TBAF-promoted elimination of vicinal dibromides having an adjacent O-functional group: Syntheses of 2-bromoalk-1-enes and alkynes

Article abstract of DOI:10.1055/s-0030-1260089

Syntheses of 2-bromoalk-1-enes and alkynes were achieved in good yields by dehydrobromination of vicinal dibromides with tetrabutylammonium fluoride. Neighboring O-functional-group participation is important in determining elimination reactivity. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0030-1260089

SPECIAL TOPIC
2377
TBAF-Promoted Elimination of Vicinal Dibromides Having an Adjacent
O-Functional Group: Syntheses of 2-Bromoalk-1-enes and Alkynes
T
BAF-Promote
d
E
o
limination
R
r
eactionsiki Kutsumura,* Keisuke Kubokawa, Takao Saito*
Department of Chemistry, Faculty of Science, Tokyo University of Science, Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan
Fax +81(3)52614631; E-mail: nkutsu@rs.kagu.tus.ac.jp; E-mail: tsaito@rs.kagu.tus.ac.jp
Received 4 April 2011
exploited for the total synthesis of natural products11,12,14
and extended to the development of a novel reaction
method.15 For promoting the two-step elimination, only
the base DBU has thus far been shown to be a suitable
candidate. We therefore evaluated the suitability of vari-
ous additional mild bases for promoting two-step elimina-
tion to produce O-functionalized alkynes, screening the
bases using 1,2-dibromo-3-(4-nitrophenoxy)propane (1a)
as a model substrate. The results are shown in Table 1.
Abstract: Syntheses of 2-bromoalk-1-enes and alkynes were
achieved in good yields by dehydrobromination of vicinal dibro-
mides with tetrabutylammonium fluoride. Neighboring O-function-
al-group participation is important in determining elimination
reactivity.
Key words: tetrabutylammonium fluoride, elimination, 2-bromo-
alk-1-enes, alkynes, vicinal dibromides
2-Bromoalk-1-enes are useful as building blocks in the
preparation of vinyllithiums,1 vinyl Grignard reagents,2 a-
halo ketones,3 and heterocycles,4 and as substrates in a
wide range of transition-metal-catalyzed C–C coupling
reactions and radical reactions.5 Alkynes are important as
precursors of cis- and trans-1-iodoalk-1-enes,6 2-iodoalk-
1-enes,7 metalated alkenes,6b,8 and metalated alkynes,9
and as substrates in organometallic coupling reactions.10
Table 1 Screening of Mild Bases for Two-Step Elimination
Br
Br
Br
base (5.0 equiv)
+
DMF
80 °C, 10 h
OR1
OR1
2a
OR1
3a
1a
R1 = 4-O2NC6H4
Recently, Ohgiya, Nishiyama, and co-workers reported
regioselective hydrogen bromide elimination (synthesis
of 2-bromoalk-1-enes)11,12 and two-step elimination (syn-
thesis of alkynes)11,13 from vicinal dibromides
(Scheme 1). They also discussed the significance of the
electron-withdrawing effect of O-functional groups at ad-
jacent positions for achieving high yields and selectivities
for both reactions.
Entry
Base
Yielda (%)
1a
2a (ratio)b
3a
–
1
2
Proton-Sponge®
2,6-lutidine
i-Pr2NEt
(TMS)3N
AgF
95
81
31
14
4
2
16 (20:1)
59 (20:1)
56 (20:1)
76 (15:1)
81 (15:1)
87 (13:1)
92 (>99:1)
79 (40:1)
–
–
3
–
4
–
1.05 equiv
DBU or
DBN or
5
–
6
K2CO3
8
–
DABCO
5.0 equiv
DBU
Br
Br
R3
R3
R3
Br
R2
OR1
R2
OR1
R2
OR1
or
7
NaOAc
–
–
DMF, 80 °C
2.0 equiv
NaOAc or
NaOPiv or
K2CO3 or
i-Pr2NEt
8
DABCO
CsF
–
–
two-step elimination
9
–
14
75d
10c
TBAF
–
regioselective elimination
a Isolated yield.
Scheme 1 Regioselective elimination and two-step elimination pro-
posed by Ohgiya, Nishiyama, and co-workers
b Ratio (determined by 1H NMR spectroscopy): 2-bromoalk-1-ene/1-
bromoalk-1-ene.
c 60 °C, 2 h.
d The corresponding allene was obtained (21%).
