Irreversible Oxy‐2‐azonia‐Cope Rearrangements for the Synthesis of Functionalized Allyl α‐Amino Acid Derivatives

Abstract

A general method to synthesize functionalized allyl α‐amino acid derivatives through an irreversible oxy‐2‐azonia‐Cope rearrangement is reported. In the presence of AlCl3, the reaction of imino ethyl glyoxalates with various β,γ‐unsaturated ketones furnished the corresponding allyl α‐amino acid derivatives. The key to the success of this method is the amide bond formation, which makes the rearrangement irreversible. This reaction system constitutes a new strategy for the synthesis of unusual allyl glycine derivatives, which are valuable synthetic intermediates. An efficient and operationally simple three‐component version of this reaction was also performed.

α-Imino Esters in Organic Synthesis: Recent Advances

“…AlCl 3 -catalyzed tandem nucleophilic addition/oxy-2-azonia-Cope rearrangement was reported by Wang et al to prepare allylglycine amide derivatives. Reactions were performed by stirring a solution of β,γ-unsaturated ketones with α-imino ester (1.5 equiv) and AlCl 3 (1 equiv) in DCE at room temperature for 1–72 h, and the desire products 655 were obtained in 27–87% yields.…”

Synthesis of Dihydromotuporamine C via 3‐Azonia‐Cope Rearrangement of 11‐Membered Cyclic α‐Vinylamine

“…Thus, by using the oxy-2-azonia-Cope reaction as the key strategy, the first total synthesis of motuporamine G has been accomplished. [11,12] This permitted us to resolve, with high accuracy, the structural uncertainty regarding the actual position of the methyl substituent in the ring. [11] A literature survey exposed that compound 5 has only been prepared from hydrogenation of motuporamine C (3), which, in turn, was produced via ring-closing metathesis (RCM) methods.…”

“…During the past few years, we were engaged in the study of new [3,3]‐sigmatropic rearrangements and their application in the synthesis of diverse biologically significant compounds and natural products. Thus, by using the oxy‐2‐azonia‐Cope reaction as the key strategy, the first total synthesis of motuporamine G has been accomplished [11,12] . This permitted us to resolve, with high accuracy, the structural uncertainty regarding the actual position of the methyl substituent in the ring [11] .…”

A Practical Domino‐Claisen–Cope Sequence in the Synthesis of New Blooming Citrus and Potent Floral Rose Alcohols

“…Herein, we describe our attempts to develop a greener, more sustainable one‐pot, mercury and pressure‐free version of this domino‐ Claisen–Cope rearrangement to unsaturated aldehydes 10 as intermediates for the synthesis of innovative floral and citrus odorants 13 – 16 ( Scheme ). Another motivation to perform this study was to explore the possibility of selectively intercepting intermediate β , γ ‐aldehydes 9 ( Scheme ) as substrates for oxy‐2‐oxonia(azonia)‐ Cope rearrangements to compounds of type 12 which have been of interest to us during the past few years …”