Samarium(II) triflate as a new reagent for the grignard-type carbonyl addition reaction

Article abstract of DOI:10.1021/jo960260s

On treatment of a THF solution of Sm(OTf)₃ with 1 equiv of an organolithium or organomagnesium reagent at ambient temperature, the purple or deep green solution of the divalent samarium triflate [Sm(OTf)₂] was readily obtained. For this preparation, s-BuLi was the most effective as was evidenced by the reduction of 2-phenylethyl iodide in the presence of HMPA. The Sm(OTf)₂ reagent mediated the Grignard-type reaction effectively in THF/HMPA; alkylation and allylation of ketones or aldehydes with alkyl, allyl, or benzyl halides proceeded via organosamarium intermediates. Diastereoselectivity of the samarium-Grignard reaction was examined using 2-methylcyclohexanone, 4-tert-butylcyclohexanone, and 2-phenylpropanal and was found to be higher in each case than that with SmI₂. With 2-methylcyclohexanone, for example, Sm(OTf)₂ gave the greatest ratio of axial alcohol:equatorial alcohol = 99:1, and SmI₂ gave a ratio of 91:9. Halides containing an ester or a silyl group were reactive in the Reformatsky- or Peterson-type reaction, respectively, using the Sm(OTf)₂ reagent.

Full text of DOI:10.1021/jo960260s

5400
J . Org. Chem. 1996, 61, 5400-5405
Sa m a r iu m (II) Tr ifla te a s a New Rea gen t for th e Gr ign a r d -Typ e
Ca r bon yl Ad d ition Rea ction
Shin-ichi Fukuzawa,*,† Keisuke Mutoh,† Teruhisa Tsuchimoto,‡ and Tamejiro Hiyama‡
Department of Applied Chemistry, Chuo University, Kasuga, Bunkyo-ku, Tokyo 112, J apan, and
Research Laboratory of Resources Utilization, Tokyo Institute of Technology,
Nagatsuda, Midori-ku, Yokohama 226, J apan
Received February 7, 1996X
On treatment of a THF solution of Sm(OTf)3 with 1 equiv of an organolithium or organomagnesium
reagent at ambient temperature, the purple or deep green solution of the divalent samarium triflate
[Sm(OTf)2] was readily obtained. For this preparation, s-BuLi was the most effective as was
evidenced by the reduction of 2-phenylethyl iodide in the presence of HMPA. The Sm(OTf)2 reagent
mediated the Grignard-type reaction effectively in THF/HMPA; alkylation and allylation of ketones
or aldehydes with alkyl, allyl, or benzyl halides proceeded via organosamarium intermediates.
Diastereoselectivity of the samarium-Grignard reaction was examined using 2-methylcyclohex-
anone, 4-tert-butylcyclohexanone, and 2-phenylpropanal and was found to be higher in each case
than that with SmI2. With 2-methylcyclohexanone, for example, Sm(OTf)2 gave the greatest ratio
of axial alcohol:equatorial alcohol ) 99:1, and SmI2 gave a ratio of 91:9. Halides containing an
ester or a silyl group were reactive in the Reformatsky- or Peterson-type reaction, respectively,
using the Sm(OTf)2 reagent.
In the past decade, samarium(II) diiodide (SmI2) has
Thus, reagents have been reacted with amides to produce
unsymmetrical ketones without contamination by the
tertiary alcohols6 and react in highly diastereoselective
fashion with chiral ketones.7 However, synthetic utilities
are limited because certain organolithium compounds are
not easily available. We present here an alternative
method of preparation of organolanthanide triflates by
reduction of alkyl halides with a divalent lanthanide
triflate, i.e., Sm(OTf)2 or Yb(OTf)2. We also demonstrate
that the Sm(OTf)2-mediated Grignard-type carbonyl ad-
dition is highly stereoselective and unique in its reactiv-
ity.
been proven to be a useful and essential reagent for
reduction of organic functional groups and for carbon-
carbon bond formation.1 Typical examples are the reduc-
tion of carbonyl compounds and Barbier-type reactions.
However, SmI2 occasionally induces ring opening of the
solvent tetrahydrofuran (THF).2 Other divalent sa-
marium compounds are of interest with respect to their
reducing ability for organic functional groups and ste-
reocontrolled carbon-carbon bond-forming reactions. For
example, samarium(II) dibromide reduces ketones3a and
aromatic esters3b to give dimerization products. Sama-
rocene, dicyclopentadienylsamarium4 which is prepared
by the reaction of SmI2 with cyclopentadienylsodium, is
an efficient reagent for the Barbier-type reactions where
it affords the stable organosamarium intermediates
including allylic and benzylic samariums.4 We have been
interested in the divalent derivatives of lanthanides for
selective organic synthesis. In our preliminary com-
munication, we succeeded in the preparation of divalent
samarium(II) triflate [Sm(OTf)2] by treatment of samari-
um(III) triflate [Sm(OTf)3] with s-BuLi in THF.5
Resu lts a n d Discu ssion
P r ep a r a tion of Sm (OTf)2 a n d Sim p le Red u ction
of th e Alk yl Ha lid e. On treatment of a THF solution
of Sm(OTf)3 with 1 equiv of an organolithium or organo-
magnesium reagent at ambient temperature, the purple
or deep green solution of the divalent samarium triflate
[Sm(OTf)2]8 was readily obtained.9 Generation of the
Sm(II) species was unsuccessful in the presence of
hexamethylphosphoric triamide (HMPA), a pale orange
solution being formed. We first surveyed which organo-
metallic reagent was most effective for preparing Sm(II)
species in the simple reduction of 2-phenylethyl iodide
into ethylbenzene as a probe reaction. To the THF
solution of Sm(II) species obtained by the procedure
described above was added HMPA followed by addition
of 2-phenylethyl iodide and tert-butyl alcohol, and then
the mixture was stirred at room temperature for 1 h,
Organolanthanide triflates prepared from organolith-
ium compounds and trivalent lanthanide triflates are one
of the useful reagents for selective organic synthesis.
