DBU-catalyzed condensation of acyldiazomethanes to aldehydes in water and a new approach to ethyl β-hydroxy α-arylacrylates

Article abstract of DOI:10.1016/j.tetlet.2006.12.062

DBU-catalyzed condensation of ethyl diazoacetate (EDA) with aldehydes in pure water afforded corresponding β-hydroxy α-diazo carbonyl compounds. The β-hydroxy group of the products was further converted into β-siloxy group. The Rh(II)-catalyzed reaction of the β-aryl β-siloxy α-diazo carbonyl compounds gave 1,2-aryl shift products predominantly. The three-step transformation constitutes an efficient synthesis of ethyl β-hydroxy α-arylacrylates.

Full text of DOI:10.1016/j.tetlet.2006.12.062

Tetrahedron Letters 48 (2007) 1147–1149
DBU-catalyzed condensation of acyldiazomethanes to aldehydes
in water and a new approach to ethyl b-hydroxy a-arylacrylates
Fengping Xiao, Yu Liu and Jianbo Wang*
Beijing National Laboratory of Molecular Sciences (BNLMS), Green Chemistry Center (GCC)
and Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education,
College of Chemistry, Peking University, Beijing 100871, China
Received 24 October 2006; revised 12 December 2006; accepted 13 December 2006
Available online 8 January 2007
Abstract—DBU-catalyzed condensation of ethyl diazoacetate (EDA) with aldehydes in pure water afforded corresponding
b-hydroxy a-diazo carbonyl compounds. The b-hydroxy group of the products was further converted into b-siloxy group.
The Rh(II)-catalyzed reaction of the b-aryl b-siloxy a-diazo carbonyl compounds gave 1,2-aryl shift products predominantly.
The three-step transformation constitutes an efficient synthesis of ethyl b-hydroxy a-arylacrylates.
Ó 2006 Elsevier Ltd. All rights reserved.
a-Diazo carbonyl compounds have attracted a great
attention because they can undergo diverse synthetically
useful transformations.1 Among them, b-hydroxy a-di-
azo carbonyl compounds2 have been studied in some
detail. A variety of b-substituted a-diazo carbonyl
compounds can be prepared from them through simple
nucleophilic substitution, and their Rh(II)-catalyzed
reactions have been investigated. Although 1,2-hydro-
gen migration is a facile process,3 1,2-acetoxyl, 1,2-vinyl,
and 1,2-acetylenyl migrations may become predominant
depending on the substrates and reaction conditions.4,5
In some cases, 1,2-alkyl migration6 and 1,3-C–H inser-
tion4 are also possible. The change of migratory apti-
tude is attributed to the steric and electronic effects of
non-migrating substituents.
gen migration products in a high yield, which constitutes
an efficient synthesis of 1,3-dicarbonyl compounds from
aldehydes and acyldiazomethanes. Various Lewis acids,
including Rh2(OAc)4, ½ðg5-C5H5ÞFeþðCOÞ2ðTHFÞꢀ-
BF4ꢁ, ZnCl2, SnCl2, BF3, GeCl2, ZnCl2, ZnBr2, AlCl3,
and SnCl4 have been reported to affect the transforma-
tion.2,3 As a continuation of our investigation on b-
hydroxy a-diazo carbonyl compounds, we report here (1)
DBU-catalyzed condensation of EDA with aldehydes
in water (2) predominant 1,2-aryl migration in
Rh2(OAc)4-catalyzed reaction of b-aryl b-siloxy a-diazo
carbonyl compounds. The overall three-step transfor-
mation is an efficient and green synthesis of b-hydroxy
a-arylacrylates.
O
OH
O
X
O
cat. DBU
TMSCl
Et3N
Ar
OEt
OH
H
Ar
OEt
OEt
Ar
H
EDA, H2O
r.t.
X
O
N2
H
+
cat.
OEt
Ar
TMSO
Ar
O
H
O
X
O
N2
1) Rh2(OAc)4
2) Silica gel
OEt
H
OEt
X = Cl3CCONH, TsNH,
Ts, SR', NHCOCF3, OTMS
N2
Ar
Ar
On the other hand, Lewis acid-catalyzed reaction of b-
hydroxy a-diazo carbonyl compounds afford 1,2-hydro-
The nucleophilic addition of acyldiazomethane to
carbonyl compound, which is a straightforward way to
obtain b-hydroxy a-diazo carbonyl compounds, needs
deprotonation of the acyldiazomethane. This is usually
achieved by treating the diazo compound with a strong
base, such as butyllithium, lithium diisopropylamide,
Keywords: Diazo compounds; Rh(II) carbene; DBU-catalyzed con-
densation; 1,2-Aryl shift.
