Rhodium-catalyzed addition of arylboronic acids to alkynyl aza-heteroaromatic compounds in water

Article abstract of DOI:10.1021/jo0205255

Alkynyl heteroaromatic compounds reacted with arylboronic acids to give addition products in the presence of a rhodium catalyst. The best results were obtained when a novel pyridine-substituted water-soluble phosphine ligand was used. The reactions proceed to give trisubstituted alkenes from various arylboronic acids and alkynyl heteroaromatic compounds with high regioselectivity. Only alkynes with a nitrogen atom in proximity to the triple bond were converted to the corresponding alkenes, as expected for a chelation-controlled addition.

Full text of DOI:10.1021/jo0205255

Rh od iu m -Ca ta lyzed Ad d ition of Ar ylbor on ic Acid s to Alk yn yl
Aza -Heter oa r om a tic Com p ou n d s in Wa ter
Mark Lautens* and Masahiro Yoshida
Davenport Research Laboratories, Department of Chemistry, University of Toronto, Toronto,
Ontario, Canada M5S 3H6
mlautens@chem.utoronto.ca.
Received August 9, 2002
Alkynyl heteroaromatic compounds reacted with arylboronic acids to give addition products in the
presence of a rhodium catalyst. The best results were obtained when a novel pyridine-substituted
water-soluble phosphine ligand was used. The reactions proceed to give trisubstituted alkenes from
various arylboronic acids and alkynyl heteroaromatic compounds with high regioselectivity. Only
alkynes with a nitrogen atom in proximity to the triple bond were converted to the corresponding
alkenes, as expected for a chelation-controlled addition.
In tr od u ction
unsaturated compounds (Scheme 1).7 In these reactions,
only olefins activated by the presence of a conjugated
Organic reactions in aqueous medium have received
significant attention as a result of environmental and
economic considerations. The formation of carbon-carbon
bonds using a transition-metal catalyst in water repre-
sents one of the most attractive strategies in this area.1
Because normal transition-metal catalysts generally have
low solubility and low reactivity in water, various water-
soluble ligands have been developed to solve these
problems.2 TPPDS (1) and TPPTS (2) are the most
(4) For recent representative reactions using TPPTS: (a) Mignani,
G.; Morel, D.; Colleuille, Y. Tetrahedron Lett. 1985, 26, 6337. (b)
Mignani, G.; Morel, D.; Colleuille, Y. Tetrahedron Lett. 1986, 27, 2591.
(c) Grosselin, J . M.; Mercier, C.; Allmang, G.; Grass, F. Organometallics
1991, 10, 2126. (d) Genet, J . P.; Linquist, A.; Blard, E.; Mouries, V.;
Savignac, M.; Vaultier, M. Tetrahedron Lett. 1995, 36, 1443. (e)
Amatore, C.; Blart, E.; Genet, J . P.; J utand, A.; Lemaire-Audoire, S.;
Savignac, M. J . Org. Chem. 1995, 60, 6829. (f) Galland, J .-C.; Savignac,
M.; Genet, J .-P. Tetrahedron Lett. 1997, 38, 8695. (g) Galland, J .-C.;
Savignac, M.; Genet, J .-P. Tetrahedron Lett. 1999, 40, 2323. (h)
Bhanage, B. M.; Ikushima, Y.; Shirai, M.; Arai, M. Tetrahedron Lett.
1999, 40, 6427. (i) Djoman, M. C. K.-B.; Ajjou, A. N. Tetrahedron Lett.
2000, 41, 4845. (j) Michelet, V.; Galland, J .-C.; Charruault, L.;
Savignac, M.; Genet, J .-P. Org. Lett. 2001, 3, 2065. (k) Dupuis, C.;
Adiey, K.; Charruault, L.; Michelet, V.; Savignac, M.; Geneˆt, J .-P.
Tetrahedron Lett. 2001, 42, 6523. (l) Francisco, L. W.; Moreno, D. A.;
Atwood, J . D. Organometallics 2001, 20, 4237.
(5) For reactions using TPPDS, see: (a) Thorpe, T.; Brown, S. M.;
Crosby, J .; Fitzjohn, S.; Muxworthy, J . P.; Williams, J . M. J . Tetrahe-
dron Lett. 2000, 41, 4503. (b) Lautens, M.; Roy, A.; Fukuoka, K.;
Fagnou, K.; Mart´ın-Matute, B. J . Am. Chem. Soc. 2001, 123, 5358. (c)
Chen, H.; Li, Y.; Chen, J .; Cheng, P.; Li, X. Catal. Today 2002, 74,
131.
popular water-soluble ligands,3 which are utilized in a
variety of transition metal-catalyzed reactions.4-6
Rhodium-catalyzed reactions of boronic acids to acti-
vated alkenes in aqueous media have emerged as a highly
efficient methods for the formation of carbon-carbon
bonds. Hayashi and Miyaura reported the asymmetric
1,4-addition of organoboronic acids to various R,â-
(6) For representative other examples of transition metal chemistry
of water-soluble phosphine, see: (a) Smith, R. T.; Ungar, R. K.;
Sanderson, L. J .; Baird, M. C. Organometallics 1983, 2, 1138. (b)
Darensbourg, D. J .; J oo, F.; Kannisto, M.; Katho, A.; Reibenspies, J .
H. Organometallics 1992, 11, 1990. (c) To´th, I.; Hanson, B. E.
Organometallics 1993, 12, 1506. (d) J ones, A.; Roberts, D. L.; Davis,
M. E. Nature 1994, 370, 449. (e) Ding, H.; Hanson, B. E.; Bakos, J .
Angew. Chem., Int. Ed. Engl. 1995, 34, 1645. (f) Mohr, B.; Lynn, D.
M.; Grubbs, R. H. Organometallics 1996, 15, 4317. (g) Shin, S.;
RajanBabu, T. V. Org. Lett. 1999, 1, 1229. (h) Yonehara, K.; Hashi-
zume, T.; Mori, K.; Ohe, K.; Uemura, S. J . Org. Chem. 1999, 64, 5593.
(i) Kovacs, J .; Todd, T. D.; Reibenspies, J . H.; J oo, F.; Darensbourg, D.
J . Organometallics 2000, 19, 3963. (j) Ueda, M.; Nishimura, M.;
Miyaura, N. Synlett, 856. (k) Shaughnessy, K. H.; Booth, R. S. Org.
Lett. 2001, 3, 2757. (l) Lucey, D. M.; Atwood, J . D. Organometallics
2002, 21, 2105. (m) Raghuraman, K.; Pillarsetty, N.; Volkert, W. A.;
Barnes, C.; J urisson, S.; Katti, K. V. J . Am. Chem. Soc. 2002, 124,
7276.
(1) For reviews of organic synthesis in water, see: (a) Organic
Synthesis in Water; Grieco, P. A., Ed.; Blacky Academic and Profes-
sional: London, 1998. (b) Li, C. J .; Chan, T. H. Organic Reactions in
Organic Media; J ohn Wiley and Sons: New York, 1997. (c) Cornils,
B.; Herrmann, W. A. Aqueous Phase Organometallic Chemistry:
Concepts and Applications; Wiley-VCH: Weinheim, 1998. (d) Li, C. J .
Chem. Rev. 1993, 93, 2023. (e) Li, C. J .; Chan, T. H. Tetrahedron 1999,
55, 11149. (f) Li, C. J . Tetrahedron 1996, 52, 5643.
(2) For review of water-soluble ligands, see: (a) Herrmann, W. A.;
Kohlpaintner, C. W. Angew. Chem., Int. Ed. Engl. 1993, 32, 1524. (b)
J oo´, F.; Katho´, AÄ . J . Mol. Catal. A 1997, 116, 3. (c) Katti, K. V.; Gali,
H.; Smith, C. J .; Berning, D. E. Acc. Chem. Res. 1999, 32, 9. (d) Genet,
J . P.; Saignac, M. J . Organomet. Chem. 1999, 576, 305. (e) Genet, J .
P.; Saignac, M.; Lemaire-Audoire, S. In Transition Metal Catalysed
Reactions; Murahashi, S.; Davies, S. G., Eds.; Blackwell Science:
Oxford, 1999; p 55.
(7) For additions to enones, see: (a) Sakai, M.; Hayashi, M.;
Miyaura, N. Organometallics 1997, 16, 4229. (b) Takaya, Y.; Ogasawara,
M.; Hayashi, T.; Sakai, M.; Miyaura, N. J . Am. Chem. Soc. 1998, 120,
5579. For additions to R,â-unsaturated esters, see: (c) Sakuma, S.;
Sakai, M.; Itooka, R.; Miyaura, N. J . Org. Chem. 2000, 65, 5951. For
additions to vinyl phosphonates, see: (d) Hayashi, T.; Senda, T.;
Takaya, Y.; Ogasawara, M. J . Am. Chem. Soc. 1999, 121, 11591. For
additions to vinyl nitro compounds, see: (e) Hayashi, T.; Senda, T.;
Ogasawara, M. J . Am. Chem. Soc. 2000, 122, 10716.
