The first DMAP-mediated palladium-free Tsuji-Trost-type reaction of cyclic and acyclic Baylis-Hillman alcohols with active methylene compounds

Article abstract of DOI:10.1016/j.tetlet.2009.11.053

Direct allylic substitution of cyclic Baylis-Hillman alcohols with active methylene compounds under modified Taber's conditions (DMAP, toluene, reflux, 4 ? molecular sieves), with no Pd catalysts/activating agents, as is usually required for the process, affords the C-allylation products in moderate to good yields.

Full text of DOI:10.1016/j.tetlet.2009.11.053

Tetrahedron Letters 51 (2010) 586–587
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Tetrahedron Letters
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The first DMAP-mediated palladium-free Tsuji–Trost-type reaction of cyclic
and acyclic Baylis–Hillman alcohols with active methylene compounds
*
Olfa Mhasni, Farhat Rezgui
Laboratoire de Chimie Organique, Faculté des Sciences Campus Universitaire 2092 Tunis, Tunisia
a r t i c l e i n f o
a b s t r a c t
Article history:
Direct allylic substitution of cyclic Baylis–Hillman alcohols with active methylene compounds under
modified Taber’s conditions (DMAP, toluene, reflux, 4 Å molecular sieves), with no Pd catalysts/activating
agents, as is usually required for the process, affords the C-allylation products in moderate to good yields.
Ó 2009 Elsevier Ltd. All rights reserved.
Received 2 September 2009
Revised 23 October 2009
Accepted 13 November 2009
Available online 18 November 2009
The type of compound obtained from the reaction of allylic
alcohols with 3-oxoesters, is strongly dependent on the experi-
mental conditions. Indeed, the Tsuji–Trost reaction1 is a powerful
tool in organic synthesis for the construction of carbon–carbon
bonds, and involves Pd-catalyzed allylation of 1,3-dicarbonyl com-
pounds with allyl substrates bearing various types of leaving
group.
1
R
EWG
pathway a
allylation
EWG
2
OR
1
2
R
OH
OR
+
O
EWG
O
O
O
pathway b
Pathway a: Pd/activating agents
Pathway b: DMAP, toluene, 110 ºC
Gilbert transesterification
1
R
The direct allylation of 1,3-dicarbonyl compounds with allylic
alcohols, instead of their corresponding allylic derivatives (i.e., ha-
lides, acetates, triflates, phosphates, etc.) is a very attractive ap-
proach because of the ready availability of alcohols, the atom-
economy and the formation of water as the only side product. Since
the hydroxy group is not a good leaving group, all previous allylation
methods for accomplishing this task, need catalysts. Recently, using
Pd catalysts/activating agents, several research groups have re-
ported the direct allylic substitution of allyl alcohols by pronucleo-
philes in water,2 toluene3,4 or under neat conditions5 (Scheme 1,
pathway a).
Scheme 1.
direct allylation of active methylene compounds with allylic
alcohols.
In connection with our previous study on the behaviour of Bay-
lis–Hillman (BH) derivatives towards various nucleophiles,18 we
report in this Letter a straightforward procedure for the allylation
of active methylene compounds (i.e., 1,3-dicarbonyl compounds
and nitroalkanes) with cyclic and acyclic BH alcohols using DMAP
as an efficient Lewis-base catalyst.
Moreover, Lewis or Bronsted acids such as BF3ÁOEt2,6 InCl3,7
FeCl3,8 p-TsOH,9 iodine10 and H-Montmorillonite11 have been re-
ported to mediate the allylation of 1,3-dicarbonyl compounds. Re-
cent reports have demonstrated that gold, silver,12 certain metal
triflates13 as well as rare earth metals14 could also be used as effi-
cient catalysts for the allylation of 1,3-dicarbonyl compounds.
On the other hand, in a modified transesterification using Ta-
ber’s methodology,15 Gilbert16 reported that treatment of allylic
alcohols in refluxing toluene with 3-oxoesters and a catalytic
amount of 4-dimethylaminopyridine (DMAP), afforded the corre-
sponding allylic esters, as useful starting materials for Carroll rear-
rangements17 (Scheme 1, pathway b).
Thus, BH alcohol 1 reacted with ethyl benzoylacetate on treat-
ment with DMAP (1.2 equiv) and 4 Å molecular sieves in refluxing
toluene, with no formation of the expected transesterification
product15,16 nor the corresponding Carroll rearrangement prod-
uct,19 to generate exclusively, the b-dicarbonyl monoallyl deriva-
tive 2a20 in 80% yield (Scheme 2, Table 1, entry 1).
Mechanistically, we believe that the reaction starts with conju-
gate addition of DMAP to Michael acceptor 1, followed by the elim-
ination of the hydroxy moiety to afford intermediate I. Similarly,
further conjugate addition of ethyl benzoylacetate enolate to I,
then elimination of DMAP, provides compound 2a (Scheme 3).
It is notable that none of the previous allylating methods has
described Lewis bases such as DMAP as efficient catalysts for the
O
O
O
O
O
1
DMAP, 110 ºC
R
OH
1
+
2
R
°
2
R
toluene, 4 A MS
R
O
1
2a-h
* Corresponding author. Tel.: +216 95737399; fax: +216 71883424.
E-mail address: rez_far@yahoo.fr (F. Rezgui).
Scheme 2.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.11.053

