3510
M. Magrez et al. / Tetrahedron 68 (2012) 3507e3511
4.2. General procedure for the Cu-catalysed ACA of enone
with Et2Zn
CH2CH3), 1.33e1.22 (m, 1H, CH2CH3), 0.95 (d, J¼6.4 Hz, 3H, CH3CH),
0.92 (t, J¼6.8 Hz, 3H, CH3CH2); 13C NMR:
d 199.2 (CO), 139.2 (Car),
135.7 (Car), 129.5 (2 CHar), 128.8 (2 CHar), 45.5 (CH2CO), 31.4
A flame-dried Schlenk tube was charged with copper source
(1e4 mol %) and ligand (1e4 mol %). Next, 3 mL of ethyl acetate
was added and the resulting green mixture was stirred at room
temperature for 15 min, after which Et2Zn (3 mmol) was added
dropwise. Finally, acyclic enone (1 mmol, 1 equiv) was added at
required temperature. The resulting brown solution was
allowed to stir at the required temperature for 0.1e20 h and the
reaction was quenched by the addition of 5e8 mL of a 1 N HCl
solution. The product was extracted with AcOEt. The organic
phase was washed with a saturated NaHCO3 solution and brine,
dried over MgSO4, filtrated and concentrated under vacuo. The
product was purified by silica gel column chromatography
(pentane/Et2O).
(CHCH3), 29.7 (CH2CH3), 19.5 (CH3CH), 11.4 (CH3CH2). The ee was
determined by chiral GC: Capillary column Chiraldex GTA (0.12 mm,
30 m, 0.25 mm), pression 105 kPa, total He flow 50 mL/min; 85 ꢀC
(140 min)e0.2 ꢀC/mine120 ꢀCe10 ꢀC/mine160 ꢀC (8 min); tR (1)¼
261.8 min, tR (2)¼263.5 min. [
a
]
D20
þ9.1 (c 1.5, Et2O, ee¼98%).
HRMS: [MþNa]þ (C12H15O3ClNa) calcd 233.07091; found 233.0708
(0 ppm).
4.3.6. Compound 7d: 1-(4-methoxyphenyl)-3-methylpentan-1-one.-
Yellow oil. 1H NMR (CDCl3):
d 7.96e7.92 (m, 2H, Har), 6.95e6.91
(m, 2H, Har), 3.87 (s, 3H, OCH3), 2.89 (dd, J¼15.4, 5.7 Hz, 1H, CH2CO),
2.68 (dd, J¼15.4, 8 Hz, 1H, CH2CO), 2.13e2.01 (m, 1H, CHCH3),
1.48e1.37 (m, 1H, CH2CH3), 1.32e1.21 (m, 1H, CH2CH3), 0.94 (d,
J¼6.8 Hz, 3H, CH3CH), 0.92 (t, J¼7.2 Hz, 3H, CH3CH2); 13C NMR:
4.3. Analytical data
d 199.2 (CO), 163.3 (Car), 130.6 (Car), 130.4 (2 CHar), 113.6 (2 CHar),
55.4 (OCH3), 45.3 (CH2CO), 31.6 (CHCH3), 29.7 (CH2CH3), 19.5
(CH3CH), 11.4 (CH3CH2). The ee was determined by chiral HPLC: two
4.3.1. Compound 4: 4-ethylnonan-2-one. The ee was determined by
chiral GC: Capillary column Chiraldex GTA (0.12
m
m, 30 m,
OD-H columns; n-hexane/i-PrOH: 99.9/0.1; flow: 0.5 mL minꢁ1
;
0.25 mm), pression 104 kPa, total He flow 9.9 mL/min; 80 ꢀC
(60 min)e2 ꢀC/mine100 ꢀCe10 ꢀC/mine160 ꢀC (5 min); tR (R)¼
254 nm; tR (1): 220.63 min, tR (2) 234.7 min. [
a
]
þ16.7 (c 1.5,
D20
Et2O, ee >97%). HRMS: [MþNa]þ (C13H18O2Na) calcd 229.12045;
44.4 min, tR (S)¼47.6 min. [
a
]
D20
þ2.4 (c 2.3, CHCl3, ee¼97%) {lit.
found 229.1204 (0 ppm).
