New bis(oxazoline) ligands with secondary binding sites for the asymmetric cyclopropanation of furans
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Introduction
The concept of C2-symmetry has proved to be invaluable for asymmetric catalysis.1 Among the vast number of ligands known, the most successful ones such as the binaphthyls2 or the bisoxazolines3 contain a C2-symmetry axis, and only a few notable exceptions such as phosphinooxazolines4., 4.(a), 4.(b), 4.(c) or ferrocenyl ligands5., 5.(a), 5.(b), 5.(c) are equally effective chiral inductors.
In a C2-symmetrical chiral catalyst two diagonally opposite quadrants are sterically blocked, which allows the unambiguous side approach of a trans-alkene in copper-catalyzed, asymmetric carbene and nitrene transfer reactions following the model proposed by Pfaltz (Fig. 1a)6 for semicorrin ligands and the experimental data available.7., 7.(a), 7.(b) In contrast, the approach of a cis-alkene is ambiguous if R and R1 are similar in their steric volume, which should result in a less effective differentiation of the enantiotopic faces of the double bond (Fig. 1b),7b being reflected in only limited success in the asymmetric cyclopropanation of such substrates to date.8., 8.(a), 8.(b) However, if the sterically blocking substituent in the ligand could form an attractive interaction to one of the substituents of the cis-alkene, its selective recognition might become possible (Fig. 1c). The concept of molecules being able to interact with substrates by means of secondary interactions is long known from enzymes, but has only recently led to the successful development of unnatural ligands for asymmetric catalysis.9., 9.(a), 9.(b), 9.(c), 9.(d), 9.(e)
Section snippets
Preparation of the ligands
In order to test this concept in the cyclopropanation of alkenes, we synthesized the bisoxazoline 1a according to literature precedent.10., 11. It was felt that 1a would be a suitable starting ligand as it would allow further attachment of side chains with the possibility of exerting a secondary interaction with a substrate. Indeed, 1a was readily acylated with carboxylic acids by the method of Steglich,12 giving rise to 1b and the protected α-amino acid containing ligands 2 (Scheme 1).
Asymmetric cyclopropanation of styrene
To
Conclusion
In conclusion, the new ligands 2 effect the enantioselective cyclopropanation of 5a, in which hydrogen bonding as a secondary interaction from the ligands to the substrate appears to control the selectivity, as was suggested by control experiments with ligands 1 and substrates 3, 4, 5b and 7.
Furthermore, the cyclopropanation of 5a seems to be useful for the stereoselective synthesis of γ-butyrolactones 10, which have been used as precursors for paraconic acids (Scheme 2). Cyclopropane 6a-Et can
General remarks
Reactions with moisture-sensitive chemicals were performed under nitrogen in a flame-dried reaction flask. Solvents were dried by standard methods.
Chromatography was completed using Macherey-Nagel silica gel (0.03–0.06 mm). Enantiomeric excesses were determined by analytical HPLC using a ‘Chiracel OD-H’ column (50×4.6 mm, 10 μm, flow: 1 ml/min, 20°C) and a UV detector at 254 nm. TLC analysis was completed using commercially pre-coated aluminium sheets 60 F 254 (Merck). Melting points
Acknowledgements
Financial Support of the Deutsche Forschungsgemeinschaft (SPPP1118, Re 948/5-1) and the Fonds der Chemischen Industrie as well as generous gifts of chemicals by Degussa AG are gratefully acknowledged.
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