Synthesis of trisubstituted alkenes by reductive dehydroxylation of Baylis-Hillman adducts using polymethylhydrosiloxane (PMHS) and catalytic B(C6F5)3

Article abstract of DOI:10.1016/j.tetlet.2006.03.014

B(C₆F₅)₃ as a catalyst and polymethylhydrosiloxane as a hydride source have been employed for the reductive dehydroxylation of Baylis-Hillman adducts wherein the hydride adds in an S_N2′ manner onto the unactivat

Full text of DOI:10.1016/j.tetlet.2006.03.014

Tetrahedron Letters 47 (2006) 3475–3478
Synthesis of trisubstituted alkenes by reductive dehydroxylation of
Baylis–Hillman adducts using polymethylhydrosiloxane
I
(PMHS) and catalytic B(C6F5)3
S. Chandrasekhar,* G. Chandrashekar, K. Vijeender and M. Srinivasa Reddy
Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 7 January 2006; revised 20 February 2006; accepted 2 March 2006
Abstract—B(C6F5)3 as a catalyst and polymethylhydrosiloxane as a hydride source have been employed for the reductive dehydr-
oxylation of Baylis–Hillman adducts wherein the hydride adds in an SN20 manner onto the unactivated allyl alcohol moiety with
concomitant elimination of the hydroxy group along with double bond migration. The products formed were found to be E in
the case of ester adducts and Z in the case of nitrile adducts.
ꢀ 2006 Elsevier Ltd. All rights reserved.
1. Introduction
reduction to methyl cinnamate, the hydroxy group has
been protected as the acetate. We have observed previ-
14
The Baylis–Hillman coupling is a versatile and ‘atom
economic’ reaction.1 In addition, this protocol provides
a well functionalized synthon, which allows one to per-
form diverse functional transformations. It generates an
allyl alcohol, which can be advantageous in certain cir-
cumstances whilst it can be a hindrance in other cases.
ously that B(C6F5)3 activates polymethylhydrosilox-
ane (PMHS)15 to produce a hydride source, which can
even deoxygenate a carbonyl group to a methylene.16
We were interested in exploring the possibility of displac-
ing the 20 allylic alcohol group in Baylis–Hillman ad-
ducts using this hydride source. We discovered that the
hydroxy group did not require prior acetylation and
smooth SN20 hydride transfer was observed and resulted
in trisubstituted alkenes with exclusive E geometry11a for
ester adducts (Scheme 1) and Z geometry12 for nitrile ad-
ducts (Scheme 2) as evidenced from NMR spectal
data.17,18 The details of this study are presented herein.
The stereodefined trisubstituted alkene moiety manifests
a significant role in many biologically active com-
pounds,2,3 various terpenoids and insect pheromones.4
The biological properties of these alkenes are highly
dependent on their isomeric purity.5 Deoxygenation of
this hydroxy group and halogenation via SN20 displace-
ment have been studied by the groups of Basavaiah,6
Das7 and others.8 Also, carbon nucleophiles9 efficiently
add to allylic acetate adducts when mediated by Zn.
We initially treated Baylis–Hillman adduct 1a (Table 1,
entry 1) with PMHS (2 equiv) and B(C6F5)3 (0.5 mol %)
in CH2Cl2 as solvent at room temperature. Rapid dehydr-
oxylation and hydride addition to the double bond
occurred yielding ethyl (4-nitrophenyl)-2-methyl-(2E)-
propionate 1b in 85% yield in 20 min. It was interesting
10
The TiCl3–LiAlH4 combination was also efficient in
hydride transfer onto Baylis–Hillman adducts whilst
11
12
their reduction with NaBH4 and LiAlH4 furnished
the methyl cinnamate derivatives. Palladium catalysis13
was also efficient in the stereoselective reduction to pro-
duce methyl cinnamates. However, in all the cases of
OH
COOEt
B(C6F5)3
(0.5 mol%)
COOEt
R
R
PMHS, DCM, rt
Keywords: Baylis–Hillman adducts; E and Z-trisubstituted alkenes;
PMHS-B(C6F5)3; Dehydroxylation.
q IICT Communication No. 060103.
Corresponding author. Tel.: +91 40 27193434; fax: +91 40
27160512; e-mail addresses: srivaric@iict.res.in; srivaric@gmail.com
II
E - alkenes
I
R = aryl, alkyl
Scheme 1.
*
0040-4039/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.03.014

