Chemoselective Hydrogenation of α,β-Unsaturated Sulfones and Phosphonates via Palladium-Assisted Hydrogen Transfer by Ammonium Formate

Full text of DOI:10.1021/jo980128n

5250
J . Org. Chem. 1998, 63, 5250-5251
Sch em e 1
Ch em oselective Hyd r ogen a tion of
r,â-Un sa tu r a ted Su lfon es a n d
P h osp h on a tes via P a lla d iu m -Assisted
Hyd r ogen Tr a n sfer by Am m on iu m F or m a te
Brindaban C. Ranu,* Sankar K. Guchhait, and
Keya Ghosh
Department of Organic Chemistry, Indian Association
for the Cultivation of Science,
Ta ble 1. Hyd r ogen a tion of r,â-Un sa tu r a ted Su lfon es
J adavpur, Calcutta 700 032, India
a n d P h osp h on a tes by Am m on iu m F or m a te/P d -C
Received J anuary 26, 1998
The reduction of R,â-unsaturated sulfones and phos-
phonates to the corresponding saturated analogues con-
stitutes a useful process as these compounds are of great
importance in the studies of biological systems1 as well
as in synthetic strategy.2 Surprisingly, there are only a
few methods available in the literature for effecting the
reduction of the carbon-carbon double bond in R,â-
unsaturated sulfones and phosphonates. The most com-
monly used reagents for the reduction of sulfones are
sodium borohydride,3 lithium triethyl borohydride,2 and
(triphenylphosphine)copper hydride hexamer [(PPh3)-
CuH]6.3 The yield in the NaBH4 reaction is not always
satisfactory,3 while the use of LiEt3BH and [(PPh3)CuH]6
is not very economical. The reduction of phosphonates
is usually carried out under high-pressure (50 psi)
hydrogenation over palladium on activated carbon.4
Recently, a binuclear palladium complex, [(t-Bu2PH)PdP-
t-Bu2]2, has been used for the hydrogenation of the double
bond of R,â-unsaturated sulfones and phosphonates at 1
atm of hydrogen pressure, producing the saturated
compound in 49-93% yield.5 Although this method is
quite satisfactory, the operation is not very straightfor-
ward and the reagent is costly and also not easily
accessible. Thus, a simple and efficient method for this
useful transformation is still in demand. The ammonium
formate/Pd-C system is a versatile catalytic hydrogen-
transfer agent,6 and recently, we have utilized this
reagent system for the regio- and stereoselective hydro-
genation of conjugated carbonyl compounds.7 We now
wish to disclose that ammonium formate/Pd-C is also
very efficient in the reduction of the CdC bond in R,â-
unsaturated sulfones and phosphonates (Scheme 1).
In a typical experimental procedure. the conjugated
sulfone or phosphonate was stirred with ammonium
formate and 10% Pd-C in dry methanol at room tem-
perature under argon for a certain period of time as
entry
R1
R2
Z
time, h yielda (%)
1
2
3
4
5
6
7
8
9
Me2CHCH2CH(OH)
H
H
H
H
SO2-p-Tol
SO2-p-Tol
SO2-p-Tol
SO2-p-Tol
22
18
20
24
22
20
24
18
20
20
24
24
90
92
82
85
86
82
85
88
93
82
90
83
Ph
p-MeOC6H4
p-ClC6H4
Ph
Me SO2-p-Tol
Me SO2-p-Tol
Ph SO2-p-Tol
H
H
H
H
p-MeC6H4
Ph
H
Ph
PO(OEt)2
PO(OEt)2
PO(OEt)2
PO(OEt)2
10
11
12
m-MeOC6H4
p-ClC6H4
Ph
Ph PO(OEt)2
a
Yields refer to those of pure isolated products, fully character-
ized by spectral and analytical data.
required to complete the reaction (TLC). The catalyst
was filtered through a short plug of silica gel, and the
product was isolated by solvent evaporation and extrac-
tion of the residue with ether. The carbon-carbon double
bond in several structurally varied sulfones and phos-
phonates underwent hydrogenation to give the corre-
sponding saturated analogues in high yields by this
procedure. The results are reported in Table 1. The
reactions are very clean, and no chromatographic separa-
tion is required to obtain spectrally pure substances. No
side products were isolated from any reaction. For the
compounds in Table 1, the substituents on the aromatic
ring apparently do not have any influence on the course
of hydrogenation. The chloro and methoxy groups on the
aromatic ring remain unaffected under these conditions.
