Modular Furanoside Phosphite‐Phosphoroamidites, a Readily Available Ligand Library for Asymmetric Palladium‐Catalyzed Allylic Substitution Reactions. Origin of Enantioselectivity

Abstract

A library of furanoside phosphite-phosphoroamidite ligands has been synthesized and screened in the palladium-catalyzed allylic substitution reactions of several substrate types. These series of ligands can be prepared efficiently from easily accessible d-xylose and d-glucose. Their modular nature enables the position of the phosphoroamidite group, configuration of C-3 of the furanoside backbone and the substituents/configurations in the biaryl phosphite/phosphoroamidite moieties to be easily and systematically varied. By carefully selecting the ligand components, therefore, high regio-and enantioselectivities (ees up to 98%) and good activities have been achieved in a broad range of mono-and disubstituted hindered and unhindered linear and cyclic substrates. The NMR studies on the palladium-p-allyl intermediates provide a deeper understanding about the effect of the ligand parameters on the origin of enantioselectivity. They also indicate that the nucleophilic attack takes place predominantly at the allylic terminal carbon atom located trans to the phosphoroamidite moiety.

A new and efficient asymmetric synthesis of oseltamivir phosphate (Tamiflu) from d-glucose

“…12 Protection of the amino group of compound 2 as N-Boc was accomplished by its treatment with ditert-butyl dicarbonate in methanol to afford compound 3 in 83% yield. Alcohol 3 was converted to the corresponding iodide 4 in 64% yield by treatment with I 2 , PPh 3 , imidazole and refluxing in a mixed solvent of tolueneeacetonitrile (2:1) (Scheme 1).…”

“…4.1.15. Ethyl (3R,4R,5S)-4-(acetylamino)-5-azido-3-(1-ethylpropoxy) cyclohex-1-ene-1-carboxylate (12). To a solution of 11 (82 mg, 0.21 mmol) in CH 2 Cl 2 (2 mL) at 0 C was added trifluoro acetic acid (0.32 mL, 4.14 mmol).…”

Modular Furanoside Pseudodipeptides and Thioamides, Readily Available Ligand Libraries for Metal‐Catalyzed Transfer Hydrogenation Reactions: Scope and Limitations

“…[12] These compounds (4-7) were chosen as intermediates for preparing ligands because the various elements that make it possible to study the position in which the aamino acid/thioamide is coupled (at either C-5 or C-3) and the configuration of C-3 of the sugar amino alcohol can be easily incorporated. Initially, we synthesized the pseudodipeptide ligand library L1-L4a-i by coupling a series of N-Boc-protected amino acids with the corresponding amino alcohols 4-7 using isobutyl chloroformate in the presence of N-methylmorpholine (Scheme 1, step i).…”

Palladium-Catalyzed Enantioselective Allylic Substitution

“…Sugar-based ligands L28 have been developed by Dieguez and Pamies [54]. Hybrids of phosphite and phosphoramidites of the same class have also been explored [55][56][57].…”