þ2.7 (c 2.3, CHCl3, ee¼90%, (R) enantiomer)16}.
D20
[
a]
4.3.7. Compound 7e: 1-(2-naphthyl)-3-methylpentan-1-one. Yellow
4.3.2. Compound 6: 4-phenylhexan-2-one. The ee was determined
oil. 1H NMR (CDCl3):
d 8.46 (s, 1H, CHar), 8.05e7.87 (m, 4H, CHar),
by chiral GC: Capillary column Chiraldex GTA (0.12
m
m, 30 m,
7.62e7.53 (m, 2H, CHar), 3.08 (dd, J¼15.6, 5.7 Hz, 1H, CH2CO), 2.88
(dd, J¼15.6, 7.9 Hz, 1H, CH2CO), 2.22e2.10 (m, 1H, CHCH3),
1.54e1.43 (m, 1H, CH2CH3), 1.38e1.27 (m, 1H, CH2CH3), 1.00 (d,
J¼6.8 Hz, 3H, CH3CH), 0.96 (t, J¼7.6 Hz, 3H, CH3CH2); 13C NMR:
0.25 mm), pression 108 kPa, total He flow 9.7 mL/min; 90 ꢀC
(85 min)e2 ꢀC/mine120 ꢀCe10 ꢀC/mine160 ꢀC (5 min); tR (R)¼
83.5 min, tR (S)¼86.9 min. [
a]
þ30.6 (c 1, EtOH, ee¼99%) {lit.
D20
[
a]
þ27 (c 1.32, EtOH, ee¼81%, (S) enantiomer)16}.
d 200.5 (CO), 135.5 (Car), 134.8 (Car), 132.5 (Car), 129.6 (CHar), 129.5
D20
(CHar), 128.4 (CHar), 128.3 (CHar), 127.7 (CHar), 126.7 (CHar), 124.0
(CHar), 45.6 (CH2CO), 31.6 (CHCH3), 29.7 (CH2CH3), 19.6 (CH3CH),
11.5 (CH3CH2). The ee was determined by chiral HPLC: OD-H col-
umn; n-hexane/i-PrOH: 99.9/0.1; 0.8 mL minꢁ1; 254 nm; tR (1)¼
4.3.3. Compound 7a: 1-phenyl-3-methyl pentan-1-one. Colourless
oil. 1H NMR (CDCl3):
7.97e7.93 (m, 2H, Har), 7.58e7.52 (m,1H, Har),
d
7.48e7.43 (m, 2H, Har), 2.95 (dd, J¼15.6, 5.6 Hz, 1H, CH2CO), 2.74
(dd, J¼15.6, 7.8 Hz, 1H, CH2CO), 2.15e2.03 (m, 1H, CH), 1.49e1.38
(m, 1H, CH2CH3), 1.33e1.22 (m, 1H, CH2CH3), 0.95 (d, J¼6.4 Hz, 3H,
84.4 min, tR (2)¼93.7 min. [
a
]
D20
þ22.1 (c 1.5, Et2O, ee¼94%). HRMS:
[MþNa]þ (C16H18ONa) calcd 249.12554; found 249.1256 (0 ppm).
CH3CH), 0.93 (t, J¼7.6 Hz, 3H, CH3CH2); 13C NMR:
d 200.5 (CO), 137.4
(Car), 132.8 (CHar), 128.5 (2 CHar), 128.1 (2 CHar), 45.6 (CH2CO), 31.4
4.3.8. Compound 9: 1,3-diphenylpentan-2-one. The ee was de-
termined by chiral HPLC: OD-H column; n-hexane/i-PrOH: 99.75/
0.25; flow: 1 mL minꢁ1; 254 nm; tR (S): 25.1 min, tR (R): 30.5 min.
