformation by the stereospecific locking of both stereolabile (N and S) donor atoms. In contrast, compound 4a forms rapidly equilibrating palladium species due to the fast inversion of the sulfur donor. Ligands with stereochemically fixed donor atoms provided robust and efficient catalytic systems that can be effectively applied in alkylene carbonates as green reaction media. Remarkably, the phosphine‐free catalysts are air‐stable, and at room temperature in the presence of moisture gave excellent ee’s (up to 93%) in asymmetric allylation processes thanks to the double stereoselective coordination.

Recent Advances in Enantioselective Pd-Catalyzed Allylic Substitution: From Design to Applications

“…Heterodonor N,S/Se-ligands with a variety of donor group combinations (e.g., imine-thioether, oxazoline-sulfoxide, thiazoline-thioether) have also been studied. 339 − 351 In most cases, they provided only moderate enantioselectivities. As a notable exception, up to 98% ee was obtained with the simple amine-selenoether ligand L112 in the alkylation of rac -1,3-diphenylallyl acetate with dimethyl malonate ( Scheme 95 a).…”

“…Heterodonor N,S/Se-ligands with a variety of donor group combinations (e.g., imine-thioether, oxazoline-sulfoxide, thiazoline-thioether) have also been studied. − In most cases, they provided only moderate enantioselectivities. As a notable exception, up to 98% ee was obtained with the simple amine-selenoether ligand L112 in the alkylation of rac -1,3-diphenylallyl acetate with dimethyl malonate (Scheme a). , Similar enantioselectivities were achieved using the ferrocene-based thiazoline-thioether ligands L113 and L114 (Scheme a). , X-ray and NMR spectroscopic studies of the π-allyl intermediates indicated that the sulfur atom was a stronger π-acceptor than the nitrogen atom.…”

Tuning Rh(II)-Catalyzed Cyclopropanation with Tethered Thioether Ligands

“…A stereogenic center is created at the sulfur atom upon coordination to the Rh center. [51][52][53][54] As a result, a mixture of diastereomers are present, (SC, RS) and (SC, SS), due to the sulfur stereogenic center and the S configuration at the asymmetric carbon on the bridging oxazolidinate (Figure 3). Of the four paddlewheel units, two are (SC, RS) and two structures are (SC, SS), with minor structural variations between them.…”

Exploring the Mechanism of the Palladium-Catalyzed 3-Butene-2-ol Amination Reaction: A DFT Study

“…More broadly effective palladium catalysts for nucleophiles have also been determined over the years (Yang et al, 2015(Yang et al, , 2016Jiang et al, 2017). Recently, it has been reported that the chirality of catalytic ligand could significantly influence the stereoselective coordination (Major et al, 2019). In consideration of the enormous raw reactants and catalysts mentioned above, the mechanism of the high enantioselectivity for the N-alkylation reaction still needs further elaboration.…”