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Synthesis 2010(13): 2207-2212  
DOI: 10.1055/s-0029-1218788
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Ruthenium Lewis Acid Catalyzed Asymmetric 1,3-Dipolar Cycloadditions between N-Methylnitrones and Enals

Andrei Bãdoiu, Gérald Bernardinelli, E. Peter Kündig*
Department of Organic Chemistry, University of Geneva, Quai Ernest Ansermet 30, 1211 Geneva 4, Switzerland
Fax: +41(22)3793215; e-Mail: Peter.Kundig@unige.ch;
Further Information

Publication History

Received 22 April 2010
Publication Date:
20 May 2010 (online)

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Abstract

N-Methylisoxazolidines are formed in good yields and high regio-, diastereo- and enantioselectivity via asymmetric 1,3-dipolar cycloaddition of nitrones with enals catalyzed by a chiral ruthenium Lewis acid. Electronic effects in the dipole are the key to activation of these substrates for efficient catalysis.

Key words

asymmetric catalysis - Lewis acid - ruthenium - N-methyl nitrones - 1,3-dipolar cycloaddition

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12

Optimization of the reaction conditions was performed with 3e and 2 in the presence of 5 mol% of (R,R)-1. Screening showed -5 ˚C to be the optimal temperature for this combination of substrates and catalyst. Parallel runs in anhyd and commercial grade CH2Cl2, respectively, led to the same result (85% yield, 94:6 endo/exo, 92% ee); consequently, solvent screening was done with nondried, undistilled, commercial grade solvents. The same results as above were obtained with THF and EtOAc. Lower yields (60%) and selectivities were obtained when using CHCl3 (>95:5 endo/exo, 81% ee) or toluene (84:16 endo/exo, 90% ee). Alcohols, DMF, DMSO, or acetone led to extensive decomposition of the nitrone. Surprisingly, good selectivities (95:5 endo/exo, 88% ee) were obtained when running the reaction in H2O (at 0 ˚C), albeit in low yield (30%).

14

For the X-ray structure of (S,S)-1˙methacrolein, see ref. 4a. The approach of the nitrone is modeled.

15

Crystallographic data for compound 4d have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication CCDC-773807. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.