Highly diastereoselective reformatsky-type reaction promoted by tin iodide Ate complex

Article abstract of DOI:10.1021/ol0171214

Chemical equation presented An ate type of tin complex, Li⁺[n-Bu₂Snl₃]^-/HMPA, works as a novel type of reagent to accomplish the highly diastereoselective Reformatsky-type reaction by the halogen-metal exchange method.

Full text of DOI:10.1021/ol0171214

ORGANIC
LETTERS
2002
Vol. 4, No. 2
301-303
Highly Diastereoselective
Reformatsky-Type Reaction Promoted
by Tin Iodide Ate Complex
Ikuya Shibata, Toshihiro Suwa, Hideaki Sakakibara, and Akio Baba*
Department of Molecular Chemistry & Frontier Research Center, Graduate School of
Engineering, Osaka UniVersity, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan
shibata@ap.chem.eng.osaka-u.ac.jp
Received November 26, 2001
ABSTRACT
An ate type of tin complex, Li+[n-Bu2SnI3]-/HMPA, works as a novel type of reagent to accomplish the highly diastereoselective Reformatsky-
type reaction by the halogen−metal exchange method.
The Reformatsky reaction is a convenient and useful protocol
for carbon-carbon bond formation using R-halocarbonyl
compounds.1 However, the yield and diastereoselectivity of
the â-hydroxycarbonyl compounds produced are unsatisfac-
tory. To overcome these problems, many types of modified
procedures have been developed so far. Oxidative addition
using low-valent metal reagents2 is a representative method
in which diastereoselective reactions have been accomplished
in some cases.2a,b,e However, in most of them, using low-
valent metals causes undesirable side reactions involving
dehydration and reduction of unsaturation. As an alternative
facile and general route, the halogen-metal exchange method
of R-haloketones with ordinal-valent metal reagents can
generate various metal enolates.3 Recently, hypervalent Mn
complexes have been focused on as novel reagents for the
Reformatsky-type reaction.4 However, these halogen-metal
exchange methods have not attained high diastereoselectiv-
ity.3,4 During our investigation of organotin ate complexes,5
we found that the tin ate complex Li+[n-Bu2SnI3]-/HMPA
accomplishes the highest class of syn-diastereoselectivity in
the Reformatsky-type reaction via halogen-metal exchange
method in R-haloketones.
Initially, we performed the reaction of R-iodopropiophe-
none (1a) with benzaldehyde (2a) for investigating an
effective promotor (Table 1). The equimolar combination
of di-n-butyltin diiodide (n-Bu2SnI2) and lithium iodide (LiI)
afforded the desired â-hydroxy ketone 3a in 67% yield (entry
3). Of particular interest is the high syn-selectivity. The sole
use of either n-Bu2SnI2 or LiI afforded no product at all
(entries 1 and 2). The addition of excess amounts of LiI did
not change the yield and selectivity (entry 4). Further addition
of an equimolar amount of HMPA to the n-Bu2SnI2-LiI
(3) EtMgBr, n-BuLi, Et2Zn, Me3Al, Et3B: (a) Aokia, Y.; Oshima, K.;
Uchimoto, K. Chem. Lett. 1995, 463. Et2AlCl-Zn: (b) Maruoka, K.;
Hashimoto, S.; Kitagawa, Y.; Yamamoto, H.; Nozaki, H. Bull. Chem. Soc.
Jpn. 1980, 53, 3301. Et2AlCl-Bu3SnLi: (c) Matsubara, S.; Tsuboniwa,
N.; Morizawa, Y.; Oshima K.; Nozaki, H. Bull. Chem. Soc. Jpn. 1984, 57,
3242. CeI3 : (d) Fukuzawa, S.; Tsuruta, T.; Fujinami, T.; Sakai, S. J. Chem.
Soc., Perkin Trans. 1 1987, 1473. AlI3 : (e) Borah, H. N.; Boruah, R. C.;
Sandhu, J. S. J. Chem. Soc., Chem. Commun. 1991, 154. R3SnSnR3: (f)
Kosugi, M.; Koshiba, M.; Sano H.; Migita, T. Bull. Chem. Soc. Jpn. 1985,
58, 1075. (g) Shibata, I.; Yamaguchi, T.; Baba, A.; Matsuda, H. Chem.
