Samarium-induced convenient reductive dimerization of aromatic ketones in aqueous methanol: A mechanistic approach

Article abstract of DOI:10.1016/j.tetlet.2005.08.034

Samarium metal has been used for the reductive dimerization of aromatic ketones in the presence of additives; the most probable mechanism has been advanced to explain the diastereoselectivity of this dimerization reaction.

Full text of DOI:10.1016/j.tetlet.2005.08.034

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 7065–7068
Samarium-induced convenient reductive dimerization of
aromatic ketones in aqueous methanol: a mechanistic approach
Bimal K. Banik,a,* Indrani Banik,b Nacer Aounallaha, and Mark Castilloa,
aDepartment of Chemistry, The University of Texas-Pan American, 1201 West University Drive, Edinburg, TX 78541, USA
bThe University of Texas, M. D. Anderson Cancer Center, Houston, TX 77030, USA
Received 17 July2005; accepted 5 August 2005
Available online 25 August 2005
Abstract—Samarium metal has been used for the reductive dimerization of aromatic ketones in the presence of additives; the most
probable mechanism has been advanced to explain the diastereoselectivityof this dimerization reaction.
Ó 2005 Elsevier Ltd. All rights reserved.
Dissolving metal reduction of carbonyl compounds is a
veryattractive procedure. 1 Manymetals, such as Li, Na,
Mg, Ca, In, Zn, and Al, can be used in the presence of
different solvent compositions.2 Samarium metal is well
suited to overcoming the drawbacks of dissolving metal
reductions because of its stabilityin air and strong
reducing power. The operational simplicityof using
samarium metal in various chemical reactions has been
demonstrated in recent publications.3,4
In this letter, we report a facile, convenient method of
reductive dimerization of aromatic ketones bysamarium
metal in the presence of different additives (Scheme 1).
Interestingly, samarium metal/ammonium chloride or
bromide in aqueous methanol has been identified as
the best reagent for the reductive dimerization of car-
bonyl compounds. A most probable mechanism is also
presented herein to explain the diastereoselectivityof
this dimerization reaction.
Scheme 1.
Keywords: Samarium; Reductive dimerization; Aromatic ketones; Electron transfer.
*
Corresponding author. Tel.: +1 956 380 8741; fax: +1 956 384 5006; e-mail: banik@panam.edu
These authors contributed equally.
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.08.034

