Asymmetric total syntheses of xanthatin and 11,13-dihydroxanthatin using a stereocontrolled conjugate allylation to γ-butenolide

Article abstract of DOI:10.1016/j.tet.2012.11.077

The stereocontrolled conjugate allylation to an optically pure γ-butenolide provided direct and reliable access to a trans-fused series of xanthanolide sesquiterpenoids and allowed for the enantioselective total syntheses of xanthatin and 11,13-dihydroxanthatin to be efficiently achieved.

Full text of DOI:10.1016/j.tet.2012.11.077

Tetrahedron 69 (2013) 1043e1049
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Asymmetric total syntheses of xanthatin and
11,13-dihydroxanthatin using a stereocontrolled conjugate
allylation to -butenolide
g
,
Kenji Matsumoto a, Kuniyoshi Koyachi b, Mitsuru Shindo a
*
a Institute for Materials Chemistry and Engineering, Kyushu University, 6-1, Kasugako-en, Kasuga 816-8580, Japan
b Interdisciplinary Graduate School of Engineering Sciences, Kyushu University, 6-1, Kasugako-en, Kasuga 816-8580, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 30 October 2012
Received in revised form 22 November 2012
Accepted 23 November 2012
Available online 29 November 2012
The stereocontrolled conjugate allylation to an optically pure g-butenolide provided direct and reliable
access to a trans-fused series of xanthanolide sesquiterpenoids and allowed for the enantioselective total
syntheses of xanthatin and 11,13-dihydroxanthatin to be efficiently achieved.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Xanthanolides
Sesquiterpene lactones
Total synthesis
Conjugate allylation
1. Introduction
they consist of a seven-membered carbocycle containing a cis- or
trans-fused
g-butyrolactone at their C8 position (Fig. 1). These
Xanthanolide sesquiterpenoids are primarily isolated from the
plants of the genus Xanthium (family Compositae), with more than
100 compounds having been reported so far.1 These compounds
exhibit impressive biological properties, including allelopathic,
antitumor, antimicrobial, anti-MRSA, anti-ulcerogenic, and anti-
inflammatory activities. With regard to their chemical structure,
compounds have attracted increasing and considerable levels of
attention from synthetic organic chemists and biological scientists
because of their unique structures and promising biological pro-
files. Since the first total synthesis of 11,13-dihydroxanthatin (2)
reported by Morken in 2005,2,3 several syntheses of xanthanolide
sesquiterpenoids have been reported by Martin,4 Shishido,5 Taki-
kawa,6 Tang,7 and our own group.8 Recently, Aramaki et al. reported
the potent cell growth inhibitory activity of xanthatin (1) against
the highly aggressive human breast cancer cell line MDA-MB-231,
with the compound acting via a unique mechanism; selectively
inducing the expression of the GADD45g
gene isoform.9 With this
in mind, the development of an efficient synthetic method for the
construction of these compounds together with an understanding
of their structureeactivity relationship would be invaluable for
investigating their mechanism of action and clinical potential.
During the course of our studies toward the development of
a systematic synthetic approach to xanthanolides,8 we recently
reported our initial syntheses of the trans-fused xanthanolides,
xanthatin (1) and 11,13-dihydroxanthatin (2), that involved an
intramolecular acylation and one-pot Wittig lactonization. Un-
fortunately, however, this method was not amenable to large scale
preparation because it involved too many steps (28 steps in the
Fig. 1. Naturally occurring xanthanolides.
linear sequence). In our previous work, the cis-fused
g-butyr-
olactone 4 was used as a common chiral building block, as it
was the synthetic intermediate in our previous synthesis of
* Corresponding author. Tel.: þ81 92 583 7802; fax: þ81 92 583 7875; e-mail
address: shindo@cm.kyushu-u.ac.jp (M. Shindo).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.11.077

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K. Matsumoto et al. / Tetrahedron 69 (2013) 1043e1049
sundiversifolide (3),8a,c and thus several tedious steps were re-
quired to transform the cis-fused bicyclic lactone 4 into the trans-
fused lactone 5 (Fig. 2). The development of an alternative route for
the direct stereocontrolled construction of the trans-fused xan-
thanolide core skeleton therefore represents a significant chal-
lenge. In the current work, we have described the efficient and
step-economical second-generation asymmetric syntheses of xan-
thatin (1) and 11,13-dihydroxanthatin (2), based on the highly
stereoselective conjugate allylation of the g-butenolide.
Fig. 2. Our previous studies on the syntheses of xanthanolides.
Scheme 2. Synthesis of the g-butenolide (8).
2. Results and discussion
Our retrosynthetic analysis is shown in Scheme 1. The key point
of our synthetic strategy was the development of a direct and
general synthetic route for the stereoselective construction of
a series of trans-fused xanthanolides. With this in mind, enyne 6
was targeted as the required intermediate because the seven-
membered ring with the (E)-conjugated dienone moiety could be
efficiently constructed by the enyne ring closing metathesis (RCM)
and cross metathesis processes according to the approach reported
by Morken3 and Martin.4 The rapid and stereoselective assembly of
enantioselective dihydroxylation of simple terminal alkenes has
been reported as a challenging reaction.11 Pleasingly, an enhanced
level of selectivity was obtained using the Pt-catalyzed enantiose-
lective diboration method developed by Morken et al.12 According
to this procedure, 3 was treated with bis(pinacolato)diboron in the
presence of Pt2(dba)3 and the phosphonite ligand 12 at 60 ꢀC fol-
lowed by oxidative workup with H2O2 to give diol 13 in yields of
70e90% with a high level of diastereoselectivity. The diol 13 was
then selectively oxidized with TEMPO13 to provide the
a-hydroxy
the trans-3,4-disubstituted-g-butyrolactone bearing an allyl sub-
aldehyde 14, which was subjected to lactonization. Although our
initial attempts at the lactonization of 14 using our own methods
involving ynolate-initiated lactonization14 or tandem acylation-
Wittig lactonization15 resulted in low yields, we found that the Z
selective olefination of 14 with the phosphonic ester 1516 and
stituent was particularly challenging. We anticipated that the
stereoselective installation of the allyl moiety of enyne 6 could be
achieved by the conjugate allylation of the optically active
g-butenolide 8, because this conjugate reaction was expected to
proceed from the opposite face of the side chain in 8.
subsequent lactonization proceeded smoothly to afford the
g-
butenolide 8 in 89% yield.
