Catalytic Enantioselective Reaction of α‐Phenylthioacetonitriles with Imines Using Chiral Bis(imidazoline)–Palladium Catalysts

Abstract

The catalytic enantioselective reaction of α-phenylthioacetonitriles with imines has been developed. The reaction of various imines proceeds in good yields and diastereo- and enantioselectivities in the presence of chiral bis(imidazoline)-palladium catalysts. The obtained products can be converted into β-aminonitrile or β-aminoamide compounds without loss of enantiopurity.

Mannich-Type Reaction of α-Sulfanyl N-tert-Butanesulfinylimidates: Diastereoselective Access to α-Mercapto-β-amino Acid Derivatives

“…The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The combined organic phases were washed with brine, dried over anhydrous Na (9). To a stirred solution of 8 (103.3 mg, 0.2 mmol, 1.0 equiv) in THF/H 2 O (6 mL, v/v = 5:1) was added iodine (10.1 mg, 0.04 mmol, 0.2 equiv) at room temperature.…”

“…Recently, several asymmetric catalytic methods have been developed for the enantioselective synthesis of α-mercapto-β-amino acid analogues, such as chiral secondary amine-catalyzed aminosulfenylation of α,β-unsaturated aldehydes, chiral picolinamide-catalyzed hydrosilylation–transacylation of α-acylthio-β-enamino esters, and reactions involving imine addition, which include the organocatalytic reaction between α-thio-acetaldehydes with imines, the chiral bis­(imidazoline)–palladium-catalyzed reaction of α-(phenylthio)­acetonitriles with imines, and the reaction of α-diazo esters, thiols, and imines cocatalyzed by rhodium­(II) and chiral phosphoric acid . Methods using chiral starting materials have also been reported, such as ring opening of chiral oxazoline-5-carboxylate using thiolacetic acid and conjugate addition of homochiral lithium amides to cinnamate, followed by enolate trapping with electrophilic sulfur sources …”

Chiral Imidazoline Ligands and Their Applications in Metal‐Catalyzed Asymmetric Synthesis†

“…The four catalysts were employed in the nucleophilic addition of α ‐cyanocarbanions with imines. Utilizing benzyl nitrile, [ 100 ] acrylonitrile [ 101 ] (via aza‐Morita‐Baylis‐Hillman reaction promoted by DABCO), α ‐cyanoacetic acid [ 102 ] (via decarboxylative cyanoalkylation), α ‐aminoacetonitrile [ 103 ] (using α ‐iminonitriles), α ‐phenylthioacetonitrile, [ 104 ] α , α ‐dichloroacetonitrile [ 105 ] , α , α ‐dithioacetonitrile, [ 106 ] allenylnitrile [ 107 ] as precursors of α ‐cyanocarbanion, different α ‐substituted‐ β ‐aminonitriles could be synthesized (Scheme 47).…”

Enantioselective Reaction Using Palladium Pincer Complexes with <i>C</i>₂-Symmetric Chiral Bis(imidazoline)s

“…We expected that bis(imidazoline) palladium pincer complexes would enhance the acidity of the α proton in alkylnitriles to afford palladium ketenimides, which would then react with imines to give products under mild reaction conditions ( Figure 6). 16,17,18 To prove this hypothesis, we rst examined the enantioselective reaction of benzylnitrile with N (p toluenesulfonyl)-imine as a benchmark reaction of phebim Pd catalyst. The results are shown in Table 1.…”