Lett. 1993, 97. (h) Shibata, I.; Kawasaki, M.; Yasuda, M.; Baba, A. Chem.
Lett. 1999, 689.
(1) (a) Rathke, M. W.; Weipert, P. In ComprehensiVe Organic Synthesis;
Trost, B. M., Fleming, I., Eds.; Pergamon Press: Oxford, 1991; Vol. 2,
Chapter 1.8, pp 277-299. (b) Rathke, M. W. In Organic Reactions; John
Wiley & Sons: New York, 1975; Vol. 22, Chapter 2, pp 30-59.
(2) For example, Ge: (a) Kagoshima, H.; Hashimoto, Y.; Oguro, D.;
Saigo, K. J. Org. Chem. 1998, 63, 691. Sn: (b) Harada, T.; Mukaiyama,
T. Chem. Lett. 1982, 467. (c) Chan, T. H.; Li, C. J.; Wei, Z. Y. J. Chem.
Soc., Chem. Commun. 1990, 505. Co: (d) Orsini, F. J. Org. Chem. 1997,
62, 1159. In: (e) Chan, T. H.; Li, C. J.; Lee M. C.; Wei, Z. Y. Can. J.
Chem. 1994, 72, 1181. R3Sb: (f) Huang, Y. Z.; Chen. C.; Shen, Y. J. Chem.
Soc., Perkin Trans. 1 1988, 2855. TiCl4-Bu4NI: (g) Tsuritani, T.; Ito, S.;
Shinokubo, H.; Oshima, K. J. Org. Chem. 2000, 65, 5066.
(4) Mn complex: Hojo, M.; Harada, H.; Ito, H.; Hosomi, A. J. Am. Chem.
Soc. 1997, 119, 5459.
(5) We have already reported a similar ate complex of tin hydrides, Li+[n-
Bu2SnI2H]-, which afforded conjugate hydrostannation of enals where high
nucleophilicity of apical tin-iodine bond played an important role. Suwa,
T.; Shibata, I.; Baba, A. Organometallics 1999, 18, 3965.
10.1021/ol0171214 CCC: $22.00 © 2002 American Chemical Society
Published on Web 01/03/2002

Table 1. Reformatsky-Type Reactions of R-Halo
Table 2. syn-Selective Reformatsky-Type Reactiona
Acetophenone with PhCHOa
entry R1
R2
X
R3
product yield (%) syn:antib
entry
X
reagent (mmol)
Bu2SnI2 (2)
yield (%)b syn:antib
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Ph Me
Ph Me
Ph Me
Ph Me
Ph Me
Ph Me
Ph Me
Ph Me
Ph Me
Ph Me
I
Ph
3a
3b
3c
3d
3e
3f
3g
3h
3i
89
70
86
89
53
65
77
9
65
45
93
50
56
37
95:5
93:7
91:9
91:9
86:14
84:16
91:9
-
1
2
3
4
5
6
I
tr
tr
I
I
I
I
I
I
I
I
I
p-MeC6H4
p-ClC6H4
p-O2NC6H4
n-C5H11
PhCH2CH2
i-Pr
I
I
I
I
LiI (2)
Bu2SnI2 (2), LiI (2)
Bu2SnI2 (2), LiI (4)
Bu2SnI2 (2), LiI (2), HMPA (2)
67
66
89
89
94:6
94:6
95:5
86:14
Cl Bu2SnI2 (2), LiI (2), HMPA (2)
a 1 (2 mmol), 2a (1 mmol), THF (1 mL), 6 °C, 12 h. b Yields and ratios
were determined by H NMR based on 2a.