With a significant quantity of the optically active g-butenolide 8
in hand, our attention turned to the development of a stereo-
controlled conjugate allylation that would provide direct access to
the required trans-3,4-disubstituted-
allyl side chain. Conjugate allylation reactions to
g
-butyrolactone bearing the
-unsaturated
a,b
carbonyl compounds are fundamentally important methods in
organic synthesis, and catalytic and enantioselective versions of
these processes have been extensively studied.17,18 Unfortunately
however, to the best of our knowledge, the majority of these re-
Scheme 1. Retrosynthetic strategy of xanthatin (1) and 11,13-dihydroxanthatin (2).
actions are limited to
and the conjugate allylation of lactones, with particularly emphasis
on five-membered -unsaturated lactones, has been scarcely
reported.19 With this in mind, we therefore examined the conju-
gate allylation of the -butenolide 8 to identify an efficient pro-
tocol for the synthesis of trans-3,4-disubstituted- -butyrolactone
(Table 1). Our initial attempts using allylsilane were unsuccessful,
and in the case of allylstannane, only the unreacted starting ma-
terial was found in the reaction mixture (entries 1 and 2). The
copper catalyzed addition of allylmagnesium chloride resulted
only in the formation of the undesired product 18, which was
formed from the 1,2-addition of the allyl reagent followed by
a,b-unsaturated ketones, esters, and amides,
Our synthesis commenced with the asymmetric alkylation of
the Evans oxazolidinone 9 with allyl bromide to give 10 in 87% with
a high level of diastereoselectivity (Scheme 2).10 The amide 10 was
subjected to reduction with lithium aluminum hydride and the
resulting alcohol was protected with TBDPSCl to give 11 in 96%
yield over the two steps. We then examined the stereocontrolled
construction of the chiral center at C8 (xanthatin numbering).
Unfortunately, however, the application of the standard Sharpless
asymmetric dihydroxylation conditions to the terminal alkene of 11
provided an unsatisfactory level of selectivity (almost 3:1). This lack
of selectivity did not come as too much of a surprise, because the
a,b
g
g

K. Matsumoto et al. / Tetrahedron 69 (2013) 1043e1049
1045
Table 1
Conjugate allylation of the optically active g-butenolide 8
Entry
Allyl reagent
Temp (ꢀC)
Yield (%) 16þ17
16/17
1
2
3
4
5
6
AllylSiMe3, Tf2NH
AllylSnBu3, TiCl4
AllylMgCl, CuI (cat.)
(Allyl)2CuLi
(Allyl)2Cu(CN)Li2
(Allyl)Cu$MgCl$I, TMSCl
ꢁ78 to 0
ꢁ78 to rt
ꢁ78
Messy
0
d
d
0a
d
ꢁ100 to 0
ꢁ78 to 0
ꢁ78 to ꢁ40
0
21
64
d
21:0
39:25
a
The 1,2-adduct 18 was obtained in 53% yield.
dehydration (entry 3). Pleasingly, when lithium diallylcuprate and
lithium diallylcyanocuprate were employed in the conjugate ad-
dition, the 1,4-adduct 16 was isolated in moderate yield (entry 5).
Encouraged by this result, we screened the reaction extensively
using of CuBr2$SMe2, lithium salts, and several other Lewis acids.
Following the screening process, the use of an allylcopper reagent
in the presence of TMSCl, as reported by Lipshutz,20 was found to
work most efficiently for this transformation (entry 6). Under these
conditions, the trans-1,4-adducts 16 and the corresponding TMS
enol ether 17 were isolated in a combined yield of 64%. Pleasingly,
the cis isomer was not detected in the crude products by 1H NMR
spectroscopy.
Scheme 4. Syntheses of xanthatin and 11,13-dihydroxanthatin.
This mixture of 16 and 17 was then treated with TBAF to give
alcohol 19 in 70% yield (Scheme 3). The alcohol 19 was then oxi-
dized with DesseMartin periodinane, and the resulting aldehyde
was treated with Gilberts reagent21 at ꢁ78 ꢀC to provide enyne 6 in
good overall yield without any epimerization at the C10 position.22
3. Conclusion
In conclusion, we have achieved the development of a direct and
highly efficient synthetic strategy for the construction of trans-
fused xanthanolides using a stereocontrolled conjugate allylation
to a g-butenolide, allowing for the synthesis of xanthatin and 11,13-
dihydroxanthatin in only 14 and 13 steps, respectively, and pro-
viding a level of efficiency much greater than that achieved by any
of the previously reported synthetic approaches. Our synthetic
route provides a powerful and general approach to the xanthano-
lides and other natural products possessing the trans-fused
g
-butyrolactone.24
Scheme 3. Synthesis of the enyne 6.
4. Experimental
With the key compound 6 in hand, we proceeded to complete
the total syntheses of the xanthanolides (Scheme 4). The ring
closing metathesis of the enyne 6 was performed using the Grubbs
catalyst 21 to give the seven-membered carbocycle 20 in 85% yield.
Methylation of the lactone moiety of 20 proceeded stereo-
selectively to provide 5, which was subjected to cross metathesis
with methyl vinyl ketone using the Hoveyda catalyst 2223 to yield
11,13-dihydroxanthatin (2) in 87% yield, with the entire linear se-
4.1. General procedures
1H NMR, 13C NMR were measured in CDCl3 solution using JEOL
JNM-AL-400 spectrometer (1H NMR at 400 MHz, 13C NMR at
100 MHz) or a JNM-ECA-600 spectrometer (1H NMR at 600 MHz,
13C NMR at 150 MHz) using the reference standard (1H NMR at
0.00 ppm (TMS), 13C NMR at 77.0 ppm (CDCl3)). Chemical sifts are
reported in parts per million. Peak multiplicities are used the fol-
lowing abbreviations: s, singlet; d, doublet; t, triplet; q, quartet;
quin, quintet; sept, septet; m, multiplet; br, broadened. IR spectra
were recorded on JAS.CO FT/IR-410 or Shimadzu FT/IR-8300 spec-
trometers. Mass spectra and high-resolution mass spectra were
obtained on JMS-K9, JEOL JMS-700 or Shimadzu LCMS-2010EV
mass spectrometers. Elemental analyses were performed with
YANACO 026 CHN analyzer. Melting points were measured with
quence totaling 13 steps. For the synthesis of xanthatin, the
butyrolactone 5 was treated with LDA and diphenyl diselenide to
give the -selenylated -butyrolactone, which was treated in situ
g-
a
g
with H2O2 to give the exo-methylene lactone 23 in 82% yield for the
one-pot procedure. Finally, the cross metathesis of 23 under the
conditions described above gave xanthatin (1) in 85% yield. All the
spectra and the optical rotations of the synthetic materials 1 and 2
were identical to those of the natural products.
€
a Yanaco MP-500D apparatus or Buchi 535 melting point apparatus

1046
K. Matsumoto et al. / Tetrahedron 69 (2013) 1043e1049
and are uncorrected. Thin-layer chromatography (TLC) was per-
formed on pre-coated plates (0.25 mm, silica gel Merck 60F245).
