Synthesis of Pyrrolidine Derivatives by a Platinum/Brønsted Acid Relay Catalytic Cascade Reaction

Abstract

A new catalytic reaction for the synthesis of pyrrolidine derivatives is presented. The method implies the coupling of N-Boc-protected alkynamine derivatives and appropriate alkenes or alkynes in a process catalysed by a platinum/triflic acid catalytic binary system. This reaction is believed to proceed through a cascade process implying an initial platinum-catalysed cycloisomerization of the alkynamine derivative followed by a triflic acid promoted nucleophilic addition of the alkene or alkyne and trapping of the cationic species formed by the Boc group. Not only simple alkenes and alkynes were used in this reaction but also allyltrimethylsilane and propargyltrimethylsilane. Particularly, when allyltrimethylsilane is used as the alkene counterpart interesting bicyclic compounds containing a trimethylsilane group are obtained. However, when propargyltrimethylsilane is used in the presence of water we observed the formation of a related bicyclic compound lacking the trimethylsilane group and containing an exocyclic carbon-carbon bond.

Synthesis of Nitrogen-Containing Heterocyclic Scaffolds through Sequential Reactions of Aminoalkynes with Carbonyls

“…The aptitude to form πand σ-complexes can help in the choice of catalysts for the desired transformations when bi-or polyfunctional substrates are involved [6]. The reaction of γand δ-aminoalkynes with sulfonyl azides in the presence of Ru 3 (CO) 12 catalyst efficiently afforded cyclic amidines of relevance in medicinal and coordination chemistry as well as in materials science [7]. The gold(I)-catalyzed tandem cyclization of γ-aminoalkynes with alkynes in water led to diversely substituted pyrrolo [1,2-a]quinolines [8].…”

Simultaneous Generation and Subsequent Cycloaddition of ortho‐Quinonemethides and Cyclic Enecarbamates Promoted by a Gold/Lewis Acid Catalytic System

“…On the other hand, the dehydration reaction of 4a to obtain the corresponding o ‐QM III would require a Brønsted or Lewis acid as catalyst. In this sense, it should be noted that the use of binary metal/Brønsted acid catalytic systems is well documented in the bibliography and represents an appealing field to which our research group has recently contributed , . For this reason, we started our investigation by trying the model reaction in the presence of (JohnPhos)AuNTf 2 (5 mol‐%) as the gold‐catalyst and different Brønsted acids (5 mol‐%) including triflic acid, tetrafluoroboric acid and diphenylphosphate among others.…”

One‐Pot Stereocontrolled Synthesis of Bicyclic Pyrrolidine Derivatives by a Platinum–Brønsted Acid Relay Cascade Reaction

“…[5,6] These cascade sequences proceed by means of initial Pt II -catalyzed cyclizations of 1,5-aminoalkynes 1 to form 2,3-dihydropyrrole species 3 that possess better affinity than electron-rich alkenes 2 to undergo protonation to yield iminium species 4 chemoselectively. Subsequentf ormal [4+ +2] cycloadditions of these iminium salts with alkene partners affords bicyclic pyrrolidines 5 efficiently [Eq.…”

“…The use of allylsilane 2d increases the diversity of pyrrolidine products with examples shown in Equation (6). Herein,r esidual HOTf reacts with 2,3-dihydropyrroles 3 to form iminium salts 4, thus securingt he entity of allylsilanes;t he diastereoselectivity of resulting products 5f-5h depends on their para-phenyl substituent with dr = 4.5-5.0:1 for X = Ha nd Me, and dr = 3:2 for X = Cl.…”

“…Fańanás, Rodríguez, and co‐workers reported notable cyclization/cycloaddition cascades between N ‐Boc‐derived (Boc= tert ‐butoxycarbonyl) 1,5‐aminoalkynes 1 and electron‐rich alkenes 2 , yielding bicyclic pyrrolidine derivatives by using a mixture of Pt II and Brønsted acid catalysts 5. 6 These cascade sequences proceed by means of initial Pt II ‐catalyzed cyclizations of 1,5‐aminoalkynes 1 to form 2,3‐dihydropyrrole species 3 that possess better affinity than electron‐rich alkenes 2 to undergo protonation to yield iminium species 4 chemoselectively. Subsequent formal [4+2] cycloadditions of these iminium salts with alkene partners affords bicyclic pyrrolidines 5 efficiently [Eq.…”