† Chuo University.
‡ Tokyo Institute of Technology.
X Abstract published in Advance ACS Abstracts, J uly 15, 1996.
(1) Reviews: (a) Molander, G. A. Chem. Rev. 1992, 92, 29 Compre-
hensive Organic Synthesis; Trost B. M., Fleming, I., Eds.; Pergamon:
Oxford, 1991; Vol. 1, pp 251-282. Encyclopedia of Reagents for Organic
Synthesis; Paquette, L. A., Ed.; Wiley: Chichester, 1995; pp 4428-
4432. (b) Imamoto, T. Lanthanides in Organic Synthesis; Academic
Press: London, 1994.
(2) (a) Soupe, J .; Namy, J .-L.; Kagan, H. B. Tetrahedron Lett. 1984,
25, 2869. (b) Namy, J -L.; Colomb, M.; Kagan, H. B. Tetrahedron Lett.
1994, 35, 1723.
(3) (a) Lebrun,A.; Namy, J .-L.; Kagan,H. B. Tetrahedron Lett. 1993,
34, 2311. (b) Yoshizawa, T.; Hatajima, T.; Amano, H.; Imamoto, T.
Nippon Kagaku Kaishi 1993, 482.
(6) (a) Collins, S; Hong, Y. Tetrahedron Lett. 1987, 38, 4391. (b)
Collins, S.; Hong, Y.; Hoover, G. J .; Veit, J . R. J . Org. Chem. 1990, 55,
3565.
(7) Molander, G. A.; Burkhardt, E. R.; Weinig, P. J . Org. Chem.
1990, 55, 4990.
(4) (a) Namy, J . L.; Collins, J .; Zhang, J .; Kagan, H. B. J . Organomet.
Chem. 1987, 328, 81. (b) Collin, J .; Kagan, H. B. Tetrahedron Lett.
1988, 39, 6097. (c) Collin, J .; Namy, J .-L.; Dallemer, F.; Kagan, H. B.
J . Org. Chem. 1991, 56, 3118. (d) Bied, C.; Collin, J .; Kagan, H. B.
Tetrahedron 1992, 48, 3877.
(8) This formula may not represent the correct structure of Sm(II)
species. “Sm(OTf)2” probably forms a complex with LiOTf and THF.
(9) Imamoto et al. reported the generation of samarium(II) halides
by treatment of samarium(III) halides with butyllithium. Imamoto,
T.; Kusumoto, T.; Yokoyama, M. J . Chem. Soc., Chem. Commun. 1982,
1042. See also ref 3.
(5) Fukuzawa, S.; Tsuchimoto, T.; Kanai, T. Chem. Lett. 1994, 1981.
S0022-3263(96)00260-5 CCC: $12.00 © 1996 American Chemical Society

Samarium(II) Triflate in Grignard-Type CO Addition
J . Org. Chem., Vol. 61, No. 16, 1996 5401
Ta ble 1. Red u ction of 2-P h en yleth yl Iod id e w ith Sm (II)
Sp ecies Gen er a ted by th e Rea ction of Sm (OTf)3 w ith
Or ga n om eta llic Rea gen tsa
Sch em e 1
run
organometallic reagent
yield of ethylbenzene,b %
1
2
3
4
5
6
7
8
9
MeLi
n-BuLi
s-BuLi
t-BuLi
PhLi
EtMgBr
n-BuMgBr
s-BuMgCl
t-BuMgCl
23
63
88
32
0
81
68
73
45
a
PhCH2CH2I (0.9 mmol), t-BuOH (1.0 mmol), Sm(OTf)3 (2.0
Sch em e 2
mmol), organometallic reagent (2.0 mmol), THF (5.0 mL), HMPA
(1.0 mL). Determined by GLC.
b
during which time the purple color faded. Table 1
demonstrates that s-BuLi was superior to other organo-
metallic reagents in the preparation of Sm(II) species
among the organometallic reagents tested: n-BuLi, Et-
MgBr, n-BuMgBr, and s-BuMgCl were moderately effec-
tive, but MeLi, PhLi, t-BuLi, and t-BuMgCl were not
suitable for generating Sm(II) species. We chose s-BuLi
as a reducing agent for preparing Sm(OTf)2. On the other
hand, EtMgBr was revealed to be effective in the prepa-
ration of Sm(OTf)2 for the pinacol coupling reaction as
reported independently by Inanaga et al.10 Iodometric
titration of Sm(II) obtained by the reduction of Sm(OTf)3
with s-BuLi revealed that the concentration of the
divalent samarium was within a range of 0.086-0.091
mol/L.11,12 This result was consistent with that obtained
by the reduction of 2-phenylethyl iodide. THF was the
choice of solvent in the preparation of the samarium(II)
species with s-BuLi. The use of other solvents was less
satisfactory: The yield of reduction of 2-phenylethyl
iodide in a solvent/HMPA is given; tetrahydropyran
(78%), dimethoxyethane (63%), diethyl ether (15%), cy-
clohexane (2%), and toluene (3%). Ytterbium(II) triflate
could be prepared from Yb(OTf)3 by a similar procedure,
and its reactivity was compared to that of Sm(OTf)2 in
the following Grignard-type reaction.
which indicates the generation of divalent samarium.