Column chromatography was performed on silica gel (Kanto
Chemical Co., Inc.). Preparative HPLC was performed on a system
utilizing a HITACHI L-6250 Intelligent Pump with a gradient solvent
system of hexane and ethyl acetate and UV detector L-7400 at
254 nm, and also a system utilizing a JAS.CO PU-2087 Intelligent
Pump with Dynamic Mixer MX-2080-32 and UV detector UV-2075
and RI detector RI-2031. The recycling preparative HPLC was per-
formed with LC-908, which was consisted of UV detector UV-310B
and RI detector RI-5. All reactions were performed under an air
atmosphere unless otherwise noted, and dry dichloromethane
(CH2Cl2), diethyl ether (Et2O), and tetrahydrofuran (THF) were
purchased from Kanto Chemical Co., Inc., and other solvents were
distilled. Unless otherwise noted, reagents were obtained from
chemical sources and without further purification.
(dd, J¼10.3, 1.4 Hz, 1H), 5.00 (dd, J¼16.5, 1.4 Hz, 1H), 5.75 (ddt,
J¼16.5, 10.3, 7.6 Hz, 1H), 7.38 (t, J¼7.6 Hz, 4H), 7.42 (t, J¼7.6 Hz, 2H),
7.67 (dd, J¼7.6, 1.4 Hz, 4H). 13C NMR (150 MHz, CDCl3)
d: 16.4 (q),
19.3 (s), 26.6 (q), 35.7 (d), 37.6 (t), 68.3 (t), 115.7 (t), 127.6 (d), 129.5
(d), 134.0 (s), 135.6 (d), 137.3 (d). IR (neat): 3072, 2958, 2931, 2858,
1471, 1427, 1112 cmꢁ1. MS (FAB) m/z 337 (MþꢁH), 281 (Mþꢁt-Bu),
199 (100%). HRMS (FAB) calcd for C22H29OSi (MþꢁH): 337.1988,
found: 337.1985.
4.4. (2S,4S)-5-tert-Butyldiphenylsiloxy-4-methyl-1,2-pentandiol
13
To an oven-dried reaction vial with magnetic stir bar in the
glove box were added Pt2(dba)3 (108 mg, 0.10 mmol), (R,R)-3,5-
diethylphenyl-TADDOLPPh12 (12) (190 mg, 0.12 mmol), B2(pin)2
(580 mg, 2.2 mmol), and THF (16 mL). The vial was sealed with
a polypropylene cap, removed from the glove box, and heated to
80 ꢀC for 30 min. A solution of 11 (670 mg, 2.0 mmol) in THF (4 mL)
was added and the reaction mixture was stirred at 60 ꢀC for 12 h.
NaOH (3 M, 6 mL) and 30% hydrogen peroxide (3 mL) were added at
0 ꢀC. The mixture was warmed to room temperature, stirred for 4 h,
treated with saturated aqueous Na2S2O4 at 0 ꢀC, and extracted with
EtOAc. The combined organic layer was washed with brine, dried
over MgSO4, filtered, and concentrated in vacuo to give a crude
4.2. (4R)-4-Benzyl-3-[(2S)-2-methyl-4-pentenoyl]-1,3-
oxazolidin-2-one25 10
To a solution of HMDS (50 mL, 217 mmol) in THF (500 mL),
cooled to 0 ꢀC under N2, was added dropwise n-BuLi (90 mL,
217 mmol, 2.4 M in hexane). The reaction mixture was stirred at
0
ꢀC for 30 min, cooled to ꢁ78 ꢀC, and then the oxazolidinone26
9
(39 g, 167 mmol) was added dropwise. After being stirred for 2 h,
allyl bromide (40 mL, 501 mmol) was added dropwise. The
resulting mixture was stirred at ꢁ78 ꢀC for 2 h, warmed to room
temperature, and stirred for 2 h. The mixture was quenched with
saturated aqueous NH4Cl. The resulting mixture was extracted with
AcOEt, and the combined organic layer was washed with brine,
dried over MgSO4, filtered and, concentrated in vacuo to give
a crude product, which was purified by silica gel column chroma-
tography (30% AcOEt/Hex) to afford 40 g (87%) of 10 as a colorless
product, which was purified by silica gel column chromatography
21
(50% AcOEt/Hex) to afford 670 mg (90%) of 13 as a colorless oil. [
a]
D
ꢁ2.5 (c 0.28, CHCl3). 1H NMR (600 MHz, CDCl3)
: 0.86 (d, J¼6.9 Hz,
d
3H),1.06 (s, 9H), 1.37 (ddd, J¼14.4, 6.9, 3.4 Hz, 1H),1.90 (ddd, J¼14.4,
10.3, 6.8 Hz, 1H), 1.85e1.93 (m, 1H), 2.02 (br, 1H), 3.38 (br, 1H),
3.42e3.47 (m, 1H), 3.49 (dd, J¼10.3, 7.6 Hz, 1H), 3.56 (dd, J¼10.3,
4.8 Hz, 1H), 3.59e3.64 (m, 1H), 3.80e3.84 (m, 1H), 7.38e7.45 (m,
6H), 7.66e7.68 (m, 4H). 13C NMR (150 MHz, CDCl3)
d: 17.6 (q), 19.2
(s), 26.8 (q), 33.7 (d), 38.8 (t), 67.4 (t), 70.0 (t), 70.8 (d), 127.7 (d),
129.8 (d), 133.2 (t), 135.6 (d). IR (neat): 3383, 2930, 2857, 1471, 1427,
1111 cmꢁ1. MS (FAB) m/z 373 (MþþH),199 (100%). HRMS (FAB) calcd
for C22H33O3Si (MþþH): 373.2199, found: 373.2201.
oil. 1H NMR (600 MHz, CDCl3)
d
: 1.19 (d, J¼6.8 Hz, 3H), 2.21e2.27
(m, 1H), 2.50e2.56 (m, 1H), 2.70 (dd, J¼13.1, 9.7 Hz, 1H), 3.29 (dd,
J¼13.1, 3.4 Hz, 1H), 3.87 (tq, J¼6.9, 6.8 Hz, 1H), 4.16 (dd, J¼8.9,
3.4 Hz, 1H), 4.18 (dd, J¼8.9, 8.9 Hz, 1H), 4.67e4.71 (m, 1H), 5.07 (dd,
J¼8.9, 2.0 Hz, 1H), 5.11 (dd, J¼17.2, 2.0 Hz, 1H), 5.83 (ddt, J¼17.2, 9.7,
7.6 Hz, 1H), 7.22 (d, J¼6.9 Hz, 2H), 7.28 (t, J¼6.9 Hz, 1H), 7.33 (t,
4.5. (2S,4S)-5-tert-Butyldiphenylsiloxy-2-hydroxy-4-
methylpentanal 14
J¼6.9 Hz, 2H). 13C NMR (150 MHz, CDCl3)
d: 16.4 (q), 37.2 (d), 38.0
(t), 38.1 (t), 55.4 (d), 66.0 (t), 117.2 (t), 127.3 (d), 129.0 (d), 129.4 (d),
129.5 (d), 135.3 (d), 135.4 (s), 153.1 (s), 176.5 (s).
