2
736
G. Cahiez et al. / Tetrahedron 56 (2000) 2733±2737
Table 3. Cu-catalyzed alkylation of BrCH
CH Z in the presence of NMP
2 2
products or to authentic samples (2-methyldecane and
2
4
-methyl-2-undecene), except those described below
a
1
elemental analyses: C: ^0.2%, H: ^0.3%). H and
13
(
NMR spectra (CDCl , d ppm, H ^0.01, C ^0.05, internal
C
1
13
3
standard TMS, J values in Hz ^0.3) were recorded on a
JEOL JNM-EX 270 (270 MHz for 1H) spectrometer. IR
a
Entry
R
Z
Yield (%)
2
1
spectra (neat, n cm ) were recorded on a Nicolet Impact
00 (OMNIC software FT spectrometer).
b
56
1
2
3
Oct
Oct
Bu
Cl
BuCOO
EtOCOO
4
88
92
a
Typical procedure: preparation of 2,2-dimethyldecane
(Scheme 1)
Yield of isolated product.
0
b
% yield in the absence of NMP.
To a solution of octyl bromide (9.6 g, 50 mmol), CuCl2
(1.5 mmol, 201 mg) and anhydrous LiCl (1.5 mmol,
63 mg) in a mixture of THF (75 mL) and NMP (N-methyl-
pyrrolidinone, 19 mL) were added dropwise, at 208C,
1.05 equiv. of tert-butylmagnesium chloride (1.2 M solu-
tion in THF, 55 mmol, 45.8 mL). Stirring was continued
for 1 h and the reaction mixture was cooled at 2108C
then quenched with an aqueous hydrochloric acid solution
reacted with octylmagnesium bromide to afford 56% of
-chlorododecane (Table 3, entry 1). This yield is very satis-
factory regarding the nature of the substrate. Under similar
reaction conditions, two esters of 2-bromoethanol were
selectively converted to the expected cross-coupling
products in high yields (entries 2 and 3).
1
(
1N, 100 mL). After decantation, the aqueous layer was
Conclusion
extracted twice with pentane (2£70 mL) then the combined
organic layers were washed with an aqueous hydrochloric
acid solution (1N, 30 mL) and with water (2£70 mL). After
drying over magnesium sulfate, the solvents were elimi-
nated under vacuum and the product was isolated by distil-
In conclusion, we have shown that the presence of NMP
dramatically improves the yield and the chemoselectivity
of the Cu-catalyzed alkylation of organomagnesium
reagents by alkyl bromides or iodides. The procedure
described above is an interesting alternative to the classical
cuprate alkylation reaction, especially for large scale
preparative organic chemistry since the yields are similar
or even better (Scheme 6) and it is more environmentally
friendly, cheaper and easier to carry out (catalytic amount of
copper, one equivalent of organometallic, no expensive or
toxic additive, mild reaction conditions).
1
lation (bp: 808C/7 Torr) in 85% yield (7.24 g). H NMR:
d0.88 (t and s, 12H, CH , J6.3 Hz), 1.26 (s br, 14H,
3
1
3
CH ); C NMR: d14.15 (CH ), 22.70 (CH ), 24.60
2
3
2
(CH ), 29.70 (CH ), 30.00 (4C, CH and CH ), 30.20 (C),
2
2
2
3
30.60 (CH ), 31.90 (CH ), 44.00 (CH ).
2
2
2
2-Methyl-3-dodecanone: Bp: 1308C/7 Torr; IR n1740
1
(CvO); H NMR: d0.87 (t, 3H, CH , J6.9 Hz), 1.06
3
(
d, 6H, CH , J7.9 Hz),1.26 (m, 12H, CH ), 1.62 (m, 2H,
2 2
3
2
CH ), 2.43 (t, 2H, COCH , J7.3 Hz), 2.60 (hept, 1H, CH,
1
3
Experimental
J6.9 Hz); C NMR: d13.90 (CH ), 18.30 (2C, CH ),
2.50 (CH ), 23.60 (CH ), 29.15 (CH ), 29.20 (CH ),
2 2 2 2
3
3
2
All reactions were performed on a 50 mmol scale under a
nitrogen atmosphere. THF was distilled from sodium
benzophenone ketyl under a nitrogen atmosphere and
NMP was distilled before use. All products were isolated
by distillation and their purity ($98%) has been controlled
by GC analysis; Fisons GC 8000, capillary column SGE
29,30 (2C, CH ), 31.75 (CH ), 40.20 (CH ), 40.60 (CH),
2 2 2
214.70 (CvO).
1
Octyl pentanoate: Bp 878C/10 Torr; IR: n1735, 1170; H
NMR: d0.88 (t, 3H, CH , J6.8 Hz), 0.92 (t, 3H, CH ,
3
3
J7.3 Hz), 1.33 (m, 8H, CH ), 1.63 (m, 4H, CH ), 2.30 (t,
2
2
25QC5/BP1 (25 m£0.53 mm, 0.5 mm ®lm thickness). All
2H, CH CvO, J7.6 Hz), 4.06 (t, 2H, O±CH , J6.6 Hz);
2
2
1
3
the alkylation products were compared to commercial
C NMR: d13.70 (CH ), 13.95 (CH ), 22.40 (CH ), 22.65
3 3 2
Scheme 6.