After hydrolysis of a Sm(OTf)2 solution prepared with
s-BuLi, careful analysis by GC/MS revealed the presence
of 3,4-dimethylhexane which must have resulted from the
homo-coupling of s-BuLi. Because it is difficult to detect
smaller molecules such as butane and butenes, we
prepared the Sm(OTf)2 solution with 1-octyllithium in-
stead of s-BuLi and analyzed the hydrolyzed solution
(Scheme 1). GC/MS analysis showed the production of
hexadecane (20-25%), octane (35-40%), and 1-octene
(30-35%). These results suggest that a trivalent orga-
nosamarium compound should be produced in the initial
step of the reaction, and it would then undergo both
radical cleavage and/or â-hydride elimination processes13
to give the divalent samarium species.14
Sa m a r iu m -Gr ign a r d Rea ction of Sim p le Ha lid es
w ith Keton es a n d Ald eh yd es. We investigated the
Grignard-type reaction of simple organic halides with
acetophenone or acetone. We routinely conducted the
reaction by the “samarium-Grignard” procedure that has
been defined by Curran;15 the reaction was performed by
addition of the organic halide to the Sm(II) in THF/
HMPA solution followed by addition of a ketone or an
aldehyde (Scheme 2). When the reaction was carried out
by the “samarium-Barbier” procedure, i.e., simultaneous
addition of the halide and the ketone to Sm(II),15 the yield
of the alcohols decreased and a considerable amount of
pinacol coupling products was formed. One molar amount
of the halide and a half molar amount of the ketone were
employed for one molar amount of Sm(OTf)2. Table 2
summarizes the results of the reaction. The Grignard-
type reaction with propyl, butyl, dodecyl, or 2-phenylethyl
iodide proceeded smoothly at room temperature to pro-
duce the corresponding adducts with ketones in good
The question arises as to how the divalent samarium
species are generated by the reaction of the trivalent
samarium with an alkyllithium. Reaction of alkyllithium
with Sm(OTf)3 at -78 °C gives a clear homogeneous
solution, a trivalent organosamarium species being
formed.6,7 When the solution temperature is allowed to
warm to room temperature, the solution becomes purple
(10) Inanaga et al. independently reported the pinacol coupling
reaction with Sm(OTf)2 prepared from Sm(OTf)3 and EtMgBr. Hana-
moto, T.; Sugimoto,Y.; Sugino, A.; Inanaga, J . Synlett 1994, 377.
(11) (a) Evans, D. F.; Fazakerley, G. V.; Phillips, R. F. J . Chem. Soc.
A 1971, 1931. (b) Girard, P.; Namy, J . L.; Kagan, H. B. J . Am. Chem.
Soc. 1980, 102, 2693. (c) Girard, P.; Kagan, H. B. Nouv. J . Chim. 1981,
5, 479. (d) Imamoto, T.; Ono, M. Chem. Lett. 1987, 501.
(12) The possibility of simultaneous titration of the unreacted s-BuLi
during the iodometric titration of Sm(II) species would be ruled out
by following reasons. First, we titrated Sm(OTf)2 solution more than
1 h after treatment of Sm(OTf)3 with s-BuLi during which time the
unreacted s-BuLi is not alive any longer because a maximum lifetime
of s-BuLi in THF at 20 °C is about 1 h (Encyclopedia of Reagents for
Organic Synthesis; Paquette, L. A., Ed.; Wiley: Chichester, 1995; pp
907-914). Second, treatment of cyclohexanone with Sm(OTf)2 gave
cyclohexanol and the pinacol as reduction products, but no alkylated
product was detected;5 this suggests the absence of s-BuLi. On the
other hand, on treatment of cyclohexanone with a mixture of Sm(OTf)2
and s-BuLi (1 eqiuv to cyclohexanone), the alkylated product was
produced in addition to the reduction products.
(13) Elimination of â-hydrogen of σ-bonded organolanthanide com-
pounds have been reported. (a) Evans, W. J .; Meadows, J . H.; Wayda,
A. L; Hunter, W. E.; Atwood, J . L. J . Am. Chem. Soc. 1982, 104, 2008;
1982, 104, 2015. (b) Yokoo, K.; Mine, N.; Taniguchi, H.; Fujiwara, Y.
J . Organomet. Chem. 1985, 279, C19.
(14) The similar results were obtained by Inanaga et al. See ref 10.
(15) (a) Curran D. P.; Totleben, M. J . J . Am. Chem. Soc. 1992, 114,
6050. (b) Curran, D. P.; Fevig, T. L.; J asperse, C. P.; Totleben, M. J .
Synlett 1992, 943.

5402 J . Org. Chem., Vol. 61, No. 16, 1996
Fukuzawa et al.
Ta ble 2. Gr ign a r d -Typ e Rea ction of Alk yl Ha lid es w ith
Sch em e 3
a
Ca r bon yl Com p ou n d s Med ia ted by Sm (OTf)2
% yield
of adduct
b
run
carbonyl compound
acetophenone
alkyl halide
MeI
1
2
56
84
86
90
51
63
74
67
86
67
87
32
77
84
62
85f
82f
67
84
67
82
92
60
65
58
95
56
EtI
good yields. Both a sterically hindered ketone (2,4-
dimethyl-3-pentanone in run 14) and an enolizable
ketone (â-tetralone in run 15) afforded the corresponding
alcohols in moderate yields. With R-enones such as
2-cyclohexen-1-one and benzalacetone, the reaction was
1,2-regioselective (runs 16-17). These results were simi-
lar to those obtained in the reaction of organolanthanide
reagents, e.g., organocerium reagents, with such carbonyl
compounds.16 Yb(OTf)2 also mediated the reaction of
organic halides with ketones, but only the Barbier
procedure gave acceptable yields (runs 5 and 12); the
Grignard procedure resulted in 5-10% yield of the
product probably due to slow metal-halogen exchange
and instability of the generated organoytterbium species.
