A new synthesis of 3-amino-2-alkenoates

✍ Scribed by Tamejiro Hiyama; Kazuhiro Kobayashi

• Publisher: Elsevier Science
• Year: 1982
• Tongue: French
• Weight: 229 KB
• Volume: 23
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(00)87168-3

✦ Synopsis

Dedicated to Professor Hitosi Nozaki on the occasion of his 60th birthday.

Magnesium enolates of t-butyl (or ethyl) acetate and t-butyl propionate are found to react with nitriles to give 3-amino-2-alkenoates having Z configuration.

The title compounds are versatile intermediates for the synthesis of heterocycles such as pyridines, 1 2 pyrlmidines, indoles, 3 and isothiazoles .

4 In particular, some N-aroyl derivatives of 3-amino-2butenoic acid exhibit anti-inflammatory activity. 5 Limited approaches 436 to this class of compounds prompted us to explore a new general synthetic method.

It is logical to contemplate that the desired 3-amino-2-alkenoates (I) should be derived from nitriles and ester enolates .

7 Thus, we first applied lithium enolate of t-butyl acetate to the reaction, 8 hereby obtaining no trace of the product. This failure may be ascribed to the incapability of the lithium ion to take nitrile group in its ligand sphere and to the instability of the primary adduct as well. We have found the magnesium enolate' of t-butyl acetate fulfils the task to give t-butyl 3-amino-2-alkenoates (I, R1 = H, 2 R = t-C H ) efficiently. 49 Magnesium enolate of t-butyl acetate was prepared by treatment of the ester with the reagent derived from dlisopropylamine (2 mol) and ethylmagnesium bromide (1 mol) at 0°C in ether, 10 and then allowed to react with a nitrile at 0°C. Work-up with aqueous ammonium chloride solution followed by distillation afforded I. 11 Results are summarized in Table 1.