To a solution of 13 (4.5 g,12.1 mmol) in CH2Cl2 (60 mL), cooled to
0
ꢀC under N2, were added saturated aqueous NaHCO3 (60 mL),
TEMPO (95 mg, 0.61 mmol), and KBr (1.5 g,13.2 mmol). The mixture
was stirred at 0 ꢀC for 10 min and then 5% NaClO aqueous (19 mL,
13.2 mmol) was added. After being stirred for 20 min, the reaction
mixture was quenched with saturated aqueous Na2S2O3, and
extracted with AcOEt. The combined organic layer was washed
with brine, dried over MgSO4, filtered, and concentrated in vacuo to
give a crude product, which was purified by silica gel column
chromatography (20% AcOEt/Hex) to afford 3.5 g (79%) of 14 as
a colorless oil. The aldehyde 14, containing unidentified side-
products, was used in the next step without its purification.
4.3. (4S)-5-tert-Butyldiphenylsiloxy-4-methyl-1-pentene 11
To a suspension of LiAlH4 (3.6 g, 94 mmol) in Et2O (400 mL),
cooled to 0 ꢀC under N2, was added a solution of 10 (13 g, 47 mmol)
in Et2O (70 mL). The reaction mixture was stirred at 0 ꢀC for 1 h and
quenched by the careful addition of H2O (14 mL). The resulting
mixture was warmed to room temperature and stirred for 30 min.
NaOH solution (1 M) and H2O (14 mL) were successively added and
the resulting mixture was stirred at room temperature for 30 min,
filtered through a pad of Celite, carefully concentrated by rotary
evaporator to afford a crude product, which was used without
further purification. The obtained crude alcohol (19 g) was dis-
solved in CH2Cl2 (230 mL) and cooled to 0 ꢀC. Imidazole (4.4 g,
65 mmol) and TBDPSCl (14 mL, 56 mmol) were added. The mixture
was warmed to room temperature and stirred for 6 h. The reaction
mixture was quenched with H2O, extracted with AcOEt, and the
combined organic layer was washed with brine, dried over MgSO4,
filtered, and concentrated in vacuo to give a crude product, which
was purified by silica gel column chromatography (3% AcOEt/Hex)
4.6. (5S)-5-[(2S)-3-tert-Butyldiphenylsiloxy-2-methylpropyl]
furan-2(5H)-one 8
To a solution of ethyl [bis(o-isopropylphenyl)phosphono]ace-
tate27 (5.1 g, 13.0 mmol) in THF (90 mL) was added 60% NaH
(480 mg, 11.9 mmol) under N2. The reaction mixture was stirred at
room temperature for 30 min, then cooled to ꢁ78 ꢀC. A solution of
14 (4.0 g, 10.8 mmol) in THF (10 mL) was added to the mixture,
which was stirred at room temperature for 3 h and then Et2O and
H2O (25 mL) were added. The resultant mixture was extracted with
Et2O, and the combined organic layer was washed with brine, dried
over MgSO4, filtered, and concentrated in vacuo to give a crude
product, which was purified by silica gel column chromatography
to afford 15.3 g (96% in two steps) of 11 as a colorless oil. [
a
]
21 ꢁ2.4
D
(c 2.1, CHCl3). 1H NMR (600 MHz, CDCl3)
d
: 0.91 (d, J¼6.2 Hz, 3H),
1.05 (s, 9H), 1.72e1.78 (m, 1H), 1.87e1.94 (m, 1H), 2.22e2.29 (m,
1H), 3.48 (dd, J¼9.6, 6.2 Hz, 1H), 3.50 (dd, J¼9.6, 6.2 Hz, 1H), 4.97

K. Matsumoto et al. / Tetrahedron 69 (2013) 1043e1049
1047
21
(20% AcOEt/Hex) to afford 3.8 g (89%) of 8 as a colorless oil. [
a
]
D
(d), 34.5 (t), 36.8 (t), 38.6 (t), 41.1 (d), 68.0 (t), 83.3 (d),117.9 (t),134.4
(d), 176.2 (s). IR (neat): 3431, 3078, 2958, 2924, 2875, 1471, 1772,
1641 cmꢁ1. MS (FAB) m/z 199 (MþþH), 154 (100%). HRMS (FAB)
calcd for C11H19O3 (Mþ þH): 199.1334, found: 199.1341.
þ42.6 (c 0.65, CHCl3). 1H NMR (600 MHz, CDCl3)
: 1.00 (d, J¼6.8 Hz,
d
3H),1.05 (s, 9H),1.59 (ddd, J¼14.5, 8.9, 5.5 Hz,1H),1.79 (ddd, J¼14.5,
8.9, 5.5 Hz,1H),1.94e2.03 (m,1H), 3.50 (dd, J¼10.2, 6.0 Hz,1H), 3.54
(dd, J¼10.2, 4.8 Hz, 1H), 5.12e5.18 (m, 1H), 6.08 (dd, J¼5.5, 2.1 Hz,
1H), 7.38e7.45 (m, 7H), 7.64 (d, J¼6.9 Hz, 4H). 13C NMR (150 MHz,
4.9. (4R,5S)-4-Allyl-5-[(2S)-3-oxo-2-methylpropyl]dihy-
drofuran-2(3H)-one
CDCl3) d: 16.6 (q),19.3 (s), 26.9 (q), 32.6 (d), 37.3 (t), 68.7 (t), 81.8 (d),
121.3 (d), 127.7 (d), 129.7 (d), 133.5 (s), 135.5 (d), 156.8 (d), 173.1 (s).
IR (neat): 2958, 2931, 1759, 1427, 1111 cmꢁ1. MS (FAB) m/z 393
(MþꢁH), 337 (Mþꢁt-Bu), 317 (MþꢁC6H5, 100%). HRMS (FAB) calcd
for C24H29O3Si (MþꢁH): 393.1886, found: 393.1892.
