MeOH or H2O as efficient additive to switch the reactivity of allylSmBr towards carbonyl compounds

Article abstract of DOI:10.1016/j.tetlet.2017.01.091

A variety of carbonyl compounds were treated by allylSmBr (allylSmBr) with MeOH as the cosolvent to have further insights on the previously reported reductive coupling of aryl ketones mediated by Sm/alkyl halide/MeOH. The results demonstrate that the real reducing species in Sm/alkyl halide/MeOH system should be allylSmBr, and MeOH has elegantly switched the reactivity of allylSmBr from being nucleophilic to being good reductive coupling reagent. Besides, H₂O was also found to be a useful additive to realize the pinacol coupling of aliphatic aldehydes and ketones promoted by allylSmBr.

Full text of DOI:10.1016/j.tetlet.2017.01.091

Accepted Manuscript
MeOH or H2O as efficient additive to switch the reactivity of allylSmBr towards
carbonyl compounds
Jianyong Li, Qingsheng Niu, Shanchan Li, Yuehao Sun, Qian Zhou, Xin Lv,
Xiaoxia Wang
PII:
S0040-4039(17)30135-1
DOI:
http://dx.doi.org/10.1016/j.tetlet.2017.01.091
TETL 48594
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
23 December 2016
21 January 2017
25 January 2017
Please cite this article as: Li, J., Niu, Q., Li, S., Sun, Y., Zhou, Q., Lv, X., Wang, X., MeOH or H2O as efficient
additive to switch the reactivity of allylSmBr towards carbonyl compounds, Tetrahedron Letters (2017), doi: http://
dx.doi.org/10.1016/j.tetlet.2017.01.091
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Tetrahedron Letters
MeOH or H2O as efficient additive to switch the reactivity of allylSmBr towards
carbonyl compounds
Jianyong Li, Qingsheng Niu, Shanchan Li, Yuehao Sun, Qian Zhou, Xin Lv and Xiaoxia Wang*
Zhejiang Key Laboratory for Reactive Chemistry on Solid Surfaces, College of Chemistry and Life Sciences, Zhejiang Normal University, Jinhua 321004,
People’s Republic of China
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A variety of carbonyl compounds were treated by allylSmBr (allylSmBr) with MeOH as the
cosolvent to have further insights on the previously reported reductive coupling of aryl ketones
mediated by Sm/alkyl halide/MeOH. The results demonstrate that the real reducing species in
Sm/alkyl halide/MeOH system should be allylSmBr, and MeOH has elegantly switched the
reactivity of allylSmBr from being nucleophilic to being good reductive coupling reagent.
Besides, H2O was also found to be a useful additive to realize the pinacol coupling of aliphatic
aldehydes and ketones promoted by allylSmBr.
Available online
Keywords:
Allylsamarium bromide
MeOH
2017 Elsevier Ltd. All rights reserved.
H2O
Pinacol coupling
Diols
1. Introduction
with a small amount of MeOH or diethyl phosphate as additive. it
seems plausible that the real reducing species is allylSmBr and
The reaction between Sm and allylic bromide has been known to
generate allylic samarium bromide (allylSmBr) in THF, which is
an organosamarium reagent and proved to be highly
nucleophilic.1 Grignard reaction took place when the carbonyl
compounds were treated by the species affording homoallylic
methanol could tune the reactivity of allySmBr towards the
coupling reactions that yield pinacol products. To prove the
proposal, allylSmBr was prepared according to standard
procedure in THF and a variety of cosolvents including MeOH
was added to the mixture before the carbonyl compound was
introduced. Benzaldehyde was used as the model substrate and
the results are shown in Table 1.
alcohols in good to excellent yields (Scheme
1
(a)).2a
Interestingly, Banik group reported that aromatic ketones when
treated by Sm/allylic bromide in MeOH (Barbier reaction
condition) afforded the diols in moderate yields (Scheme 1 (b))2b.
It is noteworthy that reductive coupling occurred instead of the
normal Barbier reaction.
Table 1. The effects of a variety of additives on the reactivity
of allylSmBr towards benzaldehydea
Entry
Addtive
Yield(%)b of 3a
Yield(%)b of 2a
1
2
MeOH (5ml)
50
32
MeOH (10ml)
MeOH (20ml)
EtOH (10ml)
i-PrOH (10ml)
t-BuOH (10ml)
86
69
51
45
52
trace
Scheme 1. Reactions of carbonyl compounds with Sm, and
allylic bromide under Grignard or Barbier conditions
3
4
5
6
c
-
Apparently, the existence of a reducing species should
account for the latter pinacol coupling. The study carried out by
Banik group excluded the generation of samarium dibromide
under the condition, but the mechanism still remains unclear.
Based on our recent study3 on the reactivity of allylSmBr, whose
reducing ability was greatly enhanced by using HMPA as the
additive, and the work by Zhang’s group, who have achieved the
reductive dehalogenation4a and deoxygenation4b using allylSmBr
26
41
34

