Novel and convenient synthesis of substituted quinolines by copper- or palladium-catalyzed cyclodehydration of 1-(2-aminoaryl)-2-yn-1-ols

Article abstract of DOI:10.1021/jo071094z

(Chemical Equation Presented) A general and convenient synthesis of substituted quinolines by regioselective copper- or palladium-catalyzed 6-endo-dig cyclization-dehydration of 1-(2-aminoaryl)-2-yn-1-ols is reported. The crude substrates were easily obtained by the Grignard reaction between the appropriate alkynylmagnesium bromide and 2-aminoaryl ketones and could be used without further purification for the subsequent cyclization step. Heteroannulation reactions were carried out in MeOH or DME as the solvent at 60 or 100°C in the presence of CuCl₂ or PdX₂ (in conjunction with 10 equiv of KX, X = Cl, I) as the catalyst to afford the quinoline derivatives in good to excellent isolated yields based on starting 1-(2-aminoaryl)-2-yn-1-ols (66-90%).

Full text of DOI:10.1021/jo071094z

Novel and Convenient Synthesis of Substituted Quinolines by
Copper- or Palladium-Catalyzed Cyclodehydration of
1-(2-Aminoaryl)-2-yn-1-ols
Bartolo Gabriele,*,† Raffaella Mancuso,‡ Giuseppe Salerno,‡ Giuseppe Ruffolo,‡ and
Pierluigi Plastina‡
Dipartimento di Scienze Farmaceutiche, UniVersita` della Calabria,
87036 ArcaVacata di Rende (Cosenza), Italy, and Dipartimento di Chimica,
UniVersita` della Calabria, 87036 ArcaVacata di Rende (Cosenza), Italy
b.gabriele@unical.it
ReceiVed May 23, 2007
A general and convenient synthesis of substituted quinolines by regioselective copper- or palladium-
catalyzed 6-endo-dig cyclization-dehydration of 1-(2-aminoaryl)-2-yn-1-ols is reported. The crude
substrates were easily obtained by the Grignard reaction between the appropriate alkynylmagnesium
bromide and 2-aminoaryl ketones and could be used without further purification for the subsequent
cyclization step. Heteroannulation reactions were carried out in MeOH or DME as the solvent at 60 or
100 °C in the presence of CuCl2 or PdX2 (in conjunction with 10 equiv of KX, X ) Cl, I) as the catalyst
to afford the quinoline derivatives in good to excellent isolated yields based on starting 1-(2-aminoaryl)-
2-yn-1-ols (66-90%).
Introduction
anticancer activity.11 In view of the remarkable importance of
this class of heterocyclic compounds, during the last years many
Quinolines are a very important class of heterocyclic com-
pounds. The quinoline core is present in many biologically active
natural products, in particular, alkaloids. Moreover, substituted
quinolines are known to display a wide range of pharmacological
activities, such as antiinflammatory,1 antibacterial,2 antiproto-
zoan,3 antimalarial,4 antiasthmatic,5 antituberculosis,6 anti-
Alzheimer,7 antihypertensive,8 anthelmintic,9 anti-HIV,10 and
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† Dipartimento di Scienze Farmaceutiche.
‡ Dipartimento di Chimica.
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10.1021/jo071094z CCC: $37.00 © 2007 American Chemical Society
Published on Web 07/26/2007
J. Org. Chem. 2007, 72, 6873-6877
6873

Gabriele et al.
efforts have been devoted to the development of new regiose-
lective synthetic methodologies for their production.12 In
particular, new synthetic strategies based on metal-catalyzed
heteroannulation of acyclic precursors have attracted consider-
able attention, owing to the possibility to construct the quinoline
ring with the desired substitution pattern in one step under mild
conditions starting from readily available starting materials.13
We report here a general and convenient synthesis of
substituted quinolines 3 through copper or palladium-catalyzed
6-endo-dig heteroannulation-dehydration of 1-(2-aminoaryl)-
2-yn-1-ols 2,14,15 easily obtained by the Grignard reaction
between the appropriate alkynylmagnesium bromide and 2-ami-
noaryl ketones 1 (Scheme 1). The intermediates 2 deriving from
the first step could be used without further purification for the
second step, thus facilitating the synthetic procedure.