Moreover, ammonium formate/Pd-C system is a mild
reagent and usually does not reduce nonconjugated
double bonds.6,7
In summary, the mild conditions, high yields of prod-
ucts, operational simplicity, easy availability, and low
cost of the reagent make this methodology a more useful
and practical alternative to the existing methods for
reduction of R,â-unsaturated sulfones and phosphonates.
We believe that this method will find useful applications
in the field of organic synthesis.
(1) (a) Schneider, K. C.; Benner, S. A. Tetrahedron Lett. 1990, 31,
335. (b) Musicki, B.; Widlanski, T. S. J . Org. Chem. 1990, 55, 4231.
(2) Ley, S. V.; Simpkins, N. S.; Whittle, A. J . J . Chem. Soc., Chem.
Commun. 1983, 503.
(3) (a) Musicki, B.; Widlanski, T. S. Tetrahedron Lett. 1991, 32, 1267.
(b) Sakakibara, T.; Takai, I.; Yamamoto, A.; Iizuka, H.; Hirasawa, K.;
Ishido, Y. Tetrahedron Lett. 1990, 31, 3749.
(4) Bigge, C. F.; J ohnson, G.: Ortwine, D. F.; Drummond, J . T.; Retz,
D. M.; Brahce, L. J .; Coughenour, L. L.; Marcoux, F. W.; Probert, A.
W., J r. J . Med. Chem. 1992, 35, 1371. (b) Francis, J . E.; Webb, R. L.;
Ghai, G. R.; Hutchison, A. J .; Moskal, M. A.; deJ esus, R.; Yokoyama,
R.; Rovinski, S. L.; Contardo, N.; Dotson, R.; Barclay, B.; Stone, G. A.;
J arvis, M. F. J . Med. Chem. 1991, 34, 2570.
(5) Cho, I. S.; Alper, H. J . Org. Chem. 1994, 59, 4027 and references
therein.
(6) Ram, S.; Ehrenkaufer, R. E. Synthesis 1988, 91.
Exp er im en ta l Section
Gen er a l Meth od s. Melting points were determined on a
glass disk with an electrical bath (Reichert, Austria) and are
uncorrected. 1H NMR (300 MHz) and 13C NMR (75 MHz)
spectra were run in CDCl3 solutions. IR spectra of solid samples
were taken as KBr plates, and those of liquid samples were run
as thin films. Methanol was dried over magnesium and distilled
before use. Ammonium formate and palladium-charcoal were
(7) Ranu, B. C.; Sarkar, A. Tetrahedron Lett. 1994, 35, 8649.
S0022-3263(98)00128-5 CCC: $15.00 © 1998 American Chemical Society
Published on Web 07/08/1998

Notes
J . Org. Chem., Vol. 63, No. 15, 1998 5251
used as available commercially. The R,â-unsaturated sulfones
and phosphonates were prepared following a literature proce-
dure.5,8-10 Some of these compounds have not been reported
previously, and so their spectral (IR, 1H NMR, and 13C NMR)
data are included in Supporting Information.
128.0 (2 CH), 128.1 (C), 128.7 (C), 128.8 (2 CH), 129.6 (2 CH),
129.9 (2 CH), 135.9 (C), 144.2 (C). Anal. Calcd for C15H15O2-
SCl: C, 61.12; H, 5.13. Found: C, 61.07; H, 5.08.
2-Meth yl-2-p-tolyleth yl p -tolyl su lfon e (Ta ble 1, en tr y
6): mp 90 °C; IR 1600, 1515, 1450, 1405, 1285, 1140, 1085 cm-1
;
Gen er a l P r oced u r e for Red u ction of r,â-Un sa tu r a ted
Su lfon es a n d P h osp h on a tes. Rep r esen ta tive P r oced u r e.
A mixture of (E)-styryl p-tolyl sulfone (258 mg, 1 mmol),
ammonium formate (378 mg, 6 mmol), and palladium on
charcoal (10%, 30 mg) in dry methanol (15 mL) was stirred at
room temperature under argon for 18 h (monitored by TLC). The
reaction mixture was then filtered through a short plug of silica
gel. Methanol was stripped off from the filtrate under reduced
pressure, and the residue was extracted with ether. The ether
extract was washed with water, dried (Na2SO4), and evaporated
to furnish the product, which was, though considerably pure
(NMR), chromatographed over silica gel to provide analytically
pure compound (240 mg, 92%). The product was easily char-
acterized by comparison of its spectral results (IR, 1H NMR, and
13C NMR) with literature data.5
This procedure is followed for the reduction of other sulfones
and phosphonates included in Table 1. Although the results
reported in Table 1 were based on mmol-scale reactions, gram-
scale reactions also afforded the corresponding products in
analogously good yields.
