Palladium-catalyzed reactions of arylindium reagents prepared directly from aryl iodides and indium metal

Article abstract of DOI:10.1021/jo801074g

(Chemical Equation Presented) Treatment of aryl iodides with indium metal in the presence of lithium chloride leads to the formation of an organoindium reagent capable of participating in cross-coupling reactions under transition-metal catalysis. Combination with aryl halides in the presence of 5 mol % Cl₂Pd(dppf) furnishes biaryl compounds in good yields; similarly, reaction with acyl halides or allylic acetates/carbonates in the presence of 5-10 mol % palladium catalyst leads to arylketones and allylic substitution products, respectively, in moderate yields. The reactions are tolerant of the presence of protic solvents, and ～85% of the indium metal employed can be recovered by reduction of the residual indium salts with zinc(0).

Full text of DOI:10.1021/jo801074g

sium or organolithium reagents with indium trichloride. As a
result of the highly reactive nature of lithium or Grignard
organometallics,3 the scope of indium reagents that can be
prepared by this method may be limited.4 Furthermore, in-
dium(III) salts such as InCl3 are currently under investigation
as possible mutagens.5 A direct method of preparing organoin-
dium reagents for transition-metal-mediated reactions is thus
highly desirable.
Palladium-Catalyzed Reactions of Arylindium
Reagents Prepared Directly from Aryl Iodides
and Indium Metal
Vardan Papoian and Thomas Minehan*
Department of Chemistry and Biochemistry, California State
UniVersity-Northridge, Northridge, California 91330
Knochel has shown that highly functionalized organozinc and
organomagnesium reagents can be formed efficiently from the
corresponding organic halides and zinc or magnesium metal in
the presence of lithium chloride.6 These organometallics readily
engage in subsequent transition-metal-mediated carbon-carbon
bond-forming reactions. A recent patent from the same group7
has indicated that this method may also be extended to the
preparation of organometals containing Cu, Sn, Mn, and In,
although Zn was preferable to all others tested. Despite the utility
of zinc-mediated processes, an involved procedure for activation
of the zinc metal (including use of TMSCl and iodine) is
necessary, and the separation of the organozinc reagent solution
from any remaining finely dispersed zinc dust is often prob-
lematic (zinc metal impurities can interfere with the subsequent
cross-coupling reaction).8 Furthermore, the zinc organometallics
so formed are both air- and moisture-sensitive. In this Note we
wish to describe our studies on the utility, scope, and limitations
of the direct reaction of aryl halides with indium metal in the
preparation organoindium reagents.
thomas.minehan@csun.edu
ReceiVed May 18, 2008
Because of the ease with which allylic indium reagents are
formed upon combination of indium metal and allyl halides in
polar solvents such as water,9 we reasoned that minimal
activation of the indium metal would be necessary to obtain
successful insertion reactions with organic halides. Indeed, when
methyl 4-iodobenzoate was treated with a slight excess (1.5
equiv) of In·2LiCl (prepared by heating 1 equiv of indium metal
Treatment of aryl iodides with indium metal in the presence
of lithium chloride leads to the formation of an organoindium
reagent capable of participating in cross-coupling reactions
under transition-metal catalysis. Combination with aryl
halides in the presence of 5 mol % Cl2Pd(dppf) furnishes
biaryl compounds in good yields; similarly, reaction with
acyl halides or allylic acetates/carbonates in the presence of
5-10 mol % palladium catalyst leads to arylketones and
allylic substitution products, respectively, in moderate yields.
The reactions are tolerant of the presence of protic solvents,
and ∼85% of the indium metal employed can be recovered
by reduction of the residual indium salts with zinc(0).
(3) Yus, M.; Foubelo, F. Handbook of Functionalized Organometallics;
Knochel, P., Ed.; Wiley-VCH: Weinheim, Germany, 2005; Vol. 1, p 7.
