Reactions of coordinated geminal dichromium reagents with aldehydes: Stereoselective formation of (Z)-2-chloroalk-2-en-1-ols

Article abstract of DOI:10.1039/b102387j

Treatment of a carbonate ester of 2,2,2-trichloroethanol derivative with CrCl₂-DMF in THF gives a β-carbonate-coordinated geminal dichromium species, which adds to an aldehyde and eliminates an acyloxychromium group to afford a (Z)-2-chloroalk-

Full text of DOI:10.1039/b102387j

Reactions of coordinated geminal dichromium reagents with
aldehydes: stereoselective formation of (Z)-2-chloroalk-2-en-1-ols†‡
Kazuhiko Takai,* Ryo Kokumai and Takahumi Nobunaka
Department of Applied Chemistry, Faculty of Engineering, Okayama University, Tsushima, Okayama
700-8530, Japan. E-mail: ktakai@cc.okayama-u.ac.jp
Received (in Cambridge, UK) 13th March 2001, Accepted 8th May 2001
First published as an Advance Article on the web 31st May 2001
Table 1 Reactions of 2,2,2-trichloroalkanol derivatives and nonanal with
Treatment of a carbonate ester of 2,2,2-trichloroethanol
derivative with CrCl2–DMF in THF gives a b-carbonate-
coordinated geminal dichromium species, which adds to an
aldehyde and eliminates an acyloxychromium group to
afford a (Z)-2-chloroalk-2-en-1-ol stereoselectively.
a
chromium(II
)
Intramolecular coordination of a hetero atom to a metal center
often fixes the molecular conformation,1 and thus carbon–
carbon bond formation proceeds in a stereoselective manner.
We disclose here that the effect is observed in geminal
dichromium species, and that a stereoselective coupling be-
tween a geminal trichloroalkane having an adjacent acyloxy
group and an aldehyde leading to a (Z)-2-chloroalk-2-en-1-ol
proceeds with chromium(II) chloride. Chromium(II) reduces
geminal dihaloalkanes, such as 1,1-diiodoalkanes,2a iodo-
form,2b Me3SiCHBr2,2c and Bu3SnCHBr2,2d to give geminal
dichromium species, which add to aldehydes to afford Wittig-
type olefins with high E-selectivity. However, such Wittig-type
olefinations do not proceed in the trichloroalkane 1e, and a new
double bond is formed between the carbons bearing halogen and
the acyloxy group [eqn. (1)].
Yield (%)b
Recov. (%)
Run
R
2
5
6
7
Aldehyde 1
1
2
3
4
5
6
7
8
Ac (a)
62
30c
29
2
< 5
35
0
< 5
16
0
15
33
7
0
27d 52
56
15
94
91
8
32
13
0
COPh (b)
61
23
0
7
2
0
0
6
CO(C5H4N) (c)e < 5
89
96
19
< 5
Ms (d)
CO2Me (e)
Me3Si (f)
0
77
60
0
8
0
0
13
44
< 5
< 5
a R1 = Ph(CH2)2, R2 = n-C8H17; Reaction was conducted on a 1.0 mmol
scale. Two mmol of trichloride 1, 8 mmol of CrCl2, 8 mmol of DMF were
used per mmole of nonanal. b Isolated yields. c The reaction was
conducted in DMF solvent. d The reaction was conducted without addition
of DMF. e CO(C5H4N) = pyridine-2-carbonyl.
(1)
In 1986, Steckhan reported the reduction of 1-phenyl-
2,2,2-trichloroethanol with CrCl2 in aqueous DMF to obtain
