Enantioselective synthesis of the tricyclic core of (+)-strigol

Article abstract of DOI:10.1016/j.tet.2016.08.078

An enantioselective synthesis of the tricyclic core structure of (+)-strigol, a potent seed germination stimulant for root parasitic weeds, has been achieved from 2-iodo-4,4-dimethyl-2-cyclohexen-1-one in 14 steps. The key steps include a CBS reduction of an iodo enone to obtain a cyclohexenol derivative of high enantiomeric excess, regioselective epoxide ring opening with a Grignard reagent in a low-polarity solvent, highly diastereoselective addition of vinyllithium to a ketone, and Lewis acid-promoted installation an acetate unit onto a bicyclic allylic acetate intermediate.

Full text of DOI:10.1016/j.tet.2016.08.078

Tetrahedron 72 (2016) 6634e6639
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Enantioselective synthesis of the tricyclic core of (þ)-strigol
*
Aiko Takahashi, Yusuke Ogura, Masaru Enomoto, Shigefumi Kuwahara
Laboratory of Applied Bioorganic Chemistry, Graduate School of Agricultural Science, Tohoku University, Tsutsumidori-Amamiyamachi, Aoba-ku, Sendai
981-8555, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 30 July 2016
Received in revised form 25 August 2016
Accepted 29 August 2016
Available online 31 August 2016
An enantioselective synthesis of the tricyclic core structure of (þ)-strigol, a potent seed germination
stimulant for root parasitic weeds, has been achieved from 2-iodo-4,4-dimethyl-2-cyclohexen-1-one in
14 steps. The key steps include a CBS reduction of an iodo enone to obtain a cyclohexenol derivative of
high enantiomeric excess, regioselective epoxide ring opening with a Grignard reagent in a low-polarity
solvent, highly diastereoselective addition of vinyllithium to a ketone, and Lewis acid-promoted in-
stallation an acetate unit onto a bicyclic allylic acetate intermediate.
Keywords:
Strigol
Ó 2016 Elsevier Ltd. All rights reserved.
Strigolactone
Plant hormone
Epoxide
Total synthesis
1. Introduction
agriculturally important functions of strigolactones prompted
a great deal of studies from various aspects such as isolation of new
(þ)-Strigol (1) is the first member of the strigolactone family of
natural products discovered in 1966 as a potent seed germination
stimulant for the root parasitic weed Striga lutea (syn. Striga asiat-
ica) which causes significant damage to crops of gramineous and
leguminous plants mainly in the tropical and subtropical areas of
Africa and Asia (Fig. 1).1,2 It was originally isolated from the root
exudates of cotton (a non-host plant for the weed),1a and later from
those of its genuine hosts of economical importance (maize, proso
millet, and sorghum).3 Strigolactones are now known to be pro-
duced also by a wide range of plants other than host plants for
parasitic weeds and consist of 15 members.4 This family of natural
members, mode of action, biosynthesis, and identification of
receptor.4,8
Fig. 1. Structures of (þ)-strigol (1) and its tricyclic core (2).
products are structurally characterized by a fused tricyclic
tone core (ABC scaffold) connected through an enol ether linkage to
an -unsaturated -lactone unit (D ring). They all have the same
g-lac-
a
,
b
g
Synthetic studies on strigolactones and their analogs for struc-
tureeactivity relationship investigations have also been actively
conducted by many research groups and numerous publications
have appeared since the first total synthesis of (ꢀ)-strigol by Sih
and co-workers in 19749e11 As for the synthesis of optically active
forms of naturally occurring strigolactones, four types of synthetic
strategies have been adopted with the exception of direct resolu-
tion of their synthetic racemates: (1) preparation of an optically
active ABC scaffold via optical resolution (including enzymatic or
chiral HPLC separation) and its non-diastereoselective connection
to a racemic D ring unit followed by chromatographic separation of
the resulting diastereomeric mixture;12 (2) preparation of an op-
tically active ABC scaffold from the chiral pool followed by the same
C/D ring structure as 1, while their A/B ring portions show some
structural diversity.4 Besides the seed germination stimulatory ac-
tivity toward parasitic weeds,5 strigolactones have been elucidated
to possess some additional functions of enormous biological im-
portance, especially: (1) induction of hyphal branching in arbus-
cular mycorrhizal fungi that enables the fungi to establish their
symbiosis with plants;6 and (2) activity as a plant hormone to
suppress the growth of preformed axillary shoot buds and thereby
inhibit shoot branching.7 These plant physiologically and
* Corresponding author. Fax: þ81 22 717 8783; e-mail address: skuwahar@biochem.
tohoku.ac.jp (S. Kuwahara).
http://dx.doi.org/10.1016/j.tet.2016.08.078
0040-4020/Ó 2016 Elsevier Ltd. All rights reserved.

A. Takahashi et al. / Tetrahedron 72 (2016) 6634e6639
6635
sequence as described in (1);13 (3) preparation of a racemic ABC
scaffold and its connection to an optically active D ring unit fol-
lowed by chromatographic separation of the resulting di-
astereomeric mixture;14 and (4) asymmetric synthesis of an ABC
scaffold and its connection to a racemic D ring unit followed by
diastereomeric separation.15 However, the strategy composed of
asymmetric synthesis of an ABC scaffold and its diastereoselective
unification with a D ring moiety has never been reported so far. As
part of our efforts toward such a totally stereoselective synthesis of
strigolactones, we describe herein a synthetic approach to the tri-
cyclic ABC core (2) of (þ)-strigol. To the best of our knowledge, this
is the first example of the synthesis of 2 that uses neither optical
resolution nor naturally occurring chiral starting materials.12aec,13a
Scheme 2. Enantioselective preparation of 7 and its conversion into siloxy epoxide 13.
2. Results and discussion
allylmagnesium bromide in refluxing ether,22 gave a 1.1:1 mixture
of 14 