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Results and Discussion
We have recently reported several examples of copper- or
palladium-catalyzed cycloisomerization reactions leading to
heterocyclic derivatives starting from suitably functionalized
alkyne derivatives.16 In particular, we have reported a general
methodology for the regioselective synthesis of substituted
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(14) The formation of 6-chloro-2-cyclopropyl-4-trifluoromethylquinolin-
5-ol from 3-amino-6-chloro-2-(3-cyclopropyl-1-hydroxy-1-trifluorometh-
ylprop-2-ynyl)phenol, obtained in situ by deprotection of the corresponding
tert-butyldimethylsilyl ether with TBAF, has been briefly mentioned in the
literature as an undesired reaction, but no further experimental details
(including the product yield) have been given for this reaction: (a)
Markwalder, J. A.; Mutlib, D. D. C. A.; Cordova, B. C., Klabe, R. M.;
Seitz, S. P. Bioorg. Med. Chem. Lett. 2001, 11, 619-622. Formation of
6-chloro-2-cyclopropyl-4-trifluoromethylquinoline in 81% yield by refluxing
a solution of 2-(2-amino-5-chlorophenyl)-4-cyclopropyl-1,1,1-trifluorobut-
3-yn-2-ol in chlorobenzene for 6 h has also been reported: (b) Choudhury,
A.; Pierce, M. E.; Confalone, P. N. Synth. Commun. 2001, 31, 3707-3714.
(15) The iodocyclization of 1-(2-dimethylaminophenyl)-2-yn-1-ols to give
4-hydroxy-3-iodo-1,1-dimethyl-1,4-dihydroquinolinium iodides, which, upon
heating, underwent formal loss of MeOH to give 3-iodo-1-methylquino-
linium iodides has been recently reported: Hessian, K. O.; Flynn, B. L.
Org. Lett. 2006, 8, 243-246.
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2004, 2468-2483.
6874 J. Org. Chem., Vol. 72, No. 18, 2007

Cu- or Pd-Catalyzed Cyclodehydration of 1-(2-Aminoaryl)-2-yn-1-ols
SCHEME 1
SCHEME 2
SCHEME 3
furans,17 thiophenes,18 and pyrroles19 starting from (Z)-2-en-4-
yn-1-ols, (Z)-2-en-4-yne-1-thiols, and (Z)-(2-en-4-ynyl)amines,
respectively, through 5-exo-dig heteroannulation-aromatization
promoted by PdX2 in conjunction with KX (X ) Cl, I) or by
CuCl2 as the catalytic system. We have also reported a divergent
synthesis of (Z)-1-alkylidene-1,3-dihydroisobenzofurans and 1H-
isochromenes by PdI2/KI-catalyzed 5-exo-dig or 6-endo-dig,
respectively, cycloisomerization of 2-alkynylbenzyl alcohols.20
On the basis of these results, we have investigated the possibility
to synthesize substituted quinolines starting from 1-(2-ami-
noaryl)-2-yn-1-ols, through a metal-promoted 6-endo-dig cy-
clodehydration route, based on intramolecular nucleophilic
attack of the -NH2 group to the triple bond coordinated to the
metal center followed by protonolysis and dehydration (Scheme
2, path a) or vice versa (path b).
The first substrate we used was 2-(2-aminophenyl)oct-3-yn-
2-ol 2aa (R1 ) R2 ) H, R3 ) Me, R4 ) Bu) obtained in ca.
60% isolated yield by the reaction between commercially
available 2-aminoacetophenone 1a and 1-hexynylmagnesium
bromide. The reactivity of 2aa was initially tested at 60 °C in
MeOH as the solvent in the presence of 2 mol % of different
catalytic systems, based on zinc, palladium, and copper. The
results obtained are shown in Table S1 (see the Supporting
Information). As can be seen, 2-butyl-4-methylquinoline 3aa
was selectively formed in all cases (entries 1-12), thus
confirming the validity of our hypothesis. The best results in
terms of substrate conversion rate and product selectivity were
obtained with CuCl2 as the catalyst: after 5 h reaction time,
3aa was formed in 85% GLC yield at total substrate conversion
(78% isolated, entry 12 and Scheme 3, path a). The reaction
did not occur in the absence of the metal catalyst, as confirmed
by blank experiments (decomposition of the starting material
to give unidentified chromatographically immobile materials was
observed under these conditions, entry 13).
Using CuCl2 as the catalyst, we next tested the reactivity of
2aa in different solvents. The results, shown in Table S2, entries
14-19 (to be compared with entry 10 of Table S1, see the
Supporting Information), clearly indicate MeOH as the solvent
of choice for the reaction.
