Applications of enantioselective carbolithiation of ortho-substituted β-methylstyrenes

Article abstract of DOI:10.1021/jo800941h

(Chemical Equation Presented) The enantioselective carbolithiation of ortho-substituted (E)-β-methylstyrenes provides access to chiral lithiated intermediates with broad synthetic potential. Specifically, β- methylstyrenes with o-aminomethyl, ether, and o

Full text of DOI:10.1021/jo800941h

SCHEME 1. Benzylic Lithiums via Lateral Deprotonation
Applications of Enantioselective Carbolithiation
of Ortho-Substituted ꢀ-Methylstyrenes
Anne-Marie L. Hogan, Thomas Tricotet, Alastair Meek,
Shaista S. Khokhar, and Donal F. O’Shea*
Centre for Synthesis and Chemical Biology, School of
Chemistry and Chemical Biology, UniVersity College Dublin,
Belfield, Dublin 4, Ireland
amines,3 ethers,4 oxazolines,5 amides,6 ureas,7 carbamates,8
esters,9 carboxylates,10 sulfonamides,11 and phosphorodiamidate
groups.12 A less commonly utilized approach to the generation
of ortho-substituted benzylic lithiated species is the intermo-
lecular carbolithiation of styrenes 5 to provide the lithiated
intermediates 6, which can be transformed into heterocycles
8following reaction with electrophiles (Scheme 2).13 This
approach offers improved atom efficiency over utilizing the
alkyllithium as a base as the product includes an additional
functionality from the C-C bond-forming carbolithiation step.
donal.f.oshea@ucd.ie
ReceiVed May 1, 2008
SCHEME 2. Benzylic Lithiums via Carbolithiation of
Ortho-Substituted Styrenes
Our current efforts are directed toward the carbolithiation of
ortho-substituted ꢀ-methylstyrene substrates 9 which offers the
opportunity to introduce asymmetry into the C-C bond
formation.14The goal is to exploit the carbolithiation reaction
to provide intermediates 10 containing one configurationally
stable chiral center and to utilize in situ reaction with electro-
philes at the C-Li center to allow access to a collection of
products such as 11 and 12 (Scheme 3).15 As the chiral center
generated during C-C bond formation in the first carbolithiation
The enantioselective carbolithiation of ortho-substituted (E)-
ꢀ-methylstyrenes provides access to chiral lithiated inter-
mediates with broad synthetic potential. Specifically, ꢀ-m-
ethylstyrenes with o-aminomethyl, ether, and oxazoline
groups have been employed in the synthesis of chiral
aromatics and heteroaromatics such as isoquinolines, iso-
quinolinones, benzofurans, and isobenzofuranones.
(3) (a) Vaulx, R. L.; Jones, F. N.; Hauser, C. R. J. Org. Chem. 1964, 29,
1387. (b) Clark, R. D.; Jahangir, Tetrahedron 1993, 49, 1351. (c) Clark, R. D.;
Jahangir; Langston, J. A. Can. J. Chem. 1994, 72, 23.
(4) (a) Harmon, T. E.; Shirley, D. A. J. Org. Chem. 1974, 21, 3164. (b)
Wilkinson, J. A.; Rossington, S. B.; Ducki, S.; Leonard, J.; Hussain, N.
Tetrahedron 2006, 62, 1833. (c) Wilkinson, J. A.; Raiber, E.-A.; Ducki, S.
Tetrahedron Lett. 2007, 48, 6434.
The use of organolithium reagents as strong bases for the
generation of benzylic lithium species from ortho-substituted
toluenes (2-methylbenzenes) is a versatile synthetic strategy.
