A New and Convenient Method for the Synthesis of Dehydroamino Acids Starting from Ethyl N-Boc- and N-Z-α-Tosylglycinates and Various Nitro Compounds

Abstract

Ethyl N-Boc- and N-Z-α-tosylglycinates, which were readily available from t-butyl or benzyl carbamate, ethyl glyoxylate, and sodium p-toluenesulfinate in formic acid, were reacted with a variety of nitro compounds in the presence of a base to afford the corresponding α,β-didehydroamino acid derivatives in good yields. Eventually, it was found that the (Z)-isomer was predominantly formed in the present method.

Stereoselective Syntheses of (E)-α,β-Didehydroamino Acid and Peptide Containing Its Residue Utilizing Oxazolidinone Derivative

“…33 mmol) at ¹78°C under N 2 . After keeping at ¹78°C for 1 h, a solution of 4e (84 mg, 0.30 mmol) in dry THF (2 mL) was added followed by the addition of Ti(O i Pr) 4 (94 mg, 0.33 mmol). The solution was stirred at ¹78°C for 4 h and quenched with 1 M AcOH in THF.…”

“…4 The latter procedure was successfully applied to the synthesis of optically active 4-hydroxyprolines. 5 On the contrary, there are few reports 6 concerning stereoselective synthesis of (E)-¡,¢-didehydroamino acid since its stereochemistry is not always thermodynamically favored, for example, 1) stereoselective elimination of hydrogen chloride from erythro-¢-chloro-¡-amino acid derived from threo-¢-hydroxy-¡-amino acid derivative, 6a 2) stereospecific dehydration of erythro-¢-hydroxy-¡-amino acid derivative using DAST [(diethylamino)sulfur trifluoride], 6b 3) formation of cyclic cis-sulfamidite starting from erythro-¢-hydroxy-¡-amino acid derivative and thionyl chloride, and subsequent elimination of sulfur dioxide, 6c 4) Suzuki coupling of ¢-bromo-¡,¢-didehydroamino acid derivative with monosubstituted boronic acid, 6d 5) stereospecific dehydration of erythro-¢-hydroxy-¡-amino acid derivative using Martin's sulfurane [diphenylbis (1,1,1,3,3,3-hexafluoro-2-phenyl-2-propyl)sulfurane], 6e 6) stereospecific dehydration of threo-¢-hydroxy-¡-amino acid derivative with EDC [1-ethyl-3-(3-dimethylaminopropyl)carbodiimide], 6f 7) oxidation of 3-S-benzylthioamino acid derivative to the sulfoxide, followed by thermolysis to form ¡,¢-didehydroamino acid.…”

“…In the absence of additive, 2e, 2g, and 2h were produced only in 43%, 42%, and 31% yields, respectively (Entries 7,9,and 10). In order to improve the yields by activation of the aldehydes 4e, 4g, and 4h Lewis acids such as Ti(O i Pr) 4 and Cl 2 Ti(O i Pr) 2 were used as an additive to produce the corresponding 2e, 2g, and 2h in 66%, 51%, and 45% yields, respectively (Entries 7, 9, and 10 in Table 3). In the cases of aromatic aldehydes 4j4l the desired products 2j2l were also obtained in moderate yields (Entries 1113 in Table 3).…”

A New Synthetic Method for the Preparation of α,β‐Didehydroamino Acid Derivatives by Means of a Wittig‐Type Reaction. Syntheses of (2S,4S)‐ and (2R,4R)‐4‐Hydroxyprolines.

“…00 mmol) and molecular sieves 4A (1.00 g) in 5 mL of CH 2 Cl 2 was added a solution of 4-nitro-1-butanol (119 mg, 1.0 mmol) 5 in 0.3 mL of acetone at room temperature with vigorous stirring. After 1 h the solvent was removed in vacuo and the residue was triturated with ether.…”

“…5 In this paper, we now wish to report on a new method for preparing α , β -didehydroamino acid derivatives starting from 1a or 1b and a variety of aldehydes in the presence of Bu 3 P and a base. The results are summarized in Table 1.…”