(4) Recently, a directed ortho-lithiation/transmetalation sequence was used
in the preparation of triarylindium reagents. Pena, M. A.; Perez Sestelo, J.;
Sarandeses, L. A. J. Org. Chem. 2007, 72, 1271.
(5) Lian, Y.; Hinkle, R. J. J. Org. Chem. 2006, 71, 7071.
(6) Zinc: (a) Krasovskiy, A.; Malakhov, V.; Gavryushin, A.; Knochel, P.
Angew. Chem., Int. Ed. 2006, 45, 6040. (b) Boudet, N; Sase, S; Sinha, P; Liu,
C.-Y;Krasovskiy,A;Knochel,P.J.Am.Chem.Soc.2007,129,12358Magnesium:(c)
Knochel, P.; Dohle, W.; Gommermann, N.; Kniesel, F. F.; Kopp, F.; Korn, T.;
Sapountzis, I; Vu, V. A. Angew. Chem., Int. Ed. 2003, 42, 4302. (d) Krasovskiy,
A.; Knochel, P. Angew. Chem., Int. Ed. 2004, 43, 3333. (e) Ila, H.; Baron, O.;
Wagner, A. J.; Knochel, P. Chem. Lett. 2006, 35, 2. (f) Ila, H.; Baron, O.; Wagner,
A. J.; Knochel, P. Chem. Commun. 2006, 6, 58. (g) Krasovskiy, A.; Straub,
B. F.; Knochel, P. Angew. Chem., Int. Ed. 2006, 45, 159. (h) Knochel, P;
Krasovskiy, A; Sapountzis. I Handbook of Functionalized Organometallics;
Knochel, P., Ed.; Wiley-VCH: Weinheim, Germany, 2005; Vol. 1, p 109.
(7) Knochel, P.; Gavryushin, A.; Malakhov, V. A. German Patent DE
102006015378, 2007. In the preparation of this manuscript, we became aware
of a manuscript in review (J. Am. Chem. Soc.) by Knochel and Chen detailing
the direct insertion of indium into aryl and heteroaryl iodides and the cross-
coupling of the so-formed indium reagents with aryl halide to form biaryls.
(8) (a) Knochel, P.; Millot, N.; Rodriguez, A. L. Org. React. 2001, 58, 417.
(b) Knochel, P.; Singer, R. D. Chem. ReV. 1993, 93, 2117. (c) Handbook of
Functionalized Organometallics; Knochel, P., Ed.; Wiley-VCH: Weinheim,
Germany, 2005; Vol. 1, p 109.
Organoindium compounds have been demonstrated to par-
ticipate in a wide range of transition-metal-mediated processes
for carbon-carbon bond formation.1 These environmentally
benign reagents are air- and moisture-stable2 and can undergo
cross-coupling reactions in an atom-efficient manner. One
current limitation in the use of organoindiums is the necessity
of preparing the reagents by the combination of organomagne-
(1) (a) Perez, I.; Perez Sestelo, J.; Sarandeses, L. A. Org. Lett. 1999, 1, 1267.
(b) Perez, I.; Perez Sestelo, J.; Sarandeses, L. A. J. Am. Chem. Soc. 2001, 123,
4155. (c) Lee, P. H.; Sung, S.-Y.; Lee, K. Org. Lett. 2001, 3, 3201. (d) Lee, K.;
Lee, J; Lee, P. H. J. Org. Chem. 2002, 67, 8265. (e) Lehmann, U.; Awasthi, S.;
Minehan, T. Org. Lett. 2003, 5, 2405. (f) Rodriguez, D.; Perez Sestelo, J.;
Sarandeses, L. A. J. Org. Chem. 2003, 68, 2518. (g) Baker, L.; Minehan, T. J.
Org. Chem. 2004, 69, 3957. (h) Rodriguez, D.; Perez Sestelo, J.; Sarandeses,
L. A. J. Org. Chem. 2004, 69, 8136. (i) Riveiros, R.; Rodriguez, D.; Perez Sestelo,
J.; Sarandeses, L. A. Org. Lett. 2006, 8, 1403.
