Copper-Catalyzed Asymmetric Michael Reactions with α-Amino Acid Amides: Synthesis of an Optically Active Piperidine Derivative

Abstract

Quaternary stereocenters are obtained at room temperature in copper-catalyzed asymmetric Michael reactions with α-amino acid amides as chiral auxiliaries. L-Valine diethylamide was applied as a chiral auxiliary, and an optically active piperidine derivative was prepared with 97% ee. The

Total Synthesis of the Polyoxygenated Sesquiterpenes Guignarderemophilanes C and D

“…Additionally, the intermediacy of γ , δ ‐epoxy β ‐hydroxy ketone rules out a pathway in which nucleophilic epoxidation takes place after aldol condensation in a 1,6‐fashion to the dienone system. Cyclization of epoxy ketone 8 (major diastereoisomer) provided access to the other octalone diastereoisomer 7 . The absolute configuration of both epoxy ketones 8 and 9 as well as octalones 7 and 10 could not be established by NOESY NMR spectroscopy.…”

Asymmetric synthesis of glutamate derivatives

“…Asymmetric Michael reactions using β-enaminoesters are generally performed with Lewis acid as Michael acceptor activator, [4][5][6][7][8][9][10][11] so the preceding reactions were repeated in the presence of zinc chloride (1.4 equivalents) in order to study the influence of this catalyst on both reactivity and selectivity. The results are summarized in Table 2.…”

“…Use of an asymmetric variant of this reaction with chiral imines/enamines is proved to give an easy access to molecules presenting an asymmetric quaternary center, generally with a high degree of regio-and enantio-selectivity. Since its discovery in 1985, this methodology as generally been applied to various cyclic systems notably for the synthesis of natural products such as terpenes and steroids, [4][5][6][7][8][9][10][11] but only rarely to acyclic ones. [12][13][14][15][16][17][18] In this paper, we explore the Michael reaction between acyclic chiral β-enaminoesters exhibiting various alkoxy groups and various olefins, the effect of Lewis acid on the reactivity and the enantioselectivity of this reaction will be explored.…”

Computational studies on the copper(II) catalyzed Michael reaction

“…Enantioselectivity could be achieved starting from (chiral) enamines 3 made from b-diketones 1 and an amino acid derivative 2 which is used as a chiral auxiliary in stoichiometric quantities [10][11][12][13](Scheme 1). Although the usefulness of this reaction has widely been demonstrated, experiments have so far contributed only limited insight into mechanistic details [14][15][16][17][18][19][20]. In particular, it is not established how the chirality transfer from the auxiliary to the product becomes effective.…”