Rhodium-catalyzed tandem conjugate addition-Mannich cyclization reaction: Straightforward access to fully substituted tetrahydroquinolines

Article abstract of DOI:10.1021/jo800914c

(Chemical Equation Presented) A new Rh(I)-catalyzed tandem conjugate addition-Mannich cyclization reaction of imine-substituted electron-deficient alkenes with arylboronic acids has been developed to afford 2,3,4-trisubstituted 1,2,3,4-tetrahydroquinolines. This is the first example involving imine group as a secondary electrophile in Rh(I)-catalyzed tandem reactions.

Full text of DOI:10.1021/jo800914c

SCHEME 1. Rhodium(I)-Catalyzed Tandem Annulations
Rhodium-Catalyzed Tandem Conjugate
Addition-Mannich Cyclization Reaction:
Straightforward Access to Fully Substituted
Tetrahydroquinolines
So Won Youn,*,† Ju-Hyun Song,‡ and Dai-Il Jung‡
Department of Chemistry, Pukyong National UniVersity,
Nam-Gu, Busan 608-737, Korea, and Department of
Chemistry, Dong-A UniVersity,
Saha-Gu, Busan 604-714, Korea
sowony@pknu.ac.kr
ReceiVed April 28, 2008
bocycles via a sequential second carborhodation (Scheme 1,
routes A and B). Although several Rh(I)-catalyzed tandem
reactions have been described, the process involving an imine
group as a second electrophile has not yet been explored.5 Since
both R,ꢀ-unsaturated carbonyl compounds1e,6 and imines6c,7 are
good acceptors of organorhodium(I) species, we envisioned that
electron-deficient alkenes bearing imine moiety placed at an
appropriate position are interesting bifunctional substrates with
regard to the possibility of a tandem cyclization reaction, which
could afford N-heterocycles such as tetrahydroquinolines (Scheme
1, route C). Tetrahydroquinoline derivatives constitute an
important class possessing a wide range of biological activities
and multiple applications and are found in a variety of natural
A new Rh(I)-catalyzed tandem conjugate addition-Mannich
cyclization reaction of imine-substituted electron-deficient
alkenes with arylboronic acids has been developed to afford
2,3,4-trisubstituted 1,2,3,4-tetrahydroquinolines. This is the
first example involving imine group as a secondary electro-
phile in Rh(I)-catalyzed tandem reactions.
Transition-metal-catalyzed tandem C-C bond formations are
powerful methods for the synthesis of structurally complex
molecules from relatively simple starting materials in a convergent
way.1 Molecules that have two or more different unsaturated bonds
are particularly interesting substrates for the tandem annulation
involving multiple C-C bond formations with a single catalyst in
one operation, allowing the construction of a variety of cyclic
compounds. The more reactive functional group provides the entry
point for the addition of a carbon nucleophile by way of initial
intermolecular carbometalation, which triggers the second carbo-
metalation on the less reactive functionality in an intramolecular
way to construct a cyclic skeleton.
Recently, several examples of Rh(I)-catalyzed tandem annu-
lations with organoboron reagents have been demonstrated in
which the tandem cyclization was triggered by conjugate
addition to R,ꢀ-unsaturated carbonyl compounds or 1,2-addition
across the alkynes.1e,2–4 An organorhodium(I) intermediate
(2) For examples of Rh(I)-catalyzed tandem cyclization reactions, see: (a)
Cauble, D. F.; Gipson, J. D.; Krische, M. J. J. Am. Chem. Soc. 2003, 125, 1110.
(b) Bocknack, B. M.; Wang, L.-C.; Krische, M. J. Proc. Natl. Acad. Sci. U.S.A.
2004, 101, 5421. (c) Shintani, R.; Okamoto, K.; Otomaru, Y.; Ueyama, K.;
Hayashi, T. J. Am. Chem. Soc. 2005, 127, 54. (d) Miura, T.; Murakami, M.