(9) (a) Li, C.-J. Chem. ReV. 1993, 93, 2023. (b) Cintas, P. Synlett 1995, 1087.
(c) Li, C.-J. Tetrahedron 1996, 52, 5643. (d) Li, C.-J.; Chan, T.-H. Organic
Reactions in Aqueous Media; Wiley: New York, 1997. (e) Li, C.-J.; Chan, T.-
H. Tetrahedron 1999, 55, 11149. (f) Podlech, J.; Maier, T. C. Synthesis 2003,
633–655. (g) Li, C.-J. Chem. ReV. 2005, 105, 3095.
(2) Takami, K.; Yorimitsu, H.; Shinokobu, H.; Matsubara, S.; Oshima, K.
Org. Lett. 2001, 3, 1997.
7376 J. Org. Chem. 2008, 73, 7376–7379
10.1021/jo801074g CCC: $40.75 2008 American Chemical Society
Published on Web 08/22/2008

TABLE 1. Exploring Optimal Conditions for Formation and
Cross-Coupling of Organoindium Reagents
TABLE 2. Reaction of Diverse Aryl Iodides with In ·2LiCl: Scope
and Cross-Coupling Reactions
entry
M
X
solvent
T (°C)
time (h)
% yield 3aa
% conv
time
T (°C) (h)
% yield
1
2
3
4
5
6
7
8
In
In
In
In
In
In
InI
InCl2
I
I
I
I
I
Br
I
DMF
THF
80
65
80
12
12
12
12
2
12
12
12
85
20
25
83
80
45
42
<10
entry
R1
1a
R2
3
3b
1
2
3
4
5
6
7
8
9
4-CO2Me-C6H4
4-CO2Me-C6H4
4-CO2Me-C6H4
4-CO2Me-C6H4
4-CO2Me-C6H4
4-Ac-C6H4
3-CN-C6H4
3-CN-C6H4
3-CN-C6H4
97
4-OMe
4-Ac
4-CN
2-CO2Me
H
4-Me
4-Ac
4-OMe
2-Me
4-Cl
80
80
80
80
80
80
80
80
100
80
80
100
80
90
100
2
4
3
2
3
3
6
6
12
6
3
3
12
15
5
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
75
65
59
55
63
DME
DMFb
DMF
DMF
DMF
DMF
80
100
100
80
50d e
,
98
98
I
80
89d
75d
62d
a Refers to isolated yields after column chromatography. b Methanol
(10% by volume) was added to the DMF solution of the indium reagent
just prior to the cross-coupling reaction.
50d e
,
10 4-CN-C6H4
97
,
11 4-CN-C6H4
12 4-CN-C6H4
13 4-Cl-C6H4
14 2-Ac-C6H4
15 4-OMe-C6H4
2-F
88d f
2-OMe
4-Ac
4-CN
4-Ac
37e
61d
72d
35e
with 2 equiv of dry LiCl at 110 °C in vacuo for 20 min) in
DMF at 80 °C for 12 h, only trace amounts of the starting iodide
were evident by TLC, and GC-MS analysis of a reaction aliquot
revealed >95% consumption of stating material. A key to the
success of this method was the use of indium metal containing
0.1% magnesium10 as an anticaking reagent; when the magne-
sium was omitted, the indium metal clumped together on the
walls of the reaction flask, and thus a significant excess of
indium metal was needed in order to achieve optimal conversion.