For promoting regioselective elimination, if an O-func-
tional group exists at the neighboring position of the elim-
ination site,12 a variety of mild bases (including DBU,
DBN, DABCO, NaOAc, NaOPiv, K2CO3, and i-Pr2NEt)
are suitable candidates; this unique selectivity has been
Reaction of dibromide 1a with 5.0 equivalents of base in
N,N-dimethylformamide at 80 °C yielded some combina-
tion of 2-bromoalk-1-ene 2a and alkyne 3a. Most of the
bases gave 2a in low to high yield and no 3a (Table 1, en-
tries 3–8). The base cesium fluoride, which is moderately
basic and whose fluoride exhibits low nucleophilicity,
gave 2a in 79% yield together with 3a in 14% yield
SYNTHESIS 2011, No. 15, pp 2377–2382
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x.
x
x
.
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0
1
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Advanced online publication: 28.06.2011
DOI: 10.1055/s-0030-1260089; Art ID: C35911SS
© Georg Thieme Verlag Stuttgart · New York

2378
N. Kutsumura et al.
SPECIAL TOPIC
(Table 1, entry 9). Significantly, a solution of 1 M tetrabu- moalk-1-enes 2. The results are shown in Table 3. All
tylammonium fluoride (TBAF) in tetrahydrofuran gave entries gave high yields with high selectivities, consistent
no 2a, but 3a in 75% yield even at 60 °C for two hours, with previous reports in which other mild bases were used
thus proving to be the most effective of the bases exam- (see Scheme 1).11,12
ined for promoting two-step elimination (Table 1, entry
10).
Table 3 TBAF-Promoted Regioselective Elimination of Vicinal
Dibromides (2-Bromoalk-1-ene Synthesis)
TBAF is widely used not only as a typical deprotection re-
Br
Br
agent for silyl groups but also as a reagent for fluorina-
tion,16 a reaction activator,17 and a base catalyst.18 Herein,
we describe yet another possible role, as a promoter of
elimination reactions in vicinal dibromides having an ad-
jacent O-functional group.19
Br
TBAF (1.1 equiv)
DMF
60 °C
OR1
OR1
1
2
Entry
R1
Time (h) Yielda (%)
(ratio)b
First, we examined TBAF-promoted two-step elimination
for a variety of 3-O-substituted 1,2-dibromopropanes 1 as
simple starting materials under the conditions of the pre-
liminary experiments. The results are shown in Table 2.
Aryloxy- and benzyloxy-substituted 1,2-dibromopro-
panes 1b–f gave good yields of 3b–f (Table 2, entries 1–
5), whereas benzoyloxy-substituted compounds 1g–i gave
poor yields of 3g–i (Table 2, entries 6–8). Noteworthy is
that 1j, having a 4-methoxybenzoyl group, gave a satis-
factory yield of 3j (Table 2, entry 9). This is probably
because of the tendency of the less electrophilic 4-meth-
oxybenzoate ester to depress hydrolysis even under basic
conditions to undergo the second hydrogen bromide elim-
ination from 1. Conventional methods for preparing
alkynes from 1,2-dibromoalkanes require a strong base,
such as lithium hexamethyldisilazide or sodium amide.20
Thus, TBAF-promoted two-step elimination is a useful
method for synthesizing alkynes under mild conditions.
1c
2
4-O2NC6H4
Ph
1
2a
2b
2c
2d
2e
2f
97 (>99:1)
91 (18:1)
87 (20:1)
92 (16:1)
87 (22:1)
96 (25:1)
98 (30:1)
93 (27:1)
89 (30:1)
94 (27:1)
1
3
4-ClC6H4
1
4
4-MeOC6H4
4-ClC6H4CH2
4-MeOC6H4CH2
4-O2NC6H4C(O)
4-ClC6H4C(O)
Bz
1
5
0.5
0.5
0.5
1.5
0.5
6
7
2g
2h
2i
8
9
10
4-MeOC6H4C(O) 0.5
2j
a Isolated yield.
b Ratio (determined by 1H NMR spectroscopy): 2-bromoalk-1-ene/1-
bromoalk-1-ene.
Table 2 TBAF-Promoted Two-Step Elimination of Vicinal Dibro-
mides (Alkyne Synthesis)
c At room temperature.
