Direct Synthesis of N-Hydroxy β-Amino Acid Esters from Carboxylic Esters and Nitrones

Abstract

The direct synthesis of the title amino acid derivatives from carboxylic esters and nitrones can be achieved in fair to good yields when lithium or magnesium ester enolates were treated with nitrones in THF at -78 °C or in Et2O at -20 to 0 °C, respectively. The products from the reaction of t-butyl acetate with 3,4-dihydroisoquinoline N-oxide or 5,5-dimethylpyrroline 1-oxide were transformed into (1,2,3,4-tetrahydroisoquinolin-1-ylidene)acetate or (pyrrolidin-2-ylidene)acetate derivatives in the presence of triphenylphosphine, carbon tetrachloride, and triethylamine in refluxing dichloromethane.

Mannich-Type Reactions of Nitrones, Oximes, and Hydrazones

“…39 The corresponding enolates employed in these processes were generated by using lithium diisopropylamide and magnesium bis(diisopropylamide) and reacted at -78°C and 0°C, respectively. Under these conditions, tert-butyl b-hydroxyamino esters were obtained in 44-91% yields.…”

“…The direct synthesis of racemic N-hydroxy-b-amino acid esters, through addition of lithium and magnesium enolates derived from tert-butyl acetate to both cyclic and acyclic nitrones, has been described. 39 The corresponding enolates employed in these processes were generated by using lithium diisopropylamide and magnesium bis(diisopropylamide) and reacted at -78°C and 0°C, respectively. Under these conditions, tert-butyl b-hydroxyamino esters were obtained in 44-91% yields.…”

Asymmetric Synthesis of β-Amino Acid Derivatives Incorporating a Broad Range of Substitution Patterns by Enolate Additions totert-Butanesulfinyl Imines

“…Asymmetric induction has been achieved with chiral imine substituents (i.e. , SAMP/RAMP, carbohydrates, N -sulfinyl imines), chiral carboxylate derivatives, and enolate formation with chiral bases such as sparteine. − Recently, catalytic, asymmetric Mannich reactions have been used to prepare a subset of α , α , β -trisubstituted β -amino acid derivatives with high enantioselectivities. , …”

N-[(Z)-4-Methoxybenzylidene](methoxycarbonyl)methanamine oxide

“…For the application and synthesis of nitrones, see: Merino (2004); Mocours et al (1995); Frederickson (1997); Gothelf & Jorgensen (2000); Merino et al (1998); McCaig et al (1998); Desvergnes et al (2005); Hanselmann et al (2003); Pillard et al (2007); Merino et al (2008); Kobayashi et al (2000). For the synthesis of the title compound, see: Diez-Martinez et al (2010).…”

“…Nitrones are also useful intermediates for nucleophilic additions leading to the corresponding N,N-disubstituted hydroxylamines. Several types of nucleophile were used such as alkynes (Pillard et al, 2007), alkyl Grignard reagent (Merino et al, 2008) and enolates (Kobayashi et al, 2000).…”