With In/0.1% Mg, after 12 h at 80 °C it was noticed that the
remaining indium metal had also clumped together in the bottom
of the reaction flask, thus facilitating the separation of the
reagent solution for the subsequent cross-coupling. Addition of
the DMF solution of the indium reagent to 4-iodotoluene (0.67
equiv) and 5 mol % Cl2Pd(dppf) and heating at 80 °C for 2 h
led to the clean formation of biaryl 3 in 85% yield (Table 1,
entry 1). DMF was the most suitable solvent for the two-step
process, since yields of cross-coupled product obtained using
THF or DME instead were significantly lower (20-25%, entries
2 and 3); however, addition of methanol (10% by volume) to
the DMF solution of the indium reagent just prior to the cross-
coupling reaction had no effect on the yield of 3a11 obtained
(entry 4). Furthermore, it was discovered that the time for
efficient formation of the indium reagent can be reduced to 2 h
when the reaction temperature is raised to 100 °C. Aryl bromides
were also suitable substrates for the indium insertion, although
they were significantly less reactive than aryl iodides: methyl
4-bromobenzoate required heating with In ·2LiCl at 100 °C for
12 h to achieve >90% consumption of the starting material,
and the subsequent palladium-catalyzed cross-coupling reaction
furnished 3a in only 45% yield, indicating that reagent degrada-
tion may be taking place during the prolonged heating at
elevated temperature (entry 6). Utilizing InI instead of indium
metal gave ∼55% insertion and a 42% yield of 3a; substituting
InCl2 for indium metal gave very poor insertion (<20% by
GC-MS analysis) and <10% yield of cross-coupled product.
We next examined the ability of aryl iodides with different
substitution patterns to undergo the two-step insertion/cross-
coupling process. We surveyed the reactivity of both electron-
87
88
94c
a For the insertion reaction, conversions were assayed by GC-MS
analysis of an aliquot quenched with HCl/H2O. b Refers to isolated
yields after column chromatography, unless otherwise indicated.
c Insertion reaction performed at 120 °C for 12 h. d Yield determined by
GC-MS analysis. e Significant amounts of homodimer 4 also produced.
f Catalyst for cross-coupling was Cl2Pd(PPh3)2.
deficient (Table 2, entries 1-14) and electron-rich (entry 15)
aryl iodides 1 toward indium metal. Paralleling Knochel’s
findings on the reactivity of aryl halides toward zinc insertion,6a
we discovered that electron-poor substrates such as 4-iodoac-
etophenone, 3-and 4-iodobenzonitrile, and methyl 4-iodoben-
zoate undergo >95% insertion of indium metal at 80 °C in DMF
for 12 h. In contrast, the electron-rich 4-iodoanisole required
heating at 120 °C for 12 h to effect complete consumption of
the starting material (entry 15). Subsequent cross-coupling with
aryl iodides12 in the presence of Cl2Pd(ddpf) as catalyst gave
the desired biaryls 3b-p in 35-89% yields. Unsurprisingly,
reactions requiring higher temperatures to effect the insertion
and/or cross-coupling led to lower yields of biaryl products
(entries 9, 12, and 15); we suspect that steric issues necessitate
the higher temperatures for cross-couplings with 2-iodotoluene
and 2-iodoanisole. Furthermore, in several cases where lower
yields were obtained (entries 6, 10, 12, and 15), significant
amounts of homodimer 4 (presumably arising from palla-
dium(II)-mediated dimerization of the indium reagent) were also
isolated from the reaction mixture. To assess if the indium metal
was reducing the aryl iodides to the parent aromatic compounds
(R1-H) prior to the cross-coupling reaction, we performed a TLC
assay on the low-yielding reactions and found that no significant
amounts of reduced product were evident in the reaction
mixtures.
We wished to probe the identity of the organoindium
intermediate being formed in the insertion reaction. Araki13 has
reported that reactions of indium metal with allyl halides in
organic solvents such as DMF produce indium(III) sesquihalide
(12) Electron-deficient aryl bromides were also suitable partners for the cross-
coupling reaction with the in situ formed arylindium reagents, furnishing biaryl
products 3 in similar or slightly lower yields when compared to the corresponding
aryl iodides. Electron-rich aryl bromides, however, gave very poor yields (5-
20%) of cross-coupled products.