Br
We also performed verification experiments to confirm
the importance of neighboring O-functional-group partic-
ipation. Reaction of 1k, which has a benzyl group in place
of a phenoxy group, with 1.1 equivalents of TBAF yielded
2-bromoalk-1-ene 2k and 1-bromoalk-1-ene 2k¢ with low
regioselectivity (Scheme 2, top); in contrast, 1b gave 2b
in high yield and with high selectivity (Table 3, entry 2).
In addition, two-step elimination from 1k with 5.0 equiv-
alents of TBAF yielded 3k and 2k¢ with low selectivity
(Scheme 2, bottom); in contrast, 1b gave 3b in high yield
and with high selectivity (Table 2, entry 1). Thus, TBAF
is an efficient and mild base for promoting both elimina-
tions from 3-O-substituted 1,2-dibromoalkanes 1, and
neighboring O-functional-group participation is impor-
tant in determining elimination reactivity and selectivity.
Br
TBAF (5.0 equiv)
DMF
60 °C
OR1
OR1
1
3
Entry
R1
Ph
Time (h)
Yielda (%)
1
2
3
4
5
6
7
8
9
4
3b
3c
3d
3e
3f
90
86
89
90
97
n.d.b
10
39
76
4-ClC6H4
2
4-MeOC6H4
4-ClC6H4CH2
4-MeOC6H4CH2
4-O2NC6H4C(O)
4-ClC6H4C(O)
Bz
6
4
6
1
3g
3h
3i
6
To further extend the generality of these reactions, we ex-
amined the two elimination reactions (regioselective
elimination and two-step elimination) for more compli-
cated substrates. The results are shown in Table 4. Inter-
nal syn-dibromoalkane 1l gave 2l in 91% yield and 3l in
92% yield (Table 4, entry 1). Similarly, 1m gave 2m in
89% yield and 3m in 96% yield (Table 4, entry 2). These
results suggest that elimination might proceed in a regio-
and stereoselective trans-elimination manner. Dibro-
1.5
3
4-MeOC6H4C(O)
3j
a Isolated yield.
b n.d. = not detected.
Next, we performed regioselective elimination from di-
bromides 1 with 1.1 equivalents of TBAF to yield 2-bro-
Synthesis 2011, No. 15, 2377–2382 © Thieme Stuttgart · New York

SPECIAL TOPIC
TBAF-Promoted Elimination Reactions
2379
Br
Br
mo(2,3-dihydrobenzofuran-2-yl)alkane 1n and epoxy-
substituted dibromoalkane 1o yielded the corresponding
2-bromoalk-1-enes 2n, 2o and alkynes 3n, 3o (Table 4,
entries 3 and 4). Dibromopropanoate 1p gave 2p in high
yield but no 3p, because the cyclohexyl ester was hydro-
lyzed under the basic conditions (Table 4, entry 5). With
the hope of synthesizing natural products, we also exam-
ined the two eliminations for chiral compounds. 1,2-Di-
bromoalkane 1q, derived from commercially available
(S)-oct-1-en-3-ol, gave chirally pure alkene 2q in 91%
yield and alkyne 3q in 93% yield (Table 4, entry 6).21 The
compound 1r, having a lactone moiety and two chiral cen-
ters, gave 2r in 67% yield and 3r in 65% yield without for-
mation of any diastereomers (Table 4, entry 7).
Br
Br
Br
TBAF (1.1 equiv)
DMF
60 °C, 10 h
Bn
1k
Bn
Bn
2k (45%)
2k' (38%, 1:1)
Br
Br
TBAF (5.0 equiv)
DMF
60 °C, 10 h
Bn
1k
Bn
Bn
3k (59%)
2k' (30%, 1:1)
Scheme 2 Comparative experiments without the participation of a
neighboring O-functional group
Table 4 TBAF-Promoted Regioselective Elimination and Two-Step Elimination
Br
Br
R3
R3
R3
TBAF
(5.0 equiv) Br
TBAF
R2
R2 (1.1 equiv)
R2
DMF
DMF
OR1
OR1
OR1
3
1
2
Entry
Substrate 1
Time (h)
2-Bromoalk-1-ene 2, yielda (%)
Time (h)
Alkyne 3, yielda (%)
(ratio)b
Br
4-O2NC6H4O
3l, 92
4-O2NC6H4O
n-Pr
1
2
1
4
4-O2NC6H4O
n-Pr
Br
n-Pr
Br
2l, 91 (15:1)
1l
Br
4-MeOC6H4O
4-MeOC6H4O
n-Pr
1
4
4-MeOC6H4O
n-Pr
Br
n-Pr
Br
2m, 98 (10:1)
3m, 96
1m
Br
Br
Br
Br
3
4
1
3
3
O
O
O
Br
Br
1n
2n, 95 (>99:1)
3n, 91
O
Br
O
O
1.5
O
O
O
Br
Br
3o, 70
1o
2o, 80 (>99:1)
O
O
O
O
5
6
1.5
1.5
0.5
O
Br
O
Br
Br
3p, n.d.c
1p
2p, 90 (>99:1)
OPMB
OPMB
OPMB
7 × 2d
Br
Br
Br
Br
3q, 93 (two cycles)d
1q
O
2q, 91 (15:1)
O
O
Br
Br
O
O
O
7
1
4
OPMB
OPMB
OPMB
1r
2r, 89 (3:1)
3r, 65
a Isolated yield.