For example, directed alkyl deprotonation of 1 (DG ) directing
group) provides the lateral lithiated intermediate 2 which
following in situ reaction with suitable electrophiles can generate
the substituted aromatics 3. If a further reaction between the
ortho-substituent and reacted electrophile can occur (in situ or
in subsequent synthetic steps), this provides an efficient route
to the corresponding benzo-fused ring systems 4 (Scheme 1).1
Numerous examples of ortho substituents which have been
applied to this methodology include substituted anilines,2
(5) (a) Gschwend, H. W.; Hamdan, A. J. Org. Chem. 1975, 40, 2008. (b)
Tahara, N.; Fukuda, T.; Iwao, M. Tetrahedron Lett. 2004, 45, 5117. (c) Kurosaki,
Y.; Fukuda, T.; Iwao, M. Tetrahedron 2005, 61, 3289.
(6) (a) Mao, C.-L.; Hauser, C. R. J. Org. Chem. 1970, 35, 3704. (b) Fisher,
L. E.; Muchowski, J. M.; Clark, R. D. J. Org. Chem. 1992, 57, 2700. (c) Comins,
D. L.; Brown, J. D. J. Org. Chem. 1986, 51, 3566. (d) Clark, R. D.; Jahangir,
J. Org. Chem. 1987, 52, 5378.
(7) Clayden, J.; Dufour, J. Tetrahedron Lett. 2006, 47, 6945.
(8) Sibi, M. P.; Snieckus, V. J. Org. Chem. 1983, 48, 1935.
(9) (a) Kraus, G. A. J. Org. Chem. 1981, 46, 201. (b) Regan, A. C.; Staunton,
J. Chem. Commun. 1987, 520.
(10) (a) Creger, P. L. J. Am. Chem. Soc. 1970, 29, 1396. (b) Thompson,
R. C.; Kallmerten, J. J. Org. Chem. 1990, 55, 6076. (c) Schultz, A. G.; Green,
N. J. J. Am. Chem. Soc. 1991, 113, 4931.
(11) Watanabe, H.; Hauser, C. R. J. Org. Chem. 1968, 33, 4278.
(12) Watanabe, M.; Date, M.; Kawanishi, K.; Hori, T.; Furukawa, S. Chem.
Pharm. Bull. 1991, 39, 41.
(1) (a) Clark, R. D.; Jahangir, A. Org. React. 1995, 47, 1. (b) Clayden, J.
Organolithiums: SelectiVity for Synthesis; Pergamon Press: Oxford, U.K., 2002;
pp 73-96. (c) Reed, J. N. Sci. Synth. (Georg Thieme Verlag) 2006, 8a, 329–
355.
(13) For examples of intermolecular carbolithiation for heterocycle synthesis,
see: (a) Coleman, C. M.; O’Shea, D. F. J. Am. Chem. Soc. 2003, 125, 4054. (b)
Kessler, A.; Coleman, C. M.; Charoenying, P.; O’Shea, D. F. J. Org. Chem.
2004, 69, 7836. (c) Cottineau, B.; O’Shea, D. F. Tetrahedron Lett. 2005, 46,
1935. (d) Hogan, A.-M. L.; O’Shea, D. F. Org. Lett. 2006, 8, 3769. (e) Cotter,
J.; Hogan, A.-M. L.; O’Shea, D. F. Org. Lett. 2007, 9, 1493. (f) Cottineau, B.;
O’Shea, D. F. Tetrahedron 2007, 63, 10354. (g) Hogan, A.-M. L.; O’Shea, D. F.
J. Org. Chem. 2007, 72, 9557.
(2) (a) Fuhrer, W.; Gschwend, H. W. J. Org. Chem. 1979, 44, 1133. (b)
Houlihan, W. J.; Parrino, V. A.; Uike, Y. J. Org. Chem. 1981, 46, 4511. (c)
Katritzky, A. R.; Black, M.; Fan, W.-Q. J. Org. Chem. 1991, 56, 5045. (d) Clark,
R. D.; Muchowski, J. M.; Fisher, L. E.; Flippin, L. A.; Repke, D. B.; Souchet,
M. Synthesis 1991, 871. (e) Peters, R.; Waldmeier, P.; Joncour, A. Org. Process
Res. DeV. 2005, 9, 508.