(CH), 29.7 (CH2CH3), 19.5 (CH3CH), 11.4 (CH3CH2). The ee was de-
termined by chiral GC: Capillary column Chiraldex GTA (0.12 mm,
30 m, 0.25 mm), pression 105 kPa, total He flow 50 mL/min; 70 ꢀC
(30 min)e0.2 ꢀC/mine100 ꢀCe10 ꢀC/mine160 ꢀC (3 min); tR (1)¼
[
a
]
þ4.1 (c 1.52, EtOH, ee¼77%, S enantiomer) {lit. [
a
]
þ7.3 (c
D20
D20
1.52, EtOH, ee¼86%, (S) enantiomer)14}. [
a]
þ1.14 (c 1.93, CHCl3,
D20
151.4 min, tR (2)¼153.4 min. [
a]
þ17 (c 1.5, Et2O, ee¼96%, (S)
ee¼77%, S enantiomer) {lit. [
a
]
þ1.83 (c 1.93, CHCl3, ee¼98%, (S)
D20
D20
enantiomer) {lit. [
a
]
ꢁ15 (c 1.5, Et2O, ee¼93%, (R) enantiomer)15}.
enantiomer)13}.
D20
4.3.4. Compound 7b: 1-(4-nitrophenyl)-3-methylpentan-1-one. Yellow
oil. 1H NMR (CDCl3):
8.32e8.28 (m, 2H, Har), 8.11e8.07 (m, 2H,
4.3.9. Compound 11: 3-ethyl-1-phenyloctan-1-one. The ee was de-
termined by chiral HPLC: OD-H column; n-hexane/i-PrOH: 99.95/
0.05; flow: 1 mL minꢁ1; 254 nm; tR (1): 23.0 min, tR (2) 24.4 min.
d
Har), 2.99 (dd, J¼16.4, 5.6 Hz, 1H, CH2CO), 2.79 (dd, J¼16.1, 7.9 Hz,
1H, CH2CO), 2.15e2.02 (m, 1H, CHCH3), 1.49e1.38 (m, 1H, CH2CH3),
1.35e1.23 (m, 1H, CH2CH3), 0.96 (d, J¼6.4 Hz, 3H, CH3CH), 0.93 (t,
D20
D20
]
[a
]
þ2.3 (c 1.6, EtOH, ee¼94%) {lit. [
a
þ1.7 (c 1.6, EtOH,
ee¼62%)16}.
J¼7.5 Hz, 3H, CH3CH2); 13C NMR:
d 198.7 (CO), 150.1 (Car), 141.7
(Car), 129.0 (2 CHar), 123.7 (2 CHar), 46.0 (CH2CO), 31.1 (CHCH3),
29.5 (CH2CH3), 19.4 (CH3CH), 11.3 (CH3CH2). The ee was deter-
Acknowledgements
mined by chiral GC: Capillary column Chiraldex GTA (0.12
mm,
30 m, 0.25 mm), pression 100 kPa, total He flow 50 mL/min; 90 ꢀC
(40 min)e0.2 ꢀC/mine150 ꢀCe10 ꢀC/mine160 ꢀC (3 min); tR (1)¼
ꢁ
This work was supported by the CNRS, the Ministere de la
Recherche et de la Technologie (grant to M.M and J.W.-D.) and by
324.5 min, tR (2)¼326.1 min. [
a
]
þ19.6 (c 1.5, Et2O, ee¼95%).
D20
ꢀ
ꢀ
the Universite europeenne de Bretagne (grant to J.W.-D.).
HRMS: [MþNa]þ (C12H15NO3Na) calcd 244.09496; found 244.0948
(1 ppm).
4.3.5. Compound 7c: 1-(4-chlorophenyl)-3-methylpentan-1-one. -
Supplementary data
White solid. 1H NMR (CDCl3):
d 7.91e7.87 (m, 2H, Har), 7.45e7.41 (m,
2H, Har), 2.91 (dd, J¼15.6, 5.7 Hz, 1H, CH2CO), 2.71 (dd, J¼15.6,
Supplementary data associated with this article can be found, in
8.0 Hz, 1H, CH2CO), 2.13e2.01 (m, 1H, CHCH3), 1.47e1.37 (m, 1H,