Preparation of 1-bromo-1-chloro-,1,1-dibromo- or 1,1-dichloroalk-1-enes from ketones

Article abstract of DOI:10.1055/s-2000-6225

An efficient three steps process for converting aliphatic ketones to the homologous gem-bromochloro, or gem-dibromo alkenes is presented.

Full text of DOI:10.1055/s-2000-6225

PAPER
109
Preparation of 1-Bromo-1-chloro-, 1,1-Dibromo- or 1,1-Dichloroalk-1-enes
from Ketones
Hadi Rezaei, Jean F. Normant*
Laboratoire de Chimie des Organo-Eléments, associé au CNRS, Université Pierre et Marie Curie, 4, Place Jussieu, Tour 44-45, 2e étage,
Boite 183, F-75252 Paris cédex 05, France
Fax +33(1)44277567; E-mail: normant@ccr.jussieu.fr
Received 20 July 1999; revised 8 September 1999
previous studies that b-silyloxy carbenoids undergo a-
Abstract. An efficient three steps process for converting aliphatic
rather than b-elimination.8
ketones to the homologous gem-bromochloro, or gem-dibromo alk-
enes is presented.
We then turned to a process where gem-trihalo substrates
are first formed (Scheme 2, Table). The addition of ke-
tones to LiCBr2X is straightforward at -90°C in the pres-
ence of BF3∑OEt2, whatever the nature (cyclic or not) of
the ketone and of the carbenoid (X = Br or Cl). Transfor-
mations of the hydroxy group of 1 into various leaving
groups uniformly failed as they did for A except for the es-
ter formation, when we added an enol ether under acidic
catalysis to these hindered alcohols. Finally, the triha-
loesters 2 were converted to the desired alkenes by treat-
ment with ethyl magnesium bromide9 in THF at -90°C.
Key words: ketones, trihalomethyl carbenoids, eliminations, gem-
dihaloalkenes, halides, halogens
The MacKelvie,1 Corey, Fuchs2 conversion of aldehydes
to homologous alkynes is a commonly used straightfor-
ward process, which relies upon an initial preparation of
the gem-dibromoalkenes. The corresponding one-carbon
homologation starting from a ketone, however, is much
more troublesome and has been scarcely reported, gener-
ally with low yields, except for cycloalkanones. Olah and
Wu3 converted polycycloalkanones to the gem-dibro-
momethylene derivatives via PPh3/CBr4. Savignac and
Coutrot4 used the anion of diethyl dibromomethylphos-
phonate to convert the cycloalkanones to gem-dibro-
moalkenes in yields of 45-70%, but no example of a
linear aliphatic ketone was reported. More recently, Oku
et al.5 disclosed one example of a dibromo and a bromo-
chloroalkene bearing two geminal alkyl moieties. In a first
approach, we treated linear or cyclic ketones by
dihalomethyllithiums6 according to Scheme 1.
Scheme 2
In conclusion, the three steps sequence presented here al-
lows an efficient conversion of ketones to the homologous
geminal bromochloro or dibromo alkenes.
We also prepared 1,1-dichloroalkenes 6 and 710 from ke-
tones, with good yields (Scheme 3) only if a procedure de-
scribed for lactones11 (PPh3/CCl4, THF, reflux) is used,
instead of the classical analogous reaction in CCl4 alone.
Scheme 1
However, transformation of tertiary alcohols (A) into the
corresponding chlorides (or bromides) via SOCl2 or PPh3/
Br2 under various conditions uniformly failed, as did their
attempted transformations to phosphates via (RO)2POCl,
mesylates, or esters (via MeCOCl, MeCOBr, PhCOCl)
except for the trichloroacetylation. The Burgess reagent7
did operate, but the subsequent elimination was not
regioselective and led to allylic dihalides instead. The
silyl ethers could be obtained (from TMSOTf/lutidine)
but were of no avail for the next step, since we knew from
Scheme 3
Experiments involving organometallics were carried out under a
positive pressure of dry N2. Liquid N2 was used as a cryoscopic flu-
id. A four-necked round bottom flask was equipped with an internal
Synthesis 2000, No. 1, 109–112 ISSN 0039-7881 © Thieme Stuttgart · New York

110
H. Rezaei, J. F. Normant
PAPER
Table Preparation of 1-Bromo-1-Chloro- or 1,1-Dibromoalk-1-enes from Ketones
Entry
Ketone
LiCBr2X
(X), Equiv
Product 1
Product 2
Product 3
Yield (%)a
1.2
a
89
95
(Cl)
1.2
b
(Br)
1.2
c
d
e
84
81
60
(Br)
1.2
(Cl)
2
(Br)
a Total yield of the product via 3 steps starting from the ketone.
