Polymer-supported selenol esters as useful acylating reagents. Application to α, β-acetylenic ketones synthesis

Article abstract of DOI:10.1055/s-2001-17484

Three novel polystyrene supported selenol esters were synthesized and used as acyl transfer agents to prepare α, β-acetylenic ketones by reaction with alkynylcoppers.

Full text of DOI:10.1055/s-2001-17484

LETTER
1571
Polymer-Supported Selenol Esters as Useful Acylating Reagents. Application
to , -Acetylenic Ketones Synthesis
P
olymer-Supporte
a
d Selenol
E
o
sters as
U
seful
AcyQ
lating Reagents ian,a Li-Xiong Shao,b Xian Huang*a
a
Department of Chemistry, Zhejiang University, Xi-xi Campus, Hangzhou 310028, P. R. China
Fax +86(571)88807077; E-mail: huangx@mail.hz.zj.cn
b
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai
200032, P. R. China
Received 31 July 2001
acylation with acyl chlorides (Scheme 1).6 Resin 2 can be
stored at room temperature for several months without
diminution of capacity or the liberation of disagreeable
odors. The minimum capacity of resin 2 were determined
to be 0.92 mmol/g (R = -CH3), 0.94 mmol/g (R = -Et),
1.08 mmol/g (R = -Ph) as determined by their use in acy-
lation reactions with phenylacetyl copper (method 1).7
Abstract: Three novel polystyrene supported selenol esters were
synthesized and used as acyl transfer agents to prepare
lenic ketones by reaction with alkynylcoppers.
, -acety-
Key words: solid-phase synthesis, selenol ester, acyl transfer
agent, alkynylcopper, acetylenic ketone
Polymer-supported reagents for organic synthesis are cur-
rently enjoying a renewed popularity with the emergence
of combinatorial chemistry.1 The current trend for auto-
mation in synthesis is driving the need for the speed of
production and the ease of handling of large numbers of
discrete compounds, together with a need for a wide range
O
SeCOR
R'
Cu
R'
+
C R
SeCu
3
DMF, 80 0C
4
RCOCl
SeCOR
of possible synthetic transformations. Supported reagents Scheme 2
are allowing the integration of well-established solution-
Resin 2 reacted with variety of alkynylcoppers 8,9 to give
upon simple filtration resin 3 and the , -acetylenic ke-
tones 4 in high yield (Scheme 2) (Table). Under reaction
conditions in which the alkynylcoppers were in excess
(Method 1), recovered resin 3 no longer exhibited any car-
bonyl absorption in its infrared spectrum, indicating that
polymer reagent 2 was completely consumed in the reac-
tion. Under conditions in which the resin 2 were in excess
with respect to the alkynylcoppers (Method 2),7 almost
pure acetylenic ketones were obtained upon direct filtra-
tion of the polymer and evaporation of the solvent. Resin
2 can be regenerated by reacting resin 3 with acyl chlo-
rides.
phase chemistry with automation through the use of robot-
ics.2,3 Selenol esters frequently exhibit a high and selec-
tive reactivity toward nucleophiles, which is enhanced
even further by activation with heavy ions or oxidizing
agents. These properties make selenol esters valuable acyl
transfer agents.4 Selenol esters are expected to be a more
reactive species than the corresponding thiol esters or oxo
esters due to the comparatively weak bonding between
carbon and selenium. However, organic selenium re-
agents always have a foul smell and are quite toxic, which
is often problematic in organic synthesis.5 In this paper we
wish to report preparation of polystyrene supported sele-
nol esters and application to , -acetylenic ketones syn-
thesis. A distinct advantage of the new reagents is the
convenience of handling and odorless nature as compared
to the non-bound reagents.
In summary, we synthesized the polymer reagents of
polystyrene supported selenol esters. The use of the poly-
mer reagents as acyl transfer agents provides a simple
method for the synthesis of , -acetylenic ketones in high
yields.
The polystyrene supported selenol esters can be easily ob-
tained from the polystyrene supported selenenyl bromide
5
by reaction with sodium borohydride and subsequent
Acknowledgement
NaBH4
RCOCl
The project 29932020 was supported by the National Natural Sci-
ence Foundation of China.
SeCOR
SeBr
SeNa
THF/ DMF
1
2a. R= CH3
2b. R= Et
2c. R= Ph
Scheme 1
Synlett 2001, No. 10, 28 09 2001. Article Identifier:
1437-2096,E;2001,0,10,1571,1572,ftx,en;Y14901st.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214

