Alkylidenation of carbonyl compounds with gem-dizincioalkanes mediated with titanium dichloride

Article abstract of DOI:10.1055/s-1998-1980

Olefination of carbonyl compounds with gem-dizincio-alkanes, bis(iodozincio)methane, 1,1-bis(iodozincio)ethane, and bis(bromozincio)methyltrimethylsilane, afforded the corresponding olefins in good to excellent yields.

Full text of DOI:10.1055/s-1998-1980

December 1998
SYNLETT
1369
Alkylidenation of Carbonyl Compounds with gem-Dizincioalkanes Mediated with Titanium
Dichloride
a
a
b
Seijiro Matsubara,* Tsuyoshi Mizuno, Tasuyuiki, Otake, Masami Kobata, Kiitiro Utimoto,* and Kazuhiko Takai
aDepartment of Material Chemistry, Graduate School of Engineering, Kyoto University, Sakyo, Kyoto 606-8501, Japan
Fax +81 75853 4863; E-mail matsubara@orgrx2.kuic.kyoto-u.ac.jp
bDepartment of Applied Chemistry, Faculty of Engineering, Okayama University, Tsushima, Okayama, 700-8530, Japan
Received 27 August 1998
Abstract: Olefination of carbonyl compounds with gem-dizincio-
alkanes, bis(iodozincio)methane, 1,1-bis(iodozincio)ethane, and
bis(bromozincio)methyltrimethylsilane, afforded the corresponding
olefins in good to excellent yields.
Regiospecific olefination of carbonyl groups is one of the most
1
important reactions in organic synthesis; Wittig reagents, gem-
2
3
dimetalloalkanes, Schrock type metal-carbene complexes, Tebbe
4
5
complex and dialkyltitanocenes have been used for an olefination of
carbonyl compounds. Nysted reagent-TiCl2 has been used for
methylenation of aldehydes and ketones, but the structure of the reactive
6
,7
species has not been clarified.
Reagent systems composed of
RCHX -Zn-TiCl were also successfully applied to such an
2
4
8
olefination, where TiCl -modified gem-dizincioalkanes were assumed
4
as
a
reactive species. Recently reported preparation of
9
,10
bis(iodozincio)methane (1)
from diiodomethane enabled to examine
synthetic application of the dizincio reagent to carbonyl-olefination.
This paper describes chemoselective methylenation of carbonyl
compounds
with
1.
As
1,1-bis(iodozincio)ethane
and
bis(bromozincio)methyl-trimethylsilane were prepared from the
corresponding dihalides, the olefination of carbonyl compounds with
those reagents was also examined.
Reaction of an equimolar amount of 1 with 2-dodecanone (2a)
proceeded sluggishly. Addition of stoichiometric TiCl in the mixture
4
improved the reaction, but yield of the methylenated product is 26%.
Yield of the olefin incleased to 79% by the use of 2 equiv of 1. Addition
11
of stoichiometric TiCl2, in place of TiCl , improved the yield of 3a to
4
8
3%, even when an equimolar amount of 1 was used. These observation
indicated that in the reaction using 1–TiCl one equivalent of 1 was used
4
to reduce TiCl4 into TiCl2 that is the effective mediator of the
olefination reaction. The methylenation of various ketones with 1–TiCl2
were examined and the results are summarized in Table 1. As can be
seen from Table 1, 1-TiCl reagent can be applied to a wide variety of
2
ketones except 2d whose carbonyl group is highly sterically hindered. A
stereogenic center at α position was not touched during the reaction
6
giving the methylenated product 3f without epimerization (entry 7); an
easily enolizable ketone 2m gave the corresponding product 3m in
rather low yield.
Scheme 1
Chemoselective methylenation with 1 is performed with or without
TiCl ; 11-oxododecanal (6), a ketoaldehyde, gave 1-tridecen-2-one (7)
2
in 92% yield by the reaction with 2 eq of 1, whereas 6 afforded 2-
methyl-1,12-tridecadiene (8) in 74% yield by treatment with 2 eq of 1-
TiCl2 (Scheme 3). Selective methylenation of the keto group in
ketoester 9 is illustrated in Scheme 4, where olefinic ester 10 was
obtained in 91% yield
In contrast to the reaction with ketones, reagent 1 reacted with
aldehydes smoothly to give the corresponding methylenated products
without TiCl , although the TiCl -mediated reaction proceeded much
2
2
faster (Scheme 2). Results are summarized in Table 2. (S)-2-
Phenylpropanal was converted to (R)-3-phenyl-2-butene in complete
retention of the stereogenic center (entry 6 and 7).

