LETTER
Single-Isomer Trisubstituted Olefins
1115
mmol), and DABCO (66 mg, 0.59 mmol) under a nitrogen atmo-
sphere. Freshly distilled THF was added (1.0 mL) followed by H2O
(10.5 mL, 0.59 mmol) and a solution of ethyl but-2-ynoate (1, 22 mg,
0.20 mmol in 1 mL THF). To a second oven-dried flask equipped
with a teflon-coated stir bar were added pent-4-enyl benzoate (111
mg, 0.59 mmol) and 9-borabicyclo[3.3.1]nonane (0.5 M solution in
THF, 1.20 mL, 0.586 mmol). The resulting solution was stirred at
r.t. for 2 h. The alkylborane solution was transferred to the first flask
via cannula, and the resulting mixture was stirred for 18 h at r.t. The
solution was then diluted with Et2O and washed three times with
H2O. The organic phase was dried over anhyd MgSO4, filtered, and
concentrated in vacuo. The pure product8b (54 mg, 90%) was ob-
tained as an oil by flash chromatography (2% EtOAc in hexane). 1H
NMR (400 MHz, acetone-d6): d = 8.03–8.01 (m, 2 H), 7.66–7.61
(m, 1 H), 7.54–7.49 (m, 2 H), 5.68 (q, J = 1.2 Hz, 1 H), 4.32 (t,
J = 6.4 Hz, 2 H), 4.08 (q, J = 7.2 Hz, 2 H), 2.22 (td, J = 7.6, 1.2 Hz,
2 H), 2.15 (d, J = 1.2 Hz, 3 H), 1.82 (quint, J = 6.4 Hz, 2 H), 1.64–
1.47 (m, 4 H), 1.21 (t, J = 7.2 Hz, 3 H). 13C NMR (400 MHz, ace-
tone-d6): d = 167.8 (C), 167.7 (C), 134.8 (CH), 132.4 (C), 131.1
(CH), 130.4 (CH), 130.1 (C), 117.4 (CH), 66.4 (CH2), 60.7 (CH2),
42.1 (CH2), 30.2 (CH2), 28.7 (CH2), 27.3 (CH2), 19.6 (CH3), 15.6
(CH3). IR (neat): 1718, 1648 cm–1. MS: m/z = 304.2 [M+]. HRMS:
m/z calcd for C18H24O4: 304.1675; found: 304.1659.
smoothly undergoing coupling to produce the single-iso-
mer product in 80% yield (Table 3, entry 7). The presence
of functional groups on the borane coupling partner was
tested, and in all cases good yields were realized (Table 3,
entries 8–10). Finally, a branched substituent was tested,
that afforded the corresponding product 20 in 80% yield.
Table 3 Formation of Trisubstituted Olefins from Alkynyl Esters
and Alkyl Boranesa
R1
CO2Et
Pd(OAc)2, PCy3•HBF4
B
CO2Et
+
R2
R2
R1
DABCO, H2O, THF
H
Entry Substrate
Productb
Yield
(%)c
1
2
1 R1 = Me
1 R1 = Hd
7 R1 = Me(CH2)4
3 R2 = BzO(CH2)5
90
7e
6 R2 = BzO(CH2)5
8 R2 = BzO(CH2)5
d
3
74
55
57
41
80
79
72
87
4
9 R1 = TIPSO(CH2)4
10 R2 = BzO(CH2)5
12 R2 = BzO(CH2)5
14 R2 = BzO(CH2)5
16 R2 = BzO(CH2)5
17 R2 = Me(CH2)7
18 R2 = BnO(CH2)5
19 R2 = TIPSO(CH2)5
f
5
11 R1 = Me(CH2)4
Acknowledgment
6
13 R1 = c-C6H11
15 R1 = Ph
1 R1 = Me
The Natural Science and Engineering Research Council of Canada
(NSERC), the Canadian Foundation for Innovation, the Ontario In-
novation Trust and the University of Ottawa for generous funding.
7
8
References
9
1 R1 = Me
(1) (a) Valentine, D. H. Jr.; Hillhouse, J. H. Synthesis 2003,
317. (b) Rein, T.; Pedersen, T. M. Synthesis 2002, 579.
(c) Maryanoff, B. E.; Reitz, A. B. Chem. Rev. 1989, 89, 863.
(d) Iorga, B.; Eymery, F.; Mouriès, V.; Savignac, P.
Tetrahedron 1998, 54, 14637. (e) Wadsworth, W. S. Jr.