3476
S. Chandrasekhar et al. / Tetrahedron Letters 47 (2006) 3475–3478
OH
The Baylis–Hillman acrylonitrile adducts were also effi-
B(C6F5)3
(0.5 mol%)
CN
ciently dehydroxylated under similar conditions. The
resulting Z-trisubstituted alkenes12 were obtained in
excellent yields (Table 2, entries 1–6). Interestingly, the
cyano group was resistant to reduction.19
R
R
PMHS, DCM, rt
CN
IV
Z- alkenes
III
R = aryl, alkyl
Scheme 2.
A classical ‘Lewis acid assistance’ mechanism holds
good for this operation. We propose that complex A
(Scheme 3), which is formed from B(C6F5)3 and PMHS
is responsible for elimination of the hydroxy group and
hydride addition to the double bond of the Baylis–
Hillman adducts. The reaction of I with complex A
forms intermediate B which undergoes elimination of
the hydroxy group from the sterically preferred confor-
mation C resulting in trisubstituted alkenes with E
geometry. In contrast the cyano adduct III results in
trisubstituted alkenes with exclusive Z geometry via
preferred conformation E due to the smaller size of the
to note that under the present reduction protocol, nitro
and ester groups were unaffected. In the case of entry 2
smooth reduction of the hydroxy group with double bond
migration occurred to yield 2b, without affecting the bro-
mo group. Entries 3–7 demonstrate further the generality
of this reaction. The aliphatic example (entry 8) was also
a reasonable substrate, however, the reaction time was
longer with moderate yield. Entry 9 demonstrates the sta-
bility of a silyl group to these reaction conditions.
Table 1. Synthesis of trisubstituted E-alkenes using PMHS and catalytic B(C6F5)3
Entry
Compound a
OH O
Producta b
Time
Yield (%)b
85
O
1
20 min
OEt
OEt
O2N
O2N
Br
OH O
O
2
3
30 min
30 min
78
81
OEt
OEt
Br
OH O
O
O
OEt
OEt
OEt
OEt
NO2
NO2
OH O
4
5
30 min
75
80
OH O
O
OEt
OEt
OEt
1 h
H3C
H3C
OH O
OH O
OH O
O
OEt
6
40 min
73
CF3
CF3
O
7
8
1 h
4 h
68
65
OEt
OEt
MeO
MeO
O
OEt
OEt
OH O
O
OEt
OEt
9
2 h
60
OTBS
OTBS
a All products were characterized by 1H NMR, IR and mass spectroscopy.
b Isolated yields after column chromatography.

