A New Synthesis of α-Amino Acid Derivatives Employing Methyl Nitroacetate as a Versatile Glycine Template

Synthesis of unnatural α-amino esters using ethyl nitroacetate and condensation or cycloaddition reactions

“…The same transformation sequences were used starting with compound 6n and provided the furan-bearing α-amino ester 12 in 32% overall yield via the nitro compound 11 . We also investigated the reported [4] 1,4-addition of a methyl on compound 2n to prepare the β-methylated derivative 13 . In our hands, a rather modest 43% yield of the expected adduct 13 was achieved from purified acrylate 2n .…”

“…The retrosynthetic pathway depicted in Scheme 1 requires a reduction of ethyl nitroacrylates 2 , which are made from condensation reactions between aldehydes 3 or acetals 5 and ethyl nitroacetate ( 4 ). However, the high yield condensations with aldehydes 3 which were reported for some examples [3–4] require more than stoichiometric amounts of titanium tetrachloride thus leading to considerable amounts of metal-containing chemical waste. Moreover, far lower yields were reported in many other instances when using this reagent [5–6].…”

Nitroalkenes as Amination Tools

“…Chiral ligands such as bisoxazolines can produce moderate levels of enantioselection in the obtained α -nitro esters, which are converted into the corresponding α -amino acid derivatives by simple catalytic hydrogenation (Scheme 3.10 ) [26,27] . More traditionally, β -substituted α , β -unsaturated α -nitro esters 11 can add organolithium and Grignard reagents to give the corresponding α -nitro esters 12 , which are amenable to further functionalization at the reactive 2 -position (Scheme 3.11 ) [28] . Quaternization at C -2 can be accomplished by means of palladiumcatalyzed allylic alkylations, arylation with triphenylbismuth dichloride, and phosphine -promoted Michael additions.…”

A Stereoselective Oxy-Michael Route to Protected β-Aryl-β-Hydroxy-α-Amino Acids

“…Scheme 1 An oxy-Michael route to b-aryl-b-hydroxy-a-amino acids Thus a series of b-aryl-a-nitro-a,b-unsaturated ester Michael acceptors were prepared by the literature procedures. 21 These compounds were then subjected to our standard oxy-Michael conditions. Thus, deprotonation of (S)-6-methyl tetrahydropyran-2-ol (1) THF at -78 °C and addition of 18-crown-6 (1.0 equiv) generated the 'naked' chiral lactol alkoxide nucleophile.…”