Gold(I)-Catalyzed Diastereo- and Enantioselective 1,3-Dipolar Cycloaddition and Mannich Reactions of Azlactones

Abstract

Azlactones participate in stereoselective reactions with electron-deficient alkenes and N-sulfonyl aldimines to give products of 1,3-dipolar cycloaddition and Mannich addition reactions respectively. Both of these reactions proceed with good to excellent diastereo- and enantioselectivity using a single class of gold-catalysts, namely C2-symmetric bis(phosphinegold(I) carboxylate)complexes. The development of the azlactone Mannich reaction to provide fully protected anti-α,β-diamino acid derivatives is described. 1,3-Dipolar cycloaddition reactions of several acyclic 1,2-disubstituted alkenes, and the chemistry of the resultant cycloadducts, are examined to probe the stereochemical course of this reaction. Reaction kinetics and tandem MS studies of both the cycloaddition and Mannich reactions are reported. These studies support a mechanism in which the gold complexes catalyze addition reactions through nucleophile activation rather than the more typical activation of the electrophilic reaction component.

Binap-silver salts as chiral catalysts for the enantioselective 1,3-dipolar cycloaddition of azomethine ylides and alkenes

“…The effect of the methyl group in the azomethine ylide caused lower enantioselections in final products 12bba (Table 3, entries 5 and 6). The introduction of a substituent in the arylidene moiety of the imino ester was not very profitable because the ee of cycloadducts were very low, except in the case of para-methyl substituted derivative (Table 3, entries [7][8][9][10][11][12][13][14]. The presence of an isopropyl ester instead of the methyl one also gave a disappointing enantioselection of heterocycle 12fab ( Multicomponent reactions were attempted using the best result depicted in Tables 2 and 3.…”

Brønsted Acid-Catalyzed Dipeptides Functionalization through Azlactones

“…19 To our delight, the desired azlactones 2a and 2b were successfully synthesized and isolated in good to excellent yields (Scheme 1). 1 H nuclear magnetic resonance (NMR) data of compound 2b showed an unusual 5 J coupling (homoallylic coupling) between alanine CH hydrogen and glycine CH 2 hydrogens, due to the formation of the azlactone C=N double bond; this correlation was also observed in 2D 1 H-1 H COSY (correlation spectroscopy) experiments (see Supplementary Information).…”

“…[1][2][3] In this context, azlactones (also known as oxazolones) are promising substrates, since they basically consist of protected amino acids organized as five-membered rings bearing both electrophilic and pronucleophilic sites in their structure. 4,5 Due to this versatility, these heterocycles have been extensively employed in a wide scope of transformations, 6 in particular the preparation of quaternary amino acid derivatives. [7][8][9][10][11][12] Different 4-substituted oxazolones are easily available, as this moiety originates from the amino acid precursor 13 or by hydrogenation of the well-known Erlenmeyer azlactones 14 ( Figure 1).…”

Coinage metal complexes as chiral catalysts for 1,3-dipolar cycloadditions

“…However, classical 1,3-dipolar cycloaddition of iminoesters and electrophilic olefins was not described using gold complexes. Only Toste´s group published an efficient 1,3-DC employing alanine, phenylalanine and allylglycine derived azlactones with maleimides and acrylates in the presence of dimetallic type 24 (S)-Cy-Segphos (AuOBz) 2 complex as catalyst (2 mol%) in the absence of base [29,58].…”

“…Despite of the easy access to this mesoionicheterocycles their enantioselectivecycloadditions with electrophilic alkenes have not been exploited. Toste´s group published an efficient 1,3-dipolar cycloaddition (1,3-DC) between alanine, phenylalanine and allylglycine derived azlactones with maleimides and acrylates employing dimetallic (S)-Cy-Segphos (AuOBz) 2 complex type 24 ( Figure 4) as catalyst (2 mol%) in the absence of base [58].…”