S. Chandrasekhar et al. / Tetrahedron Letters 47 (2006) 3475–3478
3477
Table 2. Synthesis of trisubstituted Z-alkenes using PMHS and
catalytic B(C6F5)3
application of this procedure in the synthesis of complex
bioactive compounds is currently being pursued.
Entry Compound c
Producta d
Time
Yield
(%)b
2. General experimental procedure
OH
CN
1
40 min 72
40 min 78
CN
To a solution of the Baylis–Hillman adduct (2 mmol) in
anhydrous methylene chloride (5 mL) was added
B(C6F5)3 (0.01 mmol) and PMHS (4 mmol) and the
solution was stirred at room temperature for the appro-
priate period of time (monitored by TLC). Water was
added to the reaction mixture, which was extracted with
methylene chloride (3 · 5 mL). The combined organic
layers were washed with brine, dried over anhydrous
sodium sulfate, concentrated under in vacuo and the
crude product was purified by flash chromatography.
OH
CN
CN
2
3
NO2
NO2
OH
CN
1.5 h
75
CN
Br
Br
OH
OH
CN
4
5
30 min 82
CN
O2N
O2N
Acknowledgements
CN
CN
G.C., K.V. and M.S.R. thank CSIR, New Delhi, for the
financial support in the form of fellowships.
3 h
80
CN
CN
MeO
MeO
OH
6
4 h
83
References and notes
H3C
H3C
1. (a) Baylis, A. B; Hillman, M. E. D. German Patent 2155-
113, 1972; Chem. Abstr. 1972, 77, 34174q; (b) Basavaiah,
D.; Rao, P. D.; Hyma, R. S. Tetrahedron 1996, 52, 8001–
8062.
a All products were characterized by 1H NMR, IR and mass
spectroscopy.
b Isolated yields after column chromatography.
2. Senokuchi, K.; Nakai, H.; Nakayama, Y.; Odagaki, Y.;
Sakaki, K.; Kato, M.; Maruyama, T.; Miyazaki, T.; Ito,
H.; Kamiyasu, K.; Kim, S.; Kawamaura, M.; Hamanaka,
N. J. Med. Chem. 1995, 38, 2521–2523.
3. Watanabe, T.; Hayashi, K.; Yoshimatsu, S.; Sakai, K.;
Takeyama, S.; Takashima, K. J. Med. Chem. 1980, 23, 50–
59.
Me
B(C6F5)3
Si H B(C6F5)3
+
Si O
H
n
A
4. (a) Anderson, R. J.; Coleman, J. E.; Piers, E.; Wallace, D.
J. Tetrahedron Lett. 1997, 38, 317–320; (b) Tanaka, H.;
Kuroda, A.; Marusawa, H.; Hatanaka, H.; Kino, T.;
Goto, T.; Hashimoto, M. J. Am. Chem. Soc. 1987, 109,
5031–5033; (c) Ishibashi, Y.; Ohba, S.; Nishiyama, S.;
Yamamura, S. Tetrahedron Lett. 1996, 37, 2997–3000.
5. Marfat, A.; McGuirk, P. R.; Helquist, P. J. Org. Chem.
1979, 44, 3888–3901.
Si
-
OH
H
H
R
O
O
H
A
COOEt
R
OEt
R
Me
COOEt
OH
I
B
C
6. Basavaiah, D.; Rao, S. J.; Satyanarayana, T. Chem. Rev.
2003, 103, 811–891, and references cited therein.
7. (a) Das, B.; Banerjee, J.; Ravindranath, N. Tetrahedron
2004, 60, 8357–8361; (b) Das, B.; Banerjee, J.; Ravind-
ranath, N.; Venkataiah, B. Tetrahedron Lett. 2004, 45,
2425–2426; (c) Das, B.; Majhi, A.; Banerjee, J.; Chowdh-
ury, N.; Venkateswarlu, K. Tetrahedron Lett. 2005, 46,
7913–7915.
8. (a) Guriece, A.; Goucaud, A. New J. Chem. 1991, 15, 943;
(b) Rabe, J.; Hoffmann, H. M. R. Angew. Chem., Int. Ed.
Engl. 1983, 22, 795; (c) Hoffmann, H. M. R.; Rabe, J. J.
Org. Chem. 1985, 50, 3849–3859.
H
-
Si
OH
O
N
R
H
A
C
CN
R
R
Me
C
N
H
OH
III
D
E
Scheme 3.
cyano group when compared to methyl functionality and
a bulky ethoxy carbonyl group.
9. Das, B.; Banerjee, J.; Mahender, G.; Majhi, A. Org. Lett.
2004, 6, 3349–3352.
10. Shadakshari, U.; Nayak, S. K. Tetrahedron Lett. 2001, 57,
4599–4602.
In conclusion, this protocol describes for the first time,
PMHS-B(C6F5)3 as a source of hydride for SN20 dis-
placement of –OH groups in Baylis–Hillman adducts
without the need for prior acylation. This methodology
is versatile and allows one to reduce hydroxy groups in
the presence of other sensitive functional groups. The
11. (a) Basavaiah, D.; Krishnamacharyulu, M.; Hyma, R. S.;
Sarma, P. K. S.; Kumaragurubaran, N. J. Org. Chem.
1999, 64, 1197–1200; (b) Das, B.; Banerjee, J.; Majhi, A.;
Mahender, G. Tetrahedron Lett. 2004, 45, 9225–
9227.