10.1021/jo800941h CCC: $40.75
Published on Web 06/28/2008
2008 American Chemical Society
J. Org. Chem. 2008, 73, 6041–6044 6041

TABLE 1. Synthesis of (E)-9b–f
SCHEME 3. Benzylic Lithiums via Enantioselective
Carbolithiation of Ortho-Substituted (E)-ꢀ-Methylstyrenes
step is carried through the electrophile reaction sequence to the
final products, selectivity is solely dependent upon achieving
an enantioselective alkyllithium addition.
Since a considerable body of literature exists on the synthetic
exploitation of benzylic lithiated intermediates such as 2, our
work has focused on the generation of equivalent chiral
analogues 10 which could participate in a similar spectrum of
transformations but form chiral products. We have recently
reported the synthesis of chiral intermediates of this type
exploiting a (-)-sparteine-mediated carbolithiation of 2-prope-
nylphenylamine 9a (DG ) NHBn, Scheme 4).16
in coordinating (diethyl ether) and noncoordinating (cumene)
solvent conditions.
Encouragingly, the enantioselectivity for carbolithiation of
9c in ether was high with a recorded er of 88:12 and isolated
yield of 75% (entry 4). In comparison the N-Boc-substituted
analogue 9b has an inferior er of 81:19 and a poorer isolated
yield (entry 2). Selectivity was not particularly solvent sensitive
as only marginally differing results were obtained in cumene
and diethyl ether (Table 2, compare entries 3 and 4). The better
selectivity obtained for the N-Bn-substituted 9c over 9b is
consistent with our previously reported aniline analogue 9a.16b
SCHEME 4. Applications of Enantioselective
Carbolithiation of 9a
TABLE 2. Enantioselective Carbolithiation of 9b and 9c
entry
sm
solvent
R
product
yield, %
er (S:R)
1
2
3
4
9b
9b
9c
9c
cumene
Et2O
Boc
Boc
Bn
11b
11b
11c
11c
15a
46c
60
78:22b
81:19b
90:10d
88:12d
In this case, carbolithiation enables the efficient generation
of the chiral lithiated species which following reaction at the
C-Li center with varying electrophiles provides access to
2-alkylanilines, 3- and 2,3-substituted indoles, and 3-substituted
indol-2-ones with a common er of 92:8 ((1). Herein, we now
report the application of this concept to three further important
heterocyclic classes, namely the isoquinolines, benzofurans, and
isobenzofuranones as representative examples.
cumene
Et2Oe
Bn
75
a Starting material recovered in 82% yield. b Determined by chiral
HPLC (OD column) and compared to the racemic product generated
with TMEDA as additive. c Starting material recovered in 15% yield.
d Determined by conversion to 3-methylheptanoic acid phenylamide and
chiral HPLC separation (Supporting Information). e Reaction time 2 h.
The corresponding prochiral ꢀ-methylstyrene substrates con-
taining o-aminomethyl 9b,c, ether 9d,e, and oxazoline 9f
substituents were prepared by cross-coupling of (E)-1-propen-
1-ylboronic acid with the corresponding aryl bromides 13a-e
(Table 1). Substrates were examined for their ability to undergo
(-)-sparteine-mediated asymmetric carbolithiations with n-BuLi
For the o-methoxy and o-methoxymethoxy (MOM) examples
9d and 9e, no deprotonation of the heteroatom is necessary,
and consequently, the reaction sequence involved addition of
the substrate to a premixed solution of n-BuLi/(-)-sparteine
(Table 3). Once again, both cumene and diethyl ether were
investigated as solvents, and in this instance, -40 °C was
determined as the optimal reaction temperature. Pleasingly,
compounds 11d and 11e were obtained with high er from the
reaction in both solvents. It is interesting to note that the
methoxy-substituted 9e gave a better selectivity (94:6 er) and
yield (60%) than that obtained from the MOM-substituted 9d,
which would be considered a stronger coordinating group (Table
3, entries 1 and 3).
