α(δ')-Michael Addition of Alkyl Amines to Dimethyl (E)-hex-2-en-4-ynedioate: Synthesis of α,β-Dehydroamino Acid Derivatives

Abstract

Abstract:The direct nucleophilic addition of alkyl amines to the α(δ')-carbon atom of dimethyl (E)-hex-2-en-4-ynedioate to generate α,β-dehydroamino acid derivatives is reported. Herein, we have studied the reactivity of various primary and secondary alkyl amines in the α-selective nucleophilic conjugate addition to conjugated dimethyl (E)-hex-2-en-4-ynedioate. The reaction with primary alkyl amines gives only the (2E,4E)-stereoisomer, while that with secondary alkyl amines gives the (2E,4E) and (2Z,4E)-stereoisomers of dimethyl (2-alkylamino)-muconic ester.

Silver‐Catalyzed Synthesis of Substituted Pyridine Derivatives from N‐Propargylic α‐Enamino Esters

“…The configuration of the diene was found to be ( E , E ), as reported in simple amine addition. [14a] The reaction conditions were optimized to improve the yield of the product, and only selected results are presented in Table . After extensive optimization, it was found that N ‐propargylic α‐enamino ester 3a could be obtained in 56 % yield if the reaction was performed with 2 equiv.…”

“…In 2005, Ramachandran et al reported the quantitative conversion of alkyl propiolate into dialkyl ( E )‐hex‐2‐en‐4‐ynedioate by using a catalytic amount of 1,4‐diazabicyclo[2.2.2]octane (DABCO) . Dialkyl ( E )‐hex‐2‐en‐4‐ynedioate underwent α‐addition regioselectively upon reaction with amine nucleophiles . Chuang and co‐workers reported many interesting synthetic methods involving the use of a PPh 3 nucleophile for the α‐addition to diethyl ( E )‐hex‐2‐en‐4‐ynedioate .…”

Total Synthesis of Spirotryprostatins through Organomediated Intramolecular Umpolung Cyclization

“…1]) . Various nucleophiles (amines,, alcohols,,, thiols, thioureas, purine, and thymine) have been used in the intermolecular α‐addition towards alkynoates after Trost's pioneering contribution. To the best of our knowledge, however, only three examples have been reported in the literature using α‐addition of amides towards alkynamides [Scheme , Eqs.…”

Stereoselective Construction of (E,Z)‐1,3‐Dienes and Its Application in Natural Product Synthesis

“…however, they exhibit variable Z selectivities. [229][230][231][232][233] Furthermore, Ooi described in 2018 a spectacular organocatalysed 1,6-Michael addition of azlactones (235) to enynyl N-acyl pyrazoles (236). [234] The use of a P-spiro chiral triaminoiminophosphorane catalyst not only allows the perfect control of the addition regioselectivity (1,6 vs 1,4), but also the Z,Econfiguration of the diene and the enantioselectivity of the quaternary centre in the resulting compounds (237, Scheme 92).…”