*
Corresponding author. E-mail: wangjb@pku.edu.cn
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.12.062

1148
F. Xiao et al. / Tetrahedron Letters 48 (2007) 1147–1149
sodium hydride and potassium hydroxide.2 Recently, it
has been reported that the reaction can be catalyzed
by phase-transfer reagents.7 We have reported that
DBU can efficiently catalyze nucleophilic condensation
of acyldiazomethanes with aldehydes or imines in aceto-
nitrile at room temperature.8 Further investigation indi-
cated that the DBU-catalyzed reaction could be
efficiently carried out in water, as shown in Table 1.
hydrogen to migrate. We have conceived that this can
be utilized to design an efficient approach toward ethyl
b-hydroxy a-arylacrylates, which are useful building
blocks in organic synthesis.10
The b-hydroxy group was converted to siloxy group in
high yields to yield 3a–l (for 1a–k, 82–99%).11 Then,
Rh(II) catalysts were screened in order to find optimal
reaction conditions. As shown in Table 2, the ratio for
1,2-hydrogen and 1,2-phenyl migration varies with the
catalysts. The Rh2(OAc)4-catalyzed reaction gave the
highest selectivity for 1,2-phenyl migration. It is
worthwhile to note that Rh(II) catalysts with strong
electron-withdrawing ligands, such as those in
rhodium(II) trifluoracetate [Rh2(tfa)4] and rhodium(II)
perfluorobutyrate [Rh2(pfb)4], favor 1,2-hydride migra-
tion. Removal of the TMS group by silica gel afforded
the corresponding b-hydroxy a-phenylacrylate.
After optimization of the reaction conditions, it was
concluded that the reaction could proceed effectively
with 30 mol % DBU in water. As shown by the data col-
lected in Table 1, the reaction proceeded well with a
wide range of aldehydes. Most aromatic aldehydes re-
acted efficiently to afford the corresponding b-hydroxy
a-diazo carbonyl compounds in moderate to good
yields. As anticipated, the reaction with an aromatic
aldehyde with a strong electron-donating substituent,
such as a p-methoxy group, was very slow and gave
products in only 40% yield after 3 days (Table 1, entry
8). It is worthwhile to note the reactions with aliphatic
and propargylic aldehydes also proceeded well, although
the yields were lower as compared with the reaction with
aromatic aldehydes.
The scope of the Rh2(OAc)4-catalyzed was examined by
b-siloxy diazo substrates 3a–l. As shown in Table 3, b-
hydroxy arylacrylates could be obtained in moderate
to good yields for most substrates (Table 3, entries 1,
3–7). The minor products, which are from 1,2-hydrogen
migration, could not be isolated in most cases, except for
substrates 3h–j (entries 8–10). When the aromatic substi-
tuent was o-methyl, only 1,2-hydrogen products could
be isolated (entry 12). This may be due to the steric
hindrance of the ortho methyl group, which prevents
the approach of the aromatic ring to the carbene center.
On the other hand, bulkier siloxy group, such as tert-
butyldiphenylsiloxy (TBDPS), could further promote
1,2-aryl migration (entries 2 and 11).
The Lewis acid-catalyzed reaction of b-hydroxy a-diazo
carbonyl compounds has been known to give 1,2-hydro-
gen migration products. This has been developed into a
useful approach to b-ketoesters. However, our recent
study has demonstrated that the 1,2-migratory aptitude
can be dramatically affected by the non-migrating group
(bystander) in the b position. When the substituent in
the b position is a bulky group, such as siloxy group, rel-
atively bulkier aromatic group has preference over
In summary, we have demonstrated that DBU can cat-
alyze the condensation of EDA with aldehydes in water.
Since water is the most cheap and environment-friendly
solvent, this procedure is a convenient and green method
to prepare b-hydroxy a-diazo carbonyl compounds.
Converting the b-hydroxy to siloxy group enables the
Rh2(OAc)4-catalyzed reaction to proceed with 1,2-aryl
migration as the major pathway. The three-step trans-
formation from aldehydes and EDA provides a new en-
try to b-hydroxy a-arylacrylate.
Table 1. DBU-catalyzed condensation of EDA to aldehydes in water9
DBU (30 mol %)
EDA
OH
O
O
R
OEt
R
H
H2O, r. t.