To a solution of 19 (80 mg, 0.40 mmol) in CH2Cl2 (4 mL), cooled
to 0 ꢀC under N2, was added DesseMartin periodinane28 (340 mg,
0.80 mmol). The reaction mixture was stirred at 0 ꢀC for 10 min,
stirred at room temperature for 10 min, and then saturated aqueous
NaHCO3 was added. The resulting mixture was extracted with
AcOEt and the combined organic layer was washed with brine,
dried over MgSO4, filtered, and concentrated in vacuo to give
a crude product, which was purified by silica gel column chroma-
tography (30% AcOEt/Hex) to afford 71 mg (89%) of the aldehyde as
4.7. (4R,5S)-4-Allyl-5-[(2S)-3-tert-butyldiphenylsiloxy-2-
methylpropyl]dihydrofuran-2(3H)-one 16
To a solution of CuI (118 mg, 0.62 mmol) and dry LiBr (54 mg,
0.62 mmol) in THF (1 mL), cooled to ꢁ78 ꢀC under N2, were added
dropwise allylmagnesium chloride (0.30 mL, 0.60 mmol, 2 M in
THF), TMSCl (0.076 mL, 0.60 mmol), and a solution of 8 (79 mg,
0.20 mmol) in THF (1 mL). The mixture was stirred at ꢁ78 ꢀC for 1 h,
warmed to ꢁ40 ꢀC, and stirred for 3 h. The reaction mixture was
quenched with saturated aqueous NH4Cl, extracted with AcOEt, and
the combined organic layer was washed with brine, dried over
MgSO4, filtered, and concentrated in vacuo to give a crude product,
which was purified by silica gel column chromatography (10%
AcOEt/Hex) to afford 34 mg (39%) of 16 and 25 mg (25%) of 17 as
a colorless oil.
a colorless oil. 1H NMR (600 MHz, CDCl3)
d
: 1.21 (d, J¼6.8 Hz, 3H),
1.65 (ddd, J¼14.4, 8.9, 2.8 Hz, 1H), 2.26 (ddd, J¼14.4, 10.3, 4.8 Hz,
1H), 2.16e2.21 (m, 1H), 2.24e2.34 (m, 3H), 2.65e2.72 (m, 2H), 4.24
(ddd, J¼10.3, 6.2, 2.8 Hz, 1H), 5.12 (dd, J¼16.8, 1.4 Hz, 1H), 5.13 (dd,
J¼10.8, 1.4 Hz, 1H), 5.67e5.77 (m, 1H), 9.68 (s, 1H). 13C NMR
(150 MHz, CDCl3) d: 12.9 (q), 34.4 (t), 34.8 (t), 36.8 (t), 40.8 (d), 43.2
(d), 82.1 (d), 118.1 (t), 134.1 (d), 175.7 (s), 203.4 (d).
4.10. (4R,5S)-4-Allyl-5-[(2S)-2-methyl-3-butynyl]dihy-
drofuran-2(3H)-one3
6
21
4.7.1. Compound 16. [
a
]
ꢁ29.6 (c 1.0, CHCl3). 1H NMR (600 MHz,
D
To a solution of diethyl(diazomethyl)phosphonate (81 mg,
0.54 mmol) in THF (6 mL), cooled to ꢁ78 ꢀC under N2, was added t-
BuOK (0.52 mL, 0.52 mmol, 1 M in THF). The reaction mixture was
stirred at ꢁ78 ꢀC for 15 min and then a solution of the aldehyde
(70 mg, 0.35 mmol) in THF (2 mL) was added dropwise at ꢁ78 ꢀC.
The mixture was stirred at ꢁ78 ꢀC for 30 min and quenched with
a 1:1 mixture of a saturated NH4Cl solution and H2O, extracted
with Et2O. The combined organic layer was washed with brine,
dried over MgSO4, filtered, and concentrated in vacuo to give
a crude product, which was purified by silica gel column chro-
CDCl3)
d
: 0.97 (d, J¼6.2 Hz, 3H), 1.05 (s, 9H), 1.46 (ddd, J¼14.5, 10.2,
3.0 Hz, 1H), 1.78 (ddd, J¼14.5, 10.2, 4.2 Hz, 1H), 1.93e2.01 (m, 1H),
2.10e2.30 (m, 4H), 2.64 (dd, J¼17.2, 7.6 Hz, 1H), 3.47e3.53 (m, 2H),
4.23 (ddd, J¼10.2, 6.2, 3.0 Hz, 1H), 5.06e5.12 (m, 2H), 5.70 (ddt,
J¼17.2, 9.6, 6.8 Hz, 1H), 7.37e7.44 (m, 6H), 7.65 (dd, J¼6.8, 1.4 Hz,
4H). 13C NMR (150 MHz, CDCl3)
d: 16.0 (q), 19.3 (s), 26.8 (q), 32.4 (d),
34.5 (t), 36.9 (t), 38.3 (t), 40.9 (d), 68.8 (t), 83.0 (d), 117.8 (t), 127.6
(d), 129.6 (d), 133.7 (s), 134.4 (d), 135.6 (d), 176.3 (s). IR (neat): 2958,
2931, 2858, 1776, 1112 cmꢁ1. MS (FAB) m/z: 435 (MþꢁH), 379
(Mþꢁt-Bu), 359 (MþꢁC6H5), 199 (100%). HRMS (FAB) calcd for
C
27H35O3Si (MþꢁH): 435.2355, found: 435.2355.
matography (20% AcOEt/Hex) to afford 60 mg (89%) of 6 as a col-
23
orless oil. [
a]
ꢁ0.13 (c 0.42, CHCl3). 1H NMR (600 MHz, CDCl3)
d:
D
4.7.2. Compound 17. 1H NMR (600 MHz, CDCl3)
d: 0.17 (s, 9H), 0.94
1.25 (d, J¼6.9 Hz, 3H), 1.77 (ddd, J¼14.2, 6.6, 4.8 Hz, 1H), 1.93 (ddd,
J¼14.2, 7.4, 6.6 Hz, 1H), 2.10 (d, J¼2.4 Hz, 1H), 2.13e2.21 (m, 1H),
2.24e2.36 (m, 3H), 2.65e2.72 (m, 2H), 4.35 (ddd, J¼7.4, 4.8, 4.8 Hz,
1H), 5.10e5.15 (m, 2H), 5.69e5.76 (m, 1H). 13C NMR (100 MHz,
(d, J¼7.2 Hz, 3H),1.05 (s, 9H),1.38 (ddd, J¼13.8,10.8, 3.0 Hz,1H),1.80
(ddd, J¼13.8, 9.6, 3.6 Hz, 1H), 1.96e2.07 (m, 2H), 2.17e2.27 (m, 2H),
1.96e2.07 (m, 2H), 2.17e2.27 (m, 2H), 3.45e3.53 (m, 3H), 4.21 (ddd,
J¼9.6, 6.0, 3.0 Hz, 1H), 5.03e5.12 (m, 2H), 5.63e5.71 (m, 1H),
7.35e7.43 (m, 6H), 7.63e7.66 (m, 4H).