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B. K. Banik et al. / Tetrahedron Letters 46 (2005) 7065–7068
Reductive coupling of carbonyl compounds to pinacols
using samarium/iodine in methanol (a mixture of dl and
meso) and samarium/iodine-titanium isopropoxide
(meso preferred) was achieved.4e A bivalent salt-free
samarium bis (trifluoromethanesulfonate) complex was
used for intermolecular pinacol coupling reactions of
aromatic ketones to diols with a high level of diastereo-
change was so significant that the reaction did not pro-
ceed more than 10% in aqueous media. The reaction
did not proceed at all, however, when NaCl or NaBr
was used as the metal salt under identical conditions.
The NH4Cl/aqueous methanol and NH4Br/aqueous
methanol-mediated reactions were faster than alkyl
halides-mediated reactions. In the present study, dl iso-
mer was the predominant product. Inverse addition of
the reagents to the substrates was not helpful in further
improving the isomeric ratios. For example, addition of
the reagent system generated via reaction of the samar-
ium metal/NH4Cl/water/methanol to acetophenone
and 4-chloroacetophenone produced dl as the predomi-
nant isomer over the meso (80:20). In the inverse addition
method, the ratio of the isomer distribution and dimer-
ization depended on how well the reagents could be
added to the ketones. The mixed reagent generated via
reaction of samarium/NH4Cl or Sm/NH4Br in aqueous
methanol looked like a dark suspension. For better yield,
it was necessaryto add the whole reagent suspension
slowlyto the ketones. The yield of the products decreased
considerablywhen solid materials were removed via fil-
tration and the filtered reagent solution was added to
the ketones. It has been demonstrated that insoluble
samarium has a profound role in some reaction.3–5
6
selectivity( dl isomer was predominantlyformed). Dia-
stereoselective pinacol coupling of alkyl aryl ketones
with samarium in the presence of trimethylsilyl chloride
was accomplished.7 Sm/Et2AlI was used for the reduc-
tive coupling of carbonyl compounds.8 These reactions
were performed under anhydrous and inert atmosphere.
During the course of our studyof metal-induced reac-
tions, we discovered that the reductive coupling of aro-
matic ketones can be accomplished veryefficiently
using Sm/NH4Cl in aqueous methanol.5 Interestingly,
ultrasonic exposure of the same reaction mixture resulted
in a 20–30% reduction product. The steric crowding of
aromatic ketones has posed no problems in dimer forma-
tion when the reaction was performed in aqueous metha-
nol using NH4Cl/NH4Br. In addition, it improved the
ratio of the dimers (dl and meso). In a detailed study, it
was realized that the best yield could be obtained when
the proportion of methanol and water was kept at 9:1
or 8:2 (Table 1). An increase in the amount of water
resulted in a decrease of the yield of the product. This
Given the nature of the products, the most probable
mechanism would be a reaction verysimilar to our
Table 1. Reductive coupling of aromatic ketones with samarium and different additives
a
EntryKetone
Additive
ieDldio%l)(y
dl:mesob
Alcohol (yield %)a
Time (h)
1
2
3
4
5
6
7
8
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1b
1b
1b
1b
1b
1b
1c
1d
1e
1f
Allyl bromidec
2a (69)
2a (65)
2a (60)
2a (50)
2a (69)
2a (72)
2a (80)
2a (82)
2a (82)
2a (61)
2a (0)
2b (59)
2b (58)
2b (70)
2b (70)
2b (80)
2b (80)
2c (59)
2d (57)
2e (50)
2f (49)
2g (15)
2b (60)
3c (71)
3f (43)
2a (99)
58:42
55:45
55:45
58:42
58:42
60:40
80:20
80:20
80:20
82:18
3a (2)
3a (2)
3a (5)
3a (5)
3a (10)
3a (15)
3a (5)
3a (5)
3a (5)
3a (10)
3a (0)
3b (11)
3b (10)
3b (10)
3b (15)
3b (5)
3b (5)
3c (11)
3d (9)
3e (8)
3f (24)
3g (20)
3b (0)
3c (0)
3f (0)
3
3
4
Allyl iodidec
4-Bromo-1-butanec
Ethylene dibromidec
Ammonium chloridec
Ammonium chlorided
Ammonium chloridee
Ammonium chloridef
Ammonium bromidef
6
0.5
0.08
0.5
0.5
0.5
3.5
5
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
Diethyl aluminum iodideg
sodium chloridee,f
Allyl bromidec
59:41
60:40
60:40
60:40
75:25
75:25
59:41
59:41
58:42
60:40
100:0
57:43
82:18
55:45
90:10
5
5
Allyl iodidec
Ammonium chloridec
Ammonium chlorided
Ammonium chloridef
Ammonium chloridef
Allyl bromidec
0.5
0.08
0.5
0.5
5
5
5
5
20
4
Allyl bromidec
Allyl bromidec
Allyl bromidec
1g
1b
1c
1f
Allyl bromidec
Diethyl aluminum iodideg
Diethyl aluminum iodideg
Diethyl aluminum iodideg
Samarium-complexg
4
4
0.5
1a
3a (0)
a Isolated yield.
b Calculated from 300 MHz NMR.
c Methanol as the solvent.
d Methanol as the solvent in the presence of ultrasound.
e Methanol/water (8:2) as the solvent.
f Methanol/water (9:1) as the solvent.
g Acetonitrile as the solvent.