One drawback of this synthetic approach was related to the
instability of 2aa during the purification procedures, which in
several cases caused its partial decomposition after column
chromatography.21 However, we have found that the cyclization
reaction worked nicely even on the crude product, which also
facilitated the synthetic protocol (see Experimental Section for
details). Thus, when crude 2aa was let to react under the same
conditions of entry 12, quinoline 3aa was obtained in 75%
isolated yield based on starting 2-aminoacetophenone 1a (Table
1, entry 20, and Scheme 3, path b). It is worth noting that this
yield was considerably higher with respect to the overall yield
obtained using pure 2aa (47% isolated yield based on 1a,
Scheme 3, path a).
(17) (a) Gabriele, B.; Salerno, G.; Lauria, E. J. Org. Chem. 1999, 64,
7687-7692. (b) Gabriele, B.; Salerno, G. Chem. Commun. 1997, 1083-
1084.
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(19) (a) Gabriele, B.; Salerno, G.; Fazio, A. J. Org. Chem. 2003, 68,
7853-7861. (b) Gabriele, B.; Salerno, G.; Fazio, A.; Bossio, M. R.
Tetrahedron Lett. 2001, 42, 1339-1341.
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59, 6251-6259.
The generality of the process was then verified by varying
the nature of substituents R1 and R2 (on the aromatic ring), R3
(at the benzylic position), and R4 (on the triple bond) (Scheme
1). The results are shown in Table 1. As can be seen, in most
(21) Unidentified chromatographically immobile materials were formed
as a result of decomposition.
J. Org. Chem, Vol. 72, No. 18, 2007 6875

Gabriele et al.
TABLE 1. Synthesis of Substituted Quinolines 3 by
Cyclodehydration of Crude 1-(2-Aminophenyl)-2-yn-1-ols 2,
Obtained by the Reaction between R4CtCMgBr and 2-Aminoaryl
Ketones 1 in the Presence of CuCl2 as Catalysta
TABLE 2. Synthesis of 4-Substituted Quinolines 3ad and 3dd by
Cu- or Pd-Catalyzed Cyclodehydration-Desilylation of Crude
1-(2-Aminophenyl)-2-yn-1-ols 2ad and 2dd, Obtained by the
Reaction between TMS-CtC-MgBr and 2-Aminophenyl Ketones
1a and 1da
yield of 3b
entry
1
R1
R2 R3
R4
2
T (°C)
3
(%)
yield of
entry
1
R1 R2 R3
R4
2
catalyst
3b
3c (%)
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37e
38
39f
1a
1a
1b
H
H
H
H
H
H
H
H
Me Bu
Me Bu
Ph Bu
Me Bu
Me Bu
2aa
2aa
2ba
2ca
2ca
2da
2da
2ab
2ab
2bb
2bb
2cb
2cb
2db
2db
60
100
60
60
100
60
100
60
100
60
100
60
100
60
100
60
100
100
100
100
3aa
3aa
3ba
3ca
3ca
3da
3da
3ab
3ab
3bb
3bb
3cb
3cb
3db
3db
3ac
3ac
3ac
3bc
3cc
75
80
80
60
76
81
69
65
73
63
68
72
90
78
74
20c
68d
75
70
77
40 1a
41 1a
42 1a
43 1b
44 1b
45 1b
H
H
H
H
H
H
H
H
H
H
H
H
Me TMS 2ad CuCl2
3ad
50
69
73
56
66
66
Me TMS 2ad PdCl2 + 10 KCl 3ad
Me TMS 2ad PdI2 + 10 KI
Ph TMS 2bd CuCl2
Ph TMS 2bd PdCl2 + 10 KCl 3bd
Ph TMS 2bd PdI2 + 10 KI 3bd
1c OMe
1c OMe
3ad
3bd
1d
1d
1a
1a
1b
1b
H
H
H
H
H
H
Cl Me Bu
Cl Me Bu
H
H
H
H
H
H
Me Ph
Me Ph
Ph Ph
Ph Ph
Me Ph
Me Ph
a Unless otherwise noted, all reactions were carried out in MeOH (0.22
mmol of 1 per mL of MeOH, 9 mmol scale based on 1) at 100 °C for 5 h
in the presence of 2 mol % of catalyst. Conversion of 2 was quantitative
in all cases. b R3 ) H in the final product 3. c Isolated yield based on
starting 1.