CDCl3) d: 20.2 (q), 22.2 (d), 34.2 (t), 37.0 (t), 40.1 (d), 40.9 (t), 69.2
(d), 82.4 (d), 87.6 (s), 118.1 (t), 134.2 (d), 176.1 (s). MS (ESI) m/z: 215
(MþþNa).
4.8. (4R,5S)-4-Allyl-5-[(2S)-3-hydroxy-2-methylpropyl]dihy-
drofuran-2(3H)-one 19
4.11. (3aR,7S,8aS)-7-Methyl-6-vinyl-3,3a,4,7,8,8a-hexahydro-
2H-cyclohepta[b]furan-2-one3 20
To a solution of 16 (500 mg, 1.1 mmol) in THF (11 mL), cooled to
0
ꢀC under N2, was added tetrabutylammonium fluoride (2.2 mL,
To a solution of Grubbs second-generation catalyst (14 mg,
0.016 mmol) in CH2Cl2 (52 mL) was added a solution of 6 (60 mg,
0.31 mmol) in CH2Cl2 (10 mL). The reaction mixture was stirred at
room temperature for 12 h and then the solvent was removed in
vacuo to give a crude product, which was purified by silica gel
column chromatography (10% AcOEt/Hex) to afford 51 mg (85%) of
20 as a pale yellow oil, which upon prolonged sitting formed col-
2.2 mmol, 1 M in THF). The reaction mixture was stirred at 0 ꢀC for
5 min, allowed to warm to room temperature, and stirred for 4 h.
Saturated aqueous NaHCO3 was added and the resulting mixture
was extracted with AcOEt. The combined organic layer was washed
with brine, dried over MgSO4, filtered, and concentrated in vacuo to
give a crude product, which was purified by silica gel column
chromatography (40% AcOEt/Hex) to afford 152 mg (70%) of 19 as
orless needles. Mp 56e61 ꢀC. [
(400 MHz, CDCl3)
a
]
23 ꢁ40.0 (c 0.050, CHCl3). 1H NMR
D
a colorless oil. [
a]
21 ꢁ64.8 (c 0.11, CHCl3). 1H NMR (600 MHz, CDCl3)
d
: 1.15 (d, J¼7.6 Hz, 3H), 1.75 (ddd, J¼12.4, 12.4,
D
d
: 0.99 (d, J¼7.2 Hz, 3H),1.51 (ddd, J¼14.4, 8.0, 3.0 Hz,1H), 1.78 (ddd,
4.0 Hz, 1H), 2.02e2.18 (m, 2H), 2.28e2.38 (m, 2H), 2.47 (dd, J¼16.4,
8.8 Hz, 1H), 2.60 (dd, J¼16.4, 6.0 Hz, 1H), 3.03e3.10 (m, 1H), 4.36
(ddd, J¼11.6, 8.8, 2.8 Hz, 1H), 4.97 (d, J¼11.0 Hz, 1H), 5.19
(d, J¼17.3 Hz, 1H), 5.78 (dd, J¼9.3, 2.8 Hz, 1H), 6.23 (dd, J¼17.3,
11.0 Hz, 1H).
J¼14.4, 10.2, 4.8 Hz, 1H), 1.89e1.97 (m, 1H), 2.13e2.35 (m, 4H), 2.67
(dd, J¼17.4, 7.8 Hz, 1H), 3.50 (dd, J¼10.8, 6.0 Hz, 1H), 3.55 (dd,
J¼10.8, 5.4 Hz, 1H), 4.26 (ddd, J¼10.2, 7.2, 3.0 Hz, 1H), 5.09e5.14 (m,
2H), 5.68e5.77 (m, 1H). 13C NMR (150 MHz, CDCl3)
d: 16.2 (q), 33.1

1048
K. Matsumoto et al. / Tetrahedron 69 (2013) 1043e1049
4.12. (3S,3aR,7S,8aS)-3,7-Dimethyl-6-vinyl-3,3a,4,7,8,8a-hex-
ahydro-2H-cyclohepta[b]furan-2-one8c
4.15. 11,13-Dihydroxanthatin (2)8c
5
To a solution of 5 (20 mg, 0.097 mmol) in CH2Cl2 (19 mL) was
added the second-generation HoveydaeGrubbs catalyst (22,
7.0 mg, 0.011 mmol) and freshly distilled methyl vinyl ketone
(135 mg, 1.9 mmol). The reaction mixture was stirred at 45 ꢀC for
2 h and then the solvent was removed in vacuo to give a crude
product, which was purified by silica gel column chromatography
To a solution of 20 (40 mg, 0.21 mmol) in THF (2 mL), cooled
to ꢁ78 ꢀC under N2, was added LDA (0.30 mL, 0.21 mmol, 0.70 M),
prepared with diisopropylamine (0.74 mL, 5.3 mmol) and n-BuLi
(2.0 mL, 5.0 mmol, 2.5 M in hexane) in THF (5 mL). The reaction
mixture was stirred at ꢁ78 ꢀC for 1 h and then freshly distilled
iodomethane (0.030 mL, 0.25 mmol) was added. The mixture was
stirred at ꢁ78 ꢀC for 20 min, stirred at 0 ꢀC for 1 h, and then
quenched with saturated aqueous NH4Cl. The resulting mixture
was extracted with AcOEt and the combined organic layer was
washed with brine, dried over MgSO4, filtered, and concentrated in
vacuo to give a crude product, which was purified by silica gel
column chromatography (10% AcOEt/Hex) to afford 38 mg (90%) of
(30% AcOEt/Hex) to afford 21 mg (87%) of 2 as colorless needles. Mp
23
121.0e124.0 ꢀC (CH2Cl2/hexane). [
a
]
D
ꢁ75.0 (c 0.32, CHCl3). 1H
NMR (CDCl3, 600 MHz)
d
: 1.15 (d, J¼7.8 Hz, 3H), 1.23 (d, J¼7.8 Hz,
3H), 1.72 (ddd, J¼12.6, 12.6, 3.6 Hz, 1H), 2.13 (dddd, J¼12.6, 12.6, 7.8,
2.4 Hz, 1H), 2.21 (ddd, J¼12.0, 12.0, 3.0 Hz, 1H), 2.30 (s, 3H), 2.35
(ddd, J¼12.6, 4.2, 4.2 Hz, 1H), 2.45 (ddd, J¼16.2, 9.0, 2.4 Hz, 1H), 2.72
(dq, J¼7.8, 7.8 Hz, 1H), 3.05 (ddq, J¼7.8, 4.2, 4.2 Hz, 1H), 4.54 (ddd,
J¼12.6, 10.8, 3.0 Hz, 1H), 6.18 (d, J¼16.2 Hz, 1H), 6.25 (dd, J¼9.6,
3.0 Hz, 1H), 7.05 (d, J¼16.2 Hz, 1H).
5 as colorless prisms. Mp 82.5e83.5 ꢀC. [
a
]
23 ꢁ103.1 (c 0.32, CHCl3).