1572
H. Qian et al.
LETTER
(6) General procedure for preparation of polystyrene supported
selenol esters: Under a N2 atmosphere ploystyrene supported
selenenyl bromide (1.5 mmol/g, Br), prepared from 1%
cross-linked polystyrene beads,5 was swelled in THF (15
mL) and DMF (2 mL) over night. NaBH4 (6mmol) was
added to the mixture. The mixture was stirred at r.t. for 8 h,
acyl chloride (8 mmol) was added slowly at 0 °C and the
mixture was stirred at 0 °C for 0.5 h, 25 °C for 4 h. The resin
2 was collected on a filter and washed alternately with THF
(2 15 mL), H2O (3 20 mL), EtOH (2 15 mL), MeOH (1
15 mL), CH2Cl2 (2 15 mL) and finally dried in vacuum.
IR (KBr): 2a. 3024, 2922,1725, 1600, 1492, 1099, 936, 758,
698 cm-1; 2b. 3024, 2922, 1719, 1600, 1588, 1492, 1452,
1077, 907, 738, 698 cm-1; 2c. 3024, 2921, 1685, 1600, 1492,
1198, 1173, 876, 764, 698 cm-1.
(7) General procedure for preparation of , -acetylenic ketones
using resin 2 as an acyl transfer reagent: Method 1: Under a
N2 atmosphere resin 2 (0.5g) was swelled in DMF (10mL) at
r.t. overnight. To the mixture were added alkynylcoppers
(1.5 mmol ). The mixture was stirred at 80 °C for 14 h,
cooled to r.t. and filtered. The resin 3 was washed with Et2O
(3 10 ml). The IR spectrum of recovered resin 3 did not
exhibit the carbonyl absorbance characteristic of resin 2. The
filtrate was washed with brine, dried (MgSO4), evaporated to
dryness and the crude product purified by preparative TLC
on silica gel. The products were identified by m.p., NMR,
MS, and IR spectra. From the yield of 4 the minimum
capacity of resin 2 was calculated.
Table Preparation of
,
-acetylenic ketones
Product
R
R1
Yield%*
Method 1 Method 2
4a
4b
4c
4d
4e
4f
CH3
CH3
CH3
CH3
Et
Ph
84 83
86 86
90 91
77 73
90 90
87 85
90 87
92 90
80 78
p-CH3C6H4
p-BrC6H4
n-C5H11
Ph
Ph
Ph
4g
4h
4i
Ph
p-CH3C6H4
p-BrC6H4
n-C5H11
Ph
Ph
*Based on pure isolated compounds.
References and Notes
(1) Lorsbach, B. A.; Kurth, M. J. Chem. Rev. 1999, 99, 1549.
(2) Guillier, F.; Orain, D.; Bradley, M. Chem. Rev. 2000, 100,
2091.
(3) Bunin, B. A. The Combinatorial Index; Academic Press: San
Diego CA, 1998, 5.
(4) Ogawa, A.; Sonoda, N. In Comprehensive Organic Synthesi,
Vol 2; Trost, B. M.; Fleming, I., Eds.; Pergamon Press:
Oxford, 1991, 461.
Method 2: Under a N2 atmosphere resin 2 (1g), swelled in
DMF (15 mL) were added alkynylcoppers (0.6 mmol),
which were reacted at 80 °C for 14 h. The mixture was
cooled to r.t. and worked up with Et2O as described above
for method 1.
(8) Castro, C. E.; Gaughan, E. J.; Owsley, D. C. J. Org. Chem.
1966, 31, 4071.
(5) Nicolaou, K. C.; Pastor, J.; Barluenga, S.; Winssinger, N.
Chem. Commun. 1998, 1947.
(9) Zhao, C.-Q.; Huang, X.; Meng, J.-B. Tetrahedron Lett.
1998, 39, 1933.
Synlett 2001, No. 10, 1571–1572 ISSN 0936-5214 © Thieme Stuttgart · New York