Pd-Catalyzed Asymmetric Allylic Etherification Using Chiral Biphenol-Based Diphosphinite Ligands and Its Application for The Formal Total Synthesis of (−)-Galanthamine

Abstract

A library of novel chiral biphenol-based diphosphinite (BOP) ligands was designed and created. These BOP ligands were applied to a Pd-catalyzed intermolecular allylic etherification reaction, which provided a key intermediate for the formal total synthesis of (-)-galanthamine with 97% ee in 97% yield.

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

“…etherification 34 (AAE) reactions (up to 97% ee). Accordingly, we examined the efficiency of our BOP ligands in the AAA reaction of piperonylamides 8 and cyclohexenylcarbonates 7 to give cyclohexenylpiperonylamides 10 (Scheme 2).…”

“…R 1 = H, R 2 = α-OH crinine R 1 = OH, R 2 = α-OMe crinamine R 1 = OH, R 2 = β-OMe haemanthamine R 1 = H, R 2 = OMe, R 3 = OH, R 4 = H montanine R 1 = OMe, R 2 = H, R 3 = OH, R 4 = H coccinine R 1 = H, R 2 = OH, R 3 = OH, R 4 = H pancracine R 1 = H, R 2 = OH, R 3 We have been developing a library of novel chiral biphenol-based monodentate phosphite and phosphoramidite ligands, [25][26][27][28][29][30][31][32][33][34] as well as bidentate diphosphinite ligands (BOP ligands) for a variety of catalytic asymmetric reactions. 31,32,24 These ligands are easy to prepare and fine-tunable through modification of the groups at the 3,3'-positions and the substituents attached to the phosphorous atoms.…”

Catalytic Asymmetric Total Synthesis of (−)‐Galanthamine and (−)‐Lycoramine

“…[6][7][8][9][10][11][12][13][14][15][16] According to the strategy for the formation of the ring system, these syntheses can be divided into two categories:1 )synthesis proceeding from AC ring! ADC ring!ABCD ring (Scheme 2, path a), [6][7][8] and it mainly involves intramolecular phenolic oxidative coupling followed by intramolecular oxa-Michael addition to form the benzofuran Bring, and 2) synthesis proceeding from the AC(AB) ring!ABC ring!ABCD ring (Scheme 2, path b), [9][10][11][12][13][14][15][16] in which the formation of the bridged seven-membered Dring is placed at the late stage of the synthesis.T oour knowledge,no synthesis from the ABD ring!ABCD ring (Scheme 2, path c) has been reported. Structurally,galanthamine-type alkaloids contain achiral all-carbon quaternary center,a nd the enantioselective construction of this sterically congested quaternary center [17] is the critical step in the total synthesis of these alkaloids.…”

“…Structurally,galanthamine-type alkaloids contain achiral all-carbon quaternary center,a nd the enantioselective construction of this sterically congested quaternary center [17] is the critical step in the total synthesis of these alkaloids. Although numerous asymmetric total syntheses of these alkaloids have been reported, [7][8][9][10][11][12][13][14][15][16] only the groups of Trost, [9,15] and Fan, [13] as well as that of Zhou and Xie, [14] have recently achieved catalytic asymmetric synthesis of galanthamine (1) and related alkaloids.…”

Catalytic Asymmetric Total Synthesis of (−)‐Galanthamine and (−)‐Lycoramine

“…[5] Because of the high cost of its isolation and the limited natural sources,anumber of total syntheses of 1 have been reported. [6][7][8][9][10][11][12][13][14][15][16] According to the strategy for the formation of the ring system, these syntheses can be divided into two categories:1 )synthesis proceeding from AC ring! ADC ring!ABCD ring (Scheme 2, path a), [6][7][8] and it mainly involves intramolecular phenolic oxidative coupling followed by intramolecular oxa-Michael addition to form the benzofuran Bring, and 2) synthesis proceeding from the AC(AB) ring!ABC ring!ABCD ring (Scheme 2, path b), [9][10][11][12][13][14][15][16] in which the formation of the bridged seven-membered Dring is placed at the late stage of the synthesis.T oour knowledge,no synthesis from the ABD ring!ABCD ring (Scheme 2, path c) has been reported.…”