Catalytic Aza-Wacker Annulation: Tuning Mechanism by the Activation Mode of Amide and Enantioselective Syntheses of Melinonine-E and Strychnoxanthine

Abstract

An unprecedented N-substituent of the amide was found to be crucial for the successful annulation to establish 2-azabicyclo[3.3.1]nonane and other ring skeletons in good yield. The novel catalytic aza-Wacker annulation methodology was further illustrated in the concise syntheses and the absolute configuration determinations of melinonine-E and strychnoxanthine.

Delayed catalyst function enables direct enantioselective conversion of nitriles to NH 2 -amines

“…Subjection of 16 to 17 and triflic anhydride (37, 38) and then NaBH 4 in MeOH delivered 1.05 grams of the anti-cancer agent (92% yield) as a single diastereomer. The stereochemical identity of synthetic (+)-tangutorine was confirmed by x-ray crystallography (formerly only that of racemic material was reported, despite the absolute stereochemical identity being known).…”

Salient features of the aza-Wacker cyclization reaction

“…30). 36,37 Cyclization precursor 8 was constructed from chiral lactone 7 in 2 steps; this lactone had previously been synthesized by Hong and co-workers as a key intermediate in the construction of other alkaloid natural products. 38 Interestingly, the N-substituent had a marked effect on the success of the aza-Wacker cyclization.…”

Construction of Bridged Polycyclic Skeletons via Transition‐Metal Catalyzed Carbon–Carbon Bond‐Forming Reactions

“…Hong and co-workers reported an eleganta za-Wacker annulation to access 2-azabicyclo[3.3.1]nonane and otherr ing systems( Scheme 8). [30] Remarkably,t he aza-Wacker reaction was successfully applied to thee nantioselective syntheses of two morphan core-embedded alkaloids, melinonine-E and strychnoxanthine.T he deuteriuml abeling experiments revealed that the activation modeo ft he amide for the amidopalladation process were able to be tuned by the N-substituent on the amide functionality. Nucleophilic addition of the N-Ts amide to the olefin proceeded through the direction anti to the palladium coordination and as ubsequent b-D cis-elimination led to the cyclizedp roduct 42 (X = Hb) as the major product (92 %), whilet he deuterated 42 (X = D) was obtained in only 8% yield.…”