Tetrahydro-1,3-oxazin-6-ones as templates for the stereoselective synthesis of β-substituted L-aspartic acids

Diastereoselective Synthesis of α-Methyl and α-Hydroxy-β-Amino Acids via 4-Substituted-1,3-Oxazinan-6-ones

“…All alkylations performed provided the trans - 10 and cis - 11 products (Scheme , Table ). Alkylation using LDA (entry 1) or LiHMDS (entry 2) as base provided selectivity similar to the results observed by Burtin et al , However, NaHMDS (entry 3) and KHMDS (entry 4) both afforded significantly better selectivity. This trend in the results suggests the anion is less important than the metal counterion.…”

“…However, to better utilize 1,3-oxazinan-6-ones in the efficient production of α,β-disubstituted-β-amino acids, the yields of the oxazinanones 3 − 9 (30−45%) (Scheme ) we reported 17 using the procedure of Ben-Ishai needed to be improved . Several other methods were attempted without any improvement in yield until the conditions of Burtin et al , were applied. It was found that stirring the N -protected β-amino acids in toluene, with a catalytic amount of acid and activated 4 Å molecular sieves at 90 °C for 3−4 h, resulted in a marked improvement in yields of the oxazinanones 3 − 9 (65−78%).…”

“…1,3-Oxazinan-6-one 5-Alkylation. Burtin et al , is the only group to have prepared 5-alkyl-1,3-oxazinan-6-ones. The oxazinanones were derived from an N -Boc-protected aspartic acid derived residue; thus two acidic protons were present, requiring 2 equiv of base to form enolates.…”

“…The addition of hexamethylphosphoramide (HMPA) to enolate reactions had varying effects on reaction yields and stereoselectivity. Burtin et al , observed that the addition of HMPA to the α-alkylation of oxazinanones did not affect the stereochemical outcome of the reaction. In their hands, the addition of HMPA resulted only in lower yields of the desired products.…”

Asymmetric Michael Addition of Malonates to Enones Catalyzed by a Primary β-Amino Acid and Its Lithium Salt

“…The combined organic phase was washed with brine, dried over MgSO 4 , filtered, and concentrated under reduced pressure. The obtained white solid was washed with hexane and dried in air to give 4-benzyl N -benzyloxycarbonyl l -aspartate [Z-Asp(OBn)-OH] , in 98% yield (7.00 g, 19.6 mmol). In a round-bottomed flask, trimethyl borate (6.7 mL, 60 mmol) was added to a solution of Z-Asp(OBn)-OH (7.14 g, 20 mmol) in dry THF (80 mL) at 0 °C.…”