O. Mhasni, F. Rezgui / Tetrahedron Letters 51 (2010) 586–587
587
1
Table 1
O
O
R
2
2
R
DMAP-mediated allylation of b-dicarbonyl compounds with cyclic Baylis–Hillman
alcohol 1
R
DMAP, 110 ºC
OH
1
+
R
°
NO
NO
toluene, 4 A MS
2
2
Entry
Product
R1
R2
2 (yield %)
R1 = H, R2 = Et
1 = Me, R2 = Me
1
5a 62%
5b 37%
1
2
3
4
5
6
7
8
2a
2b
2c
2d
2e
2f
Ph
OEt
OEt
OMe
OBz
Ph
Ph
Me
Et
80
58
42
44
60
80
64
40
R
Me
Me
Me
Me
Ph
Scheme 5.
2g
2h
Me
Et
In summary, we have described a simple and direct allylic sub-
stitution of primary BH alcohols 1 and 3 with a variety of pronucle-
ophiles under modified Taber’s conditions. Work is in progress in
our laboratory to investigate the generality of this direct substitu-
tion of BH alcohols by various soft nucleophiles (i.e., amines and
thiols), and to establish suitable experimental conditions to enable
transesterification of the BH alcohols with 3-oxoesters.
O
O
1) 1,4-addition of DMAP
OH
N
2) elimination of the OH moiety
CH
3
1
I
N
CH
3
Acknowledgement
1) 1,4-addition of the nucleophile
2) elimination of DMAP
O
O
We would like to thank the DGRST, Ministry of Higher Educa-
tion, Tunisia, for financial support of this work.
OEt
Ph
O
2a
References and notes
Scheme 3.
1. (a) Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon:
New York, 1991; Vol. 4, p 585.; (b) Tsuji, J. Palladium Reagents and Catalysts
Innovations in Organic Chemistry; John Wiley: Chichester, 1995; (c) Trost, B. M.;
VanVanken, D. L. V. Chem. Rev. 1996, 96, 395; (d) Commandeur, C.; Thorimbert,
S.; Malacria, M. J. Org. Chem. 2003, 68, 5588; (e) Trost, B. M.; Fraisse, P. L.; Ball, Z.
T. Angew. Chem., Int. Ed. 2002, 41, 1059; Trost, B. M.; Lee, C. In On Catalytic
Asymmetric Synthesis; Ojima, I., Ed.; Wiley-VCH: New York, 2000; Tsuji, J.. In
Handbook of Organopalladium Chemistry for Organic Synthesis; Negishi, E., Ed.;
Wiley: New York, 2000; Vol. 2, p 1669.
2. Manabe, K.; Kobayashi, S. Org. Lett. 2003, 15, 3241.
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J. Am. Chem. Soc. 2002, 124, 10968.
4. Kayaki, Y.; Koda, T.; Ikariya, T. J. Org. Chem. 2004, 69, 2595.
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Iranpoor, N.; Behbahani, F. K. Tetrahedron 1998, 54, 943.
The overall reaction can be described as a palladium-free Tsuji–
Trost-type process. This particular behaviour of allylic alcohol 1 to-
wards ethyl benzoylacetate, affording the monoallylation product
2a instead of the expected transesterification product, is likely
due to the presence of an electron-withdrawing group on the acti-
vated alkene, which would appear to be essential for this
transformation.
In order to investigate the scope and limitations of this simple
monoallylation method, we investigated the behaviour of acyclic
BH alcohol 322 towards 3-oxoesters (Scheme 4, Table 2, entries
1–3) and b-diketones (Scheme 4, Table 2, entries 4–6). We found
that under the above-mentioned conditions (DMAP, toluene, re-
flux, 4 Å molecular sieves), the reaction gave the allylation prod-
ucts 4a–f23 in a 68–95% yield.