thermometer, a septum cap, a N2 inlet, and a mechanical stirrer was
used. Et2O and THF were distilled from sodium-benzophenone
ketyl. IR spectra were recorded on a Perkin-Elmer 1420 spectropho-
tometer. NMR spectra were recorded on either a Bruker ARX 400
or a Bruker AC 200 in CDCl3 as solvent. Chemical shifts are report-
ed in ppm relative to TMS.
1H NMR (200 MHz, CDCl3): d = 1.45-1.85 (m, 10 H), 2.24-2.30
(m, 4 H), 2.61 (s, 1 H).
13C NMR (50 MHz, CDCl3) d = 22.47, 24.19, 27.68, 32.04, 68.26,
83.36.
IR (neat): n = 3550, 3350, 2910, 2880, 1450, 1140, 1050, 700 cm-1.
4-(Tribromomethyl)heptan-4-ol (1c)
Trihalomethyl Alkanols 1; General Procedure
Yield: 3.68 g (~100%); yellow oil.
A 100 mL four-necked round bottom flask equipped with a mechan-
ical stirrer was charged with a solution of diisopropylamine (12
mmol, 1.7 mL) in anhyd THF (20 mL). To this solution was added
BuLi (1.6 M in hexanes, 12 mmol, 7.5 mL) at -30°C. The mixture
was warmed to 0°C for 10 min and then cooled down to -100°C and
CHBr2X (X = Br or Cl) (12mmol) was added dropwise. After 10
min at -100°C, a solution of ketone (10 mmol) in anhyd Et2O(5 mL)
was slowly added, followed by the addition of BF3∑OEt2 (10 mmol,
1.2 mL). After 4 h at -90°C aq 1M HCl (20 mL) was added at
-100°C and the mixture was warmed to r.t. The aqueous layer was
extracted with Et2O (3 î 20 mL) the combined organic layers were
washed with aq 0.5 M HCl (15 mL), then with satd NaHCO3 solu-
tion (15 mL). The organic layer was dried (MgSO4) and concentrat-
ed in vacuo to provide the crude product which can be used directly
in the next step.
1H NMR (200 MHz, CDCl3): d = 0.96 (t, 6 H, J = 7.3 Hz), 1.56
(sext, 4 H, J = 9.21 Hz), 1.96-2.08 (m, 4 H), 2.40 (s, 1 H).
13C NMR (100 MHz, CDCl3): d = 14.89, 18.88, 38.27, 66.45, 83.07.
IR (neat): n = 3575, 3495, 2980, 2885, 1515, 1140, 740, 710 cm-1.
Anal. Calcd for C8H15Br3O (366.9): C, 26.19; H, 4.12. Found: C,
26.06; H, 4.03.
6-(Dibromochloromethyl)undecan-6-ol (1d)
Yield: 3.75 g (~100%); yellow oil.
1H NMR (400 MHz, CDCl3): d = 0.92 (t, 6 H, J = 7.2 Hz), 1.29-
1.55 (m, 12 H), 1.96-2.05 (m, 4 H), 2.34 (s, 1 H).
13C NMR (50 MHz, CDCl3) d = 14.10, 22.57, 24.81, 32.48, 35.68,
82.99, 83.45.
1,1,1-Tribromo-2-phenylbutan-2-ol (1e)
Yield: 3.85 g (~100%); yellow crystals.
1-(Dibromochloromethyl)cyclohexan-1-ol (1a)
Yield: 3.1 g (~100%); colourless oil.
1H NMR (400 MHz, CDCl3): d = 0.86 (t, 3 H, J = 7.5 Hz), 2.37
(sext, 1 H, J = 7.2 Hz), 2.88 (sext, 1 H, J = 7.2 Hz), 2.94 (s, 1 H),
7.38 (m, 3 H), 7.81 (m, 2 H).
13C NMR (100 MHz, CDCl3): d = 9.37, 29.36, 64.63, 85.75, 127.30,
128.35, 129.72, 135.47.
1H NMR (200 MHz, CDCl3): d = 1.01-2.07 (m, 10 H), 2.23 (s, 1
H).
13C NMR (50 MHz, CDCl3): d = 22.47, 24.19, 19.27, 27.68, 32.04,
68.26, 83.36.