(3) These ligands are commercially available from Strem Chemicals.
10.1021/jo0205255 CCC: $25.00 © 2003 American Chemical Society
Published on Web 01/03/2003
762
J . Org. Chem. 2003, 68, 762-769

Rhodium-Catalyzed Addition of Arylboronic Acids
TABLE 1
SCHEME 1
SCHEME 2
entry
ligand
yield (%)
entry
ligand
yield (%)
1
2
3
TPPDS (1)
TPPTS (2)
PPh3
25 (35)a
NRb
4
5
6
dppe
dppe
3
<10c
NRd
51
<10c
a
The yield in parentheses is based on recovered starting
material. b No reaction. c Considerable amount of starting material
remained. The reaction was caried out in the absence of SDS in
SCHEME 3
d
dioxane/H2O ) 10/1.
SCHEME 4
electron-withdrawing group could be used, and the reac-
tions generally must be carried out in an organic solvent-
water mixture. Recently, we reported the rhodium-
catalyzed reactions of various arylboronic acids to alkenes
(Scheme 2).5b The reactions could be applied to unacti-
vated olefins such as aromatic or heteroaromatic olefins
in neat water by using TPPDS (1), and it was clear that
the reaction outcome changes completely depending on
the type of olefin. When styryl olefins were used, 1,2-
diarylethylenes were produced, which arose from a
“Heck-type” addition-â-H elimination process.8 When
heteroaromatic olefins were used, the addition products
arising from an addition-hydrolysis pathway were ob-
tained. We sought to determine whether rhodium cata-
lysts could promote the addition of boronic acids to other
unsaturated compounds such as alkynes (Scheme 3).9,10
We thought that regioselective addition occurs with
alkynyl heteroaromatic compounds to give trisubstituted
alkenes. Furthermore, it was clear that the water-soluble
ligand 3, which has a pyridyl phosphine moiety, shows
high reactivity in the reaction. We now present a full
description of our results.
Resu lts a n d Discu ssion
Alkynyl heteroaromatic compounds for rhodium-cata-
lyzed addition were synthesized as follows (Scheme 4).
Alkynes having various heteroaromatics 11-16 were
synthesized by Sonogashira coupling11 of aryl bromides
4-9 with 1-hexyne 10 in 59-92% yield. Similarly,
substrates with various substituent on the alkyl side
chain (22-26) could be made from 2-bromopyridine 4 and
alkynes 17-21 in 90-98% yield. Alkyne 24, which has
a 3-hydroxypropyl group, was converted to a silylated
compound 27 in 87% yield. From the reactions of 2,6- (28)
and 2,5-dibromopyridine (9) with 1-hexyne, dialkynes 29
and 30 in which two alkynyl groups are present on the
pyridine ring were obtained in 91% and 97% yield.
Our intitial attempt at rhodium-catalyzed addition
began with 2-(1-hexynyl)pyridine 11 and phenylboronic
acid 31a . (Table 1). According to our standard protocol
for addition to alkenes,5b the reaction of 11 with 31a in
the presence of 2 mol % [Rh(COD)Cl]2, 8 mol % TPPDS
(1), Na2CO3, and sodium dodecyl sulfate (SDS) in water
at 80 °C for 3 h gave the corresponding addition product
32a in 25% yield (35% yield based on recovered starting
material) (Table 1, entry 1). The reaction using TPPTS
(2) failed completely (entry 2), and organic-soluble phos-
phine ligands such as PPh3 and dppe led to low conver-
sion (entries 3 and 4). No reaction was observed in 10/1
dioxane/H2O solvent, in analogy with the conditions
reported by Hayashi and Miyaura7 (entry 5). Our atten-
tion turned to finding a new catalyst system that would
promote the addition. Recently, we determined that the
(8) Recently, Brown reported ruthenium-catalyzed oxidative Heck
reactions of arylboronic acids to activated alkenes: Farrington, E. J .;
Brown, J . M.; Barnard, C. F. J .; Rowsell, E. Angew. Chem., Int. Ed.
2002, 41, 169.
(9) For a previous communication, see: Lautens, M.; Yoshida, M.
Org. Lett. 2002, 4, 123.
(10) Recently, Hayashi reported a similar type addition to alkynes:
Hayashi, T.; Inoue, K.; Taniguchi, N.; Ogasawara, M. J . Am. Chem.
Soc. 2001, 123, 9918.
(11) Sonogashira, K. In Comprehensive Organic Synthesis; Trost,
B. M., Fleming, I., Eds.; Pergamon Press: Oxford, 1991; Vol. 3, p 521.
J . Org. Chem, Vol. 68, No. 3, 2003 763

Lautens and Yoshida
TABLE 2.
F IGURE 1. ROSEY correlation of 32e.
entry
boronic acid
product
yield (%)
TABLE 3. Rea ction s Usin g Va r iou s
Heter oa r om a tic-Con ta in in g Alk yn esa
1
2
3
4
5
6
7
phenyl 31a
32a
32b
32c
32d
32e
32f
51
81
86
2-methylphenyl 31b
2,6-dimethylpenyl 31c
1-naphthyl 31d
4-methoxyphenyl 31e
2-methyl-4-methoxyphenyl 31f
4-acetyl 31g
72
57a
83a
dec
a
4 mol % [Rh(COD)Cl]2, 16 mol % 3 and 5 equiv of boronic acid
were used.
rhodium-catalyzed reaction of arylboronic acids to alk-
enes effectively proceeds in the presence of pyridine.12
Additives including pyridine were found to influence the
ratio of Heck-type products to addition products in some
substrates. For example, while the reaction of 1-nitro-4-
vinylbenzene with 2-methylpheylboronic acid under stan-
dard conditions gave a mixture of addition-â-H elimi-
nation and addition-hydrolysis, the addition of pyridine
to the reaction mixture led to the generation of addition-
hydrolysis product exclusively in high yield. On the basis
of this result, we planned to use a novel water-soluble
ligand 3, which has a pyridyl phosphine moiety within
the molecule. Phosphine 3 was first synthesized by
Stelzer in 1993,13 but there are no reports of using this
compound as a ligand in catalysis. We were very pleased
to find that the reaction proceeded smoothly to afford 32a
in 51% yield when 3 was used (entry 6).
a
Reactions were carried out in the presence of 2 mol %
[Rh(COD)Cl]2, 8 mol % 3, 2.5 equiv of 2-methylphenylboronic acid,
b
SDS, and Na2CO3 in H2O at 80 °C for 1-3 h. Ar ) 2-methylphe-
nyl (entries 1, 5-7), Ar ) phenyl (entry 4). c 2.5 equiv of phenyl-
boronic acid was used. The reaction was carried out at 60 °C.e 4
d
mol % [Rh(COD)Cl]2, 16 mol % 3, and 5 equiv of 2-methylphenyl-
boronic acid 5b were used.
A series of substituted arylboronic acids 31a -g were
then subjected to the reaction conditions to further define
the reaction scope (Table 2). Substitution at the ortho
position of the arylboronic acid gave better results
(entries 2-4), and the yield increased to 86% when 2,6-
dimethylphenylboronic acid 31c was used (entry 3).
Although the catalyst loading must be increased (4 mol
% [Rh(COD)Cl]2, 16 mol % 3), the corresponding products
32e and 32f were obtained in good yield with arylboronic
acids 31e and 31f bearing a methoxyl group (entries 7
and 8). Acetylphenylboronic acid 31g was ineffective for
the addition to the alkyne (entry 8). Adducts 32a -f were
isolated as the sole products, and it was clear by 1H NMR
that the reactions proceed with high regioselectivity. The
geometry of the addition product 32e was determined by
ROESY, and the other adducts were assumed to the same
(Figure 1).
The results of the rhodium-catalyzed reactions of
alkynes containing various heteroaromatics 11-16 and
33 in the presence of ligand 3 are summarized in Table
3. In contrast to the reaction of 11 (entry 1), the reactions
of 12 and 13, which have the alkynyl group at the meta
and para positions on the pyridine ring, failed to undergo
the addition (entries 2 and 3). The desired product 34
was produced in low yield, and polymerized products
were mainly obtained when 1-phenylpropyne 33 was
subjected to the reaction conditions (entry 4). From these
results, it is expected that the nitrogen atom in the
aromatic ring is necessary and must be located adjacent
to the triple bond to promote the addition. When alkynes
14 and 15 bearing pyrimidyl and quinolyl group were
subjected to the reaction, the corresponding products 35
and 36 were obtained in good yields (entries 5 and 6).
The bromoarylalkyne 16 reacted to afford 37 in 66% yield,
demonstrating chemoselectivity (entry 7).