(10) Indium containing 0.1% Mg was prepared my mixing 102.6 mg of
indium metal with 11.4 mg of commercially available indium containing 1%
Mg (Aldrich).
(11) For a previous preparation of 3a, see: So, C. M.; Lau, C. P.; Kwong,
F. Y. Org. Lett. 2008, 9, 2795.
(13) Araki, S.; Ito, H.; Butsugan, Y. J. Org. Chem. 1988, 53, 1831.
J. Org. Chem. Vol. 73, No. 18, 2008 7377

TABLE 3. Reaction of in Situ Generated Organoindium Reagents
with Acyl and Allylic Electrophilesa
SCHEME 1. Probing the Identity of the Arylindium
Intermediate
a Typical reaction conditions: a DMF solution of the indium reagent
(∼0.81 M) was added to R1-X (1.0 equiv) and palladium catalyst (5-10
mol %) and heated to 80 °C under argon for 2 h, at which time
complete consumption of R1-X was observed by TLC. b A ) 5 mol %
Pd(PPh3)4; B ) 10 mol % Pd(dba)2. c Refers to isolated yields after
column chromatography.
intermediates; Chan14 has demonstrated that the same reaction
in water proceeds via formation of an allylindium(I) species.
We prepared a series of arylindium reagents by reaction of
phenylmagnesium bromide (3 M in diethyl ether) with 1 equiv
of InI, InCl2, or InCl3, respectively, in THF (0 °C, 1 h) and
then cross-coupled each with 1 equiv of methyl 4-iodobenzoate
in the presence of 5 mol % Cl2Pd(dppf) (DMF, 80 °C, 2 h). To
our surprise, we found that the reagents derived from both InI
and InCl2 gave >80% yield of cross-coupled product 3f; in
contrast, PhInCl2 gave only ∼55% yield of 3f. The lower
reactivity of mono- and diorganoindiums versus triorganoindi-
ums in transition-metal-mediated coupling reactions has been
previously noted.15 Interestingly, Ph2In, prepared from InCl2
by reaction with 2 equiv of PhMgBr, reacted with 2 equiv of
methyl 4-iodobenzoate to furnish 3f in 83% yield, indicating
that both phenyl groups on the In(II) reagent are transferable.
When we repeated the above experiments but added methanol
(10% by volume) to the indium reagent solution prior to the
cross-coupling reaction, we discovered that >5% 3f was
produced in the reaction involving the reagent prepared from
InI and PhMgBr. However, the reagents derived from addition
of 1 equiv of PhMgBr to InCl2 and InCl3 furnished 3f in 85%
and 50% yields, respectively (Scheme 1). On the basis of these
experiments, we can conclude that both the indium(II) and
indium(III) oxidation states may be viable candidates for the
intermediate formed in the insertion reaction.
Because of the expense of indium metal (∼$7/g), we were
interested in recovering/regenerating the indium used in our
experiments. When the indium metal is separated and weighed
after the insertion reaction (following water/acetone rinse and
drying in vacuo), we observed that for every millimole of aryl
iodide employed, between 0.83 and 1.0 mmol of indium is
consumed. The aqueous layer derived from workup of the cross-
coupling reaction was filtered, neutralized, and then treated with
∼1.5 equiv of zinc dust while stirring. Within minutes, clumps
of indium metal formed and aggregated in the bottom of the
flask; after removal of the water, rinsing with acetone, and
drying in vacuo, we found that, in total, approximately 85% of
indium metal originally employed could be recovered.16
Finally, we evaluated the ability of the intermediate arylin-
dium species to react with electrophiles other than aryl iodides.
Acyl halides and allylic acetates and carbonates were selected
as coupling partners for the in situ generated indium reagent.