Org. Lett. 2005, 7, 3339. (e) Miura, T.; Harumashi, T.; Murakami, M. Org.
Lett. 2007, 9, 741. (f) Miura, T.; Takahashi, Y.; Murakami, M. Org. Lett. 2007,
9, 5075. (g) Miura, T.; Shimada, M.; Murakami, M. J. Am. Chem. Soc. 2005,
127, 1094. (h) Lautens, M.; Mancuso, J. Org. Lett. 2002, 4, 2105. (i) Lautens,
M.; Mancuso, J. J. Org. Chem. 2004, 69, 3478. (j) Lautens, M.; Marquardt, T.
J. Org. Chem. 2004, 69, 4607. (k) Shintani, R.; Tsurusaki, A.; Okamoto, K.;
Hayashi, T. Angew. Chem., Int. Ed. 2005, 44, 3909. (l) Chen, Y.; Lee, C. J. Am.
Chem. Soc. 2006, 128, 15598. (m) Navarro, C.; Csa´kÿ, A. G., Org. Lett. 2008,
10, 217.
(3) For examples of Rh(I)-catalyzed tandem noncyclization reactions, see:
(a) Yoshida, K.; Ogasawara, M.; Hayashi, T. J. Am. Chem. Soc. 2002, 124, 10984.
(b) Oguma, K.; Miura, M.; Satoh, T.; Nomura, M. J. Organomet. Chem. 2002,
648, 297. (c) Kurahash, T.; Shinokubo, H.; Osuka, A. Angew. Chem., Int. Ed.
2006, 45, 6336.
(4) Examples of similar reactions using other transition metals. Nickel
catalysis: (a) Patel, S. J.; Jamison, T. F. Angew. Chem., Int. Ed. 2003, 42, 1364.
(b) Patel, S. J.; Jamison, T. F. Angew. Chem., Int. Ed. 2004, 43, 3941. (c) Jayanth,
T. T.; Cheng, C.-H. Angew. Chem., Int. Ed. 2007, 46, 5921. Ir catalysis: (d)
Nishimura, T.; Yasuhara, Y.; Hayashi, T. J. Am. Chem. Soc. 2007, 129, 7506.
Pd catalysis: (e) Nishikata, T.; Kobayashi, Y.; Kobayashi, K.; Yamamoto, Y.;
Miyaura, N. Synlett 2007, 3055. (f) Tsukamoto, H.; Kondo, Y. Org. Lett. 2007,
9, 4227. (g) Tsukamoto, H.; Ueno, T.; Kondo, Y. Org. Lett. 2007, 9, 3033. (h)
Tsukamoto, H.; Matsumoto, T.; Kondo, Y. J. Am. Chem. Soc. 2008, 130, 388,
and references therein.
generated via carborhodation onto the alkene or alkyne moiety
2a–c
added to the intramolecular carbonyl,
cyano,2d,e alkyne,2g
and alkene2g–m groups, providing five- or six-membered car-
† Pukyong National University.
‡ Dong-A University.
(1) For reviews, see: (a) Montgomery, J. Angew. Chem., Int. Ed. 2004, 43,
3890. (b) Negishi, E.; Cope´ret, C.; Ma, S.; Liou, S. Y.; Liu, F. Chem. ReV.
1996, 96, 365. (c) Tietze, L. F. Chem. ReV. 1996, 96, 115. (d) Grigg, R.;
Sridharan, V. J. Organomet. Chem. 1999, 576, 65. (e) Miura, T.; Murakami, M.
Chem. Commun. 2007, 217. For recent examples, see: (f) Agapiou, K.; Cauble,
D. F.; Krische, M. J. J. Am. Chem. Soc. 2004, 126, 4528. (g) Subburaj, K.;
Montgomery, J. J. Am. Chem. Soc. 2003, 125, 11210. (h) Guo, H.-C.; Ma, J.-A.
Angew. Chem., Int. Ed. 2006, 45, 354.