t-Bu
1
PhCHdCH
MeCHd CH
84:16
83:17
3j
Ph
Me Me
Et
H
H
Cl Ph
Cl Ph
Cl Ph
3k
3l
3m
3n
90:10
80:10
system gave the highest yield and syn-selectivity examined
(entry 5).6 Instead of R-iodoketones, it is possible to use more
easily available R-chloroketones (entry 6) because of easy
conversion of R-chloroketones to R-iodoketones with the
iodotin reagent. Thus the treatment of n-Bu2SnI2-LiI with
R-chloro propiophenone under the identical conditions in
Table 1 underwent halogen exchange to the corresponding
iodoketone quantitatively. The syn-selectivity of â-hydroxy-
ketone 3a is of the highest level in comparison with that of
conventional reagents for the Reformatsky-type reaction so
far.2,3
We confirmed the formation of an ate complex between
n-Bu2SnI2 and LiI. When equimolar LiI was added to n-Bu2-
SnI2 in THF solvent, 119Sn NMR indicated an upfield shift
from -58.0 to -141.4 ppm. The value of coupling constant
1J(119Sn-13C) also increased from 373.2 to 542.9 Hz. These
changes indicate the formation of TBP-type complex Li+[n-
Bu2SnI3]- (I),5,7 as shown in Scheme 1. The presence of
H
n-Bu Cl Ph
a Bu2SnI2 (2 mmol), LiI (2 mmol), HMPA (2 mmol), 1 (2 mmol), 2 (1
mmol), THF (1 mL). b Yields and ratios were determined by 1H NMR based
on 2.
complex Bu2SnI2-HMPA by ligand exchange could not be
considered, because we confirmed that the obtained values
were not consistent with the ones of Bu2SnI2-HMPA
complex (δ(119Sn) ) -204.6, J(119Sn-13C) ) 496.1 Hz).
1
In the Reformatsky-type reaction, the complex II gave a
superior result in the case of the complex I (Table 1, entries
3 and 5). Hence the basicity of II would be higher than that
of I, acting as an effective reagent.
Table 2 shows the results using complex II. Besides
benzaldehyde 2a, other aromatic aldehydes 2 reacted ef-
fectively to give 3b-d in good yields with high syn-
selectivities beyond 91% (entries 2-5). In the case of
aliphatic aldehydes, primary and secondary ones reacted well
to give 3e-g (entries 5-7). Tertiary substituted aliphatic
aldehyde, however, scarcely produced the desired 3h because
of its steric hidrance (entry 8). The reaction using R,â-
unsaturated aldehydes gave only 1,2-adducts 3i and 3j in
moderate yields with high syn-selectivities (entries 9 and 10).
Primary R-chloroketone reacted well to give a high yield of
Scheme 1
(6) General Experimental Procedure. To a THF (1 mL) solution of
n-Bu2SnI2 (0.95 g, 2 mmol) and LiI (0.266 g, 2 mmol) was added HMPA
(0.360 g 2 mmol) at 6 °C (bath temp), and the solution was stirred for 5
min. To the solution was added R-iodopropiophenone (1a) (0.520 g, 2 mmol)
and benzaldehyde (2a) (0.106 g, 1 mmol). The solution was stirred at 6 °C
(bath temp) for 12 h. MeOH (3 mL) was added to quench the reaction, and
volatiles were removed under reduced pressure. The residue was subjected
to column chromatography, eluting with hexanes-EtOAc (1:1) to give a
syn-rich mixture of â-hydroxy ketones 3a. Further purification was
performed by TLC, eluting with hexane-diethyl ether (1:1). The stereo-
chemistry of 3a was assigned by 1H NMR in comparison with the
stereochemically defined authentic samples.
(7) For example, see: (a) Davis, A. G. Organotin Chemistry; VCH: New
York, 1997; pp 18. (b) Harrison, P. G. Chemistry of Tin; Blackie; London,
1989; p 71. (c) Holecek, J.; Na´dvorn´ık, M.; Handl´ır, K.; Lycka, A. J.
