Conjugate reduction of aryl acrylates with tributyltin hydride in the presence of magnesium bromide diethyl etherate

Article abstract of DOI:10.1016/j.tetlet.2004.01.028

The conjugate reduction of aryl acrylates performed with tributyltin hydride in the presence of magnesium bromide diethyl etherate in dichloromethane gave the corresponding saturated esters in moderate to high yields. The reduction of α-methylene-γ-benzyloxycarboxylic acid esters proceeded syn-selectively, but α-methylene-β-oxycarboxylic acid esters afforded reductive elimination products under the reaction conditions.

Full text of DOI:10.1016/j.tetlet.2004.01.028

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 2207–2209
Conjugate reduction of aryl acrylates with tributyltin hydride in the
presence of magnesium bromide diethyl etherate
Satomi Hirasawa, Hajime Nagano* and Yoko Kameda
Department of Chemistry, Faculty of Science, Ochanomizu University, Otsuka, Bunkyo-ku, Tokyo 112-8610, Japan
Received 19 November 2003; revised 17December 2003; accepted 6 January 2004
Abstract—The conjugate reduction of aryl acrylates performed with tributyltin hydride in the presence of magnesium bromide
diethyl etherate in dichloromethane gave the corresponding saturated esters in moderate to high yields. The reduction of
a-methylene-c-benzyloxycarboxylic acid esters proceeded syn-selectively, but a-methylene-b-oxycarboxylic acid esters afforded
reductive elimination products under the reaction conditions.
Ó 2004 Elsevier Ltd. All rights reserved.
Organotin hydrides are effective for the conjugate
reduction of a,b-unsaturated aldehydes and ketones.1
However, the reagents undergo radical addition reaction
to a,b-unsaturated carboxylic acid alkyl esters.1d;2
Recently, Wu et al. have reported the radical-mediated
conjugate reduction of N-(a-arylacryloyl)oxazolidinones
with tributyltin hydride.3 We now report the conjugate
reduction of aryl acrylates with tributyltin hydride in the
presence of MgBr2ÆOEt2 and the chelation controlled
1,3-asymmetric induction.4–6 The conjugate reduction
with the mild and neutral organotin reagent is of interest
from the point of view that the reduction of aryl acryl-
ates would proceed chemoselectively without affecting
the unsaturated bond such as isolated double bond
C@C and alkyl acrylate moieties.7;8 Furthermore, the
chelation controlled diastereoselective reduction would
be an alternative to catalytic hydrogenation being used
commonly for the diastereoselective reduction of acrylic
acid esters.9
During the investigation on the diastereoselectivity in
the alkyl radical addition to a-methylene-c-oxycarb-
oxylic acid esters,4d we found that the reaction of phenyl
ester 1a with isopropyl iodide gave the conjugate
reduction products 2a (21%, syn:anti ¼ 1:1) together
with radical adducts 3a (40%, syn:anti ¼ 2.8:1) (Scheme
1 and Table 1, entry 1).10 The reaction of 1a performed
without isopropyl iodide gave 2a in 51% yield with a
diastereomer ratio syn:anti ¼ 1.5:1 (entry 2).5 Entry 3
shows that 2 equiv of n-Bu3SnH are required to attain
high yield. The reaction proceeded without Et3B, a
radical initiator, and gave 2a in 65% yield (entry 4):11
this indicates that the conjugate reduction should pro-
ceed through an ionic mechanism. The Lewis acid
OMe
OMe
i-PrI (3 equiv)
Ph
Ph
CO2Ph
CO2Ph
Ph
Ph
CO2Ph
n-Bu3SnH (2 equiv)
syn-2a
OMe
anti-2a
Et3B (1 eq)/O2
Ph
CO2Ph
MgBr2•OEt2 (3 equiv)
1a
OMe
OMe
°
CH2Cl2, 0 C
CO2Ph
syn-3
anti-3
Scheme 1.
Keywords: Aryl acrylate; Conjugate reduction; Tributyltin hydride; Lewis acid.
* Corresponding author. Tel.: +81-3-5978-5348; fax: +81-3-5978-5715; e-mail: nagano@cc.ocha.ac.jp
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.01.028