3
4
n-PrI
n-BuI
5c,d
6
n-BuBr
i-PrBr
c-C6H11Br
n-C12H25
PhCH2CH2I
n-BuI
7
8
9e
acetone
10e
11
12c,d
13
14
15
16
17
18
19
20
21d
22c,d
23
24
25e
26d,e
27
cyclohexanone
2-octanone
2,4-dimethyl-3-pentanone
â-tetralone
2-cyclohexen-1-one
benzalacetone
octanal
benzaldehyde
acetophenone
Organolanthanum triflates have been reported to react
with amides to give asymmetrical ketones in high yield.6
“The organosamarium reagent” prepared by the reaction
of the alkyl iodide with Sm(OTf)2 also reacted with
benzamides to afford alkyl phenyl ketones in moderate
yields: alkyl ) CH3 (50%), C2H5 (38%), and 2-phenylethyl
(37%) (Scheme 3).
CH2dCHCH2I
benzaldehyde
cyclohexanone
acetone
PhCH2Br
cyclohexanone
a
Reaction with Allylic an d Ben zylic Halides. Treat-
ment of allyl iodide with Sm(OTf)2 provided the “allyl-
samarium reagent”.16c,17 Trapping this reagent with
ketones gave the corresponding homoallylic alcohols in
good yields. Considering that SmI2 induces the Wurtz-
type coupling of allyl halides in the absence of ketones
or aldehydes, the success in generating the allylsa-
marium species was unexpected, as pointed out.11b,15 We
also succeeded in preparation of the stable “benzylsa-
marium reagent” from benzyl bromide. The reagent was
added to acetone under the same conditions which were
used for the allyl case. The results of these reactions are
shown in runs 20-27 of Table 2.
Sa m a r iu m -Refor m a tsk y a n d -P eter son Rea c-
tion . The samarium-Grignard reaction is also ap-
plicable to functionalized halides. When R- or â-halo
esters were employed in the Sm(OTf)2-mediated reaction
with carbonyl compounds, â-hydroxy esters or γ-lactones
were, respectively, obtained in good yields, the ester
group being unaffected in the reaction.11b,18 We call this
reaction the samarium-Reformatsky reaction. The re-
sults are shown in Table 3. Each reaction probably
involves the samarium enolate or homoenolate. When
Sm(OTf)2 was applied to the reaction of (iodomethyl)-
trimethylsilane with ketones and aldehydes, methyl-
Unless otherwise noted, alkylation was carried out by using
an alkyl halide, a carbonyl compound, Sm(OTf)3, and s-BuLi (0.9:
0.5:2.0:2.0 molar ratio) by the Grignard procedure at room
b
temperature for 1 h in THF/HMPA (5.0 mL/1.0 mL). Determined
by GLC based on a carbonyl compound. c Yb(OTf)2 was used
d
instead of Sm(OTf)2 using 2.0 mL of HMPA. The reaction was
carried out by the Barbier procedure. e The molar ratio of acetone:
alkyl halide ) 2.0:0.9. f 1,2-Adduct only.
yields (runs 3-10). Quenching with D2O instead of the
addition of a ketone provided a deuterated alkane,
demonstrating that the reduction of alkyl iodide with
Sm(OTf)2 should give an organosamarium intermediate.
Worthy of note is that a Sm(OTf)2-mediated samarium-
Grignard reaction with methyl or ethyl iodide was
reproducible and gave the corresponding adduct in good
yield (runs 1-2). This results contrasts sharply to the
results obtained in the SmI2-mediated samarium-Grig-
nard reaction with methyl iodide, which is not reproduc-
ible, and with the analogous reaction with ethyl iodide,
which gives a poor yield15 although the samarium-
Barbier reaction with methyl iodide on ketones gave good
yields.11b A possible explanation of this difference could
be that the expected “organosamarium species” prepared
with Sm(OTf)2 is more stable than the organosamarium
species prepared with SmI2. When bromides were used
instead of iodides, lower yields of adducts resulted. The
reaction with secondary halides such as isopropyl bro-
mide and cyclohexyl bromide similarly proceeded to
afford the corresponding alcohols in good yields (runs
6-8). Secondary iodides gave a complex mixture of
products. Thus, secondary bromides appear to be prefer-
able to a secondary iodides for synthetic applications.
The reaction of butyl iodide/Sm(II) with several car-
bonyl compounds is summarized in runs 11-19 of Table
2. With ketones and aldehydes which were examined,
the reaction proceeded smoothly to afford the adducts in
(16) (a) Imamoto, T.; Kusumoto, T.; Tawarayama, Y.; Sugiura, Y.;
Mita, T.; Hatanaka, Y.; Yokoyama, M. J . Org. Chem. 1984, 49, 3904.
(b) Imamoto, T.; Takiyama, N.; Nakamura, K.; Hatajima, T.; Kamiya,
Y. J . Am. Chem. Soc. 1989, 111, 4392. (c) Fukuzawa, S.; Sakai, S. Bull.
Chem. Soc. J pn. 1992, 65, 3308.
(17) Soupe, J .; Danon, L.; Namy, J .-L.; Kagan, H. B. J . Organomet.
Chem. 1983, 250, 227.
(18) (a) Otsubo, K.; Kawamura, K.; Inanaga, J .; Yamaguchi, M.
Chem. Lett. 1987, 1487. (b) Tabuchi, T.; Kawamura, K.; Inanaga, J .;
Yamaguchi, M. Tetrahedron Lett. 1986, 27, 3889. (c) Fukuzawa, S.;
Sumimoto, N.; Fujinami, T.; Sakai, S. J . Org. Chem. 1990, 55, 1628.