(14) For enantioselective carbolithiation of ꢀ-methylstyrene, see: (a) Nor-
sikian, S.; Marek, I.; Normant, J. F. Tetrahedron Lett. 1997, 38, 7523. (b)
Norsikian, S.; Marek, I.; Klein, S.; Poisson, J. F.; Normant, J. F. Chem. Eur. J
1999, 5, 2055.
(15) Carbolithiation results in the formation of a chiral benzylic lithium
species 6; however, this configurationally unstable chiral center is lost if converted
to aromatic heterocycle 8. For examples of resolution of configurationally unstable
benzylic lithium centers generated by lateral deprotonation, see: (a) Beak, P.;
Anderson, D. R.; Curtis, M. D.; Laumer, J. M.; Pippel, D. J.; Weisenburger,
G. A. Acc. Chem. Res. 2000, 33, 715. For examples by styrene carbolithiation,
see: (b) Wei, X.; Taylor, R. J. K. Tetrahedron: Asymmetry 1997, 8, 665.
(16) (a) Hogan, A.-M. L.; O’Shea, D. F. J. Am. Chem. Soc. 2006, 128, 10360.
(b) Hogan, A.-M. L.; O’Shea, D. F. J. Org. Chem. 2008, 73, 2503.
Finally, the methodology was extended to the carbolithiation
of o-oxazoline derivative 9f using diethyl ether as solvent at
-78 °C (Scheme 5). Using 3 equiv of a premixed solution of
6042 J. Org. Chem. Vol. 73, No. 15, 2008

TABLE 3. Enantioselective Carbolithiation of 9d and 9e
SCHEME 6. Synthesis of Chiral Isoquinolines,
Isoquinolinones, Benzofurans, and Isobenzofuranones
entry
sm
solvent
R
product
yield, %
era (S:R)
1
2
3
4
9d
9d
9e
9e
cumene
Et2O
cumene
Et2O
MOM
MOM
Me
11d
11d
11e
11e
42
89:11
89:11
94:6
39b
60
Me
61c
93:7
a Determined by conversion to the benzyl-substituted derivative and
chiral HPLC (OD column) separation (Supporting Information).
b Starting material recovered in 50% yield. c Starting material recovered
in 36% yield.
n-BuLi/(-)-sparteine to ensure a satisfactory conversion, com-
pound 11f was isolated in 79% yield and with an er of 86:14.
The oxazoline moiety, which is generally considered to be the
most powerful directing group (for o-aryl lithiation) of those
tested, appears to increase the carbolithiation reactivity of the
substrate without a substantial effect on the selectivity.
SCHEME 5. Enantioselective Carbolithiation of 9fa
a Determined by chiral HPLC (IA column).
sequence was also tolerant to carbolithiation with n-HexLi
providing the benzofuran 19b in comparable selectivity. Finally,
a representative application of the oxazoline derivative 11f to
heterocyclic synthesis was achieved by deprotection via methyl
iodide alkylation and subsequent hydrolysis to afford the benzoic
acid 20 (Scheme 6D).18 Subsequent direct γ-lactone formation
with PhI(OAc)2/KBr yielded the isobenzofuranone 21 in 63%
yield.19
In conclusion, we have shown that an enantioselective
carbolithiation of ortho-substituted ꢀ-methylstyrenes provides
chiral lithiated intermediates of broad synthetic potential which
can be applied to the generation of chiral aromatics and
heterocycles. Further synthetic applications are currently under
investigation and will be reported in due course.
