Pd-catalyzed asymmetric allylic amination with BOP ligands and its applications to the synthesis of fused polycyclic alkaloids

Abstract

Dedicated to late Professor Harry H. Wasserman for his outstanding achievements and fond memories Amaryllidaceae family consists of about 85 genera and 1,100 species. 1 To date, nearly 500 structurally diverse alkaloids have been isolated from these plants. 1 Some representative alkaloids are shown in Figure 1. Most of them exhibit various biological activities. 2-12 Crinine-type alkaloids have been shown to be active against rat hepatoma cells. 4 A preliminary structure-activity study revealed that a free secondary hydroxyl group at C11 and an α-5,10b-ethano bridge were essential for their biological activity. 2,3 Lycorine was found to be a potential therapeutic agent against acute promyelocytic leukemia. 4 Montanine and pancratistatin exhibited antiviral, anxiolytic, antidepressive, and anticonvulsive activities. 5-12

Asymmetric Synthesis of Isoquinoline Alkaloids: 2004–2015

“…Recently, in a continuation of an earlier study − on asymmetric allylic amination catalyzed by Pd/chiral BOP ligands Zang and Ojima applied this method for the construction of fused polycyclic frameworks, e.g., 843 or 845 , useful intermediates in the synthesis of Amaryllidaceae or montanine alkaloids. Carrying out a detailed study on optimization of the reaction conditions, versatile intermediates 841 (R = Ns, Ts, X = Br, H) were prepared in high yield and enantiopurity by reacting N -R derivative 838 (R = Ns, Ts, X = Br, H) with cyclohexenylcarbonate 839 in the presence of Pd/( S )- 840 .…”

Amaryllidaceae and Sceletium alkaloids

“…129 Towards the synthesis of the montanine-type alkaloids, a Pd-catalyzed asymmetric allylic amination reaction of piperonylamide 217 and 2-siloxymethylcyclohexenyl carbonate 218 has been developed for preparation of the chiral cyclohexenylpiperonylamide 219 by using chiral biphenol-based diphosphinite ligands. 130 2.3.7 Homolycorine-type alkaloids. A formal total synthesis of (+)-narseronine 220 has been achieved highlighting on an Nbromosuccinimide/tri-n-butyltin hydride-mediated cyclisation reaction to construct the unsaturated lactone.…”

Recent Developments in Asymmetric Allylic Amination Reactions

“…Significantly, Trost's conditions are also compatible with a substituted cyclohexenol derivative (entry 8), 28 The bidentate diphosphinite 52 (entry 9) promotes the enantioconvergent allylic amination of a substituted cyclohexenol derivative, albeit with an electron-donating substituent. 29 Interestingly, the novel pyridine-phosphite ligand 53 15e allows the expansion of the pronucleophile scope to aryl amines (entry 10). In addition, the palladium complex with (S,R P )-Ph-DIAPHOX (29) (entry 11) permits substantially reduced catalyst loadings for cyclohexenol derivatives bearing an electron-withdrawing substituent (0.2 mol% ligand, 0.05 mol% pre-catalyst on gram scale).…”