Amino acid synthesis via ring opening of N-sulphonyl aziridine-2-carboxylate esters with organometallic reagents.

β2‐amino acids—syntheses, occurrence in natural products, and components of β‐peptides1,2

“…In contrast to Wendisch's results, the reaction with methyl zinc gave the desired product with 99% enantioselectivity. Organometallic reagents have also been applied by Baldwin and co-workers 205,206 in their experiments devoted to the selective ring opening of aziridines toward the formation of ␣-and ␤-amino acids. Unfortunately, organocuprates and methyl-Grignard reagents led to nonselective opening of chiral aziridine-2-carboxylate esters to give mixtures of ␣-and ␤ 2 -amino acids, together with plenty of other compounds.…”

Use of the Mitsunobu reaction in the synthesis of orthogonally protected α,β-diaminopropionic acids

“…We prepared N-trityl L-serine methyl ester (2) in 75% yield from L-serine methyl ester (1) using the method of Baldwin (Scheme 1). 9 Subsequent treatment of 2 with the commercially available Weinreb nucleophile Ts-NH-Boc (3), under Mitsunobu reaction conditions (diethyl azodicarboxylate (DEAD), PPh 3 , THF), gave the orthogonally protected -diaminopropionic acid (4) in 75% isolated yield. Due to the propensity for the trityl group to be easily removed, even on treatment with mild acid, we decided to replace this group with the more stable N-allyloxycarbonyl (alloc) protecting group, which also keeps full orthogonality with the other protecting groups present.…”

An Annulation Reaction for the Synthesis of Morpholines, Thiomorpholines, and Piperazines from β‐Heteroatom Amino Compounds and Vinyl Sulfonium Salts

“…[12] Finally, the synthetic utility of this methodology is illustrated in a short, highly efficient synthesis of morpholine-(3S)-carboxylic acid, [13] an important motif in a broad range of biologically active molecules. [14] Thus, sulfonamide protection [15] of l-serine methyl ester hydrochloride (95 %), followed by reaction with diphenyl vinyl sulfonium salt 1 gave the required morpholine 3 c in 97 % yield. Detosylation, [16] 9-fluorenylmethoxycarbonyl (Fmoc) protection and hydrolysis [13] of the ester gave the morpholine amino acid 6, suitably protected for standard coupling reactions, in 84 % overall yield (Scheme 3) and without any racemization along the reaction sequence.…”