(5) Tandem reactions using imine as a secondary electrophile. Nickel
catalysis: ref 4a,b. Pd catalysis: ref 4g.
(6) (a) Sakai, M.; Hayashi, H.; Miyaura, N. Organometallics 1997, 16, 4229.
(b) Hayashi, T. Synlett 2001, 879. (c) Fagnou, K.; Lautens, M. Chem. ReV. 2003,
103, 169. (d) Hayashi, T.; Yamasaki, K. Chem. ReV. 2003, 103, 2829. (e) Hayashi,
T. Bull. Chem. Soc. Jpn. 2004, 77, 13.
5658 J. Org. Chem. 2008, 73, 5658–5661
10.1021/jo800914c CCC: $40.75 2008 American Chemical Society
Published on Web 06/17/2008

TABLE 1. Rh(I)-Catalyzed Tandem Conjugate
Addition-Mannich Cyclization Reactions of 1 with Various
Arylboronic Acidsa
SCHEME 2. Rh(I)-Catalyzed Tandem Conjugate
Addition-Mannich Cyclization Reaction of
Imine-Substituted r,ꢀ-Unsaturated Ester with Arylboronic
Acids
entry substrate
Ar
product time (h) yield (%)b 2:2′c
1
1a
1b
1a
1a
1b
1a
1a
1a
1a
1a
1a
1a
1a
Ph
Ph
2a
2b
2c
2d
2e
2f
2g
2h
2i
1
12
1
1
1
1
1
1
24
1
74
86
73
72
75
74
74
70
80
67
51
55
50
77:23
63:37
77:23
71:29
83:17
71:29
77:23
83:17
77:23
91:9
2d
3
3-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-MeC6H4
4-HOC6H4
2-naphthyl
4-FC6H4
4-ClC6H4
4-BrC6H4
3-O2NC6H4
4-CH3COC6H4
4
5
6
7
8
9d
10
2j
2k
2l
11e
12e
13e
48
48
48
63:37
83:17
67:33
2m
products and pharmaceuticals that exhibit potent and varied
biological activities.8
a The reaction was carried out with 1, ArB(OH)2 (2.5 equiv),
[Rh(OH)(cod)]2 (2 mol %, 4 mol % Rh), and K3PO4 (2 equiv) in
1,4-dioxane (0.1 M) at 80 °C, unless otherwise noted. b Isolated yields.
c The ratio of two isomers was determined by 1H NMR. d Performed at
60 °C. e Performed with 5 mol % [Rh(OH)(cod)]2 (10 mol % Rh).
To date, Rh(I)-catalyzed tandem cyclization reactions using
organoboron reagents have been reported in the context of
synthesis of carbocyclic compounds.9 In parallel with our efforts
to develop a catalytic system for heterocyclic synthesis,10 we
were interested in developing a one-pot synthesis of N-
heterocycles, tetrahydroquinolines, whereby a single catalytic
system would invoke sequential C-C bond formations in an
efficient manner. Herein we report a new Rh(I)-catalyzed tandem
conjugate addition-Mannich cyclization reaction of imine-
substituted electron-deficient alkenes with arylboronic acids. This
is the first example inVolVing imine moiety as a secondary
electrophile in Rh(I)-catalyzed tandem reactions.
The success of a tandem cyclization triggered by the conjugate
addition of an organorhodium(I) species (A) to an electron-
deficient alkene could be achieved by choosing the adequate
secondary functionality placed at an appropriate position in the
molecule. The secondary functional group should not react faster
than the electron-deficient alkene with the organorhodium(I)
species in an intermolecular way but should be reactive enough
to trap intramoleculary the (oxa-π-allyl)rhodium(I) intermediate
(B) generated in the conjugate addition step (Scheme 2). In this
regard, the combination of R,ꢀ-unsaturated ester and imine
seems plausible. On the other hand, the RhI-catalyzed conjugate
addition reactions of organoboronic acids to R,ꢀ-unsaturated
carbonyl compounds are usually carried out in water-containing
solvents. However, anhydrous solvents might be required both
to minimize imine hydrolysis and to prevent RhI-enolate (B)
from protonation in this tandem process.11 The low reactivity
and instability of imine moiety relative to other functional groups
that were used in the related RhI-catalyzed tandem reactions
could present significant challenges in this process.
