New access to racemic β3-amino acids

Cooperative Assistance in Bifunctional Organocatalysis: Enantioselective Mannich Reactions with Aliphatic and Aromatic Imines

“…This reaction is important because it provides a straightforward access to chiral b 3 -amino acids. [12][13][14] Consistent with the X-ray evidence (Figure 1), catalysts with the trans-aminoindanol linker were, typically, significantly more active and gave products with higher enantioselectivity (Table 1, entries 4-8) than those with the l-valinol linker ( Table 1, entries 1-3). Aliphatic aldimines have been viable substrates in Mannich reactions only with the use of stoichiometric quantities of catalyst B [11] or stronger base.…”

Organocatalytic Asymmetric Mannich Reactions with N‐Boc and N‐Cbz Protected α‐Amido Sulfones (Boc: tert‐Butoxycarbonyl, Cbz: Benzyloxycarbonyl)

“…In particular, our approach, which involves the use of simple malonates and easily removed protecting groups on the nitrogen atom, allows the straightforward transformation of either N ‐Boc or N ‐Cbz protected Mannich adducts into the corresponding β 3 ‐amino acid hydrochlorides (Scheme , top). For example, treatment of 3 a and 3 j with 6 M aqueous HCl for several hours resulted in malonate hydrolysis, decarboxylation and nitrogen deprotection in a single step, which cleanly gave the corresponding β 3 ‐amino acid hydrochlorides 6 a and 6 b (Scheme , top) irrespective of the nature of the side chain and the nitrogen protecting group 18. Mild basic hydrolysis followed by thermal decarboxylation instead afforded the analogous N ‐protected β 3 ‐amino acids 7 a and 7 b (Scheme , bottom), thus showing the possibility of obtaining both β‐aryl and β‐alkyl amino acids with orthogonal carbamate protecting groups that are suitable for peptide synthesis 8e…”

“…Preparation of the β 3 ‐amino acid hydrochlorides :18 Malonic acid dimethyl ester 3 a or 3 j (0.20 mmol) was suspended in 6 M aqueous HCl (0.80 mL), and the mixture was then heated at 100 °C for 1 h 30 min for 3 a and 5 h for 3 j . After cooling to room temperature, the solution was evaporated to dryness under reduced pressure.…”

Solvent- and Catalyst-Free Microwave-Assisted Decarboxylation of Malonic Acid Derivatives

“…On the other hand, since decarboxylation of malonic acid derivatives is one of the most common reactions in organic synthesis, particularly in a multistep reaction sequence this new and simple method could be useful for preparing a broad variety of biologically active compounds such as α- [36] and β-amino acids [37], known drugs such as (S)-Dapoxetine [38] [39] one of the more effective and safe drugs for treating premature ejaculation [40] [41] [42] and Tirofiban [43] [44] an antiplatelet drug (antithrombotic).…”