Michael−Stork Addition of Cyclopentyl Enamine to Allenyl Ketones and Esters

Abstract

[Chemical reaction: see text] We report the first examples of a Michael-Stork enamine addition to allenyl esters and ketones. Studies reveal that 2 equivalents of enamine are required for optimal yields. In the case of an allenyl methyl ketone, cyclopentyl enamine addition led to 8-oxobicyclo[3.2.1]octane formation, providing evidence for the in situ formation of an enamine intermediate following the initial Michael-Stork reaction.

Formation of the Main Cores Present in Natural Products by Tandem Additions

“…The conjugated allene is more electrophilic than the dienone moiety, which is also less reactive to a bimolecular nucleophilic addition due to its proximity to a quaternary carbon center. In the presence of nucleophiles such as amines, an initial nucleophilic addition on the conjugated allene (producing the Stork‐type intermediate 6 )5, 6 will lead to subsequent cyclization by intramolecular 1,4‐addition to the dienone to yield the highly functionalized bicyclic system 7 , which could be a useful intermediate in the synthesis of natural compounds. The steric hindrance of the former benzylic substituent directs the cyclization, which could therefore be made stereoselective, Scheme .…”

Syntheses and Applications of Functionalized Bicyclo[3.2.1]octanes: Thirteen Years of Progress

“…Of course, enamines derived from cyclopentanone can be used directly as pronucleophiles. Using this strategy, Lepore and co-workers reported the stereoselective preparation of the bicyclic compound 82 from N -(cyclopenten-1-yl)morpholine 80 and allenyl methyl ketone 81 as bis-electrophile (Scheme ) . The E stereochemistry of 82 is likely to be established in the initial Michael–Stork addition on the less-hindered face of the allene, whereas the endo preference of the ring-closure step has been attributed to a thermodynamically favored formation of the endo bicyclic zwitterionic intermediate relative to its exo isomer due to a better charge stabilization.…”

First Zinc Bromide Promoted Annulative Domino Reactions between Enamines and Cyclic Morita–Baylis–Hillman Alcohols: Synthesis of N,O-Ketals

“…Enamines are versatile synthetic intermediates 1,2 that are commonly involved in the chemistry of natural products such as terpenes, steroids, alkaloids and pharmaceuticals. 3 After the pioneering work of Stork 4 in the fifties, the nucleophilic behavior of this functional group has been successfully exploited in a number of conjugate additions to electron-poor alkenes such as ,-unsaturated enones, 5,6 allenyl ketones and esters, 7 as well as methyl acrylate, 8 2formylcyclohexenones, 9 and 2-acetyl-1,4-naphthoquinones. 10 Moreover, enamines are capable of undergoing palladium-as well as iridium-catalyzed S N 2 and/or S N 2′ C-allylations in the presence of allylic acetates, 11,12 phenyl ethers, 13 benzotriazoles, 14 carbonates, 15 and even allylic alcohols.…”