1c OMe
1c OMe
1d
1d
1a
1a
1a
1b
H
H
H
H
H
H
Cl Me Ph
Cl Me Ph
SCHEME 5
H
H
H
H
H
Me t-Bu 2ac
Me t-Bu 2ac
Me t-Bu 2ac
Ph t-Bu 2bc
Me t-Bu 2cc
1c OMe
a Unless otherwise noted, all reactions were carried out in MeOH (0.22
mmol of 1 per mL of MeOH, 9 mmol scale based on 1) for 5 h in the
presence of 2 mol % of CuCl2. Conversion of 2 was quantitative in all
cases. b Isolated yield based on starting 1. c The reaction also led to the
formation of 2-(1-methoxy-1,4,4-trimethylpent-2-ynyl)phenylamine 4ac
(30% isolated yield based on starting 2-aminoacetophenone 1a). d The
reaction also led to the formation of 4ac (2% isolated yield based on starting
1a). e The reaction was carried out in 1,2-dimethoxyethane (DME). f Re-
action time was 2 h.
quinoline 3ac became the main reaction product (68% isolated
yield based on 1a), 4ac being formed in less than 2% isolated
yield based on 1a (entry 36 and Scheme 4). In a non-
nucleophilic solvent such as 1,2-dimethoxyethane (DME), 3ac
was selectively obtained with a 75% isolated yield based on 1a
(entry 37 and Scheme 4). Under the same conditions of entry
36, other substrates bearing a tert-butyl group on the triple bond,
such as 1-(2-aminophenyl)-4,4-dimethyl-1-phenylpent-2-yn-1-
ol 2bc (R1 ) R2 ) H, R3 ) Ph, R4 ) t-Bu), and 2-(2-amino-
3-methoxyphenyl)-5,5-dimethylhex-3-yn-2-ol 2cc (R1 ) OMe,
R2 ) H, R3 ) Me, R4 ) t-Bu) afforded the corresponding
quinolines 3bc and 3cc, respectively, in good isolated yield (70%
and 77%, respectively) after 2-5 h reaction time (entries 38
and 39).
SCHEME 4
The cyclodehydration reaction could also be successfully
applied to substrates bearing a trimethylsilyl group on the triple
bond, such as 2-(2-aminophenyl)-4-trimethylsilanylbut-3-yn-2-
ol 2ad (R1 ) R2 ) H, R3 ) Me, R4 ) TMS). Under the same
conditions of entry 21, this substrate was converted into
4-methylquinoline 3ad (R1 ) R2 ) R4 ) H, R3 ) Me), ensuing
from loss of the TMS group under the reaction conditions, in
50% isolated yield (Table 2, entry 40, and Scheme 5).
Interestingly, a higher selectivity toward 3ad (69-73%) could
be obtained working in the presence of PdX2 + 10 KX (X )
Cl, I) as the catalytic system (entries 41 and 42 and Scheme 5).
Similar results were observed in the case of 1-(2-aminophenyl)-
1-phenyl-3-trimethylsilanylprop-2-yn-1-ol 2bd (R1 ) R2 )H,
R3 ) Ph, R4 ) TMS) to give 4-phenylquinoline 3bd (R1 ) R2
) R4 ) H, R3 ) Ph) (entries 43-45 and Scheme 5).
cases, better results in terms of product yield were obtained by
working in a Schlenk flask at 100 °C rather than 60 °C. The
benzylic position and the triple bond could be substituted with
an alkyl as well as an aryl substituent, while electron-
withdrawing as well as π-donating groups could be present on
the aromatic ring.