N2
2a-q
1a-q
Entry 1a–q, R =
Reaction Product Yieldb (%)
timea (h) 2a–q
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
1a, C6H5
24
24
24
24
24
24
24
72
24
24
24
24
24
168
72
3
2a
2b
2c
2d
2e
2f
74
72
77
78
85
74
61
40
75
84
69
69
67
60
43
49
43
Table 2. Rh(II)-catalyzed reaction of 3aa
1b, p-FC6H4
1c, p-ClC6H4
1d, p-BrC6H4
1e, m-BrC6H4
1f, o-MeC6H4
1g, p-MeC6H4
1h, p-MeOC6H
1i, m-MeOC6H4
1j, m-F3CC6H4
1k, 3,4-Cl2C6H3
1l, 3,5-(MeO)2C6H3
1m, 2-Furyl
TMSO
H
O
OEt
Rh(II)
0.5 mol %
O
TMSO
Ph
Ph
+
4a
2g
2h
2i
OEt
CH2Cl2, r. t.
N2
TMSO
Ph
O
2j
3a
OEt
2k
2l
H
5a
2m
2n
2o
2p
2q
Entry
Catalyst
4a:5ab
1n, H
1o, CH3
1p, PhC„C
1q, C5H11C„C
1
2
3
4
Rh2(OAc)4
Rh2(O2CCF3)4
Rh2(O2CC3F7)4
84:16
38:62
43:57
81:19
3
Rh2(O2CC7H15 4
)
a The reaction was carried out in water at room temperature with
30 mol % DBU.
b Yields after silica gel column chromatographic purification.
a The reaction was carried out in CH2Cl2 at room temperature.
b Ratio determined by the 1H NMR of the crude product.

F. Xiao et al. / Tetrahedron Letters 48 (2007) 1147–1149
1149
Table 3. Rh2(OAc)4-catalyzed reaction of b-siloxy diazo substrates
3a–l12
3. (a) Ikota, N.; Takamura, N.; Young, S. D.; Ganem, B.
Tetrahedron Lett. 1981, 22, 4163; (b) Holmquist, C. R.;
Roskamp, E. J. J. Org. Chem. 1989, 54, 3258; (c)
Mahmood, S. J.; Hossain, M. M. J. Org. Chem. 1998,
63, 3333; (d) Kanemasa, S.; Kannai, T.; Araki, T.; Wada,
E. Tetrahedron Lett. 1999, 40, 5055; (e) Dudley, M. E.;
Morshed, Md. M.; Brennan, C. L.; Islam, M. S.; Ahmad,
M. S.; Atuu, M.-R.; Branstetter, B.; Hossain, M. M. J.
Org. Chem. 2004, 69, 7599.
OR" O
1) Rh2(OAc)4
(0.5 mol %)
CH2Cl2, r. t.
H
R
OEt
4a-l
OR'
O
R
+
R
OEt
2) Silica gel
O
O
N2
3a-l
OEt
7a-l
4. For an account, see: Zhao, Y.; Wang, J. Synlett 2005,
2886.
5. (a) Jiang, N.; Qu, Z.; Wang, J. Org. Lett. 2001, 3, 2989; (b)
Shi, W.; Jiang, N.; Zhang, S.; Wu, W.; Du, D.; Wang, J.
Org. Lett. 2003, 5, 2243; (c) Shi, W.; Zhang, B.; Liu, B.;
Xu, F.; Xiao, F.; Zhang, J.; Zhang, S.; Wang, J.
Tetrahedron Lett. 2004, 45, 4563; (d) Xiao, F.; Zhang,
Z.; Zhang, J.; Wang, J. Tetrahedron Lett. 2005, 46, 8873;
(e) Shi, W.; Xiao, F.; Wang, J. J. Org. Chem. 2005, 70,
4318; (f) Shi, W.; Zhang, B.; Zhang, J.; Liu, B.; Zhang, S.;
Wang, J. Org. Lett. 2005, 7, 3103; (g) Xu, F.; Shi, W.;
Wang, J. J. Org. Chem. 2005, 70, 4218; (h) Xu, F.; Zhang,
S.; Wu, X.; Liu, Y.; Shi, W.; Wang, J. Org. Lett. 2006, 8,
3207; (i) Xiao, F.; Wang, J. J. Org. Chem. 2006, 71, 5789.