IR (neat): n = 3560, 3400, 2940, 2875, 1450, 1160, 990, 710 cm-1.
Anal. Calcd for C7H11Br2ClO (306.4): C, 27.44; H, 3.62. Found: C,
27.31; H, 3.65.
Acetylation of Tertiary Alcohols 1 to Acetates 2; General Proce-
dure
A 100 mL round bottom flask equipped with a magnetic stirrer was
charged with a solution of alcohol 1 (5 mmol) in isopropenyl acetate
(45 mL) under N2. To this solution was added TsOH (5.5 g, 29
1-(Tribromomethyl)cyclooctan-1-ol (1b)
Yield: 3.78 g (~100%); yellow oil.
Synthesis 2000, No. 1, 109–112 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Preparation of 1-Bromo-1-chloro-, 1,1-Dibromo- or 1,1-Dichloroalk-1-enes from Ketones
111
mmol) at 30°C. After 5 min an exothermic reaction was observed
and the solution became dark. The mixture was stirred at 30°C until
TLC showed the absence of starting material (4 to 24 h). A large
part of isopropenyl acetate was evaporated under vacuum, then
Et2O (30 mL) was added and under stirring at 0°C aq satd Na2CO3
solution (~40 mL) was added slowly until no more gas evolution
was observed . After 30 min at r.t., the aqueous layer was extracted
with Et2O (3 î 30 mL). The organic layers were washed with aq
satd NaHCO3 solution (15 mL) and dried (MgSO4). The residue was
purified by filtration on silica gel using petroleum ether/Et2O/
CH2Cl2 (90:5:5).
(2 î 20 mL). The combined organic layers were washed with aq
satd NaHCO3 solution (15 mL). The organic layer was dried
(MgSO4) and concentrated in vacuo to provide the crude product
which was purified by flash chromatography on silica gel using pe-
troleum ether to give the alkenes 3.
(Bromochloromethylene)cyclohexane (3a)
Yield: 390 mg (93%); colourless oil.
1H NMR (400 MHz, CDCl3): d = 1.79 (m, 6 H), 2.58-2.63 (m, 4 H).
13C NMR (50 MHz, CDCl3): d = 25.95, 26.82, 26.92, 32.04, 34.61,
97.54, 141.67.
IR (neat): n = 2970, 2875, 1450, 1230, 790 cm-1.
1-(Dibromochloromethyl)-1-acetoxycyclohexane (2a)
Yield: 1.65 g (96%); colourless crystals; mp 56-57°C.
Anal. Calcd for C7H10BrCl (209.5): C, 40.13; H, 4.81. Found: C,
40.17; H, 4.77.
1H NMR (400 MHz, CDCl3): d = 1.19-1.27 (m, 2 H), 1.44-1.99
(m, 8 H), 2.14 (s, 3 H), 1.13-2.18 (m, 2 H), 2.84 (d, 1 H, J = 1.2
Hz), 2.87 (s, 1 H).
(Dibromomethylene)cyclooctane (3b)
Yield: 536 mg (95%); colourless oil.
13C NMR (100 MHz, CDCl3): d = 22.81, 22.97, 24.48, 31.54, 75.11,
1H NMR (400 MHz, CDCl3): d = 1.45-1.54 (m, 6 H), 1.73-1.78
(m, 4 H), 2.39-2.42 (m, 4 H).
13C NMR (50 MHz, CDCl3): d = 25.29, 25.70, 27.50, 35.56, 84.47,
147.10.
91.92, 169.17.
IR (neat): n = 2950, 2880, 1750, 1450, 1205, 1020 cm-1.
1-(Tribromomethyl)-1-acetoxycyclooctane (2b)
Yield: 2.1 g (~100%); yellow oil.
1,1-Dibromo-2-propylpent-1-ene (3c)
1H NMR (400 MHz, CDCl3): d = 1.55-1.95 (m, 10 H), 2.12 (s, 3
H), 2.28-2.34 (m, 2 H), 2.96-3.03 (m, 2 H).
13C NMR (100 MHz, CDCl3): d = 22.58, 23.02, 23.62, 27.68, 31.13,
57.77, 93.30, 168.78.
Yield: 502 mg (93%); colourless oil.
