Palladium‐Catalyzed Enantioselective Allylic Substitution in the Presence of Monodentate Furanoside Phosphoramidites

Abstract

Figure 1. Furanoside monophosphoramidite ligands derived from 1.

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

“…Stoltz and co-workers conceived a strategy for the catalytic enantioselective synthesis of (+)-eucomic acid (63) based on intermediate 64 as the carrier of the stereodefined tetrasubstituted α-hydroxyacid present in its structure. 497 present in other important natural products, such as (−)-aspterric acid methyl ester (65), quinic acid (66), and the harringtonine alkaloids (67), thus adding interest to the catalytic enantioselective preparation of this motif (Figure 22). For the preparation of intermediate 64, a Pd-catalyzed AAA reaction of 68 with 2-chloroallyl mesylate using PHOX ligand (S)-L122 was envisaged (Scheme 172).…”

“…Among the monodentate P-donor ligands developed since 2008 for Pd-catalyzed asymmetric allylic alkylation (AAA), diamidophosphites − and phosphoramidites − were found to provide higher enantioselectivities than their phosphite, , phosphinite, and phosphine − counterparts. Scheme collects the most representative families of monodentate P-donor ligands evaluated in the allylic alkylation of rac -1,3-diphenylallyl acetate as substrate with dimethyl malonate as nucleophile.…”

“…With monodentate ligands L2 , L4 , and L5 the same levels of enantioselectivity were also achieved with pyrrolidine and sodium para -toluene sulfinate as nucleophiles. Bauer’s group also studied other substrates using Pd– L8 as catalyst . Although only low enantioselectivities (up to 49% ee ) were achieved in the Pd-allylic alkylation of less sterically hindered substrates (e.g., rac -1,3-dimethylallyl and cyclohexenyl carbonates), the Pd/ L8 catalyst yielded promising results for unsymmetrically substituted linear substrates like 4-phenylbut-3-en-2-yl acetate (with regio- and enantioselectivities up to 75% and 90% ee , respectively) and cinnamyl acetate (with regio- and enantioselectivities up to 93% and up to 79% ee , respectively).…”

Supported Ionic Liquid Phase (SILP) Allylic Alkylation of Amines in Continuous Flow

“…Due to its numerous advantages, such as mild conditions, variable chiral ligands or nucleophiles, simple implementation, and good functional group tolerance; such allylations have found wide application in the synthesis of valuable optically active compounds. Since the seminal examples of Trost, [24] a wide range of chiral ligands, including phosphinooxazolines, [25] amino‐acid derivatives, [26] amino‐phosphinites, [27] phosphoramidites, [28] and aminoalkyl‐phosphines [29] have been developed for the asymmetric allylation of stabilized C ‐nucleophiles. Despite the large number of advancements, up until today, the Trost‐type ligands still have maintained a privileged position among the chiral modifiers in the field of asymmetric allylations [30] .…”