B. K. Banik et al. / Tetrahedron Letters 46 (2005) 7065–7068
7067
Scheme 2.
samarium/iodine-induced reduction reaction of the imi-
nes.5b Single electron transfer to an unsaturated carbon–
oxygen bond can generate the ion radical A, and, be-
cause of the stabilityof the benzylic radical, the self-cou-
pling process A to B (D or E) is feasible. As a result, the
pinacol-type compound 2 is formed. Further electron
transfer to the ion radical A can be a competitive path
to the dianion C, which can be easilyprotonated by
methanol to generate the alcohol 3 (Scheme 2). If the
reaction is fast, electron transfer to form the dianion
path does not seem to be favorable, as the normal reduc-
tion of the ketone has been found to be minimal when
NH4Cl/NH4Br is the additive. If it proceeds slowly,
however, this reaction produces a significant amount
of the meso product. This has been established bythe
fact that performing the reaction in the presence of
alkyl/allyl halides produces a considerable amount of
the meso isomer. Summarizing the results on the dia-
stereoselectivity, a hypothetical transition-state model
could be proposed.
3). This happens when alkyl halides are the additives.
When the reaction is fast, particularlyif it is an NH Cl
4
and NH4Br-induced reaction, the high stereoselectivity
of pinacolic coupling can be explained bythe chelation
model, in which samarium binds with two oxygens of
the carbonyl groups. It is assumed that the use of ammo-
nium salts can enhance this type of chelation.
As a result of this chelation, there is no difference in
diastereoselectivitywhen an alternative mode of addi-
tion is used. Inverse addition would provide even better
dl selectivityif there is no chelation. In the inverse
addition method, the concentration of the reagent is
not veryhigh in the reaction media particularlyat
the initial stages, when compared with the concentra-
tion of the substrates. Therefore, a portion of the ketyl
radical should then react with the ketone due to coor-
dination of its carbonyl oxygen with the samarium spe-
cies of the ion radical, leading to a higher dl ratio. In
an earlier publication, the stereoselectivityof the prod-
ucts was rationalized byconsidering the chelation of
samarium or aluminum with an oxygen atom.8 In con-
trast to the existing method,8 our approach is simple,
moisture insensitive, and works well in the presence
of inexpensive reagent. However, the conditions of
those experiments were clearlydifferent than our pres-
ent approach.
When the substrate is added to the reagent system and
the reaction is relativelyslow, two competitive paths
mayfollow: combination of an ion radical to generate
a stericallyfavored transition state D or combination
of an ion radical with the remaining ketone (E). The
resulting product is a mixture of meso and dl (Scheme
Scheme 3.