We focused our initial efforts on establishing optimal
conditions for the Rh(I)-catalyzed tandem conjugate
addition-Mannich cyclization reaction of 1a, which was selected
as the first substrate for screening of several solvents and bases.
Gratifyingly, it was found that reaction between 1a and
phenylboronic acid in 1,4-dioxane for 1 h at 80 °C in the
presence of [Rh(OH)(cod)]2 (4 mol % Rh) and K3PO4 gave the
desired 1,2,3,4-tetrahydroquinoline 2a in 74% yield as an
inseparable mixture of two diastereomers in a ratio of 77:23
favoring the cis-trans isomer, of which substituents on C-2 and
C-3 and those on C-3 and C-4 are located in cis and trans
configuration, respectively (Table 1, entry 1). The structure of
the compound 2a was determined by examination of 1H NMR
spectrum and NOE experiment. It should be noted that direct
1,2-addition of PhB(OH)2 to the imine moiety was not observed.
With the establishment of these optimized conditions, we set
out to explore the scope of this tandem process. As shown in
Table 1, reaction of 1 with organoboronic acids took place
smoothly with good yield to provide 2,3,4-trisubstituted 1,2,3,4-
tetrahydroquinoline 2. A wide range of arylboronic acids with
electron-donating or -withdrawing substituents at various posi-
tions were found to be good nucleophiles in the reaction (Table
1, entries 1-13). Generally, electron-rich arylboronic acids
(7) For selected examples, see: (a) Wang, Z.-Q.; Feng, C.-G.; Xu, M.-H.;
Lin, G.-Q. J. Am. Chem. Soc. 2007, 129, 5336. (b) Marelli, C.; Monti, C.;
Gennari, C.; Piarulli, U. Synlett 2007, 2213. (c) Duan, H.-F.; Jia, Y.-X.; Wang,
L.-X.; Zhou, Q.-L. Org. Lett. 2006, 8, 2567. (d) Kuriyama, M.; Soeta, T.; Hao,
X.; Chen, Q.; Tomioka, K. J. Am. Chem. Soc. 2004, 126, 8128. (e) Ueda, M.;
Miyaura, N. J. Organomet. Chem. 2000, 595, 31.
(8) (a) Katritzky, A. R.; Rachwal, S.; Rachwal, B. Tetrahedron 1996, 52,
15031. (b) Steinhagen, H.; Corey, E. J. Org. Lett. 1999, 1, 823. (c) Dannhardt,
G.; Gruchalla, M. V.; Kohl, B. K.; Parsons, C. G. Arch. Pharm. 2000, 333, 267.
(d) Hoemann, M. Z.; Xie, R. L.; Ross, R. F.; Meyer, S.; Sidhu, A.; Cunny,
G. D.; Hauske, J. R. Bioorg. Med. Chem. Lett. 2002, 12, 129. (e) Smith, H. C.;
Cavanaugh, C. K.; Friz, J. L.; Thompson, C. S.; Saggers, J. A.; Michelotti, E. L.;
Garcia, J.; Tice, C. M. Bioorg. Med. Chem. Lett. 2003, 13, 1943. (f)
Theeraladanon, C.; Arisawa, M.; Nakagawa, M.; Nishida, A. Tetrahedron:
Asymmetry 2005, 16, 827. (g) Liu, H. M.; Liu, F. W.; Zou, D. P.; Dai, G. F.
Bioorg. Med. Chem. Lett. 2005, 15, 1821.
(9) There is one example for Rh(I)-catalyzed synthesis of 3-alkylideneox-
indoles using isocyanates as a secondary electrophile; see ref 2f.