(Z)-2-chlorostyrene in 44% yield, along with 2,2-dichlorostyr-
ene in 10% yield.3 Although the yield of 2-chlorostyrene was
moderate, the observed Z-selectivity was quite high. The
stereoselectivity was explained by 1) fixation of the conforma-
tion by intramolecular coordination of the b-hydroxy group to
chromium(III) of the monochromium species 3, and 2) selective
reduction of a chlorine atom at the less hindered side leading to
geminal dichromium species 4 (Scheme 1). Because the
reduction was performed in the presence of proton sources, i.e.,
aqueous conditions and the hydroxy group of the starting
trichloride, the procedure could not be applied for carbon–
carbon formation. Thus, we first examined the effects of
solvents using a hydroxy-protected 2,2,2-trichloroethanol 1a
[Table 1, R1 = Ph(CH2)2, R = Ac].
Treatment of 1a in the presence of nonanal with CrCl2 in
DMF at 0 °C for 24 h gave the desired coupling product 2 in
30% yield along with 6 and 7 in 35% and 16% yields,
respectively (Table 1 run 2).4 A Z-isomer was obtained
exclusively as expected.5 Although the yield could not be
improved in THF solvent (run 3), pre-treatment of 1 equiv. of
CrCl2 with DMF before addition of the trichloride 1a and
nonanal accelerated the reaction, and the yield was improved to
62% (run 1).2a Benzoate 1b gave almost the same yield with 2.
However, reactions with the pyridine-2-carbonyloxy compound
1c and mesylate 1d produced the 1,1-dichloroalkene 6 as a main
product, and most of the aldehyde was recovered. Among the
protecting groups examined, a carbonate gave the best result
(run 7).
There are three possible reaction pathways which have
different timings of the elimination steps of acyloxychromium
(Scheme 2). In Path A, acyloxychromium is smoothly elimi-
nated when one of the chlorine atoms is reduced, and
1,1-dichloroalkene 10 is produced as an intermediate. Then, the
chlorine atom at the less hindered trans position of 10 is
selectively reduced to give 11, which adds to an aldehyde. In
Path B, acyloxychromium is eliminated after the second
reduction to the geminal dichromium species 9.2,6 The elimina-
tion gives the alkenylchromium 11 directly, and addition to an
aldehyde proceeds. The third Path C also includes the acyloxy-
coordinated geminal dichromium species 9, and addition to an
aldehyde at a non-coordinated chromium of 9 occurs before
elimination of acyloxychromium.
Scheme 1
† Electronic supplementary information (ESI) available: experimental
procedure. See http://www.rsc.org/suppdata/cc/b1/b102387j/
‡ Dedicated to Professor Jean F. Normant on the occasion of his 65th
birthday.
The hydroxy-protecting groups with oxygen act as leaving
groups in the reaction sequence.7 Trichlorides 1c and 1d, which
1128
Chem. Commun., 2001, 1128–1129
This journal is © The Royal Society of Chemistry 2001
DOI: 10.1039/b102387j