The reactions of pyridylalkynes having various sub-
stituents on the alkyne were also examined (Table 4). A
benzyl group (22) underwent reaction to give 38 in 66%
yield (entry 1). In contrast, the phenyl-substituted alkyne
23 reacted sluggishly (entry 2), perhaps because of steric
hindrance caused by the phenyl group. A substrate
containing a siloxyl group within the alkyl side chain (27)
was successfully transformed to 40 in 83% yield (entry
3). Furthermore, alkynes with a free hydroxyl group such
as 24 and 25 were also converted to 41 and 42 in
moderate yields (entries 4 and 5); however, a substrate
containing a hydroxyl group at the propargyl position (26)
failed to react (entry 6).
We next tried the reaction of 27 and 28, in which two
alkynyl groups were present on the pyridine ring (Scheme
5). When 27 was treated with 5 equiv of 2-methylphe-
nylboronic acid 31b in the presence of 4 mol % [Rh(COD)-
(12) Lautens, M.; Roy, A.; Fukuoka, K.; Fagnou, K.; Martı´n-Matute,
B.; Yoshida, M. Manuscript in preparation.
(13) Herd, O.; Langhans, P. K.; Stelzer, O. Angew. Chem., Int. Ed.
Engl. 1993, 32, 1058.
764 J . Org. Chem., Vol. 68, No. 3, 2003

Rhodium-Catalyzed Addition of Arylboronic Acids
TABLE 4. Rea ction s Usin g Va r iou s Su bstitu ted
P yr id yla lk yn esa
F IGURE 2.
SCHEME 6
a
Reactions were carried out in the presence of 2 mol %
[Rh(COD)Cl]2, 8 mol % 3, 2.5 equiv of 2-methylphenylboronic acid,
b
SDS, and Na2CO3 in H2O at 80 °C for 1-3 h. Ar ) 2-methylphe-
nyl. c 4 mol % [Rh(COD)Cl]2, 16 mol % 3, and 5 equiv of 2-meth-
d
ylphenylboronic acid 5b were used. A considerable amount of
starting material remained.
arylboronic acid to the rhodium species 45 to give the
arylrhodium complex 46 as the initial step. Next, the
coordination of the alkynyl and pyridyl group of the
substrate to rhodium followed by regioselective insertion
into the Rh-C bond would give the alkenylrhodium
complex 47. The observation that only alkynes substi-
tuted at the ortho position on the pyridine ring reacted
with arylboronic acids supports a chelation-controlled
insertion process.15 Finally the hydrolysis of the complex
47 with water would afford the product and the regener-
ated rhodium species 45.
SCHEME 5
The cause of the increased reactivity of the pyridine-
base ligand is not clear, but it might also be related
to chelation. Simultaneous coordination of the phos-
phine and the nitrogen to rhodium as shown in 48 is
possible.
Information on the reaction mechanism was gained
when the reaction of 11 with 31b was run in D2O
(Scheme 6). In this case, deuterium was incorporated
quantitatively at the alkenyl position to give 49 in 74%
yield. Recently, Hayashi has also reported the rhodium-
catalyzed addition of arylboronic acids to alkynes.10
Cl]2 and 8 mol % 3 at 80 °C, the double addition product
43 was produced in 47% yield. The yield was increased
to 65% by conducting the reaction at 60 °C. Interestingly,
substrate 28, which has an alkynyl group at both an
ortho and meta position, was selectively converted into
the monoadduct 44 after 20 min, demonstrating that it
was possible to distinguish two alkynes within a single
molecule. The yield was dramatically decreased when the
reaction was carried out for 2 h (54 vs 15% yield),
implying that the alkynyl group at the meta position
eventually reacts but leads to complex mixtures.
(14) (a) Brune, H.-A.; Unsin, J .; Hemmer, R.; Reichhardt, M. J .
Organomet. Chem. 1989, 369, 335. (b) Uson, R.; Oro, L. A.; Cabeza, J .
A. Inorg. Synth. 1985, 23, 126. (c) Grushin, V. V.; Kuznetsov, V. F.;
Bensimon, C.; Alper, H. Organometallics 1995, 14, 3927, and see also
ref 4c. (d) Hayashi, T.; Takahasi, M.; Takaya, Y.; Ogasawara, M. J .
Am. Chem. Soc. 2002, 124, 5052.
(15) For examples of the chelation-controlled rhodium-catalyzed
reactions, see: (a) Ishiyama, T.; Hartwig, J . J . Am. Chem. Soc. 2000,
122, 12043. (b) J un, C.-H.; Lee, H.; Moon, C. H.; Hong, H.-S. J . Am.
Chem. Soc. 2001, 123, 8600. (c) J un, C.-H.; Lee, H.; Lim, S.-G. J . Am.
Chem. Soc. 2001, 123, 751. (d) J un, C.-H.; Lee, D.-Y.; Lee, H.; Hong,
J .-B. Angew. Chem., Int. Ed. 2000, 39, 3070. (e) J un, C.-H.; Lee, H. J .
Am. Chem. Soc. 1999, 121, 880. (f) J un, C.-H.; Lee, D.-Y.; Hong, J .-B.
Tetrahedron Lett. 1997, 38, 6673. (g) J un, C.-H.; Lee, H.; Hong, J .-B.
J . Org. Chem. 1997, 62, 1200.
A plausible mechanism for the reaction is shown in
Figure 2. It is presumed that (hydroxo)rhodium(I) com-
plex 45 exits as an active species in this reaction,14 and
a catalytic cycle would involve the transmetalation of the
J . Org. Chem, Vol. 68, No. 3, 2003 765

Lautens and Yoshida
SCHEME 8
F IGURE 3.
SCHEME 7
Con clu sion
In conclusion, we have developed a rhodium-catalyzed
addition of arylboronic acids to alkynes. The reactions
can be run in neat water, and it was found that the
reaction is best carried out in the presence of the novel
pyridine-substituted ligand 3. The reactions enable the
construction of trisubstituted olefins with high regiose-
lectivity using heteroaromatic contained alkynes. A
variety of alkynes can be chemoselectively converted to
the corresponding addition products. It is expected that
the addition would proceed by chelation to the nitrogen
moiety, and two alkynes at different positions on the
pyridine ring could be distinguished. The reactions also
applied to the alkynes one and two carbons away from
the pyridyl group. Application of this catalyst system to
other types of reactions are now in progress.
In this work, a 1,4-shift of rhodium from the vinylic
position to the ortho position of the phenyl group was
proposed to explain the labeling studies, but we did not
observe this 1,4-shift under our reaction conditions. It is
expected that the relatively stable chelated alkenyl-
rhodium complex 47 would prevent the 1,4-shift of
rhodium.
To confirm the proposal of a chelation-controlled regi-
oselective addition mechanism, we next examined the
reactions using alkynes having a triple bond one and two
carbons away from the pyridyl group. These substrates
would form chelated five- and six-membered ring inter-
mediates 50 and 51 to give the corresponding adducts
with high regioselectivity (Figure 3).
Syntheses of the substrates were performed as shown
in Scheme 7. 2-Acetylpyridine 52 was subjected to the
addition of 1-hexyne 10 in the presence of n-BuLi,
followed by the protection of the yielded tertiary alcohol
with the TBS group to give pyridine-ring-containing 54
in two steps in 86% yield. Pyrazine-ring-containing
substrate 55 was also prepared from 53 in two steps in
90% yield. Alkyne 57 could be made from 52 in three
steps via addition of the propargyl unit in the presence
of aluminum,16 followed by silylation of alcohol and
methylation of the terminal alkyne.
When the reaction of 54 with 2-methylphenylboronic
acid was carried out, the desired adduct 58 was produced
in 90% yield as the sole product (Scheme 8). Similarly,
59 was obtained in 88% yield from 55. Although the
product yield decreased to 47%, the reaction using 57 was
successful, giving 60 predominantly. These results pro-
vide good evidence that the chelation-controlled regiose-
lective addition is operating. The low conversion of 57
may be due to formation of a six-membered ring chelation
(51), compared to four- and five-membered ring com-
plexes.
Exp er im en ta l Section
The following includes general experimental procedures and
spectroscopic information for all illustrative new compounds.
The spectral data of 11,17 23,18 26,19 and 3420 are in complete
agreement with the literature’s data. Materials were obtained
from commercial suppliers and used without further purifica-
tion. Solvents were dried and distilled according to standard
protocols. The phrase “residue upon workup” refers to the
residue obtained when the organic layer was separated and
dried over anhydrous MgSO4 and the solvent was evaporated
under reduced pressure.
Gen er a l P r oced u r es for t h e P r ep a r a t ion of Su b -
str a tes. To a stirred suspension of 2-bromopyridine (500 mL,
3.17 mmol), PdCl2(PPh3)2 (111.2 mg, 0.158 mmol), and CuI
(0.158 mL, 30.2 mmol) in Et3N (20 mL) was added dropwise
2-hexyne (0.436 mL, 3.79 mmol) at room temperature, and
stirring was continued for 3 h at the same temperature. The
reaction mixture was diluted with water and extracted with
Et2O. The combined extracts were washed with saturated
aqueous NaCl. The residue upon workup was purified by
chromatography on silica gel with hexanes:Et2O (75:25 v/v)
as eluent to give 11 (497 mg, 98%) as a colorless oil.