Samarium(II) Triflate in Grignard-Type CO Addition
J . Org. Chem., Vol. 61, No. 16, 1996 5403
Ta ble 3. Refor m a tsk y-Typ e Rea ction w ith Ca r bon yl
Com p ou n d sa
Ta ble 4. Ster eoch em istr y of th e Rea ction of Alk yl
Ha lid es w ith Keton esa
carbonyl
compounds
type of
product
yield,b
%
run
RX
1c BrCH2CO2Et
acetophenone â-hydroxy ester
cyclohexanone â-hydroxy ester
71
81
67
85
81
2c BrCH2CO2Et
3
4
5
BrCH(CH3)CO2Et benzaldehyde â-hydroxy ester
ICH2CH2CO2Et
ICH2CH2CO2Et
acetophenone γ-lactone
cyclohexanone γ-lactone
a
Reaction was carried out by using a halo ester, a ketone,
Sm(OTf)3, and s-BuLi (0.5:0.5:2.0:2.0 molar ratio) by the Grignard
procedure at room temperature for 1 h in THF/HMPA (5.0 mL/
b
1.0 mL). Isolated yield. c The reaction was carried out by the
Barbier procedure.
Sch em e 4
a
enenation of the carbonyl proceeded smoothly (Scheme
4). We call this reaction the samarium-Peterson reac-
tion.19
Unless otherwise noted, alkylation was carried out by using
an alkyl halide, a ketone, and LnX2 (0.9:0.5:2.0 molar ratio) by
the Grignard procedure at room temperature for 1 h in THF/
b
HMPA (5.0 mL/1.0 mL). Determined by GLC based on a ketone.
Ster eoch em istr y of th e Sa m a r iu m -Gr ign a r d Re-
a ction . Molander et al. have demonstrated that the
methylytterbium reagent prepared from methyllithium
and Yb(OTf)3 reacts with 2-methylcyclohexanone with a
highly selective equatorial attack.7 The stereochemical
aspects of the lanthanide-Grignard reaction of substi-
tuted cyclohexanones using Sm(OTf)2, Yb(OTf)2, SmI2, or
YbI2 are summarized in Table 4. The “methylsamarium
reagent” prepared from methyl iodide and Sm(OTf)2
showed high diastereoselectivity in the addition reaction
with 2-methylcyclohexanone in a good yield, the ratio of
axial alcohol to equatorial alcohol being 96:4 (run 1).20
The stereoselectivity of the methyl addition to the ketone
using SmI2, YbI2, or Yb(OTf)2 turned out to be lower
(axial alcohol:equatorial alcohol ) 89-80:11-20). The
“(2-phenylethyl)samarium reagent” prepared from 2-phen-
ylethyl iodide with Sm(OTf)2 also accomplished a dia-
stereoselective reaction with 2-methylcyclohexanone
(Scheme 5). The selectivity of 99:1 was higher than that
with SmI2.15 The reaction using Yb(OTf)2 and YbI2 gave
similarly high diastereoselectivity, but low yields. Ste-
reoselective addition was observed also in the reaction
with 4-tert-butylcyclohexanone using Sm(OTf)2 (axial
alcohol:equatorial alcohol ) 81-75:19-25) (Table 4, runs
12-15). On the other hand, according to earlier reports,
the SmI2-mediated alkylation of 4-tert-butylcyclohex-
anone gave the axial alcohol with 70:30 at the best ratio.15
The stereochemical outcome of the samarium-Grig-
nard reaction of 2-phenypropanal with Sm(OTf)2 was
studied in regard to the ratio of Cram to anti-Cram
c Isomer ratio was determined by GLC using a capillary column
d
DB-WAX-25N (J &W Scientific). The reaction was carried out by
the Barbier procedure. e 2.0 mL of HMPA was used. f Ref 15.
Sch em e 5
selectivity.21 Results summarized in Table 5 demonstrate
that Sm(OTf)2 always afforded higher Cram selectivity
than SmI2 in the reaction with each alkyl iodide exam-
ined: the use of Sm(OTf)2 gave 90:10 in the reaction with
methyl iodide, whereas SmI2 gave 73:27 (runs 1-3). The
Cram selectivity with Sm(OTf)2 was higher than that
with MeMgX and MeLi21 and was as high as that with
bulky methyl organometallic reagents such as MeYb-
(OTf)2 and MeTi(OR)3.22
7
Con clu sion . The new samarium reagent, Sm(OTf)2,
was readily prepared by the reduction of Sm(OTf)3 with
s-BuLi in THF. This reagent reduces alkyl halides to
produce the “organosamarium triflate” 23 that adds to a
(21) (a) Nogradi, M. Stereoselective Synthesis; VCH: Weinheim,
1995; Chapter 5 and references cited therein. (b) Maruoka, K.; Itoh,
T.; Sakurai, M.; Nonoshita, K.; Yamamoto, H. J . Am. Chem. Soc. 1988,
110, 3588.
(22) Reetz, M. T. Organotitanium Reagents in Organic Synthesis;
Springer-Verlag: Berlin, 1986.
(23) Organosamarium reagent prepared from RX/Sm(OTf)2 behaves
differently from that prepared from RX/SmI2 or RLi/Sm(OTf)3. The
differences between the various approaches may be the result of
species, LiOTf, SmInOTf3-n etc., interacting with the organosamarium
reagent.
(19) (a) J acobson, C. R.; Tait, B. D. J . Org. Chem. 1987, 52, 281. (b)
Anderson, M. B.; Fuchs, P. L. Synth. Commun. 1987, 17, 621. (c)
Narayanan, B. A.; Bunnelle, W. H. Tetrahedron Lett. 1987, 28, 6261.