To demonstrate the potential for application of the chiral
intermediates 10b, 10c, 10e, and 10f to fused ring synthesis by
electrophile reaction and intramolecular cyclization a number
of representative examples have been carried out. Treatment of
intermediate 10b (generated in ether) with DMF as electrophile
resulted, following acidification, in the formation of the dihy-
droisoquinoline 14. Subsequent Boc deprotection with trifluo-
roacetic acid (TFA) and reaction with KOAc/iodine gave the
aromatic isoquinoline 15 in a 30% overall yield and an er of
81:19, identical to that of 11b (Scheme 6, A). Treatment of
N-benzyl lithiated intermediate 10c (reaction in ether) with CO2
provides carboxylic acid 16, which following intramolecular
amide coupling with 1-ethyl-3-(3′-dimethylaminopropyl)carbo-
diimide (EDCI) generated the C-3-substituted isoquinolinone
17 as a mixture of diastereoisomers in a 45% overall yield and
88:12 er (Scheme 6, B). In addition, the carbolithiation was
tolerant of an alternative alkyllithium as utilizing n-HexLi (under
identical reaction conditions) provided the chiral lithiated
intermediate 10g, which when applied to the electrophile
reaction sequence gave 17b in 45% yield and an er of 91:9
(Scheme 6B). Treatment of an ethereal solution of 10e with
DMF resulted, following acidification, in the formation of the
aldehyde 2-(2-methoxyphenyl)-3-methylheptanal 18a as a mix-
ture of diastereoisomers (Scheme 6C). Subsequent one-pot
demethylation, cyclization, and dehydration to the benzofuran
19a was achieved by reaction with chlorotrimethylsilane and
sodium iodide in acetonitrile at reflux.17 Separation of the
benzofuran enantiomers by chiral HPLC was not achieved, but
analysis of 18a provided the expected er of 93:7. The reaction
Experimental Section
Representative Carbolithiation Procedure. 1-Methoxy-2-(2-
methylhexyl)benzene (11e). A solution of (-)-sparteine (0.47 mL,
2.06 mmol) and n-BuLi (0.64 mL, 1.35 mmol) in diethyl ether (2
mL) was cooled to -40 °C. A solution of 9e (100 mg, 0.68 mmol)
in diethyl ether (2 mL) was added dropwise and the reaction mixture
stirred at -40 °C for 4 h. The reaction was quenched by the addition
of methanol (0.82 mL, 20.28 mmol) and warmed to room
temperature, where it was stirred for 10 min. The mixture was
diluted with diethyl ether (20 mL), washed with brine (20 mL),
dried over sodium sulfate, and concentrated to dryness. The crude
product was purified by column chromatography (eluent: 99:1,
cyclohexane/ethyl acetate) to afford the product as a colorless oil
(127 mg, 61%) (starting material was also recovered in 36% yield):
1H NMR (CDCl3, 400 MHz) δ 7.15 (m, 1H), 7.08 (dd, 1H, J )
(18) Meyers, A. I.; Gabel, R.; Mihelich, E. D. J. Org. Chem. 1978, 43, 1372.
(19) Dohi, T.; Takenaga, N.; Goto, A.; Maruyama, A.; Kita, Y. Org. Lett.
2007, 9, 3129.
(17) Beugelmans, R.; Ginsburg, H. Chem. Commun. 1980, 508.
J. Org. Chem. Vol. 73, No. 15, 2008 6043

1.7/ 7.4 Hz), 6.85 (m, 2H), 3.78 (s, 3H), 2.65 (dd, 1H, J ) 5.9,
13.2 Hz), 2.34 (dd, 1H, J ) 8.3, 13.2 Hz), 1.74 (m, 1H), 1.30 (m,
5H), 1.15 (m, 1H), 0.88 (t, 3H, J ) 6.9 Hz), 0.82 (d, 3H, J ) 6.7
Hz); 13C NMR (CDCl3, 100 MHz) δ 158.0, 131.1, 130.5, 127.0,
120.3, 110.5, 55.4, 38.0, 37.0, 33.6, 29.6, 23.2, 19.8, 14.4; IR (neat)
3021, 2926, 2856, 1600, 1587 cm-1; EI-MS m/z 206.4 [M]+. Anal.