3-(1-Hexyn yl)p yr id in e (12): Rf ) 0.44 (50% Et2O in
hexane); IR (neat) 2958, 2933, 2872, 2232, 1558 cm-1; 1H NMR
(300 MHz, CDCl3) δ 8.63 (1H, s), 8.47 (1H, d, J ) 4.8 Hz),
7.66 (1H, d, J ) 7.8 Hz), 7.20 (1H, dd, J ) 7.8, 4.8 Hz), 2.43
(17) Sato, N.; Hayakawa, A.; Takeuchi, R. J . Heteroycl. Chem. 1990,
27, 503.
(18) Okubo, J .; Shinozuka, H.; Koitabashi, T.; Yomura, R. Bull.
Chem. Soc. J pn. 1990, 63, 329.
(19) Al-Arnaout, A.; Courtois, G.; Miginiac, L. J . Organomet. Chem.
1987, 333, 139.
(20) Kawashima, T.; Ishii, T.; Inamoto, N. Bull. Chem. Soc. J pn.
1987, 60, 1831.
(16) Yamamoto, H. In Comprehensive Organic Synthesis; Trost, B.
M., Fleming, I., Eds.; Pergamon Press: Oxford, 1991; Vol. 2, p 81, and
references therein.
766 J . Org. Chem., Vol. 68, No. 3, 2003

Rhodium-Catalyzed Addition of Arylboronic Acids
(2H, t, J ) 7.2 Hz), 1.65-1.54 (2H, m), 1.54-1.42 (2H, m),
0.95 (3H, t, J ) 7.2 Hz); 13C NMR (75 MHz, CDCl3) δ 152.2,
147.8, 138.3, 122.8, 121.1, 94.0, 77.2, 30.5, 21.9, 19.0, 13.5; MS
m/z 159 (M+); HRMS m/z calcd for C11H13N 159.1048 (M+),
found 159.1039.
2,5-Di-1-h exyn ylp yr id in e (30): Rf ) 0.24 (10% Et2O in
hexane); IR (neat) 2958, 2872, 2230, 1584, 1538 cm-1; 1H NMR
(300 MHz, CDCl3) δ 8.53 (1H, d, J ) 1.8 Hz), 7.58 (1H, dd, J
) 8.4 and 1.8 Hz), 7.27 (1H, d, J ) 8.4 Hz), 2.44 (2H, t, J )
6.9 Hz), 2.43 (2H, t, J ) 6.9 Hz), 1.66-1.41 (8H, m), 0.95 (3H,
t, J ) 7.2 Hz), 0.94 (3H, t, J ) 7.2 Hz); 13C NMR (75 MHz,
CDCl3) δ 152.2, 141.8, 138.3, 125.8, 119.6, 95.3, 92.5, 80.2, 77.3,
30.5, 30.3, 22.0, 21.9, 19.1, 19.0, 13.5, 13.5; MS m/z 239 (M+);
HRMS m/z calcd for C17H21N 239.1674 (M+), found 239.1664.
4-(1-Hexyn yl)p yr id in e (13): Rf ) 0.36 (50% Et2O in
hexane); IR (neat) 2958, 2933, 2872, 2234, 1594, 1538 cm-1
;
1H NMR (300 MHz, CDCl3) δ 8.49 (2H, d, J ) 6.0 Hz), 7.21
(2H, d, J ) 6.0 Hz), 2.42 (2H, t, J ) 6.9 Hz), 1.64-1.53 (2H,
m), 1.53-1.41 (2H, m), 0.95 (3H, t, J ) 7.2 Hz); 13C NMR (75
MHz, CDCl3) δ 149.4, 132.2, 125.6, 95.9, 78.3, 30.4, 22.0, 19.2,
13.6; MS m/z 159 (M+); HRMS m/z calcd for C11H13N 159.1048
(M+), found 159.1051.
2-(5-ter t-Bu tyld im eth ylp h en ylsiloxy-1-p en tyn yl)p yr i-
d in e (27). To a stirred solution of alcohol 24 (9.60 mL, 94.7
mmol), imidazole (7.62 g, 112 mmol), and a catalytic amount
of DMAP in DMF (120 mL) was added dropwise TBDPSCl
(28.6 mL, 98.0 mmol) at room temperature, and stirring was
continued for 2 h. The reaction mixture was diluted with water
and extracted with Et2O. The combined extracts were washed
with 1 N HCl, saturated aqueous NaHCO3, and NaCl. The
residue upon workup was purified by chromatography on silica
gel with hexane-AcOEt (95:5 v/v) as eluent to give the silyl
ether 27 (32.2 g, 99%) as a colorless oil: Rf ) 0.27 (50% Et2O
2-(1-Hexyn yl)-1,3-p yr im id in e (14): Rf ) 0.42 (50% Et2O
1
in hexane); IR (neat) 2959, 2855, 2234, 1564, 1553 cm-1; H
NMR (300 MHz, CDCl3) δ 8.70 (2H, d, J ) 5.1 Hz), 7.22 (1H,
d, J ) 5.1 Hz), 2.48 (2H, t, J ) 7.2 Hz), 1.70-1.66 (2H, m),
1.56-1.44 (2H, m), 0.94 (3H, t, J ) 7.5 Hz); 13C NMR (75 MHz,
CDCl3) δ 157.1, 153.1, 119.3, 90.8, 79.8, 29.9, 21.9, 18.8, 13.4;
MS m/z 160 (M+); HRMS m/z calcd for C10H12N2 160.1000 (M+),
found 160.0993.
1
in hexane); IR (neat) 3076, 2930, 2855, 2229, 1583 cm-1; H
NMR (300 MHz, CDCl3) δ 8.51 (1H, dd, J ) 4.2 and 1.8 Hz),
7.68-7.64 (4H, m), 7.56 (1H, ddd, J ) 7.5, 7.5, and 1.8 Hz),
7.41-7.30 (6H, m), 7.28 (1H, d, J ) 7.5 Hz), 7.14 (1H, dd, J )
7.5 and 4.2 Hz), 3.79 (2H, t, J ) 6.0 Hz), 2.60 (2H, t, J ) 7.2
Hz), 1.88 (2H, dt, J ) 7.2 and 6.0 Hz), 1.06 (9H, s); 13C NMR
(75 MHz, CDCl3) δ 149.6, 143.7, 135.8, 135.4, 135.4, 135.4,
135.4, 133.6, 133.6, 129.4, 129.4, 127.5, 127.5, 127.5, 127.5,
126.7, 122.1, 90.6, 80.4, 62.4, 31.4, 26.9, 26.9, 26.9, 19.3, 16.0;
MS m/z 342 (M+ - C4H9); HRMS m/z calcd for C22H20NOSi
342.1328 (M+ - C4H9), found 342.1321.
2-(1-Hexyn yl)qu in olin e (15): Rf ) 0.24 (10% Et2O in
hexane); IR (neat) 2957, 2856, 2226, 1616, 1594, 1553, 1500
1
cm-1; H NMR (400 MHz, CDCl3) δ 8.07 (1H, d, J ) 3.6 Hz),
8.02 (1H, d, J ) 3.6 Hz), 7.73-7.65 (2H, m), 7.49-7.42 (2H,
m), 2.49 (2H, t, J ) 7.2 Hz), 1.69-1.62 (2H, m), 1.55-1.46 (2H,
m), 0.95 (3H, t, J ) 7.2 Hz); 13C NMR (100 MHz, CDCl3) δ
147.9, 144.0, 135.8, 129.6, 129.0, 127.2, 126.7, 126.5, 124.0,
91.9, 81.0, 30.2, 22.0, 19.0, 13.5; MS m/z 209 (M+); HRMS m/z
calcd for C15H15N 209.1204 (M+), found 209.1206.