Scheme 2 Possible reaction pathways for the coupling reaction.
have good leaving groups, afforded 6 as a major product, and
2-Chloroalk-2-en-1-ols having a Z-configuration were pro-
duced selectively in all cases. To reduce the amount of
chromium salt used in the reaction, we attempted a catalytic
reaction using manganese as a reductant of chromium(III).10 The
reaction proceeded at 25 °C, however, the yield decreased to
52% (run 3). When 2,2,2-tribromoethanol derivative was used
as the trihalide, the corresponding bromo and chloro com-
pounds were obtained (run 4).2b,11,12
only a small amount of the 1,1-dichloroalkene 6 was produced
when the adduct 2 was obtained in high yield. In addition,
treatment of a mixture of 1,1-dichloroalkene 12 and nonanal
with CrCl2–DMF in THF at 0 °C for 24 h produced the adduct
2 in only 4% yield, and most of 12 (75%) was recovered
unchanged [eqn. (2)].8 These results suggest that this addition
This work was supported by a Grant-in-Aid from the
Ministry of Education, Culture, Sports, Science and Technol-
ogy of Japan.
(2)
Notes and references
reaction does not proceed through the 1,1-dichloroalkene 10
(Path A) but through the geminal dichromium species 9.
During the reactions of 1a, 1b and 1e with nonanal, the
Wittig-type olefination2a leading to 1-phenyl-4-chlorotridec-
4-en-3-ol derivatives was not observed. This suggests that the
coupling reaction does not proceed via Path C either, leaving
Path B as the only possible reaction pathway.
1 (a) For geminal dimetallic species, see: I. Marek and J. F. Normant,
Chem., Rev., 1996, 96, 3241; J. F. K. Müler, Eur. J. Inorg. Chem., 2000,
789; (b) J. M. Concellón, P. L. Bernad and J. A. Pérez-Andrés, Angew.
Chem., Int. Ed., 1999, 38, 2384; (c) R. W. Hoffmann, M. Bewersdorf, K.
Ditrich, M. Krüger and R. Stürmer, Angew. Chem., Int. Ed. Engl., 1988,
27, 1176.
2 (a) T. Okazoe, K. Takai and K. Utimoto, J. Am. Chem. Soc., 1987, 109,
951; (b) K. Takai, K. Nitta and K. Utimoto, J. Am. Chem. Soc., 1986,
108, 7408; D. A. Evans and W. C. Black, J. Am. Chem. Soc., 1993, 115,
4497; (c) K. Takai, Y. Kataoka, T. Okazoe and K. Utimoto, Tetrahedron
Lett., 1987, 28, 1443; (d) D. M. Hodgson, Tetrahedron Lett., 1992, 33,
5603; D. M. Hodgson, A. M. Foley and P. J. Lovell, Tetrahedron Lett.,
1998, 39, 6419.
The results of the coupling reactions between carbonates of
2,2,2-trichloroethanols and aldehydes are shown in Table 2.9
Table 2 (Z)-Selective coupling of 2,2,2-trihaloalkyl carbonates and
a
aldehydes with chromium(II
)
3 R. Wolf and E. Steckhan, J. Chem. Soc., Perkin Trans. 1, 1986, 733.
4 The reaction in DMA gave almost the same yield in DMF. However, the
reduction of the trichloride 1a did not occur in ether, DME or
acetonitrile.
5 An authentic sample was prepared according to the following literature;
S.-i. Narita, A. Takahashi, H. Sato, T. Aoki, S.-i Yamada and M.
Shibasaki, Tetrahedron Lett., 1992, 33, 4041.
Run
R1
R2
X
Temp/°C
Yield (%)b
1
2
3
4
Ph(CH2)2 n-C8H17
Cl
210
0
25
84
77
52c
6 C. E. Castro and W. C. Kray, Jr., J. Am. Chem. Soc., 1966, 88, 4447; D.
Dodd and M. D. Johnson, J. Chem. Soc. (A), 1968, 34.
7 (a) J. K. Kochi, D. M. Singleton and L. J. Andrews, Tetrahedron, 1968,
24, 3503; (b) H. Cohen, D. Meyerstein, A. J. Shusterman and M. Weiss,
J. Am. Chem. Soc., 1984, 106, 1876.
Br
210
X = Br 16d
X = Cl 31d
5
6
7
c-C6H11
Ph
(E)-
PrCHNCH
n-C8H17
n-C8H17
Cl
Cl
Cl
210
210
210
69
71
46
8 The reaction with a nickel-doped (5 mol%) CrCl2, which is effective for
the coupling reactions between alkenyl halides and aldehydes, did not
proceed; the reactant dichloride 12 was recovered in 96% yield. See: K.
Takai, M. Tagashira, T. Kuroda, K. Oshima, K. Utimoto and H. Nozaki,
J. Am. Chem. Soc., 1986, 108, 6048; H. Jin, J.-i. Uenishi, W. J. Christ
and Y. Kishi, J. Am. Chem. Soc., 1986, 108, 5644.
9 Reactions using the corresponding benzoates gave about 5–10% less
yields of the same products.
10 A. Fürstner and N. Shi, J. Am. Chem. Soc., 1996 118, 12349.
11 For an example of the utilization of a 2-bromoalk-2-en-1-ol, see: W.-M.
Dai and A. Wu, Tetrahedron Lett., 2001, 42, 81.
8
9
c-C6H11
Ph
Cl
Cl
210
210
68
63
a Reaction was conducted on a 1.0 mmol scale. Two mmol of trihalides,
8 mmol of CrCl2, and 8 mmol of DMF were used per mmole of an
aldehyde. b Isolated yields. Isomer ratios were determined by isolation,
GLPC, and/or NMR. c 0.8 mmol of CrCl2, 9 mmol of manganese, and
9 mmol of Me3SiCl were employed per mmole of nonanal. d Z-Isomers
were obtained exclusively.
12 For the synthesis of (Z)-alkenyl bromides, see: B. M. Trost and A. B.
Pinkerton, Angew. Chem., Int. Ed., 2000, 39, 360.
Chem. Commun., 2001, 1128–1129
1129