Subscribe to RSS
DOI: 10.1055/s-0029-1219171
Copper-Catalysed Kinetic Resolution of Cyclic Alkenyl Cyclopropane Malonates with Organoaluminium and Grignard Reagents
Publication History
Publication Date:
04 January 2010 (online)
Abstract
We report herein the first copper-catalysed kinetic resolution of alkenyl cyclopropane malonates with organoaluminium and Grignard reagents. The conjugate products were exclusively obtained on five- and six-membered-ring substrates. After optimization of the reaction conditions, we observed good conversions and enantiomeric excesses using ferrocene-based ligands on five-membered-ring substrates, and phosphoramidite ligands on six-membered rings.
Key words
kinetic resolution - alkenyl cyclopropane malonates - conjugate addition - Grignard reagents - copper
-
1a
Rubin M.Rubina M.Gevorgyan V. Chem. Rev. 2007, 107: 3117 -
1b
von Angerer S.Ryu I.Murai S. Carbocyclic Three-Membered Ring Compounds In Houben-Weyl 4th ed., Vol. E17c:de Meijere A. Georg Thieme Verlag; Stuttgart, New York: 1986. p.1949 - 2
Modern
Organocopper Chemistry
Krause N. Wiley-VCH; Weinheim: 2002. -
3a
Corey EJ.Fuchs PL. J. Am. Chem. Soc. 1972, 94: 4014 -
3b
Clarck RD.Heathcock CH. Tetrahedron Lett. 1975, 15: 529 -
3c
Alexakis A.Cahiez G.Normant JF. Tetrahedron 1980, 36: 1961 -
4a
Daviaud G.Miginiac P. Tetrahedron Lett. 1972, 13: 997 -
4b
Grieco PA.Finkelhor R. J. Org. Chem. 1973, 38: 2100 -
5a
Kagan HB.Fiaud JC. Top. Stereochem. 1988, 18: 249 -
5b
Faber K. Chem. Eur. J. 2001, 7: 5004 -
5c
Vedejs E.Jure M. Angew. Chem. Int. Ed. 2005, 44: 3974 ; and references cited therein -
5d
Steinreiber J.Faber K.Griengl H. Chem. Eur. J. 2008, 14: 8060 - 6
Georgakopoulou G.Kalogiros G.Hadjiarapoglou LP. Synlett 2001, 1843 -
7a
Badalassi F.Crotti P.Macchia F.Pineschi M.Arnold A.Feringa BL. Tetrahedron Lett. 1998, 39: 7795 -
7b For a review, see:
Pineschi M. New J. Chem. 2004, 28: 657 - 8
Equey O.Alexakis A. Tetrahedron: Asymmetry 2004, 15: 1531 -
9a
Millet R.Alexakis A. Synlett 2007, 435 -
9b
Millet R.Alexakis A. Synlett 2008, 1797 -
10a
Alexakis A.Albrow V.Biswas K.d’Augustin M.Prieto O.Woodward S. Chem. Commun. 2005, 2843 -
10b
Li K.Alexakis A. Chem. Eur. J. 2007, 13: 3765 - 11
Palais L.Mikhel IS.Bournaud C.Micouin L.Falciola CA.Vuagnoux-d’Augustin M.Rosset S.Bernardinelli G.Alexakis A. Angew. Chem. Int. Ed. 2007, 46: 7462 - 12
Togni A.Breutel C.Schnyder A.Spindler F.Landert H.Tijani A. J. Am. Chem. Soc. 1994, 116: 4062 ; kindly provided by the Solvias Ligand Kit - 13
Liang L.Li Y.-M.Chan ASC. Tetrahedron: Asymmetry 2003, 14: 1865 - 14
Sturm T.Weissensteiner W.Spindler F. Adv. Synth. Catal. 2003, 345: 160 - 15
Lotz M.Polborn K.Knochel P. Angew. Chem. Int. Ed. 2002, 41: 4708
References and Notes
General Procedure
(Chiral Version): In a dried Schlenk tube flushed under nitrogen,
was placed the copper catalyst (0.04 mmol) and the specified ligand
(0.08 mmol). Anhydrous CH2Cl2 (1 mL) was then
added and the mixture was stirred at room temperature for 15 min.
The Schlenk tube was then placed in a bath at -78 ˚C,
and the indicated Grignard reagent (1 equiv) was added. The starting
material (1 mmol), solubilised in the indicated solvent (0.5 mL),
was added dropwise. The mixture was stirred for 4 h at this temperature.
Aq HCl (1N, 1 mL) was added and the reaction was allowed to warm
to r.t. The organic layer was separated and the aqueous phase was
extracted with Et2O. The organic phases were dried over
MgSO4 and the solvent was evaporated under reduced pressure.
The crude compound was purified by chromatography on silica gel
(cyclohexane-Et2O, 70:30) and the product was
isolated as an oil.
Dimethyl 2-(4-ethylcyclopent-2-enyl)malonate
(4b): ¹H NMR (400 MHz,
CDCl3): δ = 0.88 (t, J = 7 Hz,
3 H), 1.25-1.45 (m, 2 H), 1.69-1.81
(m, 2 H), 2.62 (br s, 1 H), 3.25 (m, 1 H),
3.36 (br s, 1 H), 3.73 (s, 6 H), 5.62 (d, J = 5 Hz,
1 H), 5.79 (d, J = 5 Hz,
1 H). ¹³C NMR (100 MHz, CDCl3): δ = 169.4,
169.3, 137.8, 130.9, 57, 52.6, 46.5, 45.2, 34.4, 28.6, 12.3.
Dimethyl
2-(4-ethylcyclohex-2-enyl)malonate (5b): ¹H NMR
(400 MHz, CDCl3): δ = 0.89 (t, J = 7 Hz,
3 H), 1.20-1.35 (m, 4 H), 1.82-1.95
(m, 3 H), 2.86 (br s, 1 H), 3.24 (d, J = 9 Hz,
1 H), 3.75 (s, 6 H), 5.46 (m, 1 H), 5.64-5.66
(m, 1 H). ¹³C NMR (100 MHz,
CDCl3): δ = 169.2, 169.1, 134.5, 127.1,
57.1, 52.6, 37.2, 36.4, 29.0, 28.3, 26.9, 11.4.