5-Br om o-2-(1-h exyn yl)p yr id in e (16): Rf ) 0.27 (10%
Et2O in hexane); IR (neat) 2958, 2872, 2228, 1564, 1544 cm-1
;
2-(1-ter t-Bu t yld im et h ylsiloxy-1-m et h yl-2-h ep t yn yl)-
p yr id in e (54). To a stirred solution of 1-hexyne (4.1 mL, 35.6
mmol) in THF (80 mL) was added TMEDA (5.4 mL, 35.6
mmol), and a 2.5 M solution of n-BuLi in hexane (14.2 mL,
35.6 mmol) was added dropwise at -78 °C. After stirring was
continued for 1 h, 2-acetylpyridine 52 (2.0 mL, 17.8 mmol) was
added dropwise to this reaction mixture at the same temper-
ature, and stirring was continued for 1 h at the same
temperature. The reaction mixture was diluted with water and
extracted with AcOEt. The combined extracts were washed
with saturated aqueous NaCl. To a solution of the residue upon
workup in CH2Cl2 (70 mL) were added pyridine (5.05 mL, 62.4
mmol) and TBSOTf (7.01 mL, 30.50 mmol) at 0 °C. After
stirring was continued for 1 h at the same temperature, the
reaction mixture was diluted with water and extracted with
CH2Cl2. The combined extracts were washed with saturated
NaHCO3 and NaCl. The residue upon workup was purified
by chromatography on silica gel with hexanes:Et2O (70:30 v/v)
as eluent to give the alkyne 54 (5.54 g, 2 steps 86%) as a
colorless oil: Rf ) 0.68 (50% Et2O in hexane); IR (neat) 2958,
1H NMR (300 MHz, CDCl3) δ 8.59 (1H, d, J ) 2.1 Hz), 7.74
(1H, dd, J ) 8.4 and 2.1 Hz), 7.25 (1H, d, J ) 8.4 Hz), 2.43
(2H, t, J ) 7.2 Hz), 1.66-1.55 (2H, m), 1.54-1.42 (2H, m),
0.94 (3H, t, J ) 7.2 Hz); 13C NMR (75 MHz, CDCl3) δ 150.8,
142.3, 138.6, 127.7, 119.3, 92.6, 79.5, 30.2, 22.0, 19.0, 13.6; MS
m/z 237 (M+); HRMS m/z calcd for C11H12NBr 237.0153 (M+),
found 237.0148.
2-(3-p h en ylp r op yn yl)p yr id in e (22): Rf ) 0.36 (50% Et2O
1
in hexane); IR (neat) 3029, 2228, 1582, 1558 cm-1; H NMR
(300 MHz, CDCl3) δ 8.56-8.54 (1H, m), 7.60 (1H, ddd, J )
7.8, 7.6, and 1.8 Hz), 7.43-7.39 (3H, m), 7.35-7.30 (2H, m),
7.27-7.16 (2H, m), 3.86 (2H, s); 13C NMR (75 MHz, CDCl3) δ
149.8, 143.5, 136.0, 135.8, 128.5, 128.5, 127.9, 127.9, 126.8,
126.7, 122.4, 88.0, 82.1, 25.5; MS m/z 193 (M+); HRMS m/z
calcd for C14H11N 193.0891 (M+), found 191.0885.
2-(5-Hyd r oxyp en tyn yl)p yr id in e (24): Rf ) 0.37 (100%
AcOEt); IR (neat) 3338, 2944, 2873, 2225, 1585, 1560 cm-1
;
1H NMR (300 MHz, CDCl3) δ 8.52-8.50 (1H, m), 7.65-7.58
(1H, m), 7.38-7.35 (1H, m), 7.21-7.16 (1H, m), 3.81 (2H, t, J
) 6.0 Hz), 3.30 (1H, brs) 2.58 (2H, t, J ) 6.9 Hz), 1.88 (2H, dt,
J ) 6.9 and 6.0 Hz); 13C NMR (75 MHz, CDCl3) δ 149.5, 143.5,
136.2, 126.8, 122.4, 90.6, 80.4, 61.0, 30.9, 15.8; MS m/z 161
(M+); HRMS m/z calcd for C10H11NO 161.0841 (M+), found
161.0836.
2931, 2858, 2247, 1587 cm-1 1H NMR (400 MHz, CDCl3) δ
;
8.56-8.54 (1H, m), 7.69-7.61 (2H, m), 7.12-7.09 (1H, m),
2.24-2.19 (2H, m), 1.78 (3H, s), 1.50-1.45 (2H, m), 1.39-1.33
(2H, m), 0.94 (9H, s), 0.86 (3H, t, J ) 7.2 Hz), 0.24 (3H, s),
0.15 (3H, s); 13C NMR (75 MHz, CDCl3) δ 165.5, 148.5, 136.4,
121.8, 118.8, 85.8, 83.8, 72.1, 32.9, 30.5, 25.8, 25.8, 22.0, 18.6,
18.1, 13.5, -2.9, -3.2; MS m/z (M+); HRMS m/z calcd for
2-(4-Hyd r oxybu tyn yl)p yr id in e (25): Rf ) 0.31 (100%
AcOEt); IR (neat) 3353, 2238, 1588, 1563 cm-1; 1H NMR (300
MHz, CDCl3) δ 8.50 (1H, dd, J ) 4.8 and 1.5 Hz), 7.63 (1H,
ddd, J ) 7.8, 7.8, and 1.5 Hz), 7.37 (1H, d, J ) 7.8 Hz), 7.22-
7.18 (1H, m), 4.05 (1H, brs), 3.88 (2H, t, J ) 6.3 Hz), 2.71 (2H,
t, J ) 6.3 Hz); 13C NMR (75 MHz, CDCl3) δ 149.3, 143.1, 136.4,
126.7, 122.5, 88.6, 81.2, 60.4, 23.7; MS m/ z 147 (M+); HRMS
m/z calcd for C9H9NO 147.0684 (M+), found 147.0678.
2,6-Di-1-h exyn ylp yr id in e (29): Rf ) 0.27 (10% Et2O in
C
19H31NOSi 317.2175 (M+), found 317.2190.
2-(1-ter t-Bu t yld im et h ylsiloxy-1-m et h yl-2-h ep t yn yl)-
p yr a zin e (55). By following the same procedure described for
54, the alkyne 55 was prepared from 53: yield 89%; Rf ) (50%
Et2O in hexane); IR (neat) 3051, 2957, 2249, 1471 cm-1 1H
;
NMR (300 MHz, CDCl3) δ 8.98 (1H, s), 8.50 (1H, d, J ) 2.4
Hz), 8.45 (1H, d, J ) 2.4 Hz), 2.24 (2H, t, J ) 6.9 Hz), 1.82
(3H, s), 1.55-1.33 (4H, m), 0.95 (9H, s), 0.90 (3H, t, J ) 7.2
Hz), 0.28 (3H, s), 0.20 (3H, s); 13C NMR (75 MHz, CDCl3) δ
160.0, 142.7, 142.6, 141.7, 87.0, 82.9, 71.2, 32.7, 30.6, 26.0, 26.0,
26.0, 22.2, 18.8, 18.4, 13.8, -2.6, -2.9; MS m/z (M+); HRMS
m/z calcd for C17H27NOSi 303.1893 (M+), found 303.1890.
hexane); IR (neat) 2958, 2872, 2231, 1574, 1563, 1558 cm-1
;
1H NMR (300 MHz, CDCl3) δ 7.50 (1H, dd, J ) 7.5 and 7.5
Hz), 7.22 (2H, d, J ) 7.5 Hz), 2.41 (4H, t, J ) 7.2 Hz), 1.64-
1.52 (4H, m), 1.52-1.40 (4H, m), 0.93 (6H, t, J ) 7.2 Hz); 13
C
NMR (75 MHz, CDCl3) δ 143.7, 135.9, 125.1, 91.1, 80.0, 30.4,
22.1, 19.0, 13.6; MS m/z 239 (M+); HRMS m/ z calcd for
2-(1-t er t -Bu t yld im e t h ylsiloxy-1-m e t h yl-3-b u t yn yl)-
p yr id in e (56). A suspension of powdered aluminum (445 mg,
C
17H21N 239.1674 (M+), found 239.1664.
J . Org. Chem, Vol. 68, No. 3, 2003 767

Lautens and Yoshida
16.50 mmol) and mercuric chloride (179 mg, 0.66 mmol) in
THF (40 mL) was refluxed for 30 min. After the mixture was
cooled to room temperature, propargyl bromide (1.47 mL, 16.50
mmol) was added dropwise to the suspension, and the mixture
was stirred at same temperature for 6 h. The above propargyl-
aluminum reagent was added dropwise to the acetylpyridine
52 (800 mg, 6.60 mmol) in Et2O (40 mL) at 0 °C, and stirring
was continued for 1 h. The reaction mixture was diluted with
water and extracted with Et2O. The combined extracts were
washed with saturated aqueous NaHCO3 and saturated aque-
ous NaCl. Pyridine (0.752 mL, 9.30 mmol) and TBSOTf (1.59
mL, 6.96 mmol) were added to a solution in CH2Cl2 (50 mL)
of the residue following workup at 0 °C. After stirring was
continued for 1 h at the same temperature, the reaction
mixture was diluted with water and extracted with CH2Cl2.
The combined extracts were washed with saturated NaHCO3
and NaCl. The residue upon workup chromatographed on silica
gel with hexane:AcOEt (70:30 v/v) as eluent to give the alkyne
56 (1.20 g, two steps 66%) as a colorless oil: Rf ) 0.68 (50%
Et2O in hexane); IR (neat) 3313, 2957, 2930, 2857, 2122, 1590,
120.9, 30.8, 30.0, 22.7, 13.8; MS m/z 237 (M+); HRMS m/z calcd
for C17H19N 237.1517 (M+), found 237.1525.