Interestingly, in the case of 2-(2-aminophenyl)-5,5-dimeth-
ylhex-3-yn-2-ol 2ac (R1 ) R2 ) H, R3) Me, R4 ) tert-Bu),
the reaction, carried out under the same conditions of entry 20,
led to 2-(1-methoxy-1,4,4-trimethylpent-2-ynyl)phenylamine 4ac
as the main reaction product (30% isolated yield based on
starting 2-aminoacetophenone 1a), together with smaller amounts
of the expected 2-tert-butyl-4-methylquinoline 3ac (20% isolated
yield based on 1a, entry 35 and Scheme 4). Clearly, this
undesired reaction becomes competitive owing to the diminished
reactivity of the sterically hindered triple bond. However, when
the same reaction was carried out at 100 °C rather than 60 °C,
Conclusions
We have developed a novel and practical synthesis of
substituted quinolines through a two-step procedure involving
6876 J. Org. Chem., Vol. 72, No. 18, 2007

Cu- or Pd-Catalyzed Cyclodehydration of 1-(2-Aminoaryl)-2-yn-1-ols
of EtMgBr thus obtained was transferred under nitrogen to a
dropping funnel and was added dropwise to a solution of the
1-alkyne (26.8 mmol) in anhydrous THF (7.0 mL) at 0 °C with
stirring. After additional stirring at 0 °C for 15 min, the mixture
was allowed to warm up to room temperature, maintained at 50 °C
for 2 h, and then used as such for the next step. 2-Amino ketone 1
(8.9 mmol) was dissolved under nitrogen in anhydrous THF (7.0
mL) and then added dropwise to the solution of the alkynylmag-
nesium bromide in THF (prepared as described above) at 50 °C
under nitrogen. After stirring at 50 °C for 1 h (R1 ) R2 ) H, R3 )
Me, R4 ) Bu; R1 ) OMe, R2 ) H, R3 ) Me, R4 ) Bu; R1 ) H,
R2 ) Cl, R3 ) Me, R4 ) Bu), 2 h (R1 ) OMe, R2 ) H, R3 ) Me,
R4 ) Ph; R1 ) H, R2 ) Cl, R3 ) Me, R4 ) Ph; R1 ) OMe, R2 )
H, R3 ) Me, R4 ) t-Bu; R1 ) H, R2 ) Cl, R3 ) Me, R4 ) t-Bu;
R1 ) R2 ) H, R3 ) Me, R4 ) Ph; R1 ) R2 ) H, R3 ) Me, R4 )
t-Bu; R1 ) R2 ) H, R3 ) Me, R4 ) TMS; R1 ) R2 ) H, R3 ) Ph,
R4 ) t-Bu; R1 ) R2 ) H, R3 ) Ph, R4 ) TMS) or 3 h (R1 ) R2
) H, R3 ) Ph, R4 ) Bu; R1 ) R2 ) H, R3 ) R4 ) Ph), the mixture
was cooled to room temperature. Saturated NH4Cl was added with
stirring to achieve weakly acidic pH. After additional stirring at
room temperature for 15 min, AcOEt (ca. 20 mL) was added, and
the phases were separated. The aqueous phase was extracted with
AcOEt (3 × 30 mL), and the collected organic layers were washed
with brine to neutral pH and eventually dried over Na2SO4. After
filtration, the solvent was evaporated and crude products 2 used as
such for the next step. CuCl2 (24.0 mg, 1.79 × 10-1 mmol) [or
PdX2 (1.79 × 10-1 mmol) in conjunction with KX (1.79 mmol),
X ) Cl or I, see Tables 1 and 2] was added to a solution of crude
2 in anhydrous MeOH (40.5 mL) or DME (40.5 mL) (see Tables
1 and 2) in a Schlenk flask. The resulting mixture was stirred at
the temperature and for the time indicated in Tables 1 and 2. Solvent
was evaporated and the crude product purified by column chro-
matography on silica gel: 3aa (yellow oil, 95:5 hexane-AcOEt);
3ba (yellow oil, 95:5 hexane-AcOEt); 3ca (yellow oil, 95:5
hexane-acetone); 3da (yellow oil, 90:10 hexane-acetone); 3ab
(yellow solid, mp 65-67 °C, 95:5 hexane-AcOEt); 3bb (yellow
solid, mp 107-108 °C, 95:5 hexane-AcOEt); 3cb (yellow solid,
mp 96-97 °C, 90:10 hexane-acetone); 3db (yellow solid, mp 89-
90 °C, 99:1 hexane-acetone); 3ac (yellow oil, 95:5 hexane-
AcOEt); 3bc (colorless solid, mp 86-87 °C, 95:5 hexane-acetone);
3cc (yellow oil, 95:5 hexane-acetone); 3ad (yellow oil, 90:10
hexane-acetone); 3bd (yellow solid, mp 61-62 °C, 90:10 hexane-
acetone). The yields obtained in each experiment are reported in
Tables 1 and 2.