(10) (a) Pastine, S. J.; Youn, S. W.; Sames, D. Org. Lett. 2003, 5, 1055. (b)
Pastine, S. J.; Youn, S. W.; Sames, D. Tetrahedron 2003, 59, 8859. (c) Youn,
S. W.; Pastine, S. J.; Sames, D. Org. Lett. 2004, 6, 581. (d) Youn, S. W.; Eom,
J. I. Org. Lett. 2005, 7, 3355. (e) Youn, S. W. J. Org. Chem. 2006, 71, 2521. (f)
Youn, S. W. Org. Prep. Proced. Int. 2006, 38, 505. (g) Youn, S. W.; Eom, J. I.
J. Org. Chem. 2006, 71, 6705. (h) Youn, S. W. Synlett 2007, 3050.
(11) It was found that both water and protic acid such as H3BO3 were
detrimental to the reaction presented herein (see Supporting Information). It has
been reported that boric acid is presumed to facilitate the release of rhodium
from the iminorhodium(I) intermediate by protonolysis in the Rh-catalyzed
reaction of ethyl cyanoformate with arylboronic acids; see: Shimizu, H.;
Murakami, M. Chem. Commun. 2007, 2855.
J. Org. Chem. Vol. 73, No. 14, 2008 5659

TABLE 2. Rh(I)-Catalyzed Tandem Annulations of Various
SCHEME 4. Proposed Mechanism for the Rh(I)-Catalyzed
Tandem Conjugate Addition-Mannich Cyclization Reaction
a
Imine-Substituted r,ꢀ-Unsaturated Esters 1 with PhB(OH)2
entry substrate
R
product yield (%)b 2:2′c
1
2
3
4
5
6
7
1c
1d
1e
1f
1g
1h
1i
4-MeOC6H4
4-O2NC6H4
2-BrC6H4
2-(6-methylpyridinyl)
2-(5-methylfuranyl)
cinnamyl
2n
2o
2p
2q
2r
2s
2t
83
71
45
55
55
45
33
83:17
59:41
50:50
59:41
83:17
100:0
n.d.d
CO2Et
a The reaction was carried out with 1, PhB(OH)2 (2.5 equiv),
[Rh(OH)(cod)]2 (2 mol %, 4 mol % Rh), and K3PO4 (2 equiv) in
1,4-dioxane (0.1 M) at 80 °C for 1 h. b Isolated yields. c The ratio of
two isomers was determined by H NMR. d Not determined.
1
SCHEME 3. Rh(I)-Catalyzed Tandem Annulations of
Imine-Substituted Various Alkenes 1 with PhB(OH)2
required shorter reaction time and gave higher yields than their
electron-deficient counterparts, which required higher catalyst
loadings. 2-Naphthylboronic acid also reacted with 1a to give
the corresponding tetrahydroquinoline 2h (Table 1, entry 8). In
contrast, these cyclization reactions failed with sterically
hindered aryl- (o-MeOC6H4), heteroaryl- (2-thienyl, 2-furanyl),
and alkenyl- (ꢀ-styryl, (E)-1-octenyl) boronic acids to give the
corresponding products in 15-30% yields, probably due to steric
and electronic reasons, respectively.
We proceeded to examine the reaction with various imines
(Table 2). Both electron-deficient and electron-rich aromatic
imines as well as sterically hindered aromatic imine underwent
tandem cyclization reaction to form the corresponding tetrahy-
droquinolines (Table 2, entries 1-3). Heteroaromatic imines
(Table 2, entries 4 and 5), R,ꢀ-unsaturated imine (Table 2, entry
6), and glyoxylate imine (Table 2, entry 7) also proved to be
suitable substrates, whereas aliphatic imines led to a complicated
mixture and no reaction occurred with ketimine substrates.