9. Sanz, R.; Martínez, A.; Miguel, D.; Álvarez-Gutiérrez, J. M.; Rodr?guez, F. Adv.
Synth. Catal. 2006, 348, 1841.
10. (a) Rao, W.; Tay, A. H. L.; Goh, P. J.; Choy, J. M. L.; Ke, J. K.; Chan, P. W. H.
Tetrahedron Lett. 2008, 49, 122; (b) Rao, W.; Tay, A. H. L.; Goh, P. J.; Choy, J. M.
L.; Ke, J. K.; Chan, P. W. H. Tetrahedron Lett. 2008, 49, 5112.
This protocol was successfully extended to the reaction of allyl
alcohol 1 and other 3-oxoesters (Table 1, entries 2–4) as well as b-
diketones (Table 1, entries 5–8), leading to allylation products 2b–
h21 in moderate to good yields.
11. Motokura, K.; Fujita, N.; Mori, K.; Mizugaki, T.; Ebitani, K.; Kaneda, K. Angew.
Chem., Int. Ed. 2006, 45, 2605.
Finally, we demonstrated that other carbon pronucleophiles,
that is, 1-nitro- and 2-nitropropanes, reacted with alcohol 1, under
the same conditions, to give nitro derivatives 5a–b in 37–62%
yields (Scheme 5).
12. Kothandaraman, P.; Rao, W.; Zhang, X.; Chan, P. W. H. Tetrahedron 2009, 65,
1833.
13. Noji, M.; Konno, Y.; Ishii, K. J. Org. Chem. 2007, 72, 5161.
14. Shen, M.-G.; Cai, C.; Yi, W.-B. J. Fluorine Chem. 2009, 130, 595.
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17. Carroll, M. F. J. Chem. Soc. 1941, 507.
18. Rezgui, F.; El Ga, M. M. Tetrahedron 1997, 53, 15711.
19. (a) Clemens, R. J. Chem. Rev. 1986, 86, 241; (b) Itoh, H.; Taguchi, T. Chem. Soc.
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Duclos, B. A. Tetrahedron Lett. 2004, 45, 107.
1
R
O
O
O
OH
DMAP, 110 ºC
O
1
2
+
2
R
R
°
R
toluene, 4 A MS
COOEt
COOEt
20. General procedure for the allylation of carbon pronucleophiles with cyclic BH
alcohols. Preparation of compound 2a: a mixture of allyl alcohol 1 (5 mmol,
0.63 g), ethyl benzoylacetate (10 mmol, 1.92 g) and DMAP (6 mmol, 0.372 g)
was dissolved in toluene (50 mL), containing 10 g of oven-dried 4 Å molecular
sieves. The mixture was then heated under reflux for 20 h. The reaction
mixture was washed with brine and dried. The toluene was removed and the
residue was purified by column chromatography to furnish pure 2a (1.2 g,
3
4a-f
Scheme 4.
Table 2
DMAP-mediated allylation of b-dicarbonyl compounds with acyclic BH alcohol 3
80%). Viscous yellow oil; IR (CHCl3): 1737, 1699, 1600, 1448 cmÀ1
;
1H NMR
(300 MHz, CDCl3): d 8.04–8.03 (m, 2H), 7.58–7.44 (m, 3H), 6.88 (t, J = 4.0 Hz,
1H), 4.75–4.70 (m, 1H), 4.13 (q, J = 6.9 Hz, 2H), 2.85–2.81 (m, 2H), 2.41–2.26
(m, 4H), 1.92–1.86 (m, 2H), 1.16 (t, J = 6.9 Hz, 3H); 13C NMR (75 MHz, CDCl3): d
199.4, 195.5, 172.2, 149.4, 136.1, 135.7, 133.5, 128.7, 128.6, 61.1, 52.5, 38.3,
30.6, 26.0, 22.8, 14.0; MS (m/z): 300 (M+, 2), 282 (45), 255 (15), 254 (22), 226
(5), 195 (14), 149 (22), 121 (5), 105 (100), 77 (33).
Entry
Product
R1
R2
4 (yield %)
1
2
3
4
5
6
4a
4b
4c
4d
4e
4f
Ph
OEt
OEt
OBz
Ph
Ph
Me
95
78
68
87
88
75
Me
Me
Me
Ph
21. Compounds 2 were fully characterized and their spectroscopic data were in
agreement with those of our previous work, see Ref. 18.
22. Villiéras, J.; Rambaud, M. Org. Synth. Coll. Vol. VIII 1993, 265.
23. Singh, V.; Batra, S. Synthesis 2006, 63.
Me