A versatile synthesis of 2-haloalk-2(Z)-en-1-ols and 1-chloro-1(Z)-alkenes from trichloromethylcarbinols

Article abstract of DOI:10.1016/S0040-4039(02)00210-1

CrCl₂ converts trichloromethylcarbinols under mild conditions to (E)-α-haloalkylidene chromium carbenoids which add to aldehydes or are quenched with water affording 2-haloalk-2(Z)-en-1-ols and 1-chloro-1(Z)-alkenes, respectively, in high yield.

Full text of DOI:10.1016/S0040-4039(02)00210-1

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 2183–2185
A versatile synthesis of 2-haloalk-2(Z)-en-1-ols and
1-chloro-1(Z)-alkenes from trichloromethylcarbinols
Rachid Baati,a D. K. Barma,b J. R. Falckb,* and Charles Mioskowskia,*
aUniversite´ Louis Pasteur de Strasbourg, Faculte´ de Pharmacie, Laboratoire de Synthe`se Bio-Organique (UMR 7514),
67401 Illkirch, France
bDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390-9038 USA
Received 7 January 2002; revised 24 January 2002; accepted 25 January 2002
Abstract—CrCl2 converts trichloromethylcarbinols under mild conditions to (E)-a-haloalkylidene chromium carbenoids which
add to aldehydes or are quenched with water affording 2-haloalk-2(Z)-en-1-ols and 1-chloro-1(Z)-alkenes, respectively, in high
yield. © 2002 Elsevier Science Ltd. All rights reserved.
afforded (Z)-chloroalkenol 66 in good yield (Table 1,
The continuing demand for ever more efficacious and
entry 1). Repetition of the preceding addition employ-
ing hydrocinnamaldehyde as the electrophile led to 7
(entry 2). In sharp contrast to earlier procedures,7 no
1,1-dichlorostyrene and/or related side-products were
observed during these reactions. Styrene 85 and
aliphatic aldehyde 118 behaved similarly with benzalde-
hyde and hydrocinnamaldehyde furnishing adducts 9
(entry 3), 10 (entry 4), 12 (entry 5), and 13 (entry 6),
respectively. It is worth noting that while the transfor-
mations summarized in entries 2 and 5 both utilize the
same initial precursors, i.e. benzaldehyde and hydrocin-
namaldehyde, the resultant adducts are isomeric as a
consequence of their differing sequence of reactions.
stereospecific synthetic methodology has stimulated
broad interest in organochromium chemistry and led to
the introduction of several chromium-containing
reagents,1 including several contributions from our lab-
oratories.2 Of special note is the discovery of (E)-
halovinylidene chromium carbenoids 3.2a In the
accompanying communication,3 we report the facile, in
situ generation of 3 from a wide variety of aldehydes
using CCl4 and CrCl2 and its tandem addition to a
second aldehyde giving rise to ‘symmetrical’ 2-haloalk-
2(Z)-en-1-ols 4, i.e. adducts from 2 equiv. of the same
aldehyde (R=R%). Based upon prior mechanistic stud-
ies,2a the chromate ester of trichloromethylcarbinol 1
was postulated3 to be the initial intermediate leading to
bis-chromylmethylene 2 upon further reduction by 4
equiv. of CrCl2. Herein, we report that 1, independently
prepared by addition of trichloromethyl anion to alde-
hydes,4 is transformed stereoselectively into 3 which can
be subsequently added to a different aldehyde furnish-
ing ‘unsymmetrical’ 2-haloalk-2(Z)-en-1-ols 4 (R"R%)
or quenched with water to provide the corresponding
1-chloro-1(Z)-alkene 3 (CrIII=H) (Scheme 1).
When the chromium carbenoids 3 generated from 5, 8,
or 11 were quenched with water (Table 2), the corre-
sponding 1-chloro-1(Z)-alkenes 14 (entry 1), 15 (entry
2), and 16 (entry 3), respectively, were formed in syn-
thetically useful yields. In all cases, the (Z)-stereoisomer
was formed exclusively, indicating that only (E)-
halovinylidene chromium carbenoids2a are generated
from trichloromethylcarbinols 1.
Treatment of the known 2-phenyl-1,1,1-trichloro-
ethanol5 5 with CrCl2 in the presence of benzaldehyde
(Barbier conditions) at room temperature for 8 h
OH
OCrIII
CrIII
CrIII
HCCl3
base
4 CrCl2
RCHO
R
R
CCl3
1
2
Cl
OH
-O(CrIII)2
CrIII
R'CHO
R
R
R'
Keywords: chromium; alkenylation; alcohols; vinylation; stereocon-
trol.
Cl
Cl
3
4
* Corresponding authors. E-mail: j.falck@utsouthwestern.edu;
mioskow@aspirine.u-strasbg.fr
Scheme 1.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00210-1

2184
R. Baati et al. / Tetrahedron Letters 43 (2002) 2183–2185
Table 1. Synthesis of 2-chloroalk-2(Z)-en-1-ols
Substrate
OH
Aldehyde
PhCHO
Product
OH
Ph
Entry
1
Yield (%)
6
7
78
Ph
Cl
Ph
CCl3
OH
CHO
82
2
3
5
Ph
Ph
Ph
Ph
Cl
OH
Ph
9
PhCHO
91
80
OH
CCl3
Cl
OH
Ph
CHO
10
8
4
5
Ph
Ph
Ph
Cl
OH
Ph
12
13
61
73
PhCHO
Ph
OH
CCl3
Cl
Ph
OH
CHO
11
6
Ph
Ph
Ph
Cl
General procedure
reaction mixture was quenched with water and the
resultant 1-chloro-1(Z)-alkene was isolated as described
above (Table 2).
2-Haloalk-2(Z)-en-1-ols
(4):
A
solution
of
trichloromethylcarbinol 1 (1 mmol) and aldehyde (1
mmol) in THF (4 mL) was added to a stirring, room
temperature suspension of CrCl2 (4 mmol; Strem
Chem., 99.9%) in THF (6 mL) under an argon atmo-
sphere. After 8 h, the resultant reddish reaction mixture
was quenched with water, extracted thrice with ether,
and the combined ethereal extracts were evaporated in
vacuo. The residue was purified by SiO2 chromatogra-
phy affording 2-haloalk-2(Z)-en-1-ol 4 in the indicated
yield (Table 1).
Acknowledgements
Financial support provided by the Robert A. Welch
Foundation, NIH (GM31278, DK38226), CNRS, Insti-
tuts de Recherches Pierre Fabre (to R.B.), and an
unrestricted grant from Taisho Pharmaceutical Co.,
Ltd. Dr. E. R. Fogel is warmly thanked for insightful
discussions.
1-Chloro-1(Z)-alkenes: A solution of trichloromethyl-
carbinol 1 (1 mmol) in THF (4 mL) was added to a
stirring, room temperature suspension of CrCl2 (4
mmol; Strem Chem., 99.9%) in THF (6 mL) under an
argon atmosphere. After 8 h, the resultant reddish
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R. Baati et al. / Tetrahedron Letters 43 (2002) 2183–2185
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