1
370
LETTERS
SYNLETT
Scheme 2
In contrast to highly stereoselective (E)-vinylsilane formation by
16
olefination of aldehydes with Me SiCHBr –CrCl , TiCl -mediated
3
2
2
2
reaction of 14 yielded less stereoselective products, though chemical
yields are good to excellent.
Scheme 3
Scheme 4
Scheme 6
Although direct generation of 1,1-bis(halomagnesio)ethane from 1,1-
dihaloethane by the reaction with Mg/Hg was unsuccessful,12 the
corresponding Zn compound, 1.1-bis(iodozincio)ethane (11), was
prepared in a moderate yield by the reaction of 1,1-diiodoethane with Zn
1
3
under Pb catalysis. Reaction at 25°C yielded 11 in 50% yield, whereas
reaction at –30°C gave 2,3-diiodobutane as a major product. These data
indicated that electron transfer from metal to 1,1-diiodoethane produced
α-iodoethyl radical, which gave 11 by fast electron transfer from metal
1
4
to the radical at 25°C, but yielded 2,3-diiodobutane as a radical
coupling product at low temperature.
Scheme 5
Since the structure of active species has not been solved, NMR spectra
of bis(iodozincio)methane reagent and that of TiCl -modified one
2
3
indicated that the carbon of both reagents has sp character judged from
In contrast to 1, reaction of 11 with aldehydes did not give the
corresponding ethylidenated product 12 in good yields; reduction of
aldehydes proceeded predominantly. Yield of the olefinated products
17
JCH
.
Studies on the structure of the reagents are in progress.
was remarkably improved using TiCl as a mediator; ketones were also
ethylidenated in good yields as summarized in Table 3.
2
Experimental Procedure
,1-Bis(iodozincio)ethane:
1
Bis(bromozincio)methyltrimethylsilane (14), prepared from the
A mixture of Zn (Wako Pure Chemical Industries LTD., Japan. –100
1
5
corresponding dibromide 13, was allowed to react with aldehydes and
ketones under mediation with TiCl . Results are summarized in Table 4
18,19
mesh,
25 mmol), 1,1-diiodoethane (1.0 mmol) and 2.0 ml of THF
2