(20) For a review on the stereochemistry of the alkylation and
reduction of chiral ketones, see: Ashby, E. C.; Laemmle, J . T. Chem.
Rev. 1975, 521.

5404 J . Org. Chem., Vol. 61, No. 16, 1996
Fukuzawa et al.
Ta ble 5. Cr a m /a n ti-Cr a m Selectivity in th e Alk yla tion of
P r ep a r a t ion of Sm (OTf)2 Solu t ion . Under a nitrogen
atmosphere, Sm (OTf)3 (1.2 g, 2.0 mmol) was placed in a 50-
mL Schlenk tube and equipped with a septum inlet. The tube
was heated at 200 °C in vacuo for 2 h. After the tube had
been cooled down to room temperature, a magnetic stirring
bar was placed in the flask, which was flushed with nitrogen.
THF (5 mL) was added by a syringe through the rubber
septum with stirring. The mixture was stirred at room
temperature for 1 h, and a cyclohexane solution (2.0 mL) of
s-BuLi (1.0 M, 2.0 mL, 2.0 mmol) was injected slowly into the
suspension at -20 °C. The solution was allowed to warm to
0 °C and to room temperature over a period of 1 h during which
time a purple solution of the divalent samarium triflate was
obtained. Concentration of the divalent samarium was ti-
trated to be 1.8 mmol by iodometry.11
2-P h en ylp r op a n a la
yield of
run alkyl halide
SmX2
adduct,b % Cram:anti-Cramc
1
MeI
Sm(OTf)2
SmI2
Sm(OTf)2
Sm(OTf)2
SmI2
Sm(OTf)2
Sm(OTf)2
SmI2
69
88
60
85
91
76
67
84
79
86:14
73:27
90:10
92:8f
92:8f
90:10
92:8
2d
3g
4d
5d,e
6
CH2I2
Sim p le Red u ction of 2-P h en yleth yl Iod id e w ith Sm -
(OTf)2. To the THF solution of Sm(OTf)2, prepared as
described above, was added HMPA (1.0 mL) with stirring at
room temperature, and then a mixture of 2-phenylethyl iodide
(209 mg, 0.90 mmol) and tert-butyl alcohol (70 mg, 1.0 mmol)
was added to the reagent solution. The mixture was stirred
at room temperature for 1 h until the purple color of the
solution faded. The solution was hydrolyzed with diluted HCl.
The organic phase was separated, and the aqueous phase was
extracted with diethyl ether. The combined organic extracts
were washed with brine and dried (MgSO4). GC/MS analysis
revealed the presence of ethylbenzene, the quantity of which
was determined using an internal standard (84 mg, 0.79 mmol,
88%).
n-BuI
7g
8
85:15
88:12
9g
SmI2
a
Unless otherwise noted, alkylation was carried out by using
an alkyl halide, an aldehyde, and SmX2 (0.9:0.5:2.0 molar ratio)
by the Grignard procedure at room temperature for 1 h in THF/
b
HMPA (5.0 mL/1.0 mL). Determined by GLC based on the
aldehyde. c The isomer ratio was determined by GLC using a
d
capillary column DB-WAX-25N (J &W Scientific). The reaction
was carried out by the Barbier procedure. e Tabuchi, T.; Inanaga,
J .; Yamaguchi, M. Tetrahedron Lett. 1986, 27, 3891. f Yield and
stereochemistry were determined after reduction of the iodomethyl
g
group to the methyl group. The aldehyde was added to the
Sa m a r iu m -Gr ign a r d Rea ction of Alk yl Ha lid es w ith
Ca r bon yl Com p ou n d s Usin g Sm (OTf)2. The following
provides a typical procedure for the reaction of alkyl halides
with carbonyl compounds. To the THF (5 mL)/HMPA (1.0 mL)
solution of Sm(OTf)2 (1.8 mmol) was added butyl iodide (166
mg, 0.90 mmol) at room temperature. The solution was stirred
at room temperature for 1 h during which time the purple color
of the solution faded. Acetophenone (60 mg, 0.50 mmol) was
then added to the resulting solution, and the reaction mixture
was stirred for 1 h and quenched with dilute HCl. The organic
phase was separated, and the aqueous phase was extracted
with diethyl ether. The combined organic extracts were
washed with brine and dried (MgSO4). GC/MS analysis
revealed the presence of 2-phenyl-2-hexaol, the quantity of
which was determined to be 0.45 mmol, 90% using naphtha-
lene as an internal standard. Evaporation of the solvent left
a pale yellow residue which was subjected to column chroma-
tography on silica gel; hexane/ether (1/1) eluted the alcohol.
Th e Ba r bier P r oced u r e for th e Rea ction of Alk yl
Ha lid es w ith Ca r bon yl Com p ou n d s by Diva len t La n -
th a n id e (Ln X2). The following provides the typical Barbier
procedure for the reaction of organic halides with carbonyl
compounds. To the THF/HMPA solution of LnX2 (2.0 mmol)
was added a mixture of allyl iodide (152 mg, 0.90 mmol) and
acetophenone (60 mg, 0.50 mmol). The resulting mixture was
stirred at room temperature for 1 h. The solution was
hydrolyzed with dilute HCl. The organic phase was separated,
and the aqueous phase was extracted with diethyl ether. The
combined organic extracts were washed with brine and dried
(MgSO4). GC/MS analysis revealed the presence of 2-phenyl-
4-penten-2-ol, the quantity of which was determined using
naphthalene as an internal standard.
mixture of RI and SmX2 at -78 °C.
variety of carbonyl compounds with higher diastereose-
lectivity than does the organosamarium species derived
from SmI2. Thus, Sm(OTf)2 should be a promising
reagent for selective organic synthesis.