Several of these reduced products were reported previously,5
and the spectroscopic and analytical data of those that are new
compounds are presented below.
1H NMR δ 1.40 (3H, d, J ) 6 Hz), 2.27 (3H, s), 2.41 (3H, s),
3.27-3.38 (3H, m), 6.94 (2H, d, J ) 9 Hz), 7.01 (2H, d, J ) 9
Hz), 7.24 (2H, d, J ) 9 Hz), 7.66 (2H, d, J ) 9 Hz); 13C NMR δ
20.9 (CH3), 21.5 (CH3), 22.1 (CH3), 34.6 (CH), 63.5 (CH2), 126.5
(2 CH), 127.0 (C), 127.8 (2 CH), 129.2 (2 CH), 129.6 (2 CH), 136.3
(C), 141.1 (C), 144.3 (C). Anal. Calcd for C17H20O2S: C, 70.8;
H, 7.0. Found: C, 70.73; H, 6.98.
2,2-Dip h en yleth yl p-tolyl su lfon e (Ta ble 1, en tr y 7): mp
1
146 °C; IR 1600, 1570, 1490 cm-1; H NMR δ 2.38 (3H, s), 3.90
(2H, d, J ) 6 Hz), 4.61 (1H, t, J ) 6 Hz), 7.12-7.22 (12H, m),
7.53 (2H, d, J ) 9 Hz); 13C NMR δ 21.4 (CH3), 46.1 (CH), 61.5
(CH2), 126.7 (2 CH), 127.5 (4 CH), 128.1 (2 CH), 128.6 (4 CH),
129.4 (2 CH), 136.6 (C), 141.4 (2 C), 144.1 (C). Anal. Calcd for
C21H20O2S: C, 74.97; H, 6.00. Found: C, 74.78; H, 6.20.
Dieth yl [2-(m-m eth oxyph en yl)eth yl]ph osph on ate (Table
1, en tr y 10): IR 1605, 1585, 1490, 1455, 1440 cm-1; 1H NMR δ
1.33 (6H, t, J ) 6 Hz), 2.00-2.12 (2H, m), 2.85-2.94 (2H, m),
3.80 (3H, s), 4.06-4.16 (4H, 2 q, J ) 6 Hz), 6.75-6.81 (1H, m),
7.19-7.27 (1H, m), 7.45-7.56 (1H, m), 7.64-7.71 (1H, m); 13C
NMR δ 16.43 (2 CH3), 26.5 (CH2), 28.5 (CH2), 55.1 (CH3), 61.6
(2 CH2), 111.6 (CH), 113.7 (CH), 120.3 (CH), 129.5 (CH), 131.9
(C), 159.9 (C). Anal. Calcd for C13H21O4P: C, 57.35; H, 7.77.
Found: C, 57.61; H, 7.54.
3-Hyd r oxy-5-m eth ylh exyl p-tolyl su lfon e (Ta ble 1, en tr y
1): IR (neat) 1140, 1300, 1410, 1450, 1470, 1600 cm-1; 1H NMR
δ 0.88 (d, J ) 6 Hz, 3H), 0.90 (d, J ) 6 Hz, 3H), 1.18-1.43 (m,
2H), 1.67-1.78 (m, 2H), 1.90-1.96 (m, 2H), 2.45 (s, 3H), 3.16-
3.34 (m, 2H), 3.73-3.80 (m, 1H), 7.36 (d, J ) 8 Hz, 2H), 7.79 (d,
J ) 8 Hz, 2H); 13C NMR δ 21.5 (CH), 21.9 (CH3), 23.1 (CH3),
24.5 (CH3), 30.5 (CH2), 46.6 (CH2), 53.1 (CH2), 68.0 (CH), 127.9
(2 CH), 129.8 (2 CH), 136.7 (C), 143.8 (C). Anal. Calcd for
C14H22O3S: C, 62.19; H, 8.20. Found: C, 62.36; H, 8.38.
