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DOI: 10.1055/s-2007-984889
Enantioselective Copper-Catalyzed Conjugate Addition to 2- or 3-Substituted Cyclopent-2-en-1-ones: Construction of Stereogenic Quaternary Carbon Centers
Publikationsverlauf
Publikationsdatum:
12. Juli 2007 (online)
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Abstract
Trimethyl- and triethylaluminum undergo enantioselective conjugate addition to 2- and 3-substituted cyclopent-2-en-1-ones in the presence of catalytic amount of a copper salt and a phosphoramidite or a diphosphite ligand. Thus, chiral quaternary centers can be built with up to 93% ee.
Key words
aluminum - copper - Michael addition - asymmetric catalysis - ligands
-
1a
Trost BM.Jiang C. Synthesis 2006, 369 -
1b
Christoffers J.Mann A. Angew. Chem. Int. Ed. 2001, 40: 4591 -
1c
Quaternary Stereocenters: Challenges and Solutions for Organic Synthesis
Christoffers J.Baro A. Wiley-VCH; Weinheim: 2006. -
1d
Denissova I.Barriault L. Tetrahedron 2003, 59: 10105 - For reviews on asymmetric conjugate additions, see:
-
2a
Alexakis A.Benhaim C. Eur. J. Org. Chem. 2002, 3221 -
2b
Krause N.Hoffmann-Röder A. Synthesis 2001, 171 -
2c
Hayashi T. Acc. Chem. Res. 2000, 33: 354 - 3
d’Augustin M.Palais L.Alexakis A. Angew. Chem. Int. Ed. 2005, 44: 1376 - 4
Wu J.Mampreian DM.Hoveyda AH. J. Am. Chem. Soc. 2005, 127: 4584 - 5
Hird AW.Hoveyda AH. J. Am. Chem. Soc. 2005, 127: 14988 - 6
Fillion E.Wilsily A. J. Am. Chem. Soc. 2006, 128: 2774 - 7
Lee K.-S.Brown MK.Hird AW.Hoveyda AH. J. Am. Chem. Soc. 2006, 128: 7182 - 8
Brown MK.May TL.Baxter CA.Hoveyda AH. Angew. Chem. Int. Ed. 2007, 46: 1097 - 9
Martin D.Kehrli S.d’Augustin M.Clavier H.Mauduit M.Alexakis A. J. Am. Chem. Soc. 2006, 128: 8416 -
10a
Westermann J.Neh H.Nickisch K. Chem. Ber. 1996, 129: 963 -
10b
Westermann J.Nickisch K. Angew. Chem., Int. Ed. Engl. 1993, 32: 1368 - 11
Liang L.Yan M.Li Y.-M.Chan ASC. Tetrahedron: Asymmetry 2003, 14: 1865 -
12a
Mizutani H.Degrado SJ.Hoveyda AH. J. Am. Chem. Soc. 2002, 124: 13362 -
12b
Mizutani H.Degrado SJ.Hoveyda AH. J. Am. Chem. Soc. 2002, 124: 779 - 15
Djerassi C.Records R.Ouannes C.Jacques J. Bull. Soc. Chim. Fr. 1966, 7: 2378 - 16
Kocienski PJ.Street SDA.Yeas C.Campbell SF. J. Chem. Soc., Perkin Trans. 1 1987, 2171 -
17a
Slacanin I.Vargas D.Marston A.Hosteffmann K. J. Chromatogr. 1988, 457: 325 -
17b
Rodríguez E.Dillon MO.Mabry TJ.Mitchell JC.Towers GHN. Experientia 1976, 32: 236 -
17c
Kupchan SM.Fessler DC.Eakin MA.Giacobbe TJ. Science 1970, 168: 376 -
17d
Kupchan SM.Eakin A.Thomas AM. J. Med. Chem. 1971, 14: 1147 -
17e
Wender PA.Irick A.Miller BL. J. Org. Chem. 1993, 58: 4179 -
17f
Chuang LF.Kung HF.Israel M.Chuang RY. Biochem. Pharmacol. Toxicol. 1992, 43: 865 -
17g
Droms KA.Malkinson AM. Mol. Carcinog. 1991, 4: 1
References and Notes
General Procedure for the Cu-Catalyzed A.C.A. of R
3
Al in the Presence of Phosphoramidite Ligand
A flame-dried Schlenk tube was charged with [CuOTf]2·C6H6 (2.0 mol%) and L3 (8.0 mol%). Then Et2O (2.5 mL) was added and the mixture was stirred at r.t. for 30 min. Afterwards, the substrate (1.0 equiv, 1.0 mmol) in Et2O (0.5 mL) was added dropwise at r.t. and the reaction mixture was stirred for further 5 min before being cooled to -30 °C. Then, R3Al was introduced dropwise over 2 min. Once the addition was complete the reaction mixture was left at
-30 °C overnight. The reaction was hydrolyzed by the addition of MeOH at -30 °C, followed by 2 N HCl (3 mL) at r.t. Subsequently, Et2O (10 mL) was added and the aqueous layer was separated and extracted further with Et2O (3 × 3 mL). The combined organic fractions were washed with brine (5 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The oily residue was purified by flash column chromatography (pentane-Et2O) to yield the 1,4-adduct. Gas chromatography on a chiral stationary phase indicated the ee.
General Procedure for the Cu-Catalyzed A.C.A. of R
3
Al in the Presence of Diphosphite Ligand
A flame-dried Schlenk tube was charged with Cu(OTf)2 (4.0 mol%) and L6 (8.0 mol%). Then, Et2O (8.0 mL) was added and the mixture was stirred at r.t. for 30 min. Afterwards, the substrate (1.0 equiv, 1.0 mmol) in Et2O (0.5 mL) was added dropwise at r.t. and the reaction mixture was stirred for further 5 min before being cooled to -30 °C. Then, R3Al was introduced dropwise over 2 min. Once the addition completed, the reaction mixture was left at -30 °C overnight. The reaction was hydrolyzed by the addition of MeOH at -30 °C, followed by aq sat. NH4Cl solution (3 mL) at r.t. Subsequently, Et2O (10 mL) was added and the aqueous layer was separated and extracted further with Et2O (3 × 3 mL). The combined organic fractions were washed with brine (5 mL), dried over anhyd Na2SO4, filtered, and concentrated in vacuo. The oily residue was purified by flash column chromatography (pentane-Et2O) to yield the 1,4-adduct. Gas chromatography on a chiral stationary phase indicated the ee.