1,4-Addition reactions of bis(iodozincio)methane with α,β-unsaturated ketones

Article abstract of DOI:10.1055/s-1999-2831

A reaction of bis(iodozincio)methane with acyclic enones proceeded in 1,4-addition manner to afford zinc enolate of β-zinciomethylketone. In the case of the 1,4-addition reactions of bis(iodozincio)methane with 2- cyclohexen-1-one, an assistance by copper

Full text of DOI:10.1055/s-1999-2831

LETTER
1253
1
,4-Addition Reactions of Bis(iodozincio)methane with a,b-Unsaturated
Ketones
Seijiro Matsubara,* Daisuke Arioka, Kiitiro Utimoto
Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Yoshida, Sakyo, Kyoto 606-8501, Japan
Fax 75-753-4863; E-mail: matsubar@mc.kyoto-u.ac.jp
Received 31 May 1999
Abstract: A reaction of bis(iodozincio)methane with acyclic
enones proceeded in 1,4-addition manner to afford zinc enolate of
b-zinciomethylketone. In the case of the 1,4-addition reactions of
bis(iodozincio)methane with 2-cyclohexen-1-one, an assistance by
copper salt was necessary to complete the reaction.
Key words: zinc, 1,4-addition, dimetal, copper, enolate
Scheme 2
Reaction of gem-dimetallic reagents have attracted con-
siderable attention as versatile reagents in organic synthe-
1
sis. Recently we reported the selective coupling reactions
2
of gem-dizinc compound with organic halides; 1,3-dike-
2
3
tone synthesis, and carbonyl olefination. As other appli-
cations, we examined a reaction of gem-dizinc compound
with a,b-unsaturated carbonyl compound to perform 1,4-
addition. This reaction will afford zinc enolate of b-zinci-
omethylketone.
Scheme 3
A treatment of 2-cyclohexen-1-one with bis(iodozin-
cio)methane and chlorotrimethylsilane resulted into the
recovery of enone. In this case, we tried to prepare orga-
nocopper species from gem-dizinc compound and copper
3
A reaction of bis(iodozincio)methane (1) with a,b-unsat-
urated ketone 2a was examined. The zinc enolate being
formed in situ was trapped with an equimolar amount of
4
chlorotrimethylsilane. The procedure afforded a silyl
7
salt. A reaction of bis(iodozincio)methane (1) in THF
5
,6
enolate of organozinc compound 3a. A treatment of 3a
with a THF solution of CuCN
•
2 LiCl at -30 °C was mon-
itored by H NMR. A treatment of 1 with an equimolar
amount of CuCN 2 LiCl showed a new signal at -0.7 ppm,
with D O gave 4a in 80% yield. Following the same pro-
1
2
cedure for 2b, the compound 4b was obtained in 81 %
yield (Scheme 1).
•
while the signal of bis(iodozincio)methane (1, -1.35 ppm)
disappeared completely. This fact imply the new copper
species 7 was formed by the above procedure.8
4
To the species 7, chlorotrimethylsilane and 2-cyclohex-
en-1-one were added sequentially. After the reaction was
completed, D O was added to quench C-Zn bond. The si-
2
lyl enolate 10 was obtained in 80% yield via 9 (Scheme 4).
The intermediary organozinc 9 reacted also with organic
halides. The copper salt which already existed in the reac-
tion mixture mediated reaction of 9 with allyl halide to
give 11 as a product in 78% yield.
Scheme 1
The organozinc moiety in 3 was able to be reacted with or-
ganic halide as shown in Scheme 2. The zinc species 3a
was treated with iodobenzene in the presence of a palladi-
2
um catalyst, Pd dba •CHCl / [3,5-(CF ) C H ] P. The
2
3
3
3 2
6
3 3
reaction gave 5 in 70% yield. The copper salt mediated re-
action of 3a with allyl bromide gave the coupling product
7
6
in 95% yield (Scheme 3). It is well-known that the silyl
enolate reacts with various electrophiles, so the procedure
make the four components coupling possible.
Scheme 4
Synlett 1999, No. 8, 1253–1254 ISSN 0936-5214 © Thieme Stuttgart · New York