D
1H NMR (600 MHz, CDCl3)
d
: 1.13 (d, J¼7.8 Hz, 3H), 1.22 (d, J¼7.8 Hz,
3H), 1.70 (ddd, J¼12.6, 12.6, 3.6 Hz, 1H), 2.07e2.16 (m, 2H),
2.28e2.34 (m, 2H), 2.69 (dq, J¼7.8, 7.8 Hz, 1H), 3.07 (ddq, J¼7.8, 4.2,
4.2 Hz, 1H), 4.53 (ddd, J¼12.6, 10.2, 3.0 Hz, 1H), 4.96 (d, J¼10.8 Hz,
1H), 5.17 (d, J¼17.4 Hz, 1H), 5.81 (dd, J¼9.6, 3.6 Hz, 1H), 6.23 (dd,
J¼17.4, 10.8 Hz, 1H).
Acknowledgements
This work was supported by the Program for the Promotion of
Basic and Applied Research for Innovations in the Bio-oriented
Industry (BRAIN) from the Bio-oriented Technology Research Ad-
vancement Institution, a Grant-in-Aid for Exploratory Research (No.
22659023) (M.S.) and a Grant-in-Aid for Young Scientists (B) (No.
23790131) (K.M.) from MEXT.
4.13. (3aR,7S,8aS)-7-Methyl-3-methylene-6-vinyl-3,3a,4,7,8,8a-
hexahydro-2H-cyclohepta[b]furan-2-one8c 23
To a solution of 5 (25 mg, 0.12 mmol) in THF (1.2 mL), cooled to
ꢁ78 ꢀC under N2, was added LDA (0.26 mL, 0.18 mmol, 0.70 M),
prepared with diisopropylamine (0.74 mL, 5.3 mmol) and n-BuLi
(2.0 mL, 5.0 mmol, 2.5 M in hexane) in THF (5 mL). The reaction
mixture was stirred at ꢁ78 ꢀC for 20 min and then diphenyl dis-
elenide (75 mg, 0.24 mmol) and HMPA (0.046 mL, 0.24 mmol) were
added. The mixture was stirred at ꢁ78 ꢀC for 5 min, warmed to
ꢁ40 ꢀC, and stirred for 2 h. H2O2 solution of 30% (0.27 mL,
2.4 mmol) and acetic acid (0.014 mL, 0.24 mmol) were added at
ꢁ40 ꢀC and then the reaction mixture was stirred at 0 ꢀC for 3 h,
quenched with saturated aqueous NH4Cl. The resulting mixture
was extracted with AcOEt, and the combined organic layer was
washed with brine, dried over MgSO4, filtered, and concentrated in
vacuo to give a crude product, which was purified by silica gel
column chromatography (10% AcOEt/Hex) to afford 20 mg (82%) of
Supplementary data
A supplementary data file (1H and 13C NMR) of the synthesized
compounds. Supplementary data associated with this article can be
found in the online version, at http://dx.doi.org/10.1016/
j.tet.2012.11.077.
References and notes
1. Vasas, A.; Hohmann, J. Nat. Prod. Rep. 2011, 28, 824e842.
2. Forareviewonthetotalsynthesis, see:Shishido, K.Heterocycles2009, 78, 873e889.
3. Evans, M. A.; Morken, J. P. Org. Lett. 2005, 7, 3371e3373.
4. (a) Kummer, D. A.; Brenneman, J. B.; Martin, S. F. Org. Lett. 2005, 7, 4621e4623; (b)
Kummer, D. A.; Brenneman, J. B.; Martin, S. F. Tetrahedron 2006, 62,11437e11449.
5. (a) Yokoe, H.; Sasaki, H.; Yoshimura, T.; Shindo, M.; Yoshida, M.; Shishido, K. Org.
Lett. 2007, 9, 969e971; (b) Yokoe, H.; Yoshida, M.; Shishido, K. Tetrahedron Lett.
2008, 49, 3504e3506; (c) Sasaki, H.; Yokoe, H.; Shindo, M.; Yoshida, M.; Shishido,
K. Heterocycles 2009, 77, 2046e2051; (d) Yokoe, H.; Noboru, K.; Manabe, Y.;
Yoshida, M.; Shibata, H.; Shishido, K. Chem. Pharm. Bull. 2012, 60, 1340e1342.
6. Hashimoto, T.; Tashiro, T.; Sasaki, M.; Takikawa, H. Biosci. Biotechnol. Biochem.
2007, 71, 2046e2051.
23 as colorless needles. Mp 77.2e77.7 ꢀC (Hex). [
a
]
23 ꢁ40.0 (c 0.050,
D
CHCl3). 1H NMR (600 MHz, CDCl3)
d
: 1.14 (d, J¼7.8 Hz, 3H),1.83 (ddd,
J¼12.6, 12.6, 3.6 Hz, 1H), 2.14 (ddd, J¼16.2, 11.4, 3.6 Hz, 1H), 2.35
(ddd, J¼13.2, 4.2, 3.6 Hz, 1H), 2.51e2.56 (m, 1H), 2.67 (ddd, J¼16.2,
9.0, 2.4 Hz, 2H), 3.11 (dq, J¼3.6, 3.6 Hz, 1H), 4.29 (ddq, J¼12.6, 10.2,
2.4 Hz, 1H), 4.99 (d, J¼10.8 Hz, 1H), 5.20 (d, J¼17.4 Hz, 1H), 5.45 (d,
J¼3.0 Hz,1H), 5.84 (dd, J¼9.0, 3.0 Hz,1H), 6.18 (d, J¼3.0 Hz,1H), 6.26
(dd, J¼17.4, 10.8 Hz, 1H).
7. Ren, W.; Bian, Y.; Zhang, Z.; Shang, H.; Zhang, P.; Chen, Y.; Yang, Z.; Luo, T.; Tang,
Y. Angew. Chem., Int. Ed. 2012, 51, 6984.
8. (a) Ohtsuki, K.; Matsuo, K.; Yoshikawa, T.; Moriya, C.; Tomita-Yokotani, K.;
Shishido, K.; Shindo, M. Org. Lett. 2008, 10, 1247e1250; (b) Matsuo, K.; Yokoe,
H.; Shshido, K.; Shindo, M. Tetrahedron Lett. 2008, 49, 4279; (c) Matsuo, K.;
Ohtsuki, K.; Yoshikawa, T.; Shishido, K.; Yokotani-Tomita, K.; Shindo, M. Tetra-
hedron 2010, 66, 8407e8419.