b Ratio (determined by 1H NMR spectroscopy): 2-bromoalk-1-ene/1-bromoalk-1-ene.
c n.d. = not detected.
d The two-step elimination was run for 7 h, twice.
Synthesis 2011, No. 15, 2377–2382 © Thieme Stuttgart · New York

2380
N. Kutsumura et al.
SPECIAL TOPIC
and their analytical data have been reported.23 Alkynes 3a–f, 3h–l,
3n, 3o, and 3r are known compounds and their analytical data have
been reported.24
Finally, we examined the reaction of 2-bromoalk-1-enes 2
using 2.0 equivalents of TBAF to give alkynes 3. The re-
sults are shown in Table 5. Bromoalkenes 2a, 2c–f, and
2m (R1 = Ar, CH2Ar) reacted smoothly to yield the de-
sired products 3 exclusively (Table 5, entries 1–5 and 10);
however, for entries 1 and 2, alkyne 3 was accompanied
by a small amount of undesired allene as byproduct.22 An
electron-withdrawing substituent on the benzoyl group in
R1 is not suitable for the reaction (see 2g–i); in contrast,
alkyne 3j was obtained in good yield from 2j (Table 5, en-
tries 6–9).
2-Bromoalk-1-enes 2 from 1,2-Dibromoalkanes 1; General Pro-
cedure for Regioselective Elimination
A mixture of a 1,2-dibromoalkane 1 (1.0 equiv) and 1 M TBAF in
THF (1.1 equiv) in DMF (0.1 M) was stirred at 60 °C for 0.5–1.5 h.
The reaction was quenched with sat. aq NH4Cl, and the reaction
mixture was extracted with EtOAc (2 × 15 mL). The combined ex-
tracts were concentrated under reduced pressure, and the residue
was purified by silica gel column chromatography to afford the 2-
bromoalk-1-ene 2.
Table 5 Conversion of 2-Bromoalk-1-enes 2 into Alkynes 3
2-{[(2-Bromoallyl)oxy]methyl}oxirane (2o)
Colorless oil. Yield: 51 mg (80%).
IR (neat): 2892, 1635, 1434, 1380, 1257, 1095 cm–1.
Br
R3
R3
R2
R2
TBAF (2.0 equiv)
DMF
60 °C
1H NMR (500 MHz, CDCl3): d = 2.64 (dd, J = 5.0, 3.0 Hz, 1 H),
2.82 (dd, J = 5.0, 5.0 Hz, 1 H), 3.19 (dddd, J = 6.0, 5.0, 5.0, 3.0 Hz,
1 H), 3.44 (dd, J = 11.0, 6.0 Hz, 1 H), 3.80 (dd, J = 11.0, 3.0 Hz, 1
H), 4.16 (d, J = 13.0 Hz, 1 H), 4.18 (d, J = 13.0 Hz, 1 H), 5.63 (dd,
J = 1.5, 1.0 Hz, 1 H), 5.94 (dd, J = 3.0, 1.5 Hz, 1 H).
13C NMR (126 MHz, CDCl3): d = 44.1, 50.6, 70.7, 75.1, 117.9,
129.0.
OR1
2
OR1
3
Entry
Substrate 2 Time (h)
Yielda (%)
1b
2
3
4
5
6
7
8
9
2a
2c
2d
2e
2f
0.5
1
3a
3c
3d
3e
3f
65c
85d
93
HRMS (ESI): m/z [M + Na]+ calcd for C6H9BrO2Na: 214.9678;
found: 214.9677.
