Efficient Heterogeneous Copper-Catalyzed Alder-Ene Reaction of Allenynamides to Pyrrolines

Herein, we describe an efficient nanocopper-catalyzed Alder-ene reaction of allenynamides. The copper nanoparticles were immobilized on amino-functionalized microcrystalline cellulose. A solvent-controlled chemoselectivity of the reaction was observed, leading to the chemodivergent synthesis of pyrrolines (2,5-dihydropyrroles) and pyrroles. The heterogeneous copper catalyst exhibits high efficiency and good recyclability in the Alder-ene reaction, constituting a highly attractive catalytic system from an economical and environmental point of view.


Preparation of Cu-AmP-MCC
Preparation of amino-functionalized microcrystalline cellulose (AmP-MCC): [1] In an oven dried flask, MCC (1.0 g), tartaric acid (97.6 mg, 5 mol% to silane) was dispersed in dry toluene (20 mL). Next, 3-aminopropyltrimethoxysilane (2.27 mL, 13.0 mmol) was added and the mixture was stirred at 82 ℃ for 48 h. The suspension was then centrifuged and the crude AmP-MCC was washed using soxholated extraction with acetone. After 16h, the resulting AmP-MCC was dried under vacuum for 24 h.
Preparation of the mixed valence Cu(I/II) nanocatalyst Cu-AmP-MCC: [2] To a suspension of AmP-MCC (1.0 g) in pH-adjusted H2O solution (25 ml, pH 9) by the use of 0.1 N LiOH, was added a suspension of copper(II) trifluoromethanesulfonate (Cu(OTf)2, 0.3 g) in deionized water (20 mL, pH 9) at room temperature. After stirring for 24 h, the formed Cu(II)-AmP-MCC with pale-blue color was recovered by centrifugation and was washed with deionized H2O (3 × 30 mL) and acetone (3 × 30 mL) by using centrifuge. The washed Cu(II)-AmP-MCC was collected by decantation and dried overnight under vacuum.
In the next step, the dry Cu(II)-AmP-MCC was suspended in deionized water (35 mL), and NaBH4 (190.0 mg, 5.0 mmol, 3.7 equiv to copper) in deionized water (15 mL) was added slowly at room temperature. After vigorous stirring for 1 h, the resulting mixed valence Cu(I/II) nanocatalyst Cu-AmP-MCC was recovered by centrifugation and was washed with deionized H2O (3×30 mL) and acetone (3×30 mL) by the use of a centrifuge. The washed Cu-AmP-MCC was collected by decantation, dried for 48 h under vacuum and obtained as dark blue amorphous powder. The Cu-AmP-MCC was characterized by STEM and XPS (see Figures S1 and S2).   The high resolution spectra for the Cu2p region revealed two main peaks located at 932.5 eV and 952.3 eV belonging to Cu(I) as well as peaks at 934.6 eV and 954.2 eV that are characteristic of Cu(II) ( Figure S2). Moreover, a collection of satellite features of these peaks are clearly observed at 936.2 eV, 941.4 eV, 943.9 eV, 956.2 eV and 962.6 eV, which also indicated the presence of Cu(II) species. The atomic ratio between Cu(I) and Cu(II) can be calculated from their atomic concentrations based on the ratio of the combined integrals of the peaks belonging to Cu(I) to those of the peaks belonging to Cu(II). Thus Cu(I) : Cu(II) = 5.71 : 5.2 = 1.1 : 1 (Table S1).

General procedure for the preparation of allenynamide 3
The allenic sulfonamides S1 were prepared according to a procedure described in the literature. [3] To a flame-dried 25 mL Schlenk flask were added (in the following order) allenic sulfonamide S1 (2.0 mmol, 1.0 equiv), copper(I) thiophene-2-carboxylate (CuTc) (38.1 mg, 0.20 mmol, 10 mol%) and Cs2CO3 (1.30 g, 4.0 mmol) under argon atmosphere. The flask was evacuated under vacuum and flushed with argon for three times. To this mixture toluene (10.0 mL) was added, followed by DMEDA (43.1 µL, 0.40 mmol, 20 mol%) and the alkynyl bromide S2 (2.4 mmol, 1.2 equiv). The reaction mixture was stirred under argon at 40 °C. After 4 h, the reaction mixture was cooled to rt, filtered through a pad of celite, concentrated in vacuo and purified by flash silica gel column chromatrography (petroleum ether/EtOAc with 3% Et3N as eluent) to give allenynamide 3.

Optimization of reaction conditions
To an oven-dried microwave vial equipped with a magnetic stir bar were added Cu-AmP-MCC The general procedure was followed using 3a (

General procedure for the Cu-AmP-MCC-catalyzed Alder-ene reaction of 3 to pyrroles 5
To an oven-dried microwave vial equipped with a magnetic stir bar were added Cu-AmP-MCC