9. Takeda, S.; Matsuo, K.; Yaji, K.; Okajima-Miyazaki, S.; Harada, M.; Miyoshi, H.;
Okamoto, Y.; Amamoto, T.; Shindo, M.; Omiecinski, C. J.; Aramaki, H. Chem. Res.
Toxicol. 2011, 24, 855e865.
10. Evans, D. A.; Ennis, M. D.; Mathre, D. J. J. Am. Chem. Soc. 1982, 104, 1737.
11. For a review, see: Kolb, H. C.; VanNieuwenhze, M. S.; Sharpless, K. B. Chem. Rev.
1994, 94, 2483e2547.
12. Kliman, L. T.; Mlynarski, S. N.; Morken, J. P. J. Am. Chem. Soc. 2009, 131,
13210e13211.
13. (a) Lucio Anelli, P.; Biffi, C.; Montanari, F.; Quici, S. J. Org. Chem. 1987, 52,
2559e2562; (b) Siedlecka, R.; Skarzewski, J.; Mlochowski, J. Tetrahedron Lett.
1990, 31, 2177e2180.
14. Shindo, M.; Yoshikawa, T.; Itou, Y.; Mori, S.; Nishii, T.; Shishido, K. Chem.dEur. J.
2006, 12, 524e536.
15. Matsuo, K.; Shindo, M. Org. Lett. 2010, 12, 5346e5349.
4.14. (L)-Xanthatin (1)8c
To a solution of 23 (15 mg, 0.073 mmol) in CH2Cl2 (14 mL) was
added the second-generation HoveydaeGrubbs catalyst (22,
3.9 mg, 0.0073 mmol) and freshly distilled methyl vinyl ketone
(107 mg, 1.5 mmol). The reaction mixture was stirred at 45 ꢀC for
1 h and then the solvent was removed in vacuo to give a crude
product, which was purified by silica gel column chromatography
(30% AcOEt/Hex) to afford 16 mg (85%) of 1 as colorless needles. Mp
25
112.3e113.0 ꢀC (Et2O/Hex). [
a
]
ꢁ16.8 (c 0.35, CHCl3). 1H NMR
D
(600 MHz, CDCl3)
d
: 1.17 (d, J¼7.8 Hz, 3H), 1.86 (ddd, J¼12.6, 12.6,
3.6 Hz, 1H), 2.22 (ddd, J¼12.6, 9.6, 3.6 Hz, 1H), 2.31 (s, 3H), 2.38
(ddd, J¼12.6, 4.2, 2.4 Hz, 1H), 2.53e2.58 (m, 1H), 2.80 (ddd, J¼16.2,
8.4, 2.4 Hz, 1H), 3.09 (ddq, J¼8.4, 4.2, 4.2 Hz, 1H), 4.30 (ddd, J¼12.6,
9.6, 2.4 Hz, 1H), 5.49 (d, J¼3.0 Hz, 1H), 6.20 (d, J¼16.2 Hz, 1H), 6.21
(d, J¼3.0 Hz, 1H), 6.29 (dd, J¼9.6, 2.4 Hz, 1H), 7.08 (d, J¼16.2 Hz, 1H).
16. Ando, K. J. Org. Chem. 1998, 63, 8411e8416.
17. Selected recent examples: (a) Yamamoto, Y.; Yamada, S.; Nishiyama, H. Chem.
dEur. J. 2012, 18, 3153e3156; (b) Fallan, C.; Quigley, P. F.; Lam, H. W. J. Org.
Chem. 2011, 76, 4112e4118; (c) Shaghafi, M. B.; Kohn, B. L.; Jarvo, E. R. Org. Lett.
2008, 10, 4743e4746; (d) Dumas, A. M.; Fillion, E. Org. Lett. 2009, 11, 1919e1922;
(e) Ito, H.; Nagahara, T.; Ishihara, K.; Saito, S.; Yamamoto, H. Angew. Chem., Int.

K. Matsumoto et al. / Tetrahedron 69 (2013) 1043e1049
1049
Ed. 2004, 43, 994e997; (f) Williams, D. R.; Mullins, R. J.; Miller, N. A. Chem.
Commun. 2003, 2220e2221.
21. Gilbert, J. C.; Weerasooriya, U. J. Org. Chem. 1982, 47, 1837.
22. Using OhiraeBestmann reagent, the epimerization of methyl group occurred,
due to its high basicity.
23. Garber, S. B.; Kingsbury, J. S.; Gray, B. L.; Hoveyda, A. H. J. Am. Chem. Soc. 2000,
122, 8168e8179.
24. (a) Schall, A.; Reiser, O. Eur. J. Org. Chem. 2008, 2353e2364; (b) Kitson, R. R. A.;
Millemaggi, A.; Taylor, R. J. K. Angew. Chem., Int. Ed. 2009, 48, 9426e9451.
25. Schinzer, D.; Bauer, A.; Schieber, J. Chem.dEur. J. 1999, 5, 2492e2500.
26. (a) Gage, J. R.; Evans, D. A. Org. Synth. 1990, 68, 77e82; (b) Gage, J. R.; Evans, D.
A. Org. Synth. 1990, 68, 83e91.
18. For enantioselective 1,4 allylation reactions, see: (a) Sieber, J. D.; Morken, J. P. J. Am.
Chem. Soc. 2008, 130, 4978e4983; (b) Sieber, J. D.; Liu, S.; Morken, J. P. J. Am. Chem.
Soc. 2007,129, 2214e2215; (c)Brozek, L. A.; Sieber, J. D.;Morken, J. P. Org. Lett. 2011,
13, 995e997; (d) Shizuka, M.; Snapper, M. L. Angew. Chem., Int. Ed. 2008, 47, 5049.
19. (a) Fleming, I.; Reddy, N. L.; Takaki, K.; Ware, A. C. J. Chem. Soc., Chem. Commun.
1987,1472; (b) Padakanti, S.; Pal, M.; Mukkanti, K.; Iqbal, J. Tetrahedron Lett. 2006,
47, 5969e5971; (c) Hannessian, S.; Gomtyyan, A.; Malek, N. J. Org. Chem. 2000, 65,
5623e5631.
20. (a) Lipshutz, B. H.; Hackmann, C. J. Org. Chem. 1994, 59, 7437e7444; (b) Lipshutz,
B. H.; Ellsworth, E. L.; Dimock, S. H.; Smith, R. A. J. J. Am. Chem. Soc. 1990, 112,
4404e4410.
27. (a) Ando, K. J. Org. Chem. 1997, 62, 1934e1939; (b) Ando, K. J. Org. Chem. 1999,
64, 8406e8408.
28. Frigerio, M.; Santagostino, M.; Sputore, S. J. Org. Chem. 1999, 64, 4537e4538.