1H NMR (400 MHz, CDCl3) d = 0.94 (t, 6 H, J = 7.3 Hz), 1.48 (sext,
4 H, J = 7.6 Hz), 2.22 (t, 4 H, J = 7.6 Hz).
13C NMR (100 MHz, CDCl3): d = 14.06, 20.67, 38.20, 85.66,
143.31.
IR (neat): n = 2940, 2875, 1750, 1470, 1440, 1360, 1210, 1025 cm-1.
IR (neat): n = 2980, 2875, 1470, 810 cm-1.
4-(Tribromomethyl)-4-acetoxyheptane (2c)
Yield: 1.94 g (95%); yellow oil.
Anal. Calcd for C8H14Br2 (270.0) : C, 35.59; H, 5.23. Found: C,
35.73; H, 5.31.
1H NMR (400 MHz, CDCl3): d = 0.96 (t, 6 H, J = 7.2 Hz), 1.52-
1.73 (m, 4 H), 2.12 (s, 3 H), 2.24-2.32 (m, 2 H), 2.43-2.51 (m, 2
1-Bromo-1-chloro-2-pentylhept-1-ene (3d)
Yield: 507 mg (90%); colourless oil.
H).
13C NMR (100 MHz, CDCl3): d = 14.81, 19.23, 22.59, 38.46, 55.71,
92.11, 168.71.
1H NMR (400 MHz, CDCl3): d = 0.88 (t, 6 H, J = 7.0 Hz), 1.28-
1.45 (m, 12 H), 2.18-2.26 (m, 4 H).
13C NMR (50 MHz, CDCl3): d = 14.20, 22.66, 27.08, 31.82, 33.78,
36.13, 100.99, 143.52.
6-(Dibromochloromethyl)-6-acetoxyundecane (2d)
Yield: 1.89 g (90%); yellow oil.
1H NMR (400 MHz, CDCl3): d = 0.89 (t, 6 H, J = 6.8 Hz), 1.25-
1,1-Dibromo-2-phenylbut-1-ene (3e)5
Yield: 430 mg (75%); colourless oil.
1H NMR (200 MHz, CDCl3): d = 0.98 (t, 3 H, J = 7.5 Hz), 2.65 (q,
2 H, J = 7.5 Hz), 7.18 (m, 2 H), 7.32-7.35 (m, 3 H).
13C NMR (50 MHz, CDCl3): d = 11.47, 32.85, 87.65, 127.64,
127.95, 128.36, 140.85, 148.92.
1.55 (m, 12 H), 2.12 (s, 3 H), 2.29-2.34 (m, 2 H), 2.41-2.51 (m, 2
H).
13C NMR (100 MHz, CDCl3): d = 14.14, 22.51, 22.59, 25.24, 36.04,
74.46, 92.76, 168.82.
IR (neat): n = 2980, 2885, 1750, 1465, 1230, 1010, 735 cm-1.
1,1,1-Tribromo-2-phenyl-2-acetoxybutane (2e)
Yield: 1.71 g (80%); colourless oil.
1,1-Dichloroalkenes 6 and 7; General Procedure
A 100 mL two-necked round bottom flask equipped with magnetic
stirrer and a condenser, under N2, was charged with a solution of ke-
tone 4 or 5 (10 mmol) in THF (30 mL). Ph3P (40 mmol, 10.5 g) was
added and the mixture was brought to reflux. CCl4 (25 mL, 240
mmol) was added dropwise in 2 h (the solution turned dark). When
TLC (2-3 h) showed the absence of starting material, the mixture
was cooled to 0°C and hydrolysed with H2O (30 mL). The aqueous
layer was extracted with Et2O (3 î 30 mL) the combined organic
layers were washed with aq satd NaHCO3 solution (20 mL), and
then with brine (20 mL). The organic layer was dried (MgSO4) and
concentrated in vacuo to provide a solid mixture of product and
Ph3PO. The solid was washed several times with pentane and fil-
tered. After the evaporation of pentane the crude product was puri-
fied by flash chromatography on silica gel using petroleum ether to
give the dichloroethylenes 6 or 7.
1H NMR (400 MHz, CDCl3): d = 1.18 (t, 3 H, J = 7.2 Hz), 2.31 (s,
3H), 2.92 (sext, 1 H, J = 7.6 Hz), 3.24 (sext, 1 H, J = 7.6 Hz), 7.34
(m, 3 H), 7.61 (m, 2 H).
13C NMR (100 MHz, CDCl3): d = 11.17, 22.31, 28.47, 55.36, 91.75,
126.99, 128.67, 129.79, 136.52, 168.03.