2-(p-Meth oxyp h en yl)eth yl p-tolyl su lfon e (Ta ble 1, en tr y
Dieth yl [2-p-ch lor op h en yl)eth yl]p h osp h on a te (Ta ble 1,
en tr y 11): IR 1605, 1500, 1455, 1440 cm-1; 1H NMR δ 1.31 (6H,
t, J ) 6 Hz), 2.00-2.11 (2H, m), 2.87-2.96 (2H, m), 4.12 (4H, 2
q, J ) 6 Hz), 7.19-7.32 (4H, m); 13C NMR δ 16.4 (2 CH3), 26.5
(CH2), 28.4 (CH2), 61.6 (2 CH2), 128.0 (2 CH), 128.5 (2 CH), 140.7
(C), 141.0 (C). Anal. Calcd for C12H18O3PCl: C, 52.09; H, 6.56.
Found: C, 52.38; H, 6.66.
Dieth yl (2,2-d ip h en yleth yl)p h osp h on a te (Ta ble 1, en tr y
12): IR 1605, 1450 cm-1; 1H NMR δ 1.10 (6H, t, J ) 6 Hz), 2.58
(2H, dd, J ) 6,18 Hz), 3.69-3.91 (4H, m), 4.40-4.49 (1H, m),
7.26-7.29 (10H, m); 13C NMR δ 16.2 (2 CH3), 29.7 (CH2), 45.4
(CH), 61.4 (2 CH2), 126.5 (2 CH), 127.6 (4 CH), 128.5 (4 CH),
144.0 (2 C). Anal. Calcd for C18H23O3P: C, 67.89; H, 7.29.
Found: C, 68.00; H, 7.45.
3): mp 105 °C; IR 1610, 1515, 1300, 1250, 1150, 1090, 735 cm-1
;
1H NMR δ 2.46 (3H, s), 2.94-3.00 (2H, m), 3.27-3.33 (2H, m),
3.76 (3H, s), 6.80 (2H, d, J ) 9 Hz), 7.02 (2H, d, J ) 9 Hz), 7.36
(2H, d, J ) 9 Hz), 7.80 (2H, d, J ) 9 Hz); 13C NMR δ 21.6 (CH3),
28.0 (CH2), 55.4 (CH3), 57.9 (CH2), 114.2 (2 CH), 128.1 (2 CH),
129.3 (2 CH), 129.9 (2 CH), 130.3 (C), 136.1 (C), 144.7 (C), 158.5
(C). Anal. Calcd for C16H18O3S: C, 66.18; H, 6.25. Found: C,
66.22; H, 6.45.
Ack n ow led gm en t . Financial support from CSIR,
New Delhi [Grant No. 01(1364)/95)] is gratefully ac-
knowledged. S.K.G. and K.G. also thank CSIR for their
fellowships.
2-(p-Ch lor op h en yleth yl p -tolyl su lfon e (Ta ble 1, en tr y
4): mp 86 °C; IR 1595, 1570, 1490, 1440, 1300 cm-1; 1H NMR δ
2.45 (3H, s), 2.97-3.05 (2H, m), 3.27-3.36 (2H, m), 7.03 (2H, d,
J ) 9 Hz), 7.21 (2H, d, J ) 9 Hz), 7.35 (2H, d, J ) 9 Hz), 7.78
(2H, d, J ) 9 Hz); 13C NMR δ 21.6 (CH3), 28.2 (CH2), 57.3 (CH2),
Su p p or tin g In for m a tion Ava ila ble: Spectroscopic data
for R,â-unsaturated sulfones (Table 1, entries 1, 3, 4 and 6)
and phosphonates (Table 1, entries 10-12) (2 pages). This
material is contained in libraries on microfiche, immediately
follows this article in the microfilm version of the journal, and
can be ordered from the ACS; see any current masthead page
for ordering information.
(8) Kamigata, N.; Sawada, H.; Kobayashi, M. Chem. Lett. 1979, 159.
(9) Hirao, T.; Masunaga, T.; Ohshiro, Y.; Agawa, T. Tetrahedron Lett.
1980, 21, 3595.
(10) (E)-3-Hydroxy-5-methylhex-1-enyl-p-tolyl sulfone (Table 1 entry
1) was obtained from Dr. S. Sengupta, J adavpur University, Calcutta,
India, as a gift.
J O980128N