Last, we explored the effects of substituents at the alkene
moiety. Whereas the tandem annulations of R,ꢀ-unsaturated
amide (1j) and nitrile (1k) afforded the corresponding cyclized
products in moderate to good yields, phenyl-substituted (1l) and
terminal alkenes (1m) were unsuccessful (Scheme 3).
mediate (B), which undergoes intramolecular nucleophilic
addition to the pendant imine group, forming N-rhodium(I)
species (C). The reaction was complete in the absence of proton
source such as H2O, which suggests that a proton source for
this reaction could be the organoboronic acid.2f,4c,13 Protonation
of C with arylboronic acid releases the product 2 along with
metaboric acid and A to promote the next catalytic cycle. Even
though the dependence of stereochemical bias on the substrate
structures is unclear and difficult to explain at this stage, the
observed relative stereochemistry may be understood on the
basis of a Z-enolate and a Zimmerman-Traxler-type transition
state model (Scheme 4b).2a,f,m,3a
In summary, we have developed a new Rh(I)-catalyzed
tandem conjugate addition-Mannich cyclization reaction to
afford 2,3,4-trisubstituted 1,2,3,4-tetrahydroquinolines. It is
interesting that sequential C-C bond formations, conjugate
addition and Mannich reaction, are catalyzed by a Rh complex
in a single catalytic cycle. This process represents the first
example in which an imine group can serve as a secondary
electrophile that accepts the (oxa-π-allyl)rhodium(I) intermediate
in an intramolecular way. Noteworthy is the fact that this process
can tolerate various functional groups such as methoxy, free
hydroxyl, halogen, ketone, nitro, alkene, ester, cyano, and amide
groups. Moreover, the arylboronic acids act as a proton source
as well as a carbon nucleophile. Future studies will focus on
A plausible mechanism for Rh-catalyzed tandem cyclization
presented herein is outlined in Scheme 4 and is based on the
related mechanisms established for the Rh-catalyzed tandem
cyclizations triggered by conjugate addition with organoboronic
acids.2,12 Initially, an organorhodium(I) species (A) is generated
by transmetalation of hydroxorhodium(I) with arylboronic acid.
Then, conjugate addition of the arylrhodium(I) species (A) to
substrate 1 occurs to afford the (oxa-π-allyl)rhodium(I) inter-
(13) (a) Oh, C. H.; Jung, H. H.; Kim, K. S.; Kim, N. Angew. Chem., Int. Ed.
2003, 42, 805. (b) Miura, T.; Shimada, M.; Ku, S.-Y.; Tamai, T.; Murakami,
M. Angew. Chem., Int. Ed. 2007, 46, 7101. (c) Zhao, P.; Incarvito, C. D.; Hartwig,
J. F. J. Am. Chem. Soc. 2007, 129, 1876.
(12) Hayashi, T.; Takahashi, M.; Takaya, Y.; Ogasawara, M. J. Am. Chem.
Soc. 2002, 124, 5052.
5660 J. Org. Chem. Vol. 73, No. 14, 2008

129.5, 129.8, 140.8, 141.2, 142.5, 169.8. Vmax (NaCl, cm-1) 3384,
3025, 2921, 2852, 2351, 1735, 1617, 1508, 1454, 1360, 1264, 1219,
1165, 1088, 1029, 811, 752, 701. HREIMS m/z 357.1728 (M)+,
calcd for C24H23NO2 357.1729.
the development of related catalytic tandem annulations and
asymmetric variants.