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B. K. Banik et al. / Tetrahedron Letters 46 (2005) 7065–7068
Bessho, K.; Yanada, K. Synlett 1995, 1261; (d) Yanada, R.;
Negoro, N. Tetrahedron Lett. 1996, 37, 9313; (e) Yanada,
R.; Negoro, N.; Yanada, K.; Fujita, T. Tetrahedron Lett.
1997, 38, 3271; (f) Negoro, N.; Yanada, R.; Okaniwa, M.;
Yanada, K.; Fujita, T. Synlett 1998, 835; (g) Yanada, R.;
Negoro, N.; Okaniwa, M.; Miwa, Y.; Taga, T.; Yanada,
K.; Fujita, T. Synlett 1999, 537; (h) Yanada, R.; Negoro,
N.; Okaniwa, M.; Ibuka, T. Tetrahedron 1999, 55, 13947.
5. For samarium-induced reactions reported from our labo-
ratory, see: (a) Banik, B. K.; Mukhopadhyay, C.; Venkat-
raman, M. S.; Becker, F. F. Tetrahedron Lett. 1998, 39,
7343; (b) Banik, B. K.; Zegrocka, O.; Banik, I.; Hackfeld,
L.; Becker, F. F. Tetrahedron Lett. 1999, 40, 6731; (c) Basu,
M. K.; Becker, F. F.; Banik, B. K. Tetrahedron Lett. 2000,
41, 6551; (d) Basu, M. K.; Becker, F. F.; Banik, B. K. J.
Chem. Res. 2000, 8, 406; (e) Banik, B. K.; Zegrocka, O.;
Becker, F. F. J. Chem. Res. 2000, 7, 321; (f) Ghatak, A.;
Becker, F. F.; Banik, B. K. Tetrahedron Lett. 2000, 41,
3793; (g) Basu, M. K.; Banik, B. K. Tetrahedron Lett. 2001,
42, 187; (h) Banik, B. K. Eur. J. Org. Chem. 2002, 2431; (i)
Banik, B. K.; Venkatraman, M. S.; Banik, I.; Basu, M. K.
Tetrahedron Lett. 2004, 45, 4737; (j) Banik, B. K.; Banik, I.;
Samajdar, S.; Cuellar, R. Tetrahedron Lett. 2005, 46, 2319.
6. (a) Mashima, K.; Oshiki, T.; Tani, K. J. Org. Chem. 1998,
63, 7114; (b) Collin, J.; Giuseppone, N.; Machrouhi, F.;
Namy, J.-L.; Nief, F. Tetrahedron Lett. 1999, 40, 3161.
7. Wang, L.; Zhang, Y. Tetrahedron 1998, 54, 11129.
8. Nishiyama, Y.; Shinomiya, E.; Kimura, S.; Itoh, K.;
Sonoda, N. Tetrahedron Lett. 1998, 39, 3705. For the
discussion of stereoselectivityof related reactions, see:
Hirao, T.; Hatano, B.; Imamoto, Y.; Ogawa, A. J. Org.
Chem. 1999, 64, 7665.
In conclusion, we have developed an efficient methodol-
ogyfor reductive coupling of aromatic ketones to pro-
duce the corresponding diols in aqueous methanol
under environmentallyfriendlyconditions using ammo-
nium salts as the promoter in good yield and with excel-
lent selectivity.9
Acknowledgments
We gratefullyacknowledge the partial financial support
for this research from The Universityof Texas, M. D.
Anderson Cancer Center and The Robert A. Welch
Foundation (BG-0017) departmental grant.
References and notes
1. For a general review, see: McMurray, J. E. Chem. Rev.
1989, 89, 1513, and references cited therein.
2. (a) Zhang, W.-C.; Li, C.-J. J. Org. Chem. 1999, 64, 3230; (b)
Rieke, R. D.; Kim, S.-H. J. Org. Chem. 1998, 63, 5235, and
references cited therein.
3. For various samarium metal-induced reactions, see: (a)
Murakami, M.; Hayashi, M.; Ito, Y. Synlett 1994, 179; (b)
Yanada, R.; Bessho, K.; Yanada, K. Chem. Lett. 1994,
1279; (c) Yanada, R.; Bessho, K.; Yanada, K. Synlett 1995,
443; (d) Yanada, R.; Negoro, N.; Bessho, K.; Yanada, K.
Synlett 1995, 1261; (e) Yanada, R.; Negoro, N.; Yanada,
K.; Fujita, T. Tetrahedron Lett. 1996, 37, 9313; (f) Yanada,
R.; Negoro, N.; Yanada, K.; Fujita, T. Tetrahedron Lett.
1997, 38, 3271; (g) Negoro, N.; Yanada, R.; Okaniwa, M.;
Yanada, K.; Fujita, T. Synlett 1998, 835; (h) Yanada, R.;
Negoro, N.; Okaniwa, M.; Miwa, Y.; Taga, T.; Yanada,
K.; Fujita, T. Synlett 1999, 537; (i) Ogawa, A.; Takeuchi,
H.; Hirao, T. Tetrahedron Lett. 1999, 40, 7113; (j) Yanada,
R.; Negoro, N.; Okaniwa, M.; Ibuka, T. Tetrahedron 1999,
55, 13947; (k) Lautens, M.; Ren, Y. J. Org. Chem. 1996, 61,
2210.
9. Representative experimental procedure:
A mixture of
acetophenone 1a (0.1 g, 0.83 mmol), samarium metal
(0.375 g, 2.49 mmol), ammonium chloride (5 equiv) in
methanol/water (10:1, 5 mL) was stirred at room temper-
ature, the reaction was monitored byTLC. After the ketone
was consumed (30 min), the reaction mixture was diluted
with CH2Cl2 and 0.5 mL of a saturated NaHCO3 solution
was added and then passed through a pad of Celite.
The filtrate was dried (Na2SO4) and concentrated, and
the residue was subjected to silica gel chromatography. The
diol 2a was obtained in 79% yield as a mixture of
diastereomers (dl:meso = 80:20).
4. For examples, see: (a) Yanada, R.; Bessho, K.; Yanada, K.
Chem. Lett. 1994, 1279; (b) Yanada, R.; Bessho, K.;
Yanada, K. Synlett 1995, 443; (c) Yanada, R.; Negoro, N.;