Org. React. 1977, 25, 73. (f) Nicolaou, K. C.; Bulger, P. G.;
Sarlah, D. Angew. Chem. Int. Ed. 2005, 44, 4490.
10
11
1 R1 = Me
1 R1 = Me
20 R2 = BzO(CH2)3CHMe 80
a Conditions: Pd(OAc)2 (0.05 equiv), PCy3·HBF4 (0.15 equiv),
DABCO (3.0 equiv), H2O (3.0 equiv), borane (3.0 equiv), THF (0.09
M), 23 °C, 18 h.
b Products were obtained as single isomers.
c Isolated yield.
(g) Grubbs, R. H. Tetrahedron 2004, 60, 7117.
(2) (a) Tan, Z.; Negishi, E. Angew. Chem. Int. Ed. 2006, 45,
762. (b) Tan, Z.; Negishi, E.-I. Angew. Chem. 2006, 118,
776. (c) Marek, I. Chem. Rev. 2000, 100, 2887. (d)Hata,T.;
Kitagawa, H.; Masai, H.; Kurahashi, T.; Shimizu, M.;
Hiyama, T. Angew. Chem. 2001, 113, 812. (e) Hata, T.;
Kitagawa, H.; Masai, H.; Kurahashi, T.; Shimizu, M.;
Hiyama, T. Angew. Chem. Int. Ed. 2001, 40, 790.
d The methyl ester was used in place of the ethyl ester.
e The Z-isomer was obtained
f The Weinreb amide was used in place of the ethyl ester.
The generation of trisubstituted olefins through the intro-
duction of alkyl groups onto alkyl-substituted alkynyl es-
ters and amides has been described. The method utilized
palladium catalysis employing PCy3 as an optimal ligand,
together with DABCO as a base. In all cases the products
were isolated as single stereo- and regioisomers, a signif-
icant advantage for synthesis as the separation of isomeric
olefin products is potentially difficult. Notably, the meth-
od gives products, such as 8, 10 and 14, bearing linear
alkyl appendages that would otherwise be extremely dif-
ficult to access. The reaction is simple, rapid, and pro-
ceeds under mild conditions to afford a variety of
trisubstituted olefin products.
(f) Kurahashi, T.; Hata, T.; Masai, H.; Kitagawa, H.;
Shimizu, M.; Hiyama, T. Tetrahedron 2002, 58, 6381.
(g) Itami, K.; Mineno, M.; Muraoka, N.; Yoshida, J. J. Am.
Chem. Soc. 2004, 126, 11778. (h) Rossi, R.; Bellina, F.;
Carpita, A.; Mazzarella, F. Tetrahedron 1996, 52, 4095.
(i) Normant, J. F.; Alexakis, A. Synthesis 1981, 841.
(j) Corey, E. J.; Katzenellenbogen, J. A. J. Am. Chem. Soc.
1969, 91, 1851. (k) Negishi, E.-i.; Zhang, Y.; Cederbaum,
F. E.; Webb, M. B. J. Org. Chem. 1986, 51, 4080. (l) Itami,
K.; Yoshida, J.-i. Bull. Chem. Soc. Jpn. 2006, 79, 811.
(m) Itami, K.; Yoshida, J.-i. Chem. Eur. J. 2006, 12, 3966.
(3) (a) Chen, C.; Kehr, G.; Fröhlich, R.; Erker, G. J. Am. Chem.
Soc. 2010, 132, 13594. (b) Zhou, C.-Y.; Zhu, S.-F.; Wang,
L.-X.; Zhou, Q.-L. J. Am. Chem. Soc. 2010, 132, 10955.
(c) Tsuji, H.; Ueda, Y.; Ilies, L.; Nakamura, E. J. Am. Chem.
Soc. 2010, 132, 11854. (d) Nakao, Y.; Yada, A.; Hiyama, T.
J. Am. Chem. Soc. 2010, 132, 10024. (e) Yang, C.-M.;
Jeganmohan, M.; Parthasarathy, K.; Cheng, C.-H. Org Lett.
2010, 132, 3610. (f) Hayashi, T.; Inoue, K.; Taniguchi, N.;
Typical Procedure for the Preparation of Trisubstituted Al-
kenes from Alkynyl Esters:
(6E)-8-Ethoxy-6-methyl-8-oxoocto-6-enyl Benzoate (3)
To an oven-dried flask equipped with a teflon-coated stir bar were
added Pd(OAc)2 (6.6 mg, 9.8 mmol), PCy3·HBF4 (10.8 mg, 29
Synlett 2011, No. 8, 1113–1116 © Thieme Stuttgart · New York