Carbenylative Amination with N-Tosylhydrazones

Abstract

A Pd-catalyzed reaction of vinyl iodides and N-tosylhydrazones that assembles η(3)-allyl ligands through carbene insertion is demonstrated. Intramolecular trapping with nitrogen nucleophiles generates good yields of cinnamyl and pentadienyl amines like those found in alkaloid natural products. Carbenylative amination was the key reaction to complete the synthesis of the alkaloid caulophyllumine B. Migratory insertion was biased to provide allylamines with optical purity up to 64% ee, but in a lower yield.

Crystal structure of (Z)-4-((E)-(4-chlorobenzyli-dene)hydrazono)-1-p-tolylpyrrolidine-3-carbonitrile, C19H17ClN4

“…The most e cient syntheses of pyrrolidines involve reactions of primary amines with diols in the presence of a metal complex catalyst [2,3], of primary amines with dihaloalkanes in the presence of potassium carbonate under microwave conditions [4], of cyclization of amino alcohols in the presence of thionyl chloride [5] and of N-tosylhydrazones with vinyl iodides in the presence of a Pd-catalyst [6]. They can be .…”

Using N‐Tosylhydrazone as a Double Nucleophile in the Palladium‐Catalyzed Cross‐Coupling Reaction To Synthesize Allylic Sulfones

“…They also reported a three‐component coupling of aryl halides, N ‐tosylhydrazones, and terminal alkynes for the synthesis of propargylarenes 10. The palladium‐catalyzed carbenylative amination with N ‐tosylhydrazones was shown by Van Vranken 11. Jiang described a Pd‐catalyzed intermolecular cross‐coupling reaction of terminal alkenes and N ‐tosylhydrazones 12.…”

“…[10] The palladium-catalyzed carbenylative amination with N-tosylhydrazones was shown by Van Vranken. [11] Jiang described a Pd-catalyzed intermolecular cross-coupling reaction of terminal alkenes and Ntosylhydrazones. [12] In 2014, we reported the example of utility N-tosylhydrazones as a coupling partner in the Catellani-Lautens reaction.…”

“…To our delight, product 3 a was isolated in 12 % yield in the presence of tBuOK (entry 9). Use of Na 2 CO 3 furnished the corresponding product in 69 % yield, but the yield was not improved when K 2 CO 3 was used as a base (entries [10][11]. A number of solvents, including DCE, THF, dioxane, and MeCN were then examined.…”

Enantioselective Palladium(II) Phosphate Catalyzed Three‐Component Reactions of Pyrrole, Diazoesters, and Imines

“…[8f-h] Despite ongoing progress, to the best of our knowledge, highly enantioselective palladium-carbenoid-mediated reactions have not yet been reported. [9] Pyrroles are abundant in natural products and pharmaceutical agents [10] and are valuable synthons in organic synthesis. [11] Direct CÀH functionalization of unprotected pyrrole is considered to be the most convenient approach to obtain pyrrole derivatives.…”