Exp er im en ta l Section
Gen er a l. 1H and 13C NMR spectra were measured from
CDCl3 solutions. The chemical shifts are reported in δ units
downfield from the internal reference, Me4Si. GC/MS analyses
were performed on a capillary column (DB-5-30N-STD, J &W
Scientific, 0.25 mm, 30 m) (helium as carrier gas). High-
resolution mass spectra were taken at the Institute of Physical
and Chemical Research, Wako, Saitama, J apan. Column
chromatographies on SiO2 were performed with Merck silica
gel 60. Elemental analyses were carried out in the microana-
lytical laboratory of Chuo University.
Ma ter ia ls. Samarium(III) trifluoromethanesulfonate was
prepared from samarium oxide (Nippon Yttrium Co., Ltd,
99.9%) and trifluoromethanesulfonic acid in water: the result-
ing hydrate was dried by heating under vacuum at 200 °C for
48 h.24 Butyllithium (1.6 M, hexane solution), s-butyllithium
(1.0 M, cyclohexane solution), tert-butyllithium (1.0 M, cyclo-
hexane solution), and Grignard reagents (1.0 M, THF solution)
were purchased from Kanto Chemicals and used after titra-
tion.25 THF was distilled under nitrogen from sodium ben-
zophenone ketyl just prior to use. HMPA was purchased from
Aldrich and distilled from CaH2 and kept over 4A molecular
sieves under nitrogen. The THF solution of SmI2 or YbI2 was
prepared from samarium or ytterbium metal (Nippon Yttrium
Co., Ltd, 99.9%) and 1,2-diiodoethane as described in the
literature.11b Authentic samples for GC/MS analyses were
prepared by the reaction of carbonyl compounds with Grignard
reagents. All organic compounds were commercially available
and used without purification unless otherwise noted.
Ca u tion : Sm(OTf)3 is quite hygroscopic and must be
strictly dried before use. Preparation of divalent samarium
[Sm(OTf)2] was unsuccessful if a slight amount of moisture
was present as a contaminant.
3-Meth yl-2-p h en yl-2-bu ta n ol. The title compound was
prepared by the reaction of isopropyl bromide with acetophe-
none. 1H NMR (CDCl3, 400 MHz) δ 0.80 (d, 3H, J ) 6.8 Hz),
0.89 (d, 3H, J ) 6.8 Hz), 1.52 (s, 3H), 1.66 (s, 1H, OH), 2.02
(oct, 1H, J ) 6.8 Hz), 7.2-7.4 (m, 5H). 13C NMR (CDCl3) δ
17.1, 17.3, 26.5, 38.5, 76.6, 125.2, 126.3, 127.7, 147.7. HRMS
(EI) m/ z calcd for C11H16O 164.1201, found 164.1200 (M+). IR
(neat) 3466, 2971, 1446, 1372, 1029 cm-1
.
2-Meth yl-2-tetr a d eca n ol. The title compound was pre-
pared by the reaction of 1-iodododecane with acetone. 1H NMR
(CDCl3, 400 MHz) δ 0.88 (t, 3H, J ) 7.1 Hz), 1.21 (s, 6H), 1.25-
1.51 (m, 22H), 2.28 (s, 1H). 13C NMR (CDCl3) δ 13.8, 22.5,
24.2, 28.8, 29.3, 29.5, 29.6, 30.1, 31.8, 43.8, 70.2. HRMS (EI)
m/ z calcd for C15H30 (M+ - H2O) 210.2347, found 210.2350.
(24) Smith, P. H.; Raymond, K. N. Inorg. Chem. 1985, 24, 3469.
(25) Watson, S. C.; Eastham, J . F. J . Organomet. Chem. 1967, 9,
165.

Samarium(II) Triflate in Grignard-Type CO Addition
Anal. Calcd for C15H32O: C, 78.87; H, 14.12. Found: C, 78.72;
J . Org. Chem., Vol. 61, No. 16, 1996 5405
4352-39-0; 1-butyl-1-cylohexanol, 5445-30-7; 5-methyl-5-un-
decanol, 21078-80-8; 1-phenyl-1-pentanol, 583-03-9; 1-butyl-
2-cyclohexen-1-ol, 88116-46-5; 3-methyl-1-phenyl-1-hepten-3-
ol, 91671-45-3; 2-butyl-1,2,3,4-tetrahydro-2-naphthol, 91671-
46-4; 2-phenyl-4-penten-2-ol, 4743-74-2; 1-phenyl-3-buten-1-
ol, 936-58-3; 1-(2-propenyl)-1-cyclohexanol, 1123-34-8; 1-benzyl-
1-cyclohexanol, 1944-01-0; 2-methyl-1-phenyl-2-propanol, 100-
86-7; trans-1,2-dimethyl-1-cyclohexanol, 19879-12-0; cis-1,2-
dimethyl-1-cyclohexanol, 19879-11-9; 2-methyl-1-(2′-phenyl-
ethyl)-1-cyclohexanol, 108686-39-1;2-methyl-1-(2′-phenylethyl)-
1-cyclohexanol, 142041-26-7; trans-4-tert-butyl-1-methyl-1-cy-
clohexanol, 16980-55-5; cis-4-tert-butyl-1-methyl-1-cyclohex-
anol, 16980-56-6; cis-4-tert-butyl-1-(2′-phenylethyl)-1-cyclo-
hexanol, 142041-15-4; trans-4-tert-butyl-1-(2′-phenylethyl)-1-
cyclohexanol, 142041-25-6; trans-2-methyl-1-(2′-propenyl)-1-
cyclohexanol, 24580-51-6; (R,R)-3-phenyl-2-butanol, 1502-79-
0; (R,S)-3-phenyl-2-butanol, 1502-80-3; (R,R)-2-phenyl-3-
heptanol, 96929-99-6; (R,S)-2-phenyl-3-heptanol, 96930-05-1
acetophenone, 98-86-2; propiophenone, 93-55-0; ethyl 3-hy-
droxy-3-phenylbutanoate, 2293-60-9; (R,S)-ethyl 3-hydroxy-2-
methyl-3-phenylpropionate, 17226-81-2; (R,R)-ethyl 3-hydroxy-
2-methyl-3-phenylpropionate, 17226-82-3; 4-methyl-4-phenyl-
γ-butyrolactone, 21303-80-0; 1-oxaspiro[4.5]decane-2-one, 699-
61-6, R-methylstyrene, 98-83-9; 4-phenyl-1-butene, 768-56-9.