(E)-2-[2-(2-Meth ylp h en yl)-1-h exen yl]p yr id in e (32b): Rf
) 0.71 (50% Et2O in hexane); IR (neat) 2956, 2870, 1634, 1585,
1
1558 cm-1; H NMR (300 MHz, CDCl3) δ 8.65-8.63 (1H, m),
7.64 (1H, ddd, J ) 7.8, 7.5, and 1.5 Hz), 7.26-7.18 (5H, m),
7.13-7.09 (1H, m), 6.35 (1H, s), 2.90 (2H, t, J ) 7.5 Hz), 2.37
(3H, s), 1.44-1.23 (4H, m), 0.83 (3H, t, J ) 6.9 Hz); 13C NMR
(75 MHz, CDCl3) δ 156.9, 149.2, 148.4, 144.1, 135.9, 134.9,
130.1, 128.4, 128.3, 126.8, 125.3, 124.0, 120.9, 32.5, 30.1, 22.9,
20.0, 13.8; MS m/z 251 (M+); HRMS m/z calcd for C18H21
N
251.1674 (M+), found 251.1679.
(E)-2-[2-(2,6-Dim eth ylph en yl)-1-h exen yl]pyr idin e (32c):
Rf ) 0.75 (50% Et2O in hexane); IR (neat) 2956, 2858, 1634,
1583, 1558 cm-1; 1H NMR (300 MHz, CDCl3) δ 8.65 (1H, dd, J
) 4.5 and 1.5 Hz), 7.65 (1H, ddd, J ) 7.8, 7.8, and 1.5 Hz),
7.25 (1H, d, J ) 7.8 Hz), 7.13-7.04 (4H, m), 6.30 (1H, s), 2.86
(2H, t, J ) 7.4 Hz), 2.32 (3H, s), 2.32 (3H, s), 1.46-1.24 (4H,
m), 0.86 (3H, t, J ) 6.9 Hz); 13C NMR (75 MHz, CDCl3) δ 156.9,
149.3, 147.2, 143.6, 135.9, 135.9, 135.2, 128.4, 127.4, 127.4,
126.4, 123.9, 120.9, 33.2, 30.1, 23.3, 20.4, 20.4, 13.9; MS m/z
265 (M+); HRMS m/z calcd for C19H23N 265.1830 (M+), found
265.1825.
1
1572 cm-1; H NMR (300 MHz, CDCl3) δ 8.54-8.52 (1H, m),
7.74-7.66 (2H, m), 7.18-7.13 (1H, m), 2.87 (1H, dd, J ) 16.5
and 2.7 Hz), 2.75 (1H, dd, J ) 16.5 and 2.7 Hz), 1.86 (1H, d,
J ) 2.7 Hz), 1.73 (3H, s), 0.99 (9H, s), 0.21 (3H, s), 0.10 (3H,
s); 13C NMR (75 MHz, CDCl3) δ 165.6, 148.0, 136.4, 121.8,
120.2, 81.4, 77.9, 70.3, 34.3, 28.3, 26.0, 26.0, 26.0, 18.5, -2.2,
(E)-2-[2-(1-Na p h th yl)-1-h exen yl]p yr id in e (32d ): Rf
)
0.66 (50% Et2O in hexane); IR (neat) 3058, 2956, 2870, 1634,
1584, 1558, 1505 cm-1; 1H NMR (300 MHz, CDCl3) δ 8.67 (1H,
dd, J ) 4.5 and 1.8 Hz), 8.13-8.08 (1H, m), 7.87-7.83 (1H,
m), 7.78 (1H, d, J ) 8.1 Hz), 7.64 (1H, ddd, J ) 7.5, 7.5, and
1.8 Hz), 7.49-7.44 (3H, m), 7.38 (1H, dd, J ) 7.2 and 1.2 Hz),
7.28 (1H, d, J ) 7.2 Hz), 7.12 (1H, dd, J ) 7.5 and 4.5 Hz),
6.55 (1H, s), 3.10 (2H, t, J ) 7.8 Hz), 1.45-1.22 (4H, m), 0.79
(3H, t, J ) 7.5 Hz); 13C NMR (75 MHz, CDCl3) δ 156.8, 149.3,
147.4, 142.4, 136.0, 133.7, 131.4, 129.4, 128.2, 127.2, 126.0,
125.7, 125.6, 125.2, 125.1, 124.2, 121.1, 33.3, 30.5, 22.8, 13.8;
MS m/z 287 (M+); HRMS m/z calcd for C21H21N 287.1674 (M+),
found 287.1669.
-2.3; MS m/z 260 (M+ - CH3); HRMS m/z calcd for C15H22
-
NOSi 260.1471 (M+ - CH3), found 260.1473.
2-(1-ter t-Bu t yld im et h ylsiloxy-1-m et h yl-3-p en t yn yl)-
p yr id in e (57). To a stirred solution of alkyne 56 (120 mg,
0.436 mmol) in THF (10 mL) was added a 2.0 M solution of
n-BuLi in hexane (0.218 mL, 0.436 mmol) dropwise at -78
°C. After stirring was continued for 1 h, methyl bromide (0.50
mL, 1.09 mmol) was added dropwise to this reaction mixture
at the same temperature, and stirring was continued for 1 h
at the same temperature. The reaction mixture was diluted
with water and extracted with AcOEt. The combined extracts
were washed with saturated aqueous NaCl. The residue upon
workup was purified by chromatography on silica gel with
hexanes:Et2O (80:20 v/v) as eluent to give the alkyne 57 (122
mg, 97%) as a colorless oil: Rf ) 0.73 (50% Et2O in hexane);
(E)-2-[2-(4-Meth oxyp h en yl)-1-h exen yl]p yr id in e (32e):
Rf ) 0.54 (50% Et2O in hexane); IR (neat) 2955, 2857, 1605,
1583, 1511 cm-1; 1H NMR (300 MHz, CDCl3) δ 8.62 (1H, dd, J
) 4.2 and 1.8 Hz), 7.64 (1H, ddd, J ) 7.5, 7.5, and 1.8 Hz),
7.48-7.42 (2H, m), 7.26 (1H, d, J ) 7.5 Hz), 7.09 (1H, dd, J )
7.5 and 4.5 Hz), 6.93-6.88 (2H, m), 6.66 (1H, s), 3.83 (3H, s),
3.01 (2H, t, J ) 6.9 Hz), 1.48-1.26 (4H, m), 0.85 (3H, t, J )
6.9 Hz); 13C NMR (75 MHz, CDCl3) δ 159.1, 157.3, 149.2, 146.9,
135.9, 135.4, 127.7, 127.7, 125.8, 124.1, 120.8, 113.7, 113.7,
55.2, 30.9, 29.9, 22.7, 13.9; MS m/z 267 (M+); HRMS m/z calcd
for C18H21NO 267.1623 (M+), found 267.1622.
IR (neat) 2957, 2929, 2857, 1590, 1572 cm-1 1H NMR (400
;
MHz, CDCl3) δ 8.53-8.48 (1H, m), 7.70-7.61 (2H, m), 7.13-
7.07 (1H, m), 2.71-2.67 (2H, m), 1.67 (3H, s), 1.66 (3H, t, J )
3.0 Hz), 0.95 (9H, s), 0.17 (3H, s), 0.05 (3H, s); 13C NMR (75
MHz, CDCl3) δ 166.3, 148.0, 136.0, 121.5, 120.1, 78.2, 77.5,
76.1, 34.5, 28.1, 26.0, 26.0, 26.0, 18.4, 3.5, -2.3, -2.3; MS m/z
274 (M+ - CH3); HRMS m/z calcd for C16H24NOSi 274.1627
(M+ - CH3), found 274.1634.
Gen er a l P r oced u r e for th e Rh od iu m -Ca ta lyzed Ad d i-
tion Rea ction of Ar ylbor on ic Acid s to Alk yn es (En tr y 2
in Ta ble 2). To a stirred mixture of [Rh(COD)Cl]2 (3.2 mg,
6.42 µmol) and 3 (12.8 mg, 25.7 µmol) in H2O (2 mL) were
successively added 2-methylphenylboronic acid (109 mg, 0.802
mmol), SDS (52 mg, 0.160 mmol), Na2CO3 (68 mg, 0.642 mmol),
and alkyne 11 (47.9 mg, 0.301 mmol) at room temperature.
After stirring was continued for 1 h at 80 °C, the reaction
mixture was poured into Et2O (25 mL) and the heterogeneous
mixture was vigorously stirred for 1 h at room temperature.
The two phases were separated, and the aqueous phase was
extracted with Et2O. The residue upon workup was chromato-
graphed on silica gel with hexanes:Et2O (85:15 v/v) as eluent
to give the product 32b (61.0 mg, 81%) as a colorless oil.