Calcd for C14H22O: C, 81.50; H, 10.75. Found: C, 81.55; H, 10.78.
Representative Heterocycle Synthesis. 2-(2-Methoxyphenyl)-
3-methylheptanal (18a). A solution of (-)-sparteine (0.7 mL, 3.04
mmol) and n-BuLi (1.11 mL, 2.03 mmol) in diethyl ether was
cooled to -40 °C. A solution of 9e (150 mg, 1.01 mmol) in diethyl
ether (2 mL) was added dropwise and the mixture stirred at -40
°C for 4 h. The reaction mixture was cooled to -78 °C, DMF (0.8
mL) added, and stirring continued at -78 °C for a further 1 h.
Aqueous HCl (3 M, 20 mL) was added, the reaction mixture was
warmed to room temperature and extracted with diethyl ether (2 ×
50 mL), and the combined organic layers were washed with brine
(40 mL), dried over sodium sulfate, filtered, and concentrated to
dryness. Silica gel chromatography (eluent: 98:2, cyclohexane/ethyl
acetate) gave the purified product as a colorless oil (128 mg, 54%)
(t, 3H, J ) 6.8 Hz). 13C NMR (CDCl3, 100 MHz) δ: 155.8, 140.5,
127.9, 126.3, 124.1, 122.2, 120.4, 111.7, 36.6, 30.1, 29.9, 23.0,
20.8, 14.2. IR (neat): 3053, 2960, 2929, 2860, 1454 cm-1. EI-MS:
m/z 202.5 [M]+. ES-MS: m/z 405.3 [2M+H]+. HRMS [2M+H]+:
405.2794, C28H37O2 requires 405.2787. [R]D ) -2.0 (c ) 0.1,
CH2Cl2, 20 °C). Chiral HPLC enantiomer separation was not
achieved er assigned to be 93:7 by inference from 11e.
3-(1-Methylpentyl)-3H-isobenzofuran-1-one (21). Powdered
KBr (43.0 mg, 0.36 mmol, 1.0 equiv) was added to a solution of
20 (80.0 mg, 0.36 mmol) in CH2Cl2 (2 mL). PhI(OAc)2 (140 mg,
0.43 mmol) in CH2Cl2 (1.5 mL) was added, and the suspension
was stirred vigorously under reflux for 24 h. The mixture was cooled
to room temperature, satd NaHCO3 solution (4 mL) added, and
stirring continued for 5 min. The aqueous layer was extracted with
CH2Cl2 (2 × 4 mL), and the organic phases were dried over Na2SO4
and concentrated to dryness. Purification by chromatography
through a short pad of silica gel (prepared with eluent containing
4% NEt3) eluting with pentane/diethyl ether (70:30) gave the
product as colorless oil (51 mg, 63%) (product analyzed as 60:40
mixture of diastereoisomers): 1H NMR (CDCl3, 500 MHz) (60:40
mixture of two diastereomers, signals of the minor isomer are
marked with *, signals for both isomers with **) δ 7.94-7.90 (m,
1H)**, 7.71-7.65 (m, 1H)**, 7.57-7.51 (m, 1H)**, 7.46 (br. dd,
0.6H, J ) 7.7, 0.8 Hz), 7.43 (br. dd, 0.4H, J ) 0.8 Hz)*, 5.51 (d,
0.4H, J′ ) 2.7 Hz)*, 5.44 (d, 0.6H, J′ ) 3.8 Hz), 2.22-2.08 (m,
1H)**, 1.72-1.62 (m, 0.4H)*, 1.48-1.16 (m, 5.6H)**, 1.01 (d,
1.8H, J ) 6.8 Hz), 0.94 (t, 1.2H, J ) 7.1 Hz)*, 0.87 (t, 1.8H, J )