2
1
95
(S)-1-{[(2-Bromooct-1-en-3-yl)oxy]methyl}-4-methoxybenzene
(2q)
Colorless oil. Yield: 118 mg (91%).
[a]D24 –61.7 (c 1.00, CHCl3).
3
94
2g
2h
2i
0.5
1
3g
3h
3i
n.d.e
42
IR (neat): 2931, 1612, 1488, 1257, 1072 cm–1.
1H NMR (500 MHz, CDCl3): d = 0.87 (t, J = 7.0 Hz, 3 H), 1.20–
1.38 (m, 6 H), 1.59–1.68 (m, 2 H), 3.72 (t, J = 6.5 Hz, 1 H), 3.80 (s,
3 H), 4.22 (d, J = 11.0 Hz, 1 H), 4.56 (d, J = 11.0 Hz, 1 H), 5.69 (d,
J = 1.5 Hz, 1 H), 5.86 (d, J = 1.5 Hz, 1 H), 6.88 (d, J = 9.0 Hz, 2 H),
7.26 (d, J = 9.0 Hz, 2 H).
2
58
2j
2
3j
83
10
2m
2
3m
94
a Isolated yield.
13C NMR (126 MHz, CDCl3): d = 14.0, 22.5, 24.9, 31.5, 34.0, 55.3,
b At room temperature.
70.0, 82.1, 113.8, 113.8, 118.7, 129.6, 129.6, 130.0, 135.7, 159.2.
c The corresponding allene was obtained (32% by 1H NMR spectros-
HRMS (EI): m/z [M]+ calcd for C16H23BrO2: 326.0881; found:
326.0880.
copy).
d The corresponding allene was obtained (8% by 1H NMR spectros-
copy).
Alkynes 3 from 1,2-Dibromoalkanes 1; General Procedure for
Two-Step Elimination
e n.d. = not. detected.
A mixture of a 1,2-dibromoalkane 1 (1.0 equiv) and 1 M TBAF in
THF (5.0 equiv) in DMF (0.1 M) was stirred at 60 °C for 1.5–6.0 h.
The reaction was quenched with sat. aq NH4Cl, and the reaction
mixture was extracted with EtOAc (2 × 15 mL). The combined ex-
tracts were concentrated under reduced pressure, and the residue
was purified by silica gel column chromatography to afford the
alkyne 3.
In summary, we have established that TBAF-promoted
elimination reactions of 1,2-dibromoalkanes having an
adjacent O-functional group result in 2-bromoalk-1-enes
2 and alkynes 3 in high yields with high chemo-, regio-,
and stereoselectivities.
1-(Hex-2-yn-1-yloxy)-4-methoxybenzene (3m)
Pale yellow oil. Yield: 70 mg (96%).
Infrared spectra were recorded on a Hitachi 270-30 or a Horiba FT-
1
710 spectrophotometer. H and 13C NMR spectroscopic data were
IR (neat): 3046, 2962, 2938, 2229, 1504, 1457, 1373, 1295, 1218
cm–1.
1H NMR (500 MHz, CDCl3): d = 0.96 (t, J = 7.5 Hz, 3 H), 1.52 (tq,
J = 7.5, 7.5 Hz, 2 H), 2.19 (tt, J = 7.5, 2.0 Hz, 2 H), 3.76 (s, 3 H),
4.61 (t, J = 2.0 Hz, 2 H), 6.83 (d, J = 9.0 Hz, 2 H), 6.91 (d, J = 9.0
Hz, 2 H).
obtained with a Bruker AV 600, a JEOL JNM-EX 500, or a JEOL
JNM-EX 300 instrument. Chemical shifts (d) are quoted in ppm us-
ing tetramethylsilane (TMS, d = 0 ppm) for 1H NMR spectroscopy,
and CDCl3 (d = 77.0 ppm) for 13C NMR spectroscopy, as refer-
ences. Mass spectra were measured on a Bruker Daltonics microTOF
or a Hitachi double-focusing M-80B spectrometer. Column chro-
matography was conducted on silica gel (Kanto Chemical or
Merck). All reactions were performed under an argon atmosphere.
