A Concise Palladium-Catalyzed Carboamination Route to (±)-Tylophorine

Abstract

A total synthesis of the racemic natural product tylophorine [(+/-)-1] has been demonstrated using the palladium-catalyzed carboamination method developed by Wolfe and co-workers. In this case, an electron-rich aryl bromide 18 was prepared in four steps and subjected to palladium-catalyzed Wolfe carboamination conditions with olefinic carbamate 7 to provide the racemic 2-(arylmethyl)pyrrolidine (+/-)-19 in good yield and was further elaborated to racemic tylophorine. This application of the Wolfe carboamination protocol as a key step to construct a natural product provides further evidence of the utility of the method.

Preparation of Pyridyl-substituted Monoazatriphenylenes

“…Contemporary synthetic methods broadly use a cycloaddition reaction of hard to obtain alkenes or arylacetylenes with aromatic substrates catalyzed by transition metal salts [9,10]. Finally, the cyclocondensation of phenanthrenequinone with hydrazones of (hetero)aromatic carboxylic acid amides leads to the corresponding aryl- [11,12] and hetaryl-substituted [13] triazatriphenylenes.…”

Palladium-catalyzed C–N bond formation via direct C–H bond functionalization. Recent developments in heterocyclic synthesis

“…For example, the best conditions for the previously described Bocprotected pyrrolidines were effective in a stereoselective synthesis of preussin [28]. Again, Rossiter et al obtained in this way a key intermediate for (AE)-tylophorine [29].…”

Palladium-Catalyzed Heterofunctionalization of C-H, C=C and C≡ C Bonds

“…2) [76], and synthesis of fused tetrahydrofuran rings by consecutive carboetherification reactions (eq. 1), carboamination for the total synthesis of a cytotoxic alkaloid (±)-Tylophorine, 26 (eq.…”