Catalytic Asymmetric Cycloaddition Reaction of Alkenyl Trichloroacetates with Nitrones

Abstract

A catalytic enantioselective cycloaddition reaction of alkenyl trichloroacetates with nitrones was achieved using an (S)-BINOL-derived chiral tin dibromide possessing a 4-trifluoromethylphenyl group at 3- and 3′-positions as the chiral precatalyst in the presence of sodium ethoxide, sodium iodide, and ethanol. Optically active isoxazolidines with up to 95% ee were diastereoselectively obtained in high yields even from aliphatic aldehyde derived nitrones under the influence of the in situ generated chiral tin ethoxide iodide.

Key words

asymmetric catalysis - cycloaddition - isoxazolidine - ­nitrone - tin

References and Notes

• For reviews, see:
• 1a Gothelf KV. Jørgensen KA. Chem. Commun.  2000,  1449 
• 1b Ess DH. Jones GO. Houk KN. Adv. Synth. Catal.  2006,  348:  2337 
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• 3 Gothelf KV. Thomsen I. Jørgensen KA. J. Am. Chem. Soc.  1996,  118:  59 
• 4a Kanemasa S. Oderatoshi Y. Sakaguchi S. Yamamoto H. Tanaka J. Wada E. Curran DP. J. Am. Chem. Soc.  1998,  120:  3074 
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• 7b A chiral Ti-catalyzed reaction of nitrones with ketene silyl acetals has been reported to give optically active β-siloxyamino esters instead of isoxazolidines: Murahashi S. Imada Y. Kawakami T. Harada K. Yonemushi Y. Tomita N. J. Am. Chem. Soc.  2002,  124:  2888 
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10

We attempted a stoichiometric reaction of 1a with 2f using one equivalent of chiral tin dibromide 4d in order to obtain an additional evidence for the second mechanism; however, the desired product 3af was not obtained at all because of facile decomposition of the nitrone 2f in the presence of a stoichiometric amount of 4d.

11

General Experimental Procedure for Cycloaddition Reaction of Alkenyl Trichloroacetates and Nitrones Catalyzed by Chiral Tin Dibromide 4d (Tables 1-3):
A mixture of MS4A powder (350 mg), chiral tin dibromide 4d ⁸ (21.2 mg, 0.025 mmol), and NaI (7.5 mg, 0.05 mmol) in anhyd THF (3 mL) was stirred for 10 min. Then, NaOEt in EtOH (10.7 µL, 0.025 mmol) and EtOH (0.28 mL) were added and the resulting mixture was stirred for 30 min. Subsequently, nitrone (0.5 mmol) and alkenyl trichloro-acetate (1 mmol) were added to the mixture at r.t. After being stirred for the specified time at r.t. or 60 ˚C, the reaction mixture was treated with MeOH (1 mL), brine (1 mL), and solid KF (0.5 g) at ambient temperature for 10 min. The resulting precipitate was filtered off and the filtrate was dried over Na₂SO₄ followed by concentration in vacuo. The residual crude product was purified by column chromatog-raphy on silica gel to give a cycloaddition product. The diastereomeric ratio was determined by ^¹H NMR and ^¹³C NMR.
General Experimental Procedure for Three-Component Cycloaddition Reaction of Alkenyl Trichloroacetate 1a, Aldehydes 5, and N -Hydroxyaniline Catalyzed by Chiral Tin Dibromide 4d (Table 4): A mixture of MS4A powder (350 mg), chiral tin dibromide 4d ⁸ (21.2 mg, 0.025 mmol), and NaI (7.5 mg, 0.05 mmol) in anhyd THF (3 mL) was stirred for 10 min. Then, NaOEt in EtOH (10.7 µL, 0.025 mmol) and EtOH (0.28 mL) were added and the resulting mixture was stirred for 30 min. Subsequently, aldehyde (0.5 mmol), N-hydroxyaniline (0.5 mmol), and alkenyl trichloroacetate (1 mmol) were added to the mixture at r.t. After being stirred for the specified time at r.t., the reaction mixture was treated with MeOH (1 mL), brine (1 mL), and solid KF (0.5 g) at ambient temperature for 10 min. The resulting precipitate was filtered off and the filtrate was dried over Na₂SO₄ followed by concentration in vacuo.
The residual crude product was purified by column chromatography on silica gel to give a cycloaddition product. The diastereomeric ratio was determined by ^¹H NMR and ^¹³C NMR.