Grignard addition of alkynylmagnesium bromides to 2-ami-
noaryl ketones followed by regioselective copper- or palladium-
catalyzed 6-endo-dig cyclodehydration of the corresponding
1-(2-aminophenyl)-2-yn-1-ols. The latter intermediates could be
used without further purification for the subsequent cyclization
step, thus further facilitating the synthetic procedure. The
generality of the process has been verified by varying the nature
of substituents on the aromatic ring as well as at the benzylic
position and on the triple bond.
Experimental Section
Preparation of Substrates. 2-Aminoacetophenone 1a and
2-aminobenzophenone 1b were commercially available and were
used as received. 2-Amino-3-methoxyacetophenone 1c was prepared
by nitration of commercially available 3-methoxyacetophenone
followed by reduction, as described in the literature.22 2-Amino-
5-chloroacetophenone 1d was prepared by nitration of commercially
available 3-chloroacetophenone followed by reduction, as described
in the Supporting Information. Pure 2-(2-aminophenyl)oct-3-yn-2-
ol 2aa was prepared and characterized as described in the
Supporting Information. Characterization data for quinolines 3 and
2-(1-methoxy-1-methylhept-2-ynyl)aniline 4ac can also be found
in the Supporting Information.
Cyclodehydration of 2-(2-Aminophenyl)oct-3-yn-2-ol 2aa to
2-Butyl-4-methylquinoline 3aa (Tables S1 and S2, See the
Supporting Information). In a typical experiment, the catalyst
(5.28 × 10-2 mmol) [in conjunction with KX (5.28 × 10-1 mmol)
in the case of PdX2, X ) Cl or I] was added under nitrogen to a
solution of pure 2aa (574.0 mg, 2.64 mmol) in the anhydrous
solvent (12.0 mL) (see Tables S1 and S2, see the Supporting
Information) in a Schlenk flask. The resulting mixture was stirred
under nitrogen at the temperature and for the time indicated in
Tables S1 and S2. Solvent was evaporated, and the crude product
purified by column chromatography on silica gel using 95:5 hexane-
AcOEt as the eluent to give 3aa as a yellow oil. The yields obtained
in each experiment are reported in Tables S1 and S2.
General Procedure for the Synthesis of Quinolines 3 (Tables
1 and 2). To a suspension of Mg turnings (700.0 mg, 28.8 mmol)
in anhydrous THF (2.0 mL), maintained under nitrogen and under
reflux, was added pure EtBr (0.5 mL) to start the formation of the
Grignard reagent. The remaining bromide was added dropwise (ca.
20 min) in THF solution (1.5 mL of EtBr in 15.0 mL of THF; total
amount of EtBr added: 2.92 g, 26.8 mmol). The mixture was then
allowed to reflux for additional 20 min. After cooling, the solution
Acknowledgment. This work was supported by the Minis-
tero dell’Universita` e della Ricerca (Progetto di Ricerca di
Interesse Nazionale PRIN 2006031888, Roma, Italy) and by
the Consorzio Interuniversitario Nazionale “Metodologie e
Processi Innovativi di Sintesi” (CINMPIS, Bari, Italy) for a
fellowship grant to P.P.
(22) It is interesting to note that the only mononitrated product obtained
by nitration of 3-methoxyacetophenone was 3-methoxy-2-nitroacetophenone,
1
as confirmed by H NMR (see the Supporting Information). This product
was obtained either by using the nitration procedure reported by Alford et
al.23 or by using the procedure recently reported by Robbins et al.24 (see
the Supporting Information for details). It is worth noting that in this latter
case the authors have indicated the structure of the mononitrated product
as 5-methoxy-2-nitroacetophenone rather than 3-methoxy-2-nitroacetophe-
none. The reduction of 3-methoxy-2-nitroacetophenone to give 2-amino-
3-methoxyacetophenone was carried out as described in ref 24.
(23) Alford, E. J., Irving, H.; Marsh, H. S.; Schofield, K. J. Chem. Soc.
1952, 3009-3017.
Supporting Information Available: Tables S1 and S2, general
experimental methods, preparation and characterization of 1c, 1d,
1
and 2aa, characterization data, and copies of H and 13C NMR
spectra for all products. This material is available free of charge
via the Internet at http://pubs.acs.org.
(24) Robbins, R. J.; Laman, D. M.; Falvey, D. E. J. Am. Chem. Soc.
1996, 118, 8127-8135.
JO071094Z
J. Org. Chem, Vol. 72, No. 18, 2007 6877