Palladium-Catalyzed Diorganozinc Conjugate Additions to Enones
with residual protic solvent as the internal reference (CDCl3: δH
7.26); chemical shifts (δ) are given in parts per million (ppm), and
coupling constants (J) are given in Hertz [Hz]. The proton spectra
are reported as follows: δ (multiplicity, J, number of protons, as-
signment). 13C NMR spectra were recorded at ambient temperature
with the same spectrometer at 100.62 MHz, with the central peak
of the solvent (CDCl3: δC = 77.0) as the internal reference.
DEPT135 measurements were used to aid in the assignment of sig-
nals in the 13C NMR spectra.
=
(100.62 MHz, CDCl3): δ = 209.7 (s), 46.1 (t), 40.5 (d), 39.2 (d), 32.2
(t), 31.4 (t), 30.3 (q), 30.2 (t), 29.2 (t), 27.1 (t), 26.8 (t), 26.7 (t, 2 C),
22.6 (t), 14.1 (q) ppm. HRMS (ESI+): calcd. for C15H29O
[M + H]+ 225.2219; found 225.2213. IR (NaCl): ν = 2925 (s, C–
˜
H), 2853 (s, C–H), 1717 (s, C=O), 1449 (w), 1356 (w) cm–1.
Supporting Information (see footnote on the first page of this arti-
cle): Cartesian coordinates and energies (in hartrees) for all calcu-
1
lated structures. Copies of H and 13C NMR spectra for 6c.
Procedure for Conjugate Addition of Organozinc Reagents to α,β-
Unsaturated Ketones by Using a PdII Precatalyst: In a typical ex-
periment, to a cooled (–78 °C) solution of a PdII complex (5 mol-
%) in THF (7 mL) was added a solution of a phosphane ligand (5
or 10 mol-%, where appropriate; see Table 1) and the correspond-
ing enone (1 mmol) in THF (3 mL). After 10 min, a solution of the
organozinc reagent (1.5 mmol) was added dropwise to the stirred
solution, and the reaction mixture was stirred under the indicated
conditions of temperature and time (Tables 1 and 2). The resulting
mixture was poured into a cooled (0 °C) saturated aqueous solution
of NH4Cl (10 mL), and the layers were separated. The aqueous
layer was extracted with Et2O (3ϫ), the combined organic layers
were dried (Na2SO4), and the solvent was evaporated. The residue
was purified by column chromatography (silica gel; hexane/EtOAc)
to afford a colourless oil in all cases.
Acknowledgments
We thank the Spanish Ministerio de Economía y Competitividad
(Grants CTQ2008-06647 and CTQ2009-14186, FEDER) for finan-
cial support.
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Procedure for Conjugate Additions to 5a by Using Different Relative
Ratios of Pd(OAc)2/Et2Zn: See Table 3. To a cooled (–78 °C) solu-
tion of Pd(OAc)2 (0.2 mmol) in THF (10 mL) were added P(nBu)3
(0.2 mmol) and 5a (1 mmol). After 10 min, Et2Zn (0.4–2.0 mmol)
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purified as described in the procedures above.
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By applying the procedures described above, compounds 6a–j and
7a were prepared. Compounds 6a,[45] 6b,[45] 6d,[46] 6e,[45] 6f,[47] 6g,[48]
6h,[49] 6i,[50] 6j[51] and 7a[52] had been described previously, and the
samples prepared here presented spectroscopic data that match
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4-Cyclohexylnonan-2-one (6c): According to the procedure for con-
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precatalyst, the reaction of 5a (0.03 mL, 0.18 mmol), Pd-
(O2CCF3)2 (3 mg, 0.0091 mmol) and Cy2Zn (0.68 mL, 0.4 m in
Et2O, 0.27 mmol) in THF (1.8 mL) afforded, after purification by
column chromatography (silica gel; hexane/EtOAc, 97:3), a viscous
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2
δ = 2.41 (dd, JH,H = 16.1 Hz, 3JH,H = 5.9 Hz, 1 H, 3-H), 2.23 (dd,
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3
2JH,H = 16.1 Hz, JH,H = 7.3 Hz, 1 H, 3-H), 2.13 [s, 3 H, C(O)-
1447.
CH3], 1.8 (m, 1 H, 4-H), 1.8–1.5 (m, 6 H, 3 CH2), 1.4–1.0 (m, 13
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H, CH, 6 CH2), 0.87 (t, 3JH,H = 7.0 Hz, 3 H, CH3) ppm. 13C NMR
Eur. J. Org. Chem. 2013, 2621–2626
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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