6. Vitale, M.; Lecourt, T.; Sheldon, C. G.; Aggarwal, V. K.
J. Am. Chem. Soc. 2006, 128, 2524.
Entry
3a–l
Yielda (%)
R
R0
R00
4a–l
a, 80
7a–l
1
2
3
4
5
6
7
8
9
a, C6H5
b, C6H5
c, p-FC6H4
TMS
TBDPS
TMS
TMS
TMS
TMS
TMS
TMS
TMS
TMS
TBDPS
TMS
H
a, —b
b, —
c, —
d, —
e, —
f, —
g, —
h, 12
i, 14
j, 28
k, —
l, 97
TBDPS
H
H
H
H
H
H
H
b, 92
c, 80
d, 85
e, 70
f, 76
g, 81
h, 74
i, 77
j, 47
k, 78
l, —b
d, p-PhC6H4
e, p-MeOC6H4
f, 2-Furyl
g, p-CH3C6H4
h, p-BrC6H4
i, p-ClC6H4
j, m-BrC6H4
k, m-BrC6H4
l, o-CH3C6H4
10
11
12
H
TBDPS
H
7. Arai, S.; Hasegawa, K.; Nishida, A. Tetrahedron Lett.
2004, 45, 1023.
a Yields after silica gel column chromatographic purification.
b No product could be isolated.
8. Jiang, N.; Wang, J. Tetrahedron Lett. 2002, 43, 1285.
9. General procedure for DBU-promoted reactions of 1a–q in
water. To a stirring solution of water (1 mL) containing
EDA (1.2 mmol) and aldehyde (1 mmol), DBU (30 mol %)
was added. The reaction mixture was stirred at room
temperature until completion of the reaction. Usual
workup afforded the pure 2a–q.
10. For recent report on 1,3-dicarbonyl compounds, see: (a)
Atuu, M. R.; Mahmood, S. J.; Laib, F.; Hossain, M. M.
Tetrahedron: Asymmetry 2004, 15, 3091; (b) Mahmood, S.
J.; Brennan, C.; Hossain, M. M. Synthesis 2002, 13, 1807;
(c) Schmittel, M.; Ammon, H. Eur. J. Org. Chem. 1998, 5,
785; (d) Kamaya, H.; Sato, M.; Kaneko, C. Tetrahedron
Lett. 1997, 38, 587.
Acknowledgements
The project is generously supported by Natural Science
Foundation of China (Grant Nos. 20572002, 20521202,
20225205, 20390050) and the Ministry of Education of
China (Cheung Kong Scholars Program).
11. General procedure for the conversion of b-hydroxy diazo
compounds to the corresponding b-siloxy diazo compounds.
References and notes
In
a flamed three-necked round-bottomed flask, b-
1. Doyle, M. P.; McKervey, M. A.; Ye, T. Modern Catalytic
Methods for Organic Synthesis with Diazo Compounds;
Wiley-Interscience: New York, 1998.
hydroxy-a-diazo compound (1.0 mmol) was dissolved in
CH2Cl2 (5 mL). Triethylamine (3.0 mmol) was added to
the solution at 0 °C for 5 min. Then R1R2R3SiCl
(1.1 mmol) was added via syringe at 0 °C. The mixture
was allowed to stir for 2 h between 0 °C and room
temperature. Usual workup afforded the pure b-siloxy
diazo compounds.
2. (a) Schollkopf, U.; Frasnelli, H.; Hoppe, D. Angew.
Chem., Int. Ed. Engl. 1970, 9, 300; (b) Wenkert, E.;
McPherson, A. A. J. Am. Chem. Soc. 1972, 94, 8084; (c)
Burkoth, T. L. Tetrahedron Lett. 1969, 57, 5049; (d)
Woolsey, N. F.; Khalil, M. H. J. Org. Chem. 1972, 37,
2405; (e) Schollkopf, U.; Banhidai, B.; Frasnelli, H.;
Meyer, R.; Beckhaus, H. L. Ann. Chem. 1974, 1767; (f)
Pellicciari, R.; Natalini, B. J. Chem. Soc., Perkin Trans. 1
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Lett. 1987, 28, 5351; (h) Pellicciari, R.; Natalini, B.;
Sadeghpour, B. M.; Marinozzi, M.; Snyder, J. P.;
Williamson, B. L.; Kuethe, J. T.; Padwa, A. J. Am. Chem.
Soc. 1996, 118, 1.
12. General procedure for Rh2(OAc)4-catalyzed reaction of
3a–l. To a stirring solution of anhydrous CH2Cl2 (10 mL)
containing Rh2(OAc)4 (0.5 mol %) was added diazo com-
pound 4a–l (1.0 mmol). The reaction mixture was stirred
at room temperature. When the diazo compound disap-
peared as indicated by TLC, the solvent was removed
under reduced pressure to give a crude residue, which was
purified by silica gel column chromatography.