2
Tetrahedron Letters
7
8
9
indicating the detrimental effect of excess H2O. Finally, 1.4
n-BuOH (10ml)
Pyridine (10ml)
Et3N (10ml)
10
48
52
57
equiv. of H2O was found to give useful yields of 3q (62%).
Cyclopentanone and n-nonyl aldehyde afforded the
corresponding diols in similar yields (entries 4 and 5).
Investigation has also been carried out to see if H2O as the
additive could improve the reductive coupling of 1j, il and 1n,
since with MeOH as the cosolvents, these substrates afforded
significant amounts of addition products. As shown in Table 3,
very little improvement could be observed for 2-furaldehyde 1j
(Table 3, entry 6 vs Table 2, entry 10). For 1l, however,
significant improvement was achieved. 1l afforded the diols 3l
in 91% yield and no addition product could be detected under
allylSmBr/H2O conditions (Table 3, entry 7 vs Table 2, entry
12). Substrates 1n afforded simple alcohol 4n as the only
product in 98% yield under allylSmBr/H2O conditions and the
addition product was not detected (Table 3, entry 7 vs Table 2,
entry 14).
trace
trace
a
Reaction conditions: substrate 1.0 mmol, Sm 2.5 mmol,
allylBr 1.4 mmol, additive in dry THF 10 mL under N2 at
the room temperature.
b Isolated yield
c Not detected.
When MeOH (5 mL) was used as the cosolvent, it was
satisfying to find benzaldehyde afforded the desired diols 3a in
50% yield (Table 1, entry 1). Since the homoallylic alcohol 4a
was still formed in a significant ratio (32%), the dosage of
MeOH was increased. When 10 mL of MeOH was attempted,
Gratifyingly, the yield of 2a was improved to 86% (Table 1,
entry 2). However, further increase of MeOH dosage led to
incomplete reaction and decreased yield (Table 1, entry 3). In
contrast, the influences of other cosolvents such as EtOH,
tBuOH, Pyridine and Et3N did not show comparable results.
At this stage, it is reasonable to conclude that the real
reducing species in the reactions reported by Banik was
allylSmBr. MeOH should function as a donor ligand and also is
a suitable proton source to Sm(II)5 thus switching the reactivity
of allylSmBr from being nucleophilic to good SET reagent to
facilitate the coupling reaction.
Table 3. Influences of H2O on the reactivity of allylSmBr
towards aliphatic carbonyl compoundsa
Entry Substrates 1 Additive
Yield(%)b of 3 Yield(%)b
of 2
1
H2O (1.0 quiv.)
3q, 43
2q, 38
1q
c
2
3
4
H2O (2.0 quiv.)
H2O (1.4 quiv.)
H2O (1.4 quiv.)
1q
1q
3q, 48
3q, 62
3r, 67
-
The generality of the reaction was also examined6 (table 2).
Aromatic aldehydes could afford the diols 3a-3i in good to
excellent yields with trace amounts of the alcohol 4 being
detected (Table 2, entries 1-9). Both electron-withdrawing and
electron-donating groups were tolerated, including the hydroxyl
(entry 9). 2-Furaldehyde also underwent the coupling smoothly
(entry 10). Aryl ketones and diaryl ketones afforded satisfying
yields of the diols (entry 11-16) wherein the simple reduction
affording benzhydrols 4 was inevitable in some cases. For
aliphatic ketones and aldehydes, poor or even no yield of the
diol 3 coud be obtained and 4 became the major products (entry
17-18).
In recent years, H2O has been well documented as an
additive to SmI2.7 Considering the similarity between the two
reagents, H2O was then attempted as additive to allylSmBr here
for the coupling reaction of aliphatic carbonyl compounds.
Although H2O has been reported to greatly enhance the
reducing power of SmI2,7 this simple molecule as an additive to
switch the reactivity of allylSmBr is not known partly because
the organosamarium reagents were usually believed to be
moisture sensitive. Tentatively, only 1.0 equiv. of H2O was first
added (Table 3, entry 1). It is encouraging to find allylSmBr did
tolerate the existence of H2O to some extent and afforded the
diol 3q in 43% yield. Increase of the H2O dosage to 2 equiv.
resulted in incomplete consumption of the starting materials
2q, 20
2r,15
1r
5
6
7
H2O (1.4 quiv.)
H2O (1.4 quiv.)
H2O (1.4 quiv.)
3s, 61
3j, 71
2s, 17
2j, 11
1s
1j
3l, 91
2l, trace
4n, 98
1l
8
H2O (1.4 quiv.)
3n, trace
1n
a
Reaction conditions: substrate 1.0 mmol, Sm 2.5 mmol,
allylBr 1.4 mmol, additive in dry THF 10 mL under N2 at
the room temperature.
b Isolated yield
c Not detected. Incomplete comsumption of 1q.
Table 2. Reductive coupling of aldehydes and ketones with allylSmBra
Entry
1
Substrates 1
Products 3
Yield (%) of 3b
dl : meso
41:59
Yield (%) of 4b
86
trace
1a
3a