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S. Hirasawa et al. / Tetrahedron Letters 45 (2004) 2207–2209
Table 1. Reduction of 1a with n-Bu3SnHa
the Lewis acid. However, the use of MgBr2 or MgI2 as
Lewis acid gave 2a in lower yield (entries 5 and 6).
Mg(ClO4)2, ZnCl2, Yb(OTf)3, and LiClO4 were ineffec-
tive. The reduction of 1a using Ph3SnH instead of
n-Bu3SnH did not proceed.
Entry
n-Bu3SnH Lewis acid
(3 equiv)
Et3B
(equiv)
Yield of 2a
(%)
(equiv)
1b
2
2
MgBr2ÆOEt2
MgBr2ÆOEt2
MgBr2ÆOEt2
MgBr2ÆOEt2
MgBr2
1
1
1
0
0
0
21
51
45
65
42
39
2
3
1.2
2
4
Under the optimized reaction conditions (Table 1, entry
4), we next carried out the reduction using various aryl
acrylates 1b–l (Table 2).10;11 The reduction of phenyl
acrylate 1b gave 2b in poor yield due to the dimerization
of 1b. The yields in the reduction of a-substituted
acrylates 1c12 and 1d were 66% and 87%, respectively,
but b-hydroxy-a-methylenecarboxylic acid ester (Baylis–
Hillman adduct) 1e6 afforded 2e (syn:anti ¼ 2.2:1)9 and
the reductive dehydroxylation product 413 in 25% and
5
2
6
2
MgI2
a Diastereomer ratio of 2a: syn:anti ¼ 1.5:1.
b The reaction was performed with i-PrI to give 3a (40% yield;
syn:anti ¼ 2.8:1).
MgBr2ÆOEt2 was indispensable for the reduction1c and
in fact, a complex mixture was yielded in the absence of
Table 2. Conjugate reduction of aryl acrylates 1b–l with n-Bu3SnH in the presence of MgBr2ÆOEt2
Substrate 1 Product 2 (yield/%)
Other product (yield/%)
R
R
CO2Ph
CO2Ph
2b (25)
1b R = H
1c R = Me
1d R = PhCH2CH2
2c (66)
2d (87)
Ph
Ph
Ph
Ph
CO2Ph
CO2Ph
CO2Ph
+
CO2Ph
+
OR
OR
syn
OR
anti
1e R = H
1f R = MOM
2e (25; syn:anti= 2.2:1)
2f (0)
4
4
(21)
(96)
OBn
OBn
OBn
R
CO2Ph
CO2Ph
R
CO2Ph
R
+
syn
anti
1g
1h
R = n-C7H15
R = Ph
2g (87; syn:anti= 18.0:1)
2h (56; syn:anti= 8.2:1)
CO2Ar
1i Ar = Ph
2i (14; conversion yield 37)
a
(49)
1j Ar = p-O2NC6H4
1k Ar = 1-naphthyl
2j (32; conversion yield 38)
a
(40)
2k (41; conversion yield 58)
a
(74; conversion yield 84)
x
CO2Ph
CO2Ph
no reaction
1l
2l
aReaction time: 27h.