Bromoalkenes 2a–k, 2k¢, 2l–n, 2p, and 2r are known compounds
13C NMR (126 MHz, CDCl3): d = 13.4, 20.7, 21.9, 55.6, 57.2, 75.2,
87.9, 114.5, 114.5, 116.0, 116.0, 152.0, 154.2.
Synthesis 2011, No. 15, 2377–2382 © Thieme Stuttgart · New York

SPECIAL TOPIC
TBAF-Promoted Elimination Reactions
2381
HRMS (ESI): m/z [M + Na]+ calcd for C13H16O2Na: 227.1043;
(8) (a) Cuadrado, P.; González-Nogal, A. M.; Sánchez, A.
found: 227.1047.
J. Org. Chem. 2001, 66, 1961. (b) Kato, N.; Miyaura, N.
Tetrahedron 1996, 52, 13347.
(S)-1-Methoxy-4-[(oct-1-yn-3-yloxy)methyl]benzene (3q)
Colorless oil. Yield: 67 mg (93%).
[a]D24 –116.9 (c 1.00, CHCl3).
IR (neat): 3286, 2931, 1736, 1612, 1489, 1335, 1257, 1065 cm–1.
1H NMR (500 MHz, CDCl3): d = 0.87 (t, J = 7.0 Hz, 3 H), 1.17–
1.36 (m, 4 H), 1.38–1.51 (m, 2 H), 1.63–1.81 (m, 2 H), 2.46 (d,
J = 2.0 Hz, 1 H), 3.80 (s, 3 H), 4.04 (td, J = 7.0, 2.0 Hz, 1 H), 4.44
(d, J = 11.0 Hz, 1 H), 4.73 (d, J = 11.0 Hz, 1 H), 6.88 (d, J = 9.0 Hz,
2 H), 7.29 (d, J = 9.0 Hz, 2 H).
13C NMR (126 MHz, CDCl3): d = 14.0, 22.5, 24.9, 31.4, 35.6, 55.2,
68.0, 70.1, 73.6, 83.1, 113.7, 113.7, 129.6, 129.6, 130.0, 159.2.
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Yokoyama, T.; Ohgiya, T.; Nishiyama, S. Tetrahedron Lett.
2006, 47, 4133.
HRMS (EI): m/z [M]+ calcd for C16H22O2: 246.1620; found:
246.1620.
Alkynes 3 from 2-Bromoalk-1-enes 2; General Procedure
A mixture of a 2-bromoalk-1-ene 2 (1.0 equiv) and 1 M TBAF in
THF (2.0 equiv) in DMF (0.1 M) was stirred at 60 °C for 0.5–3.0 h.
The reaction was quenched with sat. aq NH4Cl, and the reaction
mixture was extracted with EtOAc (2 × 15 mL). The combined ex-
tracts were concentrated under reduced pressure, and the residue
was purified by silica gel column chromatography to afford the
alkyne 3.
(14) (a) Ohgiya, T.; Nishiyama, S. Tetrahedron Lett. 2004, 45,
8273. (b) Ohgiya, T.; Nishiyama, S. Heterocycles 2004, 63,
2349.
(15) Kutsumura, N.; Niwa, K.; Saito, T. Org. Lett. 2010, 12,
3316.
Acknowledgment
(16) (a) Hollingworth, C.; Hazari, A.; Hopkinson, M. N.;
Tredwell, M.; Benedetto, E.; Huiban, M.; Gee, A. D.;
Brown, J. M.; Gouverneur, V. Angew. Chem. Int. Ed. 2011,
50, 2613. (b) Kim, D. W.; Jeong, H.-J.; Lim, S. T.; Sohn, M.-
H. Tetrahedron Lett. 2010, 51, 432. (c) Albanese, D.;
Landini, D.; Penso, M. J. Org. Chem. 1998, 63, 9587.
(d) Cox, D. P.; Terpinski, J.; Lawrynowicz, W. J. Org.
Chem. 1984, 49, 3216.
We thank Dr. Tadaaki Ohgiya (Manager, Organic Chemistry De-
partment, Organic Chemistry Group 1, Tokyo New Drug Research
Laboratories, Pharmaceutical Division, Kowa Company, Ltd.) for
chemical discussions. This work was partly supported by the Sa-
sakawa Scientific Research Grant from The Japan Science Society.
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Synthesis 2011, No. 15, 2377–2382 © Thieme Stuttgart · New York