2
78
trace
47:53
1b
3b
3
4
82
85
trace
trace
47:53
71:29
3c
1c
1d
3d
5
6
65
86
trace
trace
53:47
47:53
1e
3e
1f
3f
7
8
55
73
trace
trace
53:47
49:51
1g
3g
1h
3h
9
trace
12
81
67
77:23
57:43
1i
3i
10
1j
3j
11
12
80
73
trace
26
56:44
72:28
1k
3k
1l
3l
13
14
15
16
84
70
92
75
trace
21
-
62:38
1m
3m
-
-
-
1n
3n
3o
1o
1p
11
3p
17
18
40
36
77
-
-
3q
1q
trace
1r
3r
a Reaction condition: substrate 1.0 mmol, Sm 2.5 mmol, allylBr 1.4 mmol, MeOH 10 ml in dry THF 10 mL under
N2 at the room temperature.
bIsolated yields.

4
Tetrahedron Letters
Chinese U. 2003, 24, 1618–1620; (b) Ghatak, A.; Becker, F. F.;
Banik, B. K. Tetrahedron Lett. 2000, 41, 3793–3796.
In conclusion, allySmBr-induced reductive coupling of
carbonyl compounds has been developed. MeOH and H2O were
found to be effective additive being able to switch the reactivity
of allylSmBr. Thus the highly nucleophilic allylSmBr could
function as good reductive coupling or reducing reagent in their
3.
(a) Tu, Y. W.; Zhou, L. J.; Yin, R. F.; Lv. X.; Flowers, R. A. II;
Choquette, K. A.; Liu, H. L.; Niu, Q. S.; Wang, X. X. Chem.
Commun. 2012, 48, 11026–11028. (b) Shen, M. M.; Tu, Y. W.;
Xie, G. Q.; Niu, Q. S.; Mao H.; Xie, T. T.; Flowers II, R. A.; Lv,
X.; Wang, X. X. J. Org. Chem. 2015, 80, 52–61. (c) Yin, R. F.;
Zhou, L. J.; Liu, H. L.; Mao, H.; Lv, X.; Wang, X. X. Chin. J.
Chem. 2013, 31, 143–148.
presence. Since MeOH and H2O are greener additives than
HMPA,8,
the reactivity of allylSmBr switched by these
3a-b
additives is worthy of further study so as to find more
interesting applications in organic synthesis.
4.
5.
(a) Hu, Y. Y.; Zhao, T.; Zhang, S. L. Chem. Eur. J. 2010, 16,
1697–1705. (b) Li, Y.; Hu, Y. Y.; Zhang, S. L. Chem. Commun.
2013, 49, 10635–10637.
(a) Hoz, S.; Yacovan, A.; Bilkis, I. J. Am. Chem. Soc. 1996, 118,
261−262; (b) Chopade, P. R.; Prasad, E.; Flowers, R. A., II. J.
Am.Chem. Soc. 2004, 126, 44−45; (c) Procter, D. J.; Flowers, R.
A.; Skrydstrup, T. Organic Synthesis Using Samarium Diiodide:
A Practical Guide; Royal Society of Chemistry: London, 2010.
General Procedure for the pinacol coupling of aldehydes and
ketones to form the diols (3). An oven-dried 50 mL two-necked
flask containing finely powdered samarium (0.375 g, 2.5 mmol)
was evacuated and backfilled with N2 for three times. Under a
positive pressure of nitrogen, a solution of allylBr (0.12 mL, 1.4
mmol) in dry THF (10 mL) was added via a syringe, and then
added a grain of iodine. The mixture was allowed to stir at room
temperature for 1 h (the mixture was deep purple). MeOH or H2O
was then added followed by addition of a solution of aldehydes or
ketones (1 mmol) in dry THF (1 mL) via a syringe. The reaction
mixture was stirred at room temperature until the completion of