As can be seen from Table 3, moderate yields were obtained
for acyl substitution reactions involving acid chlorides under
Pd(PPh3)4 (5 mol %) catalysis (entries 1, 2, and 3). Although
there have been recent successful examples of transition-metal-
catalyzed cross-couplings between acyl fluorides and arylzinc
reagents,17 as well as between thioesters and arylindium
reagents,18 we found that acid chlorides consistently gave the
highest yields of arylketones. For example, employing hydro-
cinnamoyl fluoride instead of the corresponding chloride (entry
2) gave only 10% yield of 7b; using S-phenyl hex-5-ene thioate
instead of hex-5-enoyl chloride (entry 3) gave <5% 7c. The
use of other palladium catalysts such as Cl2Pd(dppf) or
Pd(OAc)2/PPh3 gave negligible amounts of ketone products.
Cross-coupling with the allylic electophiles cinnamyl acetate
(entry 4) and methyl cyclohex-2-enyl carbonate (entry 5) under
Pd(dba)2 (10 mol %) catalysis furnished substitution products
7d and 7e in 48% and 51% yields, respectively; several
unidentified side products as well as homodimer 4a were also
evident in the reaction mixtures. These results are most likely
due to the increased stability of the intermediate aryl-palla-
dium(II)-π allyl complex and thus the decreased rate of reductive
elimination. Furthermore, the low reactivity of PhInCl2 in allylic
substitution reactions has been previously noted.19 The addition
of phosphine ligands such as PPh3, P(t-Bu)3, or dppf to the
palladium catalyst led to no measurable improvement in the
yields of product obtained.
As part of our program directed toward the synthesis of ꢀ-C-
aryl glycosides,20 we demonstrated the utility of our acyl
substitution products by transforming aryl ketone 7c into
tetrahydropyran 8 in three steps (Upjohn dihydroxylation,21
(16) While the indium metal recovered after the insertion reaction (30% of
the total used) could be directly reused in insertion and cross-coupling reactions
with minimal (<10%) decrease in yield, the indium metal recovered after zinc-
mediated reduction of the residual aqueous indium salts (50-60% of the total
used) was a softball-like clump that could not be reused directly because of its
decreased surface area compared to indium powder. Work on preparing this
material for reuse in insertion and cross-coupling reactions is currently in progress.
(17) Zhang, Y.; Rovis, T. J. Am. Chem. Soc. 2004, 126, 15964.
(18) Fausett, B. W.; Liebeskind, L. S. J. Org. Chem. 2005, 70, 4851.
(19) See ref 15a and also: Metza, J. T.; Terzian, R. A.; Minehan, T. G.
Tetrahedron. Lett. 2006, 47, 8905.
(14) Chan, T. H.; Yang, Y. J. Am. Chem. Soc. 1999, 121, 3228.
(15) (a) Rodriguez, D.; Perez Sestelo, J.; Sarandeses, L. A. J. Org. Chem.
2004, 69, 8136. (b) Wilkinson, G.; Stone, F. G. A.; Abel, E. W. ComprehensiVe
Organometallic Chemistry; Pergamon Press: New York, 1982; Vol. I, p 711.
(20) See ref 1e and also: (a) Price, S.; Edwards, S.; Wu, T.; Minehan, T.
Tetrahedron Lett. 2004, 45, 5197. (b) Pham, M.; Allatabakhsh, A.; Minehan,
T. G. J. Org. Chem. 2008, 73, 741.
7378 J. Org. Chem. Vol. 73, No. 18, 2008

SCHEME 2. Synthesis of cis-2,6-Disubstituted Pyran 8 from
Aryl Ketone 7c
20 min. The mixture was cooled to room temperature, and the aryl
iodide (0.66 mmol) was added. Then DMF (0.5 mL) was added,
and the mixture was stirred at 80 °C under argon for 14 h, at which
time complete consumption of the iodide was observed by TLC.