Experimental Section
Data for 2b. Signals corresponding to the major isomer: δH
(CDCl3, 400 MHz) 3.41 (dd, J ) 4.4, 7.9 Hz, 1H), 3.43 (s, 3H),
4.32 (d, J ) 7.9 Hz, 1H), 4.76 (d, J ) 4.4 Hz, 1H), 6.62-7.44 (m,
14H). δC (CDCl3, 100 MHz) 42.2, 51.2, 51.7, 54.7, 113.8, 117.7,
122.0, 126.3, 126.6, 127.4, 127.8, 128.3, 128.6, 129.3, 130.5, 141.5,
143.6, 144.5, 171.5. Representative signals corresponding to the
minor isomer: δH (CDCl3, 400 MHz) 3.14 (s, 3H), 3.26 (dd, J )
3.3, 5.9 Hz, 1H), 4.69 (d, J ) 6.1 Hz, 1H), 4.92 (d, J ) 3.5 Hz,
1H), 6.62-7.44 (m, 14H). δC (CDCl3, 100 MHz) 47.3, 50.6, 52.8,
58.4, 114.5, 117.6, 121.6, 126.4, 126.5, 127.0, 127.2, 128.1, 128.4,
128.9, 129.5, 140.6, 141.0, 144.9, 169.8. Vmax (NaCl, cm-1) 3392,
3028, 2951, 2855, 2356, 1735, 1605, 1490, 1454, 1434, 1366, 1267,
1162, 1117, 1077, 1029, 802, 750, 701. HREIMS m/z 343.1570
(M)+, calcd for C23H21NO2 343.1572.
General Procedure for Rh(I)-Catalyzed Tandem Conjugate
Addition-Mannich Cyclization Reaction of Imine-Substituted
Electron-Deficient Alkenes 1 with Arylboronic Acids. To a solution
of the substrate 1 (0.15 mmol) in 1,4-dioxane (0.1 M) were added
[Rh(OH)(cod)]2 (2 mol %, 4 mol % Rh, 0.003 mmol), K3PO4 (2
equiv, 0.3 mmol), and boronic acid (2.5 equiv, 0.375 mmol). The
resulting mixture was stirred at the reported temperature for 1-48
h. After the reaction was completed, the reaction mixture was
quenched with distilled water, extracted with CH2Cl2 (three times),
washed with brine, dried over MgSO4, and concentrated in vacuo.
The residue was purified by column chromatography on silica
gel (EtOAc/n-hexane ) 1:2-1:10) to give the corresponding
product 2.
Data for 2a. Signals corresponding to the major isomer: δH
(CDCl3, 400 MHz) 2.14 (s, 3H), 3.35 (dd, J ) 4.1, 7.2 Hz, 1H),
3.42 (s, 3H), 4.30 (d, J ) 7.2 Hz, 1H), 4.71 (d, J ) 4.1 Hz, 1H),
6.55 (s, 1H), 6.60 (d, J ) 7.9 Hz, 1H), 6.90 (d, J ) 7.8 Hz, 1H),
7.16-7.42 (m, 10H). δC (CDCl3, 100 MHz) 20.5, 42.6, 51.2, 52.0,
54.6, 114.1, 121.8, 126.3, 126.5, 126.6, 126.9, 127.7, 127.9, 128.2,
128.3, 128.6, 129.3, 130.8, 141.4, 141.7, 144.9, 171.7. Representa-
tive signals corresponding to the minor isomer: δH (CDCl3, 400
MHz) 2.14 (s, 3H), 3.13 (s, 3H), 3.24 (dd, J ) 3.2, 6.0 Hz, 1H),
4.66 (d, J ) 5.8 Hz, 1H), 4.87 (d, J ) 3.1 Hz, 1H), 6.63 (d, J )
8.2 Hz, 1H), 6.66 (s, 1H), 6.90 (d, J ) 7.8 Hz, 1H), 7.16-7.42 (m,
10H). δC (CDCl3, 100 MHz) 20.5, 47.4, 50.6, 53.0, 58.6, 114.5,
114.8, 121.8, 125.2, 126.1, 127.0, 127.1, 128.1, 128.4, 128.5, 128.9,
Acknowledgment. This work was supported by the Korea
Research Foundation Grant funded by the Korean Government
(MOEHRD, Basic Research Promotion Fund) (KRF-2006-331-
C00168). We are grateful to BK21 Foundation for generous
support.
Supporting Information Available: Full experimental details
and characterization data. This material is available free of
charge via the Internet at http://pubs.acs.org.
JO800914C
J. Org. Chem. Vol. 73, No. 14, 2008 5661