the reaction (monitored by TLC). The reaction was quenched by a
sat. potassium sodium tartrate solution (5 mL). The mixture was
extracted by ethyl acetate (3 × 15 mL). The combined extracts
were washed with brine, dried over Na2SO4, and concentrated
under reduced pressure. The residue was purified by
chromatography on silica gel (200–300 mesh) using
Acknowledgments
This work was financially supported by the Natural Science
Foundation of Zhejiang Province (No. LY14B020001) and
National Natural Science Foundation of China (No. 21202152).
6.
Supplementary data
Supplementary data (the spectral data and the H NMR, 13C
1
NMR spectra of 3) associated with this article can be found in the
online version.
References and notes
1.
For selected examples: (a) Bied, C.; Collin, J.; Kagan, H. B.
Synthesis and Reactivity of Benzylic and Allylic Samarium
Compounds. Tetrahedron 1992, 48, 3877–3890; (b) Wang, J. Q.;
Zhou, J. Q.; Zhang, Y. M. Synth. Commun. 1996, 26, 3395–3399;
(c) Wang, X. X.; Li, J.; Zhang, Y. M. Synth. Commun. 2003, 33,
3575–3581; (d) Zheng, Y. F.; Bao, W. L.; Zhang, Y. M. Chin.
Chem. Lett. 2000, 11, 5–8; (e) Bao, W. L.; Zheng, Y. F.; Zhang,
Y. M. J. Chem. Res. 1999, 732–; (f) Li, Z. F.; Cao, X. J.; Lai, G.
Q. J. Organomet. Chem. 2006, 691, 4740–4746; (g) Li, Z. F.;
Zhang, Y. M. Tetrahedron 2002, 58, 5301–5306; (h) Fan, X. S.;
Zhang, Y. M. Tetrahedron Lett. 2002, 43, 5475–5478. (i) Liu, X.;
Zhang, S. L.; Di, J. Synthesis 2009, 2749–2755.
petroleum/EtOAc (10/1,
corresponding product 3.
Szostak, M.;Fazakerley, N. J.; Parmar, D.; Procter, D. J. Chem.
Rev. 2014, 114, 5959–6039 and references cited therein.
McDonald, C. E.; Ramsey, J. D.; Sampsell, D. G. Org. Lett. 2010,
12, 5178-5181 and references cited therein.
v : v) as eluent to afford the
7.
8.
2.
(a) Yu, M.-X.; Zhang, Y.-M. Synthesis of Homoallyl Alcohol by
Allylsamarium Bromide and Carbonyl Compounds. Chem. J.

Title:
MeOH or H2O as efficient additive to switch the reactivity of allylSmBr towards
carbonyl compounds
Authors:
Jianyong Li, Qingsheng Niu, Shanchan Li, Yuehao Sun, Qian Zhou, Xin Lv and Xiaoxia Wang*
Graphical
Abstract
MeOH or H2O as efficient additive to switch
the reactivity of allylSmBr towards carbonyl
compounds
Leave this area blank for abstract info.
Jianyong Li, Qingsheng Niu, Shanchan Li, Yuehao Sun, Qian Zhou, Xin Lv and Xiaoxia Wang*

4
Tetrahedron
Highlights
 The real reducing species in Sm/alkyl halide/MeOH
system should be allylSmBr.
 MeOH switched allylSmBr from a nucleophile to
good reductive coupling reagent.
 H2O was useful additive to realize the coupling of
aliphatic carbonyl compounds.
 AllylSmBr switched by greener additive is hopeful
to find more applications.