1
254
S. Matsubara et al.
LETTER
The copper-mediated reaction of 1 with a,b-unsaturated
aldehyde was also examined. As shown in Scheme 5, the
species 7 was treated with chlorotrimethylsilane and alde-
hyde, and followed by an addition of allyl bromide afford-
J = 7.2 Hz, 1H), 4.0 (dt, J = 7.2, 7.2 Hz, 1H), 1.40 (dt, J = 7.2,
0.8 Hz, 2 H).
(
(
7) Knochel, P.; Singer, R. D. Chem. Rev., 1993, 93, 2117;
Knochel, P. Synlett, 1995, 393.
8) The signal of methylene in 1 appeared at -1.3 ppm as a broad
peak (Figure 1). By an addition of a THF solution of
CuCN•2LiCl, the mixture showed newly formed signal at -0.7
ppm. This signal was supposed to be a mono copper species
9
ed the silyl enolate 12 having Z-configuration. The
reaction without copper salt proceeded to give diene 13
3
via methylenation as shown in Scheme 6.
IZn-CH -Cu 7. The substituent and ligand on copper could not
2
be identified. An addition of excess amount of copper salt
would form a dicopper species Cu-CH -Cu 8, which was
2
1
detected in H NMR spectra as the signal at -0.85 ppm. A
broad peak at -1.0 ppm in d) came from CH ZnI and copper
3
salt. From these results, the tendency of transmetalation from
zinc to copper was appeared in the following order: CH
2(
ZnI) > Cu-CH -ZnI > CH ZnI. The reaction of 2-
2 2 3
Scheme 5
cyclohexen-1-one with 8 in the presence of
chlorotrimethlsilane did not give any adduct, and resulted in
quantitative recovery of the starting material.
Scheme 6
The chlorotrimethylsilane-mediated addition of bis(io-
dozincio)-methane to acyclic a,b-unsaturated carbonyl
compounds proceeded in 1,4-manner and gave the b-zin-
ciomethylketone in a silyl enolate form. The reaction with
s-trans cyclic ketone required a mediation with copper
salt. The reaction of these highly reactive species, the re-
activity of b-zinciomethylketone in the silyl enolate form
is now under investigation.
Acknowlegement
This work was supported by a Grant-in-Aid for Scientific Research
on Priority Areas (No. 10208208), from The Ministry of Education,
Science, Sports, and Culture.
Figure 1 1H NMR Spectra of Copper Reagent Prepared from
CH (ZnI) and CuCN•2LiCl in THF at -30 ° C.
2
2
(
9) To a solution of bis(iodozincio)methane in THF3b (0.4 M, 2.0
mmol) was added dropwise a solution of CuCN (2.0 mmol)
and LiCl (4.0 mmmol) in THF (5.0 mL) at -50 ° C over 15
min. The mixture was stirred for 5 min at the same
References and Notes
(
(
(
1) Marek, I.; Normant, J.-F. Chem. Rev. 1996, 96, 3241;
Knochel, P.; Normant, J.-F. Tetrahedron Lett. 1986, 27, 4427,
temperature. To the mixture, cinnamyl aldehyde (2.0 mmol)
and chlorotrimethylsilane (2.0 mmol) were added at -50 ° C.
The resulting mixture was allowed to warm up to 0 ° C and
allyl bromide (2.0 mmol) in THF (3.0 mL) was added at 0 ° C.
The mixture was stirred for 1 h at 20 ° C. The resulting mixture
4431; Nakamura, E.; Kubota, K.; Sakata, G. J. Am. Chem.
Soc., 1997, 119, 5457.
2) Utimoto, K.; Toda, N.; Mizuno, T.; Kobata, M.; Matsubara, S.
Angew. Chem. Int. Ed. Engl. 1997, 36, 2804; Matsubara, S.;
Kawamoto, K.; Utimoto, K. Synlett 1998, 267; Matsubara, S.;
Otake, Y.; Morikawa, T.; Utimoto, K. Synlett, 1998, 1315
3) a) Takai, K.; Kakiuchi, T.; Kataoka, Y.; Utimoto, K. J. Org.
Chem. 1994, 59, 2668. b) Matsubara, S.; Mizuno, T.; Otake,
T.; Kobara, M.; Utimoto, K.; Takai, K. Synlett, 1998, 1369.
4) Matsuzawa, S.; Horiguchi, Y.; Nakamura, E.; Kuwajima, I.
was poured into ice cooled sat. NH Cl aq, and extracted with
4
ether. The organic layers were washed with sat. Na S O and
2
2
3
brine. The ethereal solution was dried over MgSO . A short
4
silica-gel column chromatography gave 12a in 72 % yield.
1
1
1
2a: H NMR (CDCl ) d 7.1-7.3 (m, 5 H), 6.26 (d, J = 11.2 Hz,
(
(
3
H), 5.82 (ddt, J = 15.5, 11.0, 7.2 Hz, 1H), 5.18 (dd, J = 11.2,
Tetrahedron, 1989, 45, 349.
1
7.5 Hz, 1H), 5.01 (d, J = 15.5 Hz, 1H), 4.96 (d, J = 11.0 Hz,
H), 3.18 (dt, J = 7.5, 7.5 Hz, 1H), 1.9-2.1 (m, 2H), 1.6-1.85
m, 2H), 0.20 (s, 9H).
5) 3a: H NMR (CDCl ) d 7.1-7.6 (m, 10 H), 5.90 (d, J = 10.2 Hz,
3
1
(
1
H), 4.24 (dt, J = 10.2, 7.6 Hz, 1H), 0.78 (d, J = 7.6 Hz, 1H),
0.10 (s, 9H).
(
6) An existence of chlorotrimethylsilane is required for
Article Identifier:
437-2096,E;1999,0,08,1253,1254,ftx,en;Y11799ST.pdf
completion of the reaction. A reaction of 2a with 1 in THF at
1
2
0 ° C for 12 h was quenched with H O. 2-Phenylpropyl
2
phenyl ketone was obtained in 43% yield; a recovery of 2a
1
was 51%. 4a: H NMR (CDCl ) d 7.1-7.6 (m, 10 H), 5.39 (d,
3
Synlett 1999, No. 8, 1253–1254 ISSN 0936-5214 © Thieme Stuttgart · New York