3478
S. Chandrasekhar et al. / Tetrahedron Letters 47 (2006) 3475–3478
12. Basavaiah, D.; Sarma, P. K. S. J. Chem. Soc., Chem.
Commun. 1992, 955–995, and references cited therein.
13. Pachamuthu, K.; Vankar, Y. D. Tetrahedron Lett. 1998,
39, 5439–5442.
J = 7.2 Hz, 2H), 2.10 (s, 3H), 1.37 (t, J = 7.2 Hz, 3H); 13
C
NMR (CDCl3, 75 MHz): d 167.8, 137.5, 135.7, 135.2,
129.3, 129.1, 124.0, 122.8, 61.2, 14.2, 13.9; IR (KBr): 2983,
1711, 1637, 1531, 1352, 1254 cmꢀ1; ESI-MS: m/z 236
(M+1)+.
14. Chandrasekhar, S.; Babu B. N.; Chandrashekar, G. Review
on tris(pentafluorophenyl)borane. Contribution for Elec-
tronic Encyclopedia of Organic Reagents for Organic
Synthesis. eEROS, 2005 and references cited therein.
15. Our contributions with PMHS: (a) Chandrasekhar, S.;
Chandrashekar, G.; Babu, B. N.; Vijeender, K.; Venka-
tram Reddy, K. Tetrahedron Lett. 2004, 45, 5497–5499; (b)
Chandrasekhar, S.; Babu, B. N.; Ahmed, Md.; Reddy, M.
V.; Srihari, P.; Jagadeesh, B.; Prabhakar, A. Synlett 2004,
1303–1305; (c) Chandrasekhar, S.; Reddy, Ch. R.; Babu, B.
N. Tetrahedron Lett. 2003, 44, 2057–2059; (d) Chandra-
sekhar, S.; Reddy, Ch. R.; Rao, R. J. Synlett 2001, 1561–
1562; (e) Chandrasekhar, S.; Reddy, Ch. R.; Rao, R. J.
Tetrahedron 2001, 57, 3435–3438; (f) Chandrasekhar, S.;
Chandraiah, L.; Reddy, M. V. Synlett 2000, 1351–1353; (g)
Chandrasekhar, S.; Reddy, Ch. R.; Ahmed, Md. Synlett
2000, 1655–1657; (h) Chandrasekhar, S.; Chandraiah, L.;
Reddy, Ch. R.; Reddy, M. V. Chem. Lett. 2000, 780–781;
(i) Chandrasekhar, S.; Ahmed, Md. Tetrahedron Lett.
1999, 40, 9325–9327; (j) Chandrasekhar, S.; Reddy, M. V.;
Chandraiah, L. Synth. Commun. 1999, 29, 3981–3987; (k)
Chandrasekhar, S.; Reddy, Y. R.; Reddy, Ch. R. Chem.
Lett. 1998, 29, 1273–1274; (l) Chandrasekhar, S.; Reddy,
Y. R.; Ramarao, C. Synth. Commun. 1997, 27, 2251–
2254.
18. The Z-stereochemistry of 1d was assigned on the basis of
1H and 13C chemical shifts in comparison with literature
values.12 1H NMR (CDCl3, 300 MHz): d 7.72–7.23 (m,
5H), 6.89 (br s, 1H), 2.17 (d, J = 1.5 Hz, 3H); 13C NMR
(CDCl3, 75 MHz): d 143.3, 133.3, 129.1, 128.1, 127.7,
118.5, 105.3, 21.1; IR (KBr): 2362, 1618 cmꢀ1: ESI-MS:
m/z 144 (M+1)+.
19. Spectral data for selected products: Compound 2b: 1H
NMR (CDCl3, 300 MHz): d 7.56 (s, 1H), 7.49 (d,
J = 8.7 Hz, 2H), 7.23 (d, J = 8.7 Hz, 2H), 4.24 (q,
J = 7.2 Hz, 2H), 2.08 (s, 3H), 1.35 (t, J = 7.2Hz, 3H); IR
(KBr): 2927, 1707, 1618, 1252 cmꢀ1; ESI-MS: m/z 269
(M+), 271 (M+2)+.
1
Compound 6b: H NMR (CDCl3, 200 MHz): d 7.65–7.45
(m, 5H), 4.25 (q, J = 7.0 Hz, 2H), 2.10 (s, 3H), 1.36 (t,
J = 7.0 Hz, 3H); IR (KBr): 1721, 1630, 620 cmꢀ1; ESI-
MS: m/z 281 (M+Na)+.
1
Compound 8b: H NMR (CDCl3, 300 MHz): d 6.76–6.68
(m, 1H) 4.15 (q, J = 7.2 Hz, 2H), 2.14 (q, J = 7.2 Hz, 2H),
1.18 (s, 3H), 1.15–1.22 (m, 9H), 0.90 (t, J = 6.8 Hz, 3H);
IR (KBr): 2930, 1719, 1620 cmꢀ1; ESI-MS: m/z 184 (M)+.
Compound 9b: 1H NMR (CDCl3, 200 MHz): d 7.57 (s,
1H), 7.25–6.92 (m, 2H), 6.82–6.50 (m, 2H), 4.23 (q,
J = 7.0 Hz, 2H), 2.10 (s, 3H), 1.25 (t, J = 7.0 Hz, 3H), 0.98
16. Chandrasekhar, S.; Reddy, C. R.; Babu, B. N. J. Org.
Chem. 2002, 67, 9080.
(s, 9H), 0.20 (s, 6H); IR (KBr): 2985, 1721, 1628 cmꢀ1
;
ESI-MS: m/z 320 (M)+.
1
17. In the H NMR spectrum of the product 3b, a resonance
Compound 4d: 1H NMR (CDCl3, 300 MHz): d 8.27 (d,
J = 9.1 Hz, 2H), 7.82 (d, J = 9.1 Hz, 2H), 6.98 (s, 1H),
2.24 (s, 3H); IR (KBr): 2211, 1617, 1519, 1345 cmꢀ1: ESI-
MS: m/z 187 (Mꢀ1)+.
at d 7.69 was assigned to the olefine proton of the E
trisubstituted alkene.11a 1H NMR (CDCl3, 300 MHz): d
8.25 (s, 1H), 8.19–8.03 (m, 1H), 7.69–7.41 (m, 3H), 4.29 (q,