Nucleophilic Addition of Amines to Ruthenium Carbenes: ortho‐(Alkynyloxy)benzylamine Cyclizations towards 1,3‐Benzoxazines

Abstract

A new ruthenium‐catalyzed cyclization of ortho‐(alkynyloxy)benzylamines to dihydro‐1,3‐benzoxazines is reported. The cyclization is thought to take place via the vinyl ruthenium carbene intermediates which are easily formed from [Cp*RuCl(cod)] and N2CHSiMe3. The mild reaction conditions and the efficiency of the procedure allow the easy preparation of a broad range of new 2‐vinyl‐2‐substituted 1,3‐benzoxazine derivatives. Rearrangement of an internal C(sp) in the starting material into a tetrasubstituted C(sp3) atom in the final 1,3‐benzoxazine is highly remarkable.

Cp*RuCl‐Vinyl Carbenes: Two Faces and the Bifunctional Role in Catalytic Processes

“…To compare the high reactivity of Cp/Cp*RuCl η 3 ‐vinylcarbenes arising from the combination of diazo compounds and alkynes in CAM processes with the unreactive ruthenium η 3 ‐vinylcarbene 5 (Figure ), we performed a thorough geometrical/electronic description of the former species by using DFT calculations. Accordingly, η 3 coordination induces an out‐of‐plane bending of the Ru‐C1‐C2‐C3 fragment of roughly 18° (Figure ), which exposes preferentially one side of the carbene towards a potential nucleophilic attack.…”

“…Alternatively, our research group and others have been reporting the use of Cp/Cp*RuCl‐based complexes (Cp=cyclopentadiene, Cp*=1,2,3,4,5‐pentamethylcyclopentadiene) for the catalytic generation of ruthenium vinyl carbenes from alkynes and diazo compounds through intermolecular CAM (Figure c) . These intermediates can lead to dienes, cyclopropanes, C−H insertion products, or ylide intermediates, which eventually afford benzoxazines, furans, vinyl dihydropyrans/dihydrooxazines, and vinyl epoxypyrrolidines . Remarkably, Cp*/CpRuCl‐based complexes were the only complexes to give productive tandem CAM processes.…”

Studies on Instructive Construction of exo-Olefin Terminated Five- and Six-Membered Nitrogen Heterocycles: SmI2-Mediated Intramolecular Cyclization of Haloalkynals

“…Mp 65− (R)-Ethyl 2-(N-(But-3-ynyl)-4-methylphenylsulfonamido)propanoate (1k′). Alkylation of N-tosyl-L-alanine ethyl ester 16 (504.1 mg, 1.86 mmol) was carried out according to the same procedure as described for 1j′ to give alkyne 1k′ (257.2 mg, 43%) as a colorless oil [eluent: hexane−AcOEt 18 (994.7 mg, 3.5 mmol) in acetone (15 mL) were added NBS (950.0 mg, 5.3 mmol) and AgNO 3 (136.1 mg, 0.8 mmol) at room temperature under Ar. After stirring for 40 min at the same temperature, the reaction was quenched with sat.…”

“…20 Methyl 2-(N-(3-Iodoprop-2-ynyl)-4-methylphenylsulfonamido)acetate (1c). To a solution of methyl 2-(4-methyl-N-(prop-2ynyl)phenylsulfonamido)acetate and N-(prop-2-ynyl)-N-tosylglycine 18 (49.9 mg, 0.18 mmol) in acetone (1 mL) were added NIS (60.9 mg, 0.27 mmol) and AgNO 3 (6.40 mg, 0.04 mmol) at room temperature under Ar. After stirring for 4 h at the same temperature, the reaction was quenched with sat.…”

“…The residue was purified by column chromatography on silica gel using hexane−AcOEt (7:3, v/v) as eluent to give pyrrolidine 3g (58.0 mg, 69%) as a colorless solid. Mp 128−130 °C; [α] D 18 = 28.25 (c 1.1, CHCl 3 ); IR ν max 3491, 1339, 1163 cm −1 ; 1 H NMR (CDCl 3 ; 400 MHz) δ 7.77 (2H, d, J = 8.3 Hz), 7.30 (2H, d, J = 8.3 Hz), 6.17 (1H, br s), 4.61 (1H, d, J = 3.3 Hz), 4.01 (1H, dd, J = 15.0, 1.6 Hz), 3.96 (1H, dd, J = 15.0, 1.6 Hz), 3.69 (1H, d, J = 6.2 Hz), 2.41 (3H, s), 1.98−1.86 (1H, m), 1.60 (1H, br s), 1.00 (3H, d, J = 6.9 Hz), 0.90 (3H, d, J = 6.8 Hz); 13 (Z)-3-(Bromomethylene)-1-tosylpiperidin-4-ol (3h). Reduction of ester 1h (111.3 mg, 0.30 mmol), followed by radical cyclization of the resulting aldehyde, was carried out according to the same procedure as described for 3a to give piperidine 3h (78.1 mg, 76%) as a colorless oil [eluent: hexane−AcOEt−CHCl 3 (9:2:9, v/v)]; IR ν max 3494, 1348, 1332, 1164 cm −1 ; 1 H NMR (CDCl 3 ; 400 MHz) δ 7.65 (2H, d, J = 8.3 Hz), 7.33 (2H, d, J = 8.3 Hz), 6.29 (1H, d, J = 1.8 Hz), 4.91 (1H, br s), 4.10 (1H, dd, J = 12.7, 1.8 Hz), 3.64 (1H, ddd, J = 12.2, 4.6, 2.3 Hz), 3.30 (1H, dd, J = 12.7, 1.8 Hz), 2.84 (1H, dt, J = 12.2, 3.1 Hz), 2.44 (3H, s), 1.94−1.78 (2H, m), 1.60 (1H, br s); 13 (Z)-4-(Bromomethylene)-1-tosylpiperidin-3-ol (3j).…”