Lewis Acid Assisted Ring-Closing Metathesis of Chiral Diallylamines:  An Efficient Approach to Enantiopure Pyrrolidine Derivatives

Abstract

Lewis acid assisted ring-closing olefin metathesis (RCM) of chiral diallylamines, using the second generation RCM ruthenium-based catalyst, leads to enantiopure pyrrolidine derivatives in 79−93% yields under very mild conditions. The scope of the olefin metathesis has been expanded.With the development of highly stable and active ruthenium alkylidenes bearing N-heterocyclic carbene ligands, 1 the ringclosing metathesis (RCM) reaction has become an important and powerful approach for the construction of many functionalized carbocycles and heterocycles from acyclic diene precursors.2 Consequently, the RCM of olefinic ethers, esters, thioethers, allylic phosphanes, and allylphosphonamides has been well established using various catalytic systems.3 To our knowledge, however, the metathesis of diallylamines possessing basic or nucleophilic nitrogen atoms has not been carried out to afford pyrrolidines, even under harsh reaction conditions. 4 These substrates have to be deactivated by the conversion to amides, carbamates, or sulfonamides or by protonation for the ruthenium-catalyzed metathesis reaction. 5The only exception is the RCM reaction of the less basic N,N-diallylanilines using the first generation Grubbs catalyst, with ortho-halo and ortho-vinyl anilines being the best substrates. 6 † Central China Normal University.

Olefin Metathesis of Amine‐Containing Systems: Beyond the Current Consensus

“…This work has led to the discovery that metathesis of amine-containing substrates could be performed in the presence of substoichiometric amount of Lewis acid. [29] Results presented in Scheme 34 indicated that cyclized product 88a may nevertheless be obtained in 17-27 % yield in the absence of Lewis acid by treatment with a reactive ruthenium catalyst such as 3 or 4. It would be interesting to explore the same reaction with the allylamine analogue of 87 bearing one or two stronger electron-withdrawing groups such as CF 3 or a ketone with the hope of increasing RCM yields.…”

“…[25][26][27] These approaches may be incompatible with acid-sensitive substrates and are not always successful. [28,29] Very recently, Xiao and Yu disclosed that RCM of diallylamines using a ruthenium-based catalyst could be performed in the presence of 20 mol % of TiA C H T U N G T R E N N U N G (O-i-Pr) 4 . [29][30][31][32] It is of course too soon to evaluate the benefit of this method but first applications appear to give contrasting results.…”

“…[28,29] Very recently, Xiao and Yu disclosed that RCM of diallylamines using a ruthenium-based catalyst could be performed in the presence of 20 mol % of TiA C H T U N G T R E N N U N G (O-i-Pr) 4 . [29][30][31][32] It is of course too soon to evaluate the benefit of this method but first applications appear to give contrasting results. [33] The nature of the catalyst seems to play an important role when the reaction is performed with tertiary amines.…”

Ring‐Closing Metathesis of Sulfoximine‐Substituted N‐Tethered Trienes: Modular Asymmetric Synthesis of Medium‐Ring Nitrogen Heterocycles

“…A similar effect of TiA C H T U N G T R E N N U N G (OiPr) 4 had been previously found in the Ru-catalyzed RCM of N-alkylsubstituted N-tethered dienes. [27] It was proposed that the Lewis acid suppresses at some stage of the catalytic cycle a deactivating coordination of the amino group to the Ruatom. Thus, one or several intermediates of the catalytic cycle of the RCM reaction of 28 a and 28 b with 19 are perhaps deactivated by an intramolecular coordination [2d, 28] of the sulfoximine group to the Ru atom as exemplary depicted for complex 30.…”

Ru‐Catalyzed Tandem Cross‐Metathesis/Intramolecular‐Hydroarylation Sequence

“…In contrast, the use of a single species to catalyze a tandem process is rare. [3] In our search for novel and efficient Ru-catalyzed reactions, [11] we envisaged the ruthenium alkylidene catalyzed cross-metathesis of w-indolyl alkenes 5 with electron-deficient alkenes 6 as the first step in the tandem reaction leading to polycyclic indoles 7. We propose that the active ruthenium species A (derived from the catalyst precursor) would catalyze not only the CM process, but also an intramolecular hydroarylation owing to its Lewis acidity (Scheme 1).…”