7.1 Hz), 0.68 (d, 1.2H, J ) 7.1 Hz)*; 13C NMR (CDCl3, 125 MHz)
(peaks of the minor isomer are marked with *) δ 170.9*, 170.7,
149.3*, 148.6, 133.8*, 133.7, 129.0, 128.9*, 127.0, 126.7*, 125.7,
125.6*, 122.2, 121.8*, 85.4, 84.3*, 37.1*, 37.0, 33.1*, 30.1, 29.4*,
29.3, 22.8*, 22.6, 15.3, 14.0*, 13.9, 12.6*; IR (neat) 843, 1072,
1
(product analyzed as an equal mixture of diastereoisomers): H
NMR (CDCl3, 400 MHz) δ 9.73 (d, 0.5H, J ) 2.3 Hz), 9.71 (d,
0.5H, J ) 2.7 Hz), 7.26 (m, 1H), 7.09 (m, 1H), 6.93 (m, 2H), 3.81
(s, 1.5H), 3.80 (s, 1.5H), 3.71 (m, 1H), 2.27 (m, 1H), 1.48 (m,
0.5H), 1.24 (m, 3.5H), 1.02 (d, 2H, J ) 6.6 Hz), 0.96 (m, 1H),
0.90 (t, 2H, J ) 7.0 Hz), 0.80 (t, 2H, J ) 7.0 Hz), 0.72 (d, 1H, J
) 6.8 Hz); 13C NMR (CDCl3, 100 MHz) δ 202.2, 202.1, 158.0,
157.9, 131.0, 130.5, 128.8, 128.7, 124.9, 124.7, 121.0, 120.9, 111.2,
111.2, 59.1, 58.8, 55.7, 55.6, 35.2, 33.4, 32.8, 32.8, 29.5, 28.9, 23.1,
22.9, 18.1, 16.9, 14.3, 14.2; IR (neat) 3072, 2954, 2859, 1729, 1598
cm-1; ES-MS m/z 235.2 [M + H]+. HRMS [M + H]+ 235.1709,
C15H23O2 requires 235.1698. Anal. Calcd for C15H22O2: C, 76.88;
H, 9.46. Found: C, 76.77; H, 9.37.
1121, 1251, 1404, 1442, 1493, 1591, 2899, 2956, 3019, 3054 cm-1
;
HRMS [M - H]+ 217.1233, C14H17O2 requires 217.1229.
3-(1-Methylpentyl)benzofuran (19a). A solution of 18a (50 mg,
0.21 mmol), chlorotrimethylsilane (0.1 mL, 0.8 mmol), and sodium
iodide (96 mg, 0.64 mmol) in acetonitrile (5 mL) was heated at
reflux for 36 h. The reaction mixture was cooled to room
temperature, water (40 mL) was added, and the mixture was
extracted with diethyl ether (3 × 20 mL). The combined organic
extracts were washed successively with saturated sodium thiosulfate
(40 mL) and brine (40 mL), dried over sodium sulfate, filtered and
concentrated to dryness. Silica gel chromatography (eluent: 98:2,
cyclohexane/ethyl acetate) gave the product as colorless oil (22 mg,
Acknowledgment. A.-M.L.H. thanks the Irish Research
Council for Science, Engineering and Technology for a stu-
dentship. Funding support from Science Foundation Ireland is
acknowledged.
Supporting Information Available: Experimental proce-
dures, characterization data, absolute configuration determina-
tions, and NMR spectra. This material is available free of charge
via the Internet at http://pubs.acs.org.
1
51%). H NMR (CDCl3, 400 MHz) δ: 7.59 (d, 1H, J ) 7.4 Hz),
7.46 (d, 1H, J ) 8.2 Hz), 7.24 (m, 3H), 2.92 (m, 1H), 1.78 (m,
1H), 1.62 (m, 1H), 1.35 (d, 3H, J ) 11.6 Hz), 1.31 (m, 4H), 0.88
JO800941H
6044 J. Org. Chem. Vol. 73, No. 15, 2008