H, 13.90. IR (neat) 3366, 2924, 2853, 1466, 1376 cm-1
.
5-Dod eca n ol. The title compound was prepared by the
reaction of butyl iodide with octanal. 1H NMR (CDCl3, 400
MHz) δ 0.89 (t, 3H, J ) 7.1 Hz), 0.91 (t, 3H, J ) 7.1 Hz), 1.2-
1.6 (m, 18 H), 1.65 (s, 1H, OH), 3.60 (m, 1H). 13C NMR (CDCl3)
δ 14.0, 22.6, 22.7, 25.6, 27.8, 29.2, 29.6, 31.8, 37.1, 37.4, 71.9.
HRMS (EI) m/ z calcd for C12H26O (M+) 186.1984, found
186.1981. IR (neat) 3341, 2956, 2927, 2857, 1465, 1041 cm-1
.
2-Meth yl-3-(2′-p r op yl)-3-h ep ta n ol. The title compound
was prepared by the reaction of butyl iodide with 2,4-dimethyl-
3-pentanone. 1H NMR (CDCl3, 400 MHz) δ 0.9-1.5 (m, 21H),
1.93 (sept, 2H, J ) 6.8 Hz). 13C NMR (CDCl3) δ 13.9, 17.0,
17.4, 23.7, 26.4, 33.7. HRMS (EI) m/ z calcd for C11H22 (M+
-
H2O) 154.1721, found 154.1720. IR (neat) 3489, 2958, 1467,
1132 cm-1
.
1,3-Dip h en yl-1-p r op a n on e. The title compound was pre-
pared by the reaction of 2-phenylethyl iodide with N,N-
dimethylbenzamide. Mp 67-69 °C. 1H NMR (CDCl3, 400
MHz) δ 3.08 (t, 2H, J ) 8.1 Hz), 3.31 (t, 2H, J ) 8.1 Hz), 7.2-
7.6 (m, 8H). 13C NMR (CDCl3) δ 30.1, 40.4, 126.1, 128.0, 128.4,
128.5, 128.6, 133.0, 136.8, 141.3, 199.2. Anal. Calcd for
C15H14O: C, 85.68; H, 6.71. Found: C, 85.51; H, 6.83. IR
(KBr) 1681 cm-1
.
1-[(E t h oxyca r b on yl)m et h yl]cycloh exa n ol.26 The title
compound was prepared by the reaction of ethyl bromoacetate
with cyclohexanone. 1H NMR (CDCl3, 400 MHz) δ 1.2-1.8
(m, 15H), 2.47 (s, 2H), 3.4 (br s, 1H), 4.17, (q, 2H). 13C NMR
(CDCl3) δ 14.1, 21.9, 25.5, 37.4, 45.2, 60.5, 69.9, 172.8. HRMS
(EI) m/ z calcd for C10H18O3 (M+)186.1256, found 186.1261. IR
Ack n ow led gm en t. This work was supported by a
Grant-in-Aid for Scientific Research on Priority Areas,
“New Development of Rare Earth Complexes”, from the
Ministry of Education, Science and Culture. We are
also grateful to the Asahi Glass Foundation for financial
support. We are grateful to Dr. Tetsuya Kajimoto and
Ms. Maki Takebayashi, the Institute of Physical and
Chemical Research, Wako, Saitama, for recording the
high-resolution mass spectra. We thank Central Glass
Co. Ltd. (J apan) for kindly supplying us trifluo-
romethanesulfonic acid.
(neat) 3522, 2933, 1715, 1194, 1029 cm-1
.
Meth ylen ecyclod od eca n e. The title compound was pre-
pared by the reaction of (iodomethyl)trimethylsilane with
cyclododecanone. 1H NMR (CDCl3, 400 MHz) δ 1.2-2.0 (m,
22H), 4.72 (m, 2H). 13C NMR (CDCl3) δ 22.7, 23.3, 23.8, 24.2,
24.5, 33.1, 110.4, 147.1. HRMS (EI) m/ z calcd for C13H24 (M+)
180.1878, found 180.1881. IR (neat) 2930, 2861, 1643 cm-1
.
Su p p or tin g In for m a tion Ava ila ble: Copies of 1H spectra
of all known and new compounds (35 pages). This material is
contained in libraries on microfiche, immediately follows this
article in the microfilm version of the journal, and can be
ordered from the ACS; see any current masthead page for
ordering information.
Registr y Nu m ber s (su p p lied by a u th or ): 2-Phenyl-2-
propanol, 617-94-7; 2-phenyl-2-butanol, 1565-75-9; 2-phenyl-
2-pentanol, 4383-18-0; 2-phenyl-2-hexanol, 4396-98-9; 2-methyl-
4-phenyl-2-butanol, 103-05-9; 1-cyclohexyl-1-phenylethanol,
(26) Fukuzawa, S.; Hirai, K. J . Chem. Soc., Perkin Trans. 1 1993,
1963.
J O960260S