An additional portion of DMF (0.5 mL) was added, and the amber
solution was withdrawn from the flask by syringe and added to a
mixture of aryl iodide or bromide (0.44 mmol, 0.67 equiv) and
Cl2Pd(dppf) (18.0 mg, 0.022 mmol, 5 mol %). The reaction was
stirred at 80 °C under argon for 1-3 h, at which time TLC indicated
complete conversion. The reaction was cooled to room temperature,
then diluted with ether (20 mL), and washed with 1 N HCl (2 ×
20 mL). The combined aqueous phases were back-extracted with
ether (1 × 50 mL). The combined organic extracts were then dried
over Na2SO4, filtered, and concentrated in vacuo. The residue was
purified by flash chromatography (silica gel, hexane/Et2O ) 99:1
to 95:5).
Methyl 4′-Methylbiphenyl-4-carboxylate (3a). Following the
general procedure, methyl 4-iodobenzoate (173 mg, 0.66 mmol)
and 4-iodotoluene (96 mg, 0.44 mmol) were combined to provide
3a as a white solid (84 mg, 0.37 mmol, 85%). 1H NMR (400 MHz,
CDCl3): δ 8.09 (d, J ) 8.4 Hz, 2H); 7.64 (d, J ) 8.4 Hz, 2H);
7.52 (d, J ) 8.0 Hz, 2H); 7.27 (d, J ) 8.4 Hz, 2H); 3.94 (s, 3H);
2.41 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 144.4; 142.5; 128.4;
127.5; 125.8; 109.3; 80.6; 43.0. GC/MS m/z ) 226 (M+).
primary alcohol silylation, and triisopropylsilane-mediated ketol
reduction22) in 62% overall yield (Scheme 2). The silane
reduction proceeded with >10:1 stereoselectivity, and the 2,6-
syn stereochemistry of the product was indicated by the C.1
proton-C.5 proton cross-peaks in the NOESY spectrum of 8
(see Supporting Information for details).
In summary, we have demonstrated that indium reagents
capable of participating in transition-metal-catalyzed cross-
coupling and substitution reactions can be formed by direct
treatment of aryl iodides with In·2LiCl. Some noteworthy
characteristics of this process are that minimal activation of the
indium is required, biaryls are formed efficiently even in the
presence of protic solvents, and the indium used can be
regenerated by reduction of the residual indium salts with zinc
metal. Further experiments to extend the scope and delineate
the mechanism of this process are underway and will be reported
in due course.
Acknowledgment. We thank the National Institutes of Health
(SC2 GM081064-01), the ACS Petroleum Research Fund (No.
PRF 45277-B1), Research Corporation (No. CC3343), and the
Henry-Dreyfus Teacher-Scholar Award for their generous
support of our research program. We also thank Dr. Paul Shin
(CSUN) for assistance in obtaining high-resolution mass spectra.
Experimental Section
General Procedure for Synthesis of 3a-p. LiCl (84 mg,
2mmol) was heated at 150 °C for 20 min. Then indium powder
(containing 0.1% Mg)10 (114 mg, 1 mmol) was added, and the
solids were heated with stirring in vacuo at 110 °C for an additional
Supporting Information Available: Detailed experimental
1
procedures, spectroscopic data, and H NMR spectra for all
(21) (a) Van Rheenen, V.; Kelly, R. C.; Cha, D. Y. Tetrahedron Lett. 1976,
17, 1973. (b) Van Rheenen, V.; Cha, D. Y.; Hartley, W. M. Organic Synthesis;
Wiley: New York, 1988; Collect. Vol. VI, p 342.
(22) Ellsworth, B. A.; Doyle, A. G.; Patel, M.; Caceres-Cortes, J.; Meng,
W.; Deshpande, P. P.; Pullockaran, A.; Washburn, W. N. Tetrahedron:
Asymmetry 2003, 14, 3243.
compounds in Tables 2 and 3 and Scheme 2, as well as NOESY
data for compound 8. This material is available free of charge
via the Internet at http://pubs.acs.org.
JO801074G
J. Org. Chem. Vol. 73, No. 18, 2008 7379