A New Family of Cinchona-Derived Amino Phosphine Precatalysts: Application to the Highly Enantio- and Diastereoselective Silver-Catalyzed Isocyanoacetate Aldol Reaction

Abstract

A new class of readily accessible chiral amino-phosphine precatalysts derived from 9-amino(9-deoxy) epicinchona alkaloids has been developed. In combination with Ag(I) salts, these amino-phosphines performed as effective cooperative Brønsted base/Lewis acid catalysts in the asymmetric aldol reaction of isocyanoacetate nucleophiles. Under optimal conditions, high diastereoselectivities (up to 98%) and enantioselectivities (up to 98%) were obtained.

Protecting-group directed stereospecific organocatalytic [3+2] cycloadditions: a facile access to chiral spirocyclic oxindoles

“…Cinchona alkaloids [26][27][28][29][30][31][32][33][34][35][36][37] and their derivatives ( Figure 2) have proven to be powerful organocatalysts for various organocatalytic [38][39][40][41][42] asymmetric C-C bond formations. Recently, isocyanide has been reported as an efficient nucleophile, [43][44][45][46] as the α-hydrogen atom is sufficiently acidic to be deprotonated by cinchona alkaloids. Inspired by this discovery, it is envisioned that the [3+2] cycloaddition of isocyanide and methyleneindolinone may be promoted by bifunctional cinchona alkaloid catalysts, leading to a direct stereoselective access to dihydrospirocyclic oxindoles, which may be easily transformed into the spiro[pyrrolidin-3,3′-oxindole] derivatives (Scheme 1).…”

Synthesis of Optically Active Oxazolines by an Organocatalytic Isocyanoacetate Aldol Reaction with α-Keto Esters

“…6 In 2011 Dixon et al utilized a chiral amino phosphine Ag(I) complex to obtain oxazolines with excellent cis selectivity. 7 In sharp contrast, the organocatalytic variant for such conversions has been studied and only a single example was presented by Gong et al 8 There has been no report of the combination involving a ketone group, which would afford direct access to oxazolines bearing one or two quaternary asymmetric centers. In this paper, we describe the first asymmetric aldol-type transformation of α-keto esters with α-isocyanoacetate catalyzed by a thiourea/amine bifunctional catalyst and leading to a precursor of β-hydroxy-α-amino acids.…”

Assembly of Enantioenriched cis‐3a,8a‐Hexahydropyrrolo[2,3‐b]indole Scaffolds by Silver(I)‐Catalyzed Asymmetric Domino Reaction of Isocyanoacetates in the Presence of Cinchona‐Derived Chiral Phosphorus Ligands

“…Inspiredb yt he recent reportso nt he transition metalscatalyzed asymmetric [3+ +2] cycloadditions of isocyanoacetates with aldehydes, [6] ketones, [7] imines [8] and allenes [9] by the use of Cinchona-derived chiral phosphines as catalytic ligands,w ew onderedw hether this kind of ligandc ouldb eu sed in our transition metalcatalyzed domino reaction of isocyanoacetates and2 -(2-amidophenyl)acrylates,l eading to an asymmetric pathwayfor the assembly of enantioenriched HPIs.…”

“…Pleasingly,s witching the reactionc atalyst from CuI to Ag 2 Op roved to be positive,w ith av ery high reaction efficiency (99% yield after 3h)a nd good enantioselectivities( 72% and 78% ees) being obtained ( Table 1, entry 3). The screeningo ft he chiral ligands revealedt hat L4 was the best, providing an almostq uantitative overall yield (99%) and highest enantioselectivities( 86% ees, Table 1, entries [4][5][6]. Using other kinds of ligands such as axially chiral ligand L5 and C 2 -symmetric ligand L6 gave lower overall yields,u nimproved diastereoselectivities,a nd very lowe nantioselectivities (Table 1, entries7and 8).…”