IR (neat): n = 3180, 2970, 1760, 1495, 1445, 1370, 1220, 1020, 710
cm-1.
1,1-Dihalo-2,2-dialkylethylenes 3; General Procedure
A 100 mL four-necked round bottom flask equipped with mechan-
ical stirrer was charged with a solution of ethylmagnesium bromide
[1.2 M in THF] (6.7 mL, 8 mmol) in THF (10 mL). To this solution
at -95°C was added dropwise a THF solution of the acetate 2 (2
mmol). The mixture was then stirred at -90°C for 30 min, cooled to
-100°C and hydrolysed with aq 1 M HCl (15 mL). The mixture was
then warmed to r.t. and the aqueous layer was extracted with Et2O
1,1-Dichloro-2-propylpent-1-ene (6)
Yield: 2.1g (88%); colourless oil.
Synthesis 2000, No. 1, 109–112 ISSN 0039-7881 © Thieme Stuttgart · New York

112
H. Rezaei, J. F. Normant
PAPER
1H NMR (400 MHz, CDCl3): d = 0.92 (t, 6 H, J = 7.0 Hz), 1.30-
1.49 (m, 12 H), 2.23 (t, 4 H, J = 8.0 Hz).
13C NMR (100 MHz, CDCl3) d = 14.06, 22.57, 26.98, 31.74, 33.55,
114.69, 139.79.
(5) Harada, T.; Katsuhira, T.; Hara, D.; Kotani, Y.; Maejina, K.;
Kaji, R.; Oku, A. J. Org. Chem. 1993, 58, 4897.
(6) Villieras, J.; Bacquet, C.; Masure, D.; Normant, J.F. J.
Organomet.Chem. 1973, 50, C7; and references cited therein.
(7) Burgess, E.M. J. Org. Chem. 1973, 38, 26.
(8) Villiéras, J.; Baquet, C.; Normant, J.F. Bull. Soc. Chim. Fr.
1974, 1731.
IR (neat): n = 2985, 2875, 1475 cm -1
.
9-Dichloromethylene-9-fluorene (7)
(9) Shimizu, M.; Yamada, N.; Takebe, Y.; Hata, T.; Kuroboshi,
M.; Hiyama, T. Bull. Chem. Soc. Jpn. 1998, 71, 2903.
(10) The homologation of ketones to the gem-dichloroalkenes,12 on
the contrary, has been described in a number of cases, see for
example:
Yield: 2.21g (89%); yellow solid; mp 131-133 °C.
1H NMR (400 MHz, CDCl3): d = 7.33-7.37 (m, 2 H), 7.40-7.44
(m, 2 H), 7.71 (d, 2 H, J = 7.2 Hz), 8.34 (d, 2 H, J = 7.7 Hz).
13C NMR (100 MHz, CDCl3): d = 112.45, 120.03, 126.19, 127.94,
239.54, 134.62, 136.92, 140.60.
IR (KBr): n = 3080, 1610, 1575, 910, 720 cm-1.
Appel, R. Angew. Chem. 1975, 87, 863; Angew. Chem. Int.
Ed. Eng. 1975, 14, 801.
Du Jassonneix, B. Bull.Soc.Chim.Fr. 1975, 758.
Colonge, J.; Lartigau, G. Bull. Soc. Chim. Fr. 1965, 738.
(11) Lakhrissi, M.; Chapleur, Y. J. Org. Chem. 1994, 59, 5752.
(12) gem-Diiodoalkenes derived from aliphalic ketones have been
prepared from diethyl diiodomethylphosphonate:
Bonnet, B.; Le Gallic, Y.; Plé, G.; Duhamel, L. Synthesis
1993, 1071.
Anal. Calcd for C14H8Cl2 (247.1): C, 68.04; H, 3.26. Found: C,
67.92; H, 3.16.
References
(1) Ramirez, F.; Desai, N.B.; Mac Kelvie, N. J. Am. Chem. Soc.
1962, 84, 1745.
(2) Corey, E.J.; Fuchs, P.L. Tetrahedron Lett. 1972, 3769.
(3) Olah, G.A.; Wu, A. Synthesis 1990, 885.
(4) Savignac. Ph.; Coutrot, Ph. Synthesis 1976, 197.
Article Identifier:
1437-210X,E;1999,0,01,0109,0112,ftx,en;H05899SS.pdf
Synthesis 2000, No. 1, 109–112 ISSN 0039-7881 © Thieme Stuttgart · New York