Dirhodium(II)-catalyzed [3 + 2] cycloaddition of N-arylaminocyclopropane with alkyne derivatives

Dirhodium(II) complex-catalyzed [3 + 2] reactions between N-arylaminocyclopropanes and alkyne derivatives are described. The cycloaddition products proved to be versatile synthetic intermediates. trans-Cyclic β-amino acids and derivatives thereof can be conveniently synthesized using this cycloaddition protocol.


General considerations
All reactions were carried out under a nitrogen or argon atmosphere unless otherwise stated. Commercially available metal catalysts and reagents were purchased from Adamas-beta, Sigma-Aldrich, Alfa-Aesar or TCI. Rh2(5S,R-MenPY) 4 [1] was prepared as described in the literature. 2j [2] and 2k [3] were prepared as described in the literature. All the solvents, unsaturated esters, and alkynes were distilled or purified before using. column chromatography was carried out with silica gel (200-300 mesh) using hexane and ethyl acetate as eluent.

General procedure:
The N-aryl aminocyclopropanes were synthesized according to the literature. [5] An oven-dried Schlenk tube equipped with a stirring bar was charged with [Pd(allyl)(brettphos)]OTf (0.025 mmol, 0.5 mol %), and NaOt-Bu (7.5 mmol). The tube was evacuated and backfilled with nitrogen for three times. The amine (7.5 mmol), aryl bromine (5.0 mmol), and anhydrous toluene (40 mL) were added S4 sequentially via syringe. The tube was placed in a preheated oil bath and the contents were stirred for the indicated time. The tube was then removed from the oil bath and allowed to cool to room temperature. The reaction mixture was diluted with 10 mL of dichloromethane and filtered through a pad of Celite. The solution was concentrated in vacuo, and the residue was purified on silica gel using n-hexane/ethyl acetate as eluent.

Synthesis of trans-ethyl 2-aminocyclopentanecarboxylate
General procedure was performed to provide the [3 + 2] product 3b. For the hydrogenation: To a clean dried 2-neck round bottom flask equipped with a stirring bar was added 3b (131 mg, 0.5 mmol). After stirring in anhydrous MeOH (2 mL) for 5 min. Pd(C) (20 mg) was added carefully under N 2 atmosphere. A balloon filled with H 2 was equipped to the flask and the stirring was continued for 12 h at room temperature. After completion, celite was added to the reaction and stirred for additional 5 min prior to filtering through a pad of celite and washing with MeOH.
Deprotection of PMP: To a pre-cooled solution of trans-p-methoxyphenyl amine 5a (50 mg, 0.19 mmol) in 2 mL CH 3 CN/H 2 O (v/v = 3:1) was slowly added concentrated H 2 SO 4 (26 μL, 0.38 mmol) at 0 °C. Ceric ammonium nitrate (208 mg, 0.38 mmol) was then added in one portion, and the mixture was stirred for one hour at 0 °C. The resulting mixture was then diluted with water (2 mL) and dichloromethane (2 mL). The aqueous phase was separated and basified to pH 10-11 using Na 2 CO 3 S16 solution. The basic aqueous layer was then extracted with ethyl acetate (3 × 5 mL).
The combined organic layers were dried over Na 2 SO 4 and concentrated to give the product 5b (24 mg, 80%) as a colorless oil.