December 1998
SYNLETT
1371
was sonicated for 1 h. To the mixture 10 mmol of 1,1-diiodoethane
and 20 ml of THF was added, then the mixture was stirred for 30 min at
Tetrahedron Lett. 1988, 29, 1065; Takai, K.; Kataoka, Y.; Miyai,
J.; Okazoe, T.; Oshima, K.; Utimoto, K. Org. Synth. 1996, 73, 73;
Lombardo, L. Org. Synth. 1987, 65, 81.
1
3
2
5°C.
(9) (a) Eisch, J. J.; Piotuwski, A. Tetrahedron Lett. 1983, 24, 2043. (b)
Olefination with Dimetal Reagent–TiCl2:
Takai, K.; Kakiuchi, T.; Kataoka, Y.; Utimoto, K. J. Org. Chem.,
1
994, 59, 2668.
To a TiCl2 (0.48 g, 4.0 mmol) was added THF (8 ml) at -40°C. The
mixture was stirred for 10 min at 20°C. To the obtained dispersion was
(10) Utimoto, K.; Toda, N.; Mizuno, T.; Kobata, M.; Matsubara, S.
added CH (Znl) (4.0 mmol) at 20°C and the resulting mixture was
2
2
Angew. Chem. Int. Ed. Engl. 1997, 36, 2804; CH2(Znl)2 in THF-
d : C NMR (75 MHz) δ -14.3 (-20°C) (JC-H = 119 Hz); 1
13
H
stirred for 2 h. Ketone (4.0 mmol) in THF (4.0 ml) was added dropwise
to the resulting mixture at 0°C . The mixture was stirred for 1 h at 20°C.
To the mixture was added ether (16 ml) . The mixture was filtered
through cerite column and washed with ether (20 ml) . The filtrate was
concentrated. The product was isolated with a short silica gel column
chromatogtaphy.
8
1
NMR (300 MHz) δ -1.34 (at -20°C). Although H NMR of 1 in
THF was reported in ref. 9b, but temperature dependence has not
been recorded. A broad proton signel (-0.6 – -1.2 ppm) at room
temperature, a broad singlet (-1.34 ppm) at -20°C, and a sharp
singlet (-1.56 ppm) at -60°C were recorded.
(
(
(
11) Narula, S. P.; Sharma, H. K. Inorg. Syn. 1985, 24. 181.
12) F. Bickelhaupt, Angew. Chem. Int. Ed. Engl. 1987, 26, 990.
13) CH CH(ZnI) in THF-d : 13C NMR (75 MHz, 20°C) δ 3.47, 12.1;
Acknowledgment. Finantial support from the Ministry of Education,
Science, Sports and Culture, Japan (No. 06403025, 09231223,
0
9238221, 10125217 and 10132227) is acknowledged.
3
2
8
1
H NMR (300 MHz, 20°C) δ -0.08 (q, J = 7.8 Hz, 1H), 1.45 (d, J
7.8 Hz, 3H).
=
References and Notes
1
(
14) A trace amount of 2-butene was observed by H NMR analysis.
The observation indicated that initially produced 2,3-diiodobutane
was converted into 2-butene by the action of Zn.
(
1) Maercker, A. Org. React. 1965, 14, 270; Maryanoff, B. E.; Reits,
A. B. Chem. Rev. 1989, 89, 863.
(
(
2) Marek, I.; Normant, J.-F. Chem. Rev. 1996, 96, 3241.
(15) Matsubara, S.; Otake, Y.; Morikawa, T.; Utimoto, K. Synlett 1998
3) Schrock, R. R.; Depue, R. T.; Feldman, J.; Yap, K. B.; Yang, D.
C.; Davis, W. M.; Park, L.; Dimare, M.; Schofield, M.; Anhaus, J.;
Walborsky, E.; Evitt, E.; Kruger, C.; Betz, P. Organometallics
1
315. The detailed preparation procedure of 14 is described in this
paper.
1
990, 9, 2262.
4) Tebbe, F. N.; Parshall, G. W.; Reddy, G. S. J. Am. Chem. Soc.
978, 100, 3611.
(16 Takai, K.; Kataoka, Y.; Okazoe, T.; Utimoto, K. Tetrahedron Lett.
987, 28, 1443.
1
(
(
1
13
1
(17) NMR data (300 MHz for H; 75 MHz for C) of TiCl -modified
2
1 (-20°C): 13C NMR δ -16.7; H NMR δ -1.46; JCH = 118 Hz.
1
5) Petasis, N. A.; Browej, E. I. J. Am. Chem. Soc. 1990, 112, 6392;
Petasis, N. A.; Staszewski, J. P.; Fu, D. K. Tetrahedron Lett. 1995,
(
18) The Zn powder from Wako Pure Chemical Industries LTD., Japan,
contains 0.04–0.07 mol% of lead based on zinc. Zinc powder was
washed with 5% hydrochloric acid according to the following
literature: Fieser, L. F.; Fieser, M. In Reagents for Organic
Synthesis, Vol 1; Wiley: New York, 1967, p1276.
36, 3619.
(
(
6) Matsubara, S.; Sugihara, M.; Utimoto, K. Synlett 1998, 313.
7) Tochtermann,W.; Bruhn, S.; Meints, M.; Wolff, C.; Peters, E-M.,
Peters, K.; von Schnering, H. G. Tetrahedron, 1995, 51, 1623;
Gleiter, R.; Herb, T.; Hofmann, J. Synlett, 1996, 987.
(
19) The same results were obtained by using pure Zn powder (–100
mesh, purchased from Aldrich Chemical Company, Inc.) with
catalytic amount (0.1 mol%) of PbCl2
(
8) Okazoe, T.; Takai, K.; Oshima, K.; Utimoto, K. J. Org. Chem.
1
987, 52, 4410; Takai, K.; Kataoka, Y.; Okazoe, T.; Utimoto, K.