(E)-2-[2-(4-Met h oxy-2-m et h ylp h en yl)-1-h exen yl]p yr i-
d in e (32f): Rf ) 0.42 (50% Et2O in hexane); IR (neat) 2956,
2857, 1634, 1606, 1584, 1504 cm-1; 1H NMR (300 MHz, CDCl3)
δ 8.61-8.59 (1H, m), 7.62 (1H, ddd, J ) 7.8, 7.8, and 2.1 Hz),
7.22 (1H, d, J ) 7.8 Hz), 7.10-7.06 (2H, m), 6.75-6.69 (2H,
m), 6.31 (1H, s), 3.80 (3H, s), 2.86 (2H, t, J ) 7.2 Hz), 2.34
(3H, s), 1.41-1.23 (4H, m), 0.83 (3H, t, J ) 6.9 Hz); 13C NMR
(75 MHz, CDCl3) δ 158.1, 156.9, 149.1, 148.0, 136.6, 136.3,
135.8, 129.3, 128.5, 123.9, 120.8, 115.4, 110.5, 55.2, 32.8, 30.2,
23.0, 20.4, 14.0; MS m/z 281 (M+); HRMS m/z calcd for C19H23
-
NO 281.1780 (M+), found 281.1775.
(E)-2-[2-(2-Meth ylp h en yl)-1-h exen yl]p yr im id in e (35):
Rf ) 0.69 (50% Et2O in hexane); IR (neat) 2957, 2870, 1634,
1
1568, 1553 cm-1; H NMR (300 MHz, CDCl3) δ 8.73 (2H, d, J
) 4.8 Hz), 7.21-7.18 (4H, m), 7.04 (1H, dd, J ) 4.8 and 4.8
Hz), 6.46 (1H, s), 3.13 (2H, t, J ) 7.5 Hz), 2.37 (3H, s), 1.46-
1.26 (4H, m), 0.85 (3H, t, J ) 6.9 Hz); 13C NMR (75 MHz,
CDCl3) δ 165.7, 156.6, 156.6, 154.7, 144.1, 134.6, 130.1, 128.1,
127.8, 126.9, 125.3, 117.6, 32.8, 30.0, 22.9, 19.9, 13.8; MS m/z
252 (M+); HRMS m/z calcd for C17H20N2 252.1626 (M+), found
252.1632.
(E)-2-(2-P h en yl-1-h exen yl)p yr id in e (32a ): Rf ) 0.72 (50%
Et2O in hexane); IR (neat) 2956, 2858, 1626, 1584, 1558 cm-1
;
1H NMR (300 MHz, CDCl3) δ 8.63 (1H, dd, J ) 4.5 and 1.8
Hz), 7.64 (1H, ddd, J ) 7.8, 7.8, and 1.5 Hz), 7.52-7.49 (2H,
m), 7.39-7.25 (4H, m), 7.10 (1H, dd, J ) 7.8 and 4.5 Hz), 6.70
(1H, s), 3.05 (2H, t, J ) 7.5 Hz), 1.48-1.26 (4H, m), 0.84 (3H,
t, J ) 7.2 Hz); 13C NMR (75 MHz, CDCl3) δ 157.1, 149.2, 147.5,
143.2, 135.9, 128.3, 128.3, 127.4, 127.1, 126.7, 126.7, 124.2,
(E)-2-[2-(2-Meth ylp h en yl)-1-h exen yl]qu in olin e (36): Rf
) 0.55 (10% Et2O in hexane); IR (neat) 3057, 2955, 2857, 1596,
1
1557, 1500 cm-1; H NMR (400 MHz, CDCl3) δ 8.09 (1H, d, J
) 3.6 Hz), 8.06 (1H, d, J ) 3.6 Hz), 7.75 (1H, d, J ) 8.0 Hz),
768 J . Org. Chem., Vol. 68, No. 3, 2003

Rhodium-Catalyzed Addition of Arylboronic Acids
7.70-7.66 (1H, m), 7.49-7.45 (1H, m), 7.35 (1H, d, J ) 8.0
Hz), 7.24-7.17 (4H, m), 6.50 (1H, s), 3.06 (2H, t, J ) 8.0 Hz),
2.39 (3H, s), 1.54-1.46 (2H, m), 1.43-1.33 (2H, m), 0.89 (3H,
t, J ) 7.2 Hz); 13C NMR (100 MHz, CDCl3) δ 156.9, 150.7,
148.1, 144.3, 135.7, 134.9, 130.2, 129.4, 129.3, 128.4, 128.4,
127.3, 126.9, 126.4, 125.9, 125.4, 122.8, 33.1, 30.2, 23.1, 20.0,
14.0; MS m/z 301 (M+); HRMS m/z calcd for C22H23N 301.1830
(M+), found 301.1837.
(E )-5-Br om o-2-[2-(2-m e t h ylp h e n yl)-1-h e xe n yl]p yr i-
d in e (37): Rf ) 0.61 (10% Et2O in hexane); IR (neat) 2956,
2857, 1634, 1568 cm-1; 1H NMR (300 MHz, CDCl3) δ 8.66 (1H,
d, J ) 2.7 Hz), 7.73 (1H, dd, J ) 8.1 and 2.7 Hz), 7.19-7.08
(5H, m), 6.24 (1H, s), 2.88 (2H, t, J ) 7.5 Hz), 2.34 (3H, s),
1.43-1.22 (4H, m), 0.84 (3H, t, J ) 6.9 Hz); 13C NMR (75 MHz,
CDCl3) δ 155.2, 150.1, 149.8, 143.9, 138.4, 134.7, 130.1, 128.2,
126.8, 126.8, 125.3, 125.2, 117.7, 32.8, 30.1, 23.0, 20.0, 14.0;
MS m/z 329 (M+); HRMS m/z calcd for C18H20NBr 329.0779
(M+), found 329.0787.
CDCl3) δ 156.2, 147.8, 144.2, 135.8, 134.9, 130.0, 128.8, 128.4,
126.6, 125.2, 121.4, 32.7, 30.3, 23.1, 20.1, 14.1; MS m/z 423
(M+); HRMS m/z calcd for C31H37N 423.2926 (M+), found
423.2915.
(E)-5-(1-H exyn yl)-2-[2-(2-m et h ylp h en yl)-1-h exen yl]-
p yr id in e (44): Rf ) 0.56 (10% Et2O in hexane); IR (neat) 2957,
2871, 2230, 1634, 1587, 1538 cm-1; 1H NMR (300 MHz, CDCl3)
δ 8.62 (1H, d, J ) 1.5 Hz), 7.60 (1H, dd, J ) 8.1 and 1.5 Hz),
7.20-7.11 (5H, m), 6.28 (1H, s), 2.90 (2H, t, J ) 7.2 Hz), 2.44
(2H, t, J ) 6.9 Hz), 2.34 (3H, s), 1.65-1.55 (2H, m), 1.55-1.43
(2H, m), 1.41-1.23 (4H, m), 0.96 (3H, t, J ) 7.2 Hz), 0.83 (3H,
t, J ) 6.9 Hz); 13C NMR (75 MHz, CDCl3) δ 155.0, 151.6, 149.2,
144.1, 138.2, 134.8, 130.0, 128.3, 127.8, 126.7, 125.3, 123.2,
118.1, 93.7, 77.8, 32.8, 30.8, 30.2, 23.0, 22.1, 20.1, 19.3, 14.0,
13.7; MS m/z 331 (M+); HRMS m/z calcd for C24H29N 331.2300
(M+), found 331.2300.
(E)-2-[1-Deu t er io-2-(2-m et h ylp h en yl)-1-h exen yl]p yr i-
d in e (49): Rf ) 0.71 (50% Et2O in hexane); IR (neat) 3058,
2956, 2927, 2870, 1622, 1585, 1558 cm-1; 1H NMR (300 MHz,
CDCl3) δ 8.63-8.60 (1H, m), 7.62 (1H, ddd, J ) 7.8, 7.8, and
1.5 Hz), 7.24-7.15 (5H, m), 7.08 (1H, ddd, J ) 7.8, 4.8, and
1.8 Hz), 2.90 (2H, t, J ) 7.8 Hz), 2.36 (3H, s), 1.42-1.23 (4H,
m), 0.83 (3H, t, J ) 6.9 Hz); 13C NMR (75 MHz, CDCl3) δ 156.8,
149.1, 148.3, 144.0, 135.8, 134.8, 130.0, 128.3, 127.5(t), 126.7,
125.2, 123.9, 120.9, 32.5, 30.2, 23.0, 20.1, 14.0; MS m/z 252
(M+); HRMS m/z calcd for C18H20DN 252.1736 (M+), found
252.1738.