S. Hirasawa et al. / Tetrahedron Letters 45 (2004) 2207–2209
2209
ꢀ
2. Mandolesi, S. D.; Koll, L. C.; Chopa, A. B.; Podesta, J. C.
J. Organomet. Chem. 1998, 555, 151–159.
3. Wu, M.-J.; Fu, C.-L.; Duh, T.-H.; Yeh, J.-Y. Synthesis
1996, 462–464.
21% yields, respectively. In the case of the corresponding
MOM ether 1f, the a,b-unsaturated ester 4 was yielded
exclusively in 96% yield. The reduction of benzyl ethers
1g and 1h proceeded in good yields with high syn-
selectivities.5 In contrast to the methyl ether 1a (Table
1), the benzyl ethers showed higher diastereoselectivity.
4. (a) Nagano, H.; Toi, S.; Yajima, T. Synlett 1999, 53–54;
(b) Nagano, H.; Hirasawa, T.; Yajima, T. Synlett 2000,
1073–1075; (c) Nagano, H.; Matsuda, M.; Yajima, T.
J. Chem. Soc., Perkin Trans. 1 2001, 174–182; (d) Nagano,
H.; Toi, S.; Matsuda, M.; Hirasawa, T.; Hirasawa, S.;
Yajima, T. J. Chem. Soc., Perkin Trans. 1 2002, 2525–
2538; (e) Nagano, H.; Ohkouchi, H.; Yajima, T. Tetrahe-
dron 2003, 59, 3649–3663; (f) Yajima, T.; Nagano, H.;
Saito, C. Tetrahedron Lett. 2003, 44, 7027–7029.
5. The chelation-controlled stereoselective catalytic hydro-
genation of c-hydroxy-a-methylene carboxylic acid esters
will be reported elsewhere.
6. It has been reported that aryl acrylates react much faster
than their alkyl counterparts in the Baylis–Hillman
reactions. (a) Perlmutter, P.; Puniani, E.; Westman, G.
Tetrahedron Lett. 1996, 37, 1715–1718; (b) Lee, W.-D.;
Yang, K.-S.; Chen, K. Chem. Commun. 2001, 1612–1613;
(c) Yang, K.-S.; Lee, W.-D.; Pan, J.-F.; Chen, K. J. Org.
Chem. 2003, 68, 915–919.
Although the reduction of a-substituted acrylates pro-
ceeded in moderate to high yields as mentioned above,
the reduction of phenyl crotonate 1i12 was sluggish and
gave 2i in only 14% yield. A longer reaction time (27h)
was required to increase the yield of 2i (49%). p-Nitro-
phenyl crotonate 1j gave 2j in 32% yield, but in this case
only a slight increase of yield was observed even after
27h of the reaction. Further improvements were
observed for the reduction of 2-naphthyl crotonate 1k,
although the reaction was not completed even after 27h.
The reduction of aryl crotonates ( ¼ nonterminal olefins)
is very slow because the access to b-reaction center is
hindered. With phenyl sorbate 1l, no reaction occurred.
7. No reduction of alkyl acrylate was observed under the
reaction conditions.
The LUMO energy of phenyl acrylates is lower than
that of the corresponding alkyl acrylates (semiempirical
AM1 calculations).7;14 Furthermore, the coordination of
the carbonyl oxygen atom of phenyl acrylates to the
Lewis acid lowers their LUMO energy. The synergistic
effects lowering the LUMO energy of acrylates may
accelerate the conjugate reduction. The higher reactivity
of p-nitrophenyl crotonate 1j and 2-naphthyl crotonate
1k compared to phenyl crotonate 1i is due to the LUMO
energies of 1j and 1k being lower than that of 1i.
8. It has been reported that the catalytic hydrogenation of
methyl acrylate proceeds much faster than octyl, cyclo-
hexyl or cyclododecyl acrylate over montmorillonitedi-
phenylphoshinepalladium(II) chloride. Choudary, B. M.;
Rao, K. K. Tetrahedron Lett. 1992, 33, 121–124.
9. Bouzide, A. Org. Lett. 2002, 4, 1347–1350, and references
cited therein.
10. All new compounds showed satisfactory IR, 1H NMR,
13C NMR, MS, and HRMS spectroscopic data. The
stereochemistries and diastereomer ratios of 2a, 2g, and 2h
were determined based on the chemical shift values and
integrations of their a-protons.
11. Typical procedure: To a solution of 1 in dry dichloromethane
(0.1 mol dmꢀ3) was added MgBr2ÆOEt2 (3 equiv) under nitro-
gen atmosphere. The mixture was stirred at room temperature
for 15min and then was cooled to 0°C. n-Bu3SnH (2 equiv)
was added and the mixture was stirred at 0 °C for 5h. After
treatment with KF and water and subsequent filtration
through a column of Florisil, product was purified by column
chromatography on silica gel to afford 2.
In summary, the phenyl esters of a-substituted acrylic
acids ( ¼ terminal olefins) were reduced with tributyltin
hydride in the presence of magnesium bromide diethyl
ether to give the corresponding saturated esters in
moderate to high yields. However, the b-substituted
acrylic acids ( ¼ nonterminal olefins) were less reactive.
References and notes
12. Jabin, I.; Revial, G.; Tomas, A.; Lemoine, P.; Pfau, M.
Tetrahedron: Asymmetry 1995, 6, 1795–1812.
13. For the reductive elimination reactions of Baylis–Hillman
adducts, see: (a) Shadakshari, U.; Nayak, S. K. Tetra-
hedron 2001, 57, 4599–4602; (b) Basavaiah, D.; Krishna-
macharyulu, M.; Hyma, R. S.; Sarma, P. K. S.;
Kumaragurubaran, N. J. Org. Chem. 1999, 64, 1197–1200.
14. Kondo, S.; Murase, K.; Kuzuya, M. Chem. Pharm. Bull.
1994, 42, 768–773.
1. (a) Leusink, A. J.; Noltes, J. G. Tetrahedron Lett. 1966,
2221–2225; (b) Keinan, E.; Gleize, P. A. Tetrahedron Lett.
1982, 23, 477–480; (c) Four, P.; Guibe, F. Tetrahedron
Lett. 1982, 23, 1825–1828; (d) Nozaki, K.; Oshima, K.;
Utimoto, K. Bull. Chem. Soc. Jpn. 1991, 64, 2585–2587; (e)
Hays, D. S.; Scholl, M.; Fu, G. C. J. Org. Chem. 1996, 61,
6751–6752.