Organomet. Chem. 1983, 241, 177. (d) Na´dvorn´ık, M.; Holecek, J.; Handl´ır,
K.; Lycka, A. J. Organomet. Chem. 1984, 275, 43.
equimolar HMPA in the equimolar mixtures of n-Bu2SnI2
and LiI afforded a slight change of chemical shift (-158.0
ppm) and coupling constant (1J(119Sn-13C) ) 548.0 Hz). It
is considered that HMPA interacts with lithium cation to form
a complex such as II. In this case, the formation of alternative
302
Org. Lett., Vol. 4, No. 2, 2002

3k (entry 11). The regiospecificity of the reaction was
obtained by the reaction of halogenated 2-butanone deriva-
tives such as 3-chloro-2-butanone and 1-chloro-2-butanone
(entries 12 and 13). Each isomer afforded the corresponding
â-hydroxy ketone 3l, 3m without any isomerization of the
enolate. Although the yield was not good, R-chloroaldehyde
gave an acceptable syn-selectivity of â-hydroxy aldehyde 3n
(entry 14).
recovered. This limitation could be solved by the use of
MgBr2‚OEt2 instead of LiI, and desired â-hydroxy ester 5a
was obtained in 80% yield (Scheme 3). Moreover, the use
Scheme 3
As to the reaction path, the tin ate complex reacts with
R-iodoketone to form highly coordinated tin enolate (III),
accompanying iodine (Scheme 2).8,9 Unfortunately, when the
Scheme 2
of EtOAc as a solvent afforded a quantitative yield. In the
reaction of secondary iodoester 4b, although high syn-
selectivity could not be attained (63% selectivity), the
reaction proceeded in moderate yield (64%). In this case,
we also confirmed the ate tin complex,12 by the fact that
119Sn NMR indicated an upfield shift from -58.0 to -114.6
ppm when equimolar MgBr2‚OEt2 was added to n-Bu2SnI2
in ethyl acetate-d8. Namely, the ate complex MgBr+[n-Bu2-
SnBrI2]- also works in the Reformatsky reactions.
1
mixture of 1a and complex II was monitored by H NMR
at room temperature, no peaks other than 1a were detected.10
We consider that the small amount of enolates (III) in the
equilibrium is immediately trapped by an aldehyde to form
a â-stannyloxyketone. The high syn-selectivity could be
explained by the noncyclic antiperiplaner transition state11
because the hypervalent tin center cannot coordinate to the
oxygen of an aldehyde any more.
In conclusion, we developed ate-type tin complexes to
perfom Reformatsky-type reaction with high syn-selectivities.
It is not necessary to isolate the tin complex, which was
generated in situ by simply mixing easily available n-Bu2-
SnI2 with LiI or MgBr2‚OEt2. The further investigation of
mechanistic studies is now in progress.
When iodomethyl ethylester 4a was treated with benzal-
dehyde 2a, no reaction occurred and starting substrates were
(8) For the generation of tin enolate (III), we tentatively consider that
the reaction of 1 with tin complex (I) affords a lithium enolate initially,
which reacts with Bu2SnI2.
Acknowledgment. This work was supported financially
by a Grant-in Aid for Scientific Research from Ministry
Education, Science and Culture. Thanks are due to the
Analytical Center, Osaka University, for assistance in obtain-
ing HRMS spectra.
Supporting Information Available: Experimental pro-
cedures and IR, H NMR, 13C NMR, and HRMS spectrum
1
Although the possibility of the contribution of the lithium enolates to react
with aldehydes cannot be excluded, we consider that the tin enolates react
with aldehydes, because lower diastereoselectivities have been obtained in
the case of lithium enolates.3a
(9) The enolate formation via attack of iodine anion has been reported
for AlI33e and TiI4 systems.9a (a)Hayakawa, R.; Shimizu, M. Org. Lett. 2000,
2, 4079.
for 3a-g, 3i-n, 5a and 5b, and 13C- and 119Sn NMR data
for the tin ate complex I and II. This material is available
free of charge via the Internet at http://pubs.acs.org.
OL0171214
(10) There is also another possibility that the reaction may proceed
through a SET mechanism, which is already suggested in the indium-
mediated reaction,2e although no homocoupling products of haloketones or
aldehydes have been obtained.
(12) We have already revealed the structure of a similar ate complex of
tin hydrides MrBr+[n-Bu2SnBrIH]-, which afforded hydrostannation of
alkynes. Suwa, T.; Shibata, I.; Ryu, K.; Baba, A. J. Am. Chem. Soc. 2001,
123, 4101.
(11) Yamamoto, Y. Acc. Chem. Res. 1987, 20, 243.
Org. Lett., Vol. 4, No. 2, 2002
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