(E)-2-[2-(2-Met h ylp h en yl)-3-p h en yl-1-p r op en yl]p yr i-
d in e (38): Rf ) 0.71 (50% Et2O in hexane); IR (neat) 3060,
3025, 2922, 1634, 1585, 1558 cm-1; 1H NMR (400 MHz, CDCl3)
δ 8.68-8.67 (1H, m), 7.65 (1H, ddd, J ) 7.6, 7.6, and 1.6 Hz),
7.25 (1H, d, J ) 7.6 Hz), 7.16-6.98 (10H, m), 6.43 (1H, s),
4.43 (2H, s), 2.20 (3H, s); 13C NMR (100 MHz, CDCl3) δ 156.6,
149.2, 146.1, 143.4, 139.3, 136.2, 135.1, 130.1, 129.3, 129.3,
128.9, 128.7, 128.0, 128.0, 126.8, 125.8, 125.2, 124.4, 121.4,
38.4, 19.7; MS m/z 285 (M+); HRMS m/z calcd for C21H19
N
285.1517 (M+), found 285.1513.
(E)-2-[1-ter t-Bu tyld im eth ylsiloxy-1-m eth yl-3-(2-m eth -
ylp h en yl)-2-h ep ten yl]p yr id in e (58): Rf ) 0.65 (25% Et2O
(E)-2-[5-ter t-Bu tyld im eth ylsiloxy-2-(2-m eth ylp h en yl)-
1-p en ten yl]p yr id in e (40): Rf ) 0.57 (50% Et2O in hexane);
in hexane); IR (neat) 3058, 2955, 2857, 1729, 1644, 1587 cm-1
;
1
IR (neat) 3070, 2930, 2857, 1634, 1585, 1558 cm-1; H NMR
1H NMR (400 MHz, CDCl3) δ 8.58-8.56 (1H, m), 7.86 (1H, d,
J ) 8.0 Hz), 7.69 (1H, ddd, J ) 8.0, 8.0, and 1.6 Hz), 7.16-
7.10 (4H, m), 7.07-7.05 (1H, m), 5.77 (1H, s), 2.31 (3H, s), 2.29
(1H, dt, J ) 12.8 and 4.4 Hz), 1.98 (1H, dt, J ) 12.8 and 4.4
Hz), 1.84 (3H, s), 1.01 (9H, s), 0.92-0.68 (4H, m), 0.57 (3H, t,
J ) 7.2 Hz), 0.19 (3H, s), 0.07 (3H, s); 13C NMR (100 MHz,
CDCl3) δ 168.7, 148.0, 143.7, 143.3, 137.7, 135.9, 135.5, 129.9,
128.5, 126.3, 125.1, 121.1, 120.4, 77.6, 32.7, 31.7, 28.6, 26.1,
26.1, 26.1, 22.9, 19.8, 18.4, 13.7, -2.1, -2.2; MS m/z 409 (M+);
HRMS m/z calcd for C26H39NOSi 409.2801 (M+), found 409.2811.
(E)-2-[1-ter t-Bu tyld im eth ylsiloxy-1-m eth yl-3-(2-m eth -
ylp h en yl)-2-h ep ten yl]p yr a zin e (59): Rf ) 0.68 (50% Et2O
(300 MHz, CDCl3) δ 8.58-8.55 (1H, m), 7.61-7.52 (5H, m),
7.39-7.24 (7H, m), 7.19-7.11 (4H, m), 7.07-7.02 (1H, m), 6.36
(1H, s), 3.64 (2H, t, J ) 6.0 Hz), 3.04-2.99 (2H, m), 2.34 (3H,
s), 1.71-1.62 (2H, m), 1.00 (9H, s); 13C NMR (75 MHz, CDCl3)
δ 156.6, 149.1, 147.7, 143.7, 135.8, 135.4, 135.4, 135.4, 135.4,
134.8, 133.8, 133.8, 130.0, 129.3, 129.3, 128.6, 128.4, 127.4,
127.4, 127.4, 127.4, 126.8, 125.3, 123.9, 120.9, 63.9, 31.0, 29.4,
26.9, 26.9, 26.9, 20.1, 19.3; MS m/z 491 (M+); HRMS m/z calcd
for C33H37NOSi 491.2644 (M+), found 491.2658.
(E)-2-[5-Hyd r oxy-2-(2-m eth ylp h en yl)-1-p en ten yl]p yr i-
d in e (41): Rf ) 0.34 (50% AcOEt in hexane); IR (neat) 3286,
2932, 1634, 1589, 1563 cm-1
;
1H NMR (400 MHz, CDCl3) δ
in hexane); IR (neat) 2957, 2858, 1644 cm-1 1H NMR (300
;
8.57 (1H, dd, J ) 5.2 and 1.2 Hz), 7.69 (1H, ddd, J ) 7.9, 7.9,
and 1.2 Hz), 7.22-7.13 (6H, m), 6.53 (1H, brs), 6.43 (1H, s),
3.74 (2H, t, J ) 5.2 Hz), 3.09 (2H, t, J ) 6.4 Hz), 2.36 (3H, s),
1.63 (2H, dt, J ) 6.4 and 5.2 Hz); 13C NMR (100 MHz, CDCl3)
δ 155.8, 148.1, 147.6, 143.0, 137.1, 134.9, 130.5, 129.0, 128.4,
127.1, 125.5, 125.4, 121.6, 59.6, 29.2, 27.7, 19.8; MS m/z 253
(M+); HRMS m/z calcd for C17H19NO 253.1467 (M+), found
253.1474.
MHz, CDCl3) δ 9.13 (1H, s), 8.50 (1H, d, J ) 2.4 Hz), 8.44 (1H,
d, J ) 2.4 Hz), 7.15-7.02 (4H, m), 5.73 (1H, s), 2.31-2.21 (1H,
m), 2.28 (3H, s), 2.04-1.94 (1H, m), 1.82 (3H, s), 0.99 (9H, s),
0.90-0.66 (3H, m), 0.56 (3H, t, J ) 7.2 Hz), 0.39-0.25 (1H,
m), 0.19 (3H, s), 0.09 (3H, s); 13C NMR (75 MHz, CDCl3) δ
163.9, 144.2, 143.1, 143.0, 142.6, 142.0, 136.6, 135.3, 130.0,
128.3, 126.5, 125.2, 76.8, 32.8, 31.7, 28.7, 26.0, 26.0, 26.0, 22.8,
19.8, 18.3, 13.7, -2.1, -2.2; MS m/z (M+); HRMS m/z calcd
for C25H38N2OSi 410.2753 (M+), found 410.2757.
(E)-2-[4-H yd r oxy-2-(2-m et h ylp h en yl)-1-b u t en yl]p yr i-
d in e (42): Rf ) 0.44 (50% Et2O in hexane); IR (neat) 3242,
2853, 1634, 1590, 1562 cm-1 1H NMR (300 MHz, CDCl3) δ
;
Ack n ow led gm en t. We would like to thank NSERC,
Merck Frosst, the ORDCF, and the University of Tor-
onto for valuable support of our programs. M.Y. ac-
knowledges support in the form of Postdoctoral Fellow-
ships from the Uehara Memorial Foundation. We are
grateful to Dr. Koichiro Fukuoka for helpful suggestions
and the synthesis of ligand 3.
8.54 (1H, dd, J ) 5.1 and 1.8 Hz), 7.71 (1H, ddd, J ) 7.8, 7.8,
and 1.8 Hz), 7.26-7.19 (6H, m), 7.01 (1H, brs), 6.56 (1H, s),
3.81 (2H, t, J ) 5.7 Hz), 2.98 (2H, t, J ) 5.7 Hz), 2.38 (3H, s);
13C NMR (75 MHz, CDCl3) δ 154.9, 147.7, 146.4, 143.3, 137.1,
135.2, 130.2, 129.5, 128.6, 127.2, 125.4, 124.6, 122.0, 60.3, 35.7,
19.8; MS m/z 239 (M+); HRMS m/z calcd for C16H17NO
239.1310 (M+), found 239.1304.
(E,E)-2,6-Bis[2-(2-m et h ylp h en yl)-1-h exen yl]p yr id in e
(43): Rf ) 0.61 (10% Et2O in hexane); IR (neat) 3015, 2956,
2858, 1634, 1558 cm-1; 1H NMR (300 MHz, CDCl3) δ 7.60 (1H,
dd, J ) 7.8 and 7.8 Hz), 7.21-7.14 (8H, m), 7.08 (2H, d, J )
7.8 Hz), 6.36 (2H, s), 2.93 (4H, t, J ) 7.2 Hz), 2.37 (6H, s),
1.43-1.23 (8H, m), 0.82 (6H, t, J ) 7.2 Hz); 13C NMR (75 MHz,
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectrum of 12-16, 22, 24, 25, 27, 29, 30, 32a -f, 35-44, 49,
and 54-60 and ROESY spectrum of 32e. This material is
available free of charge via the Internet at http://pubs.acs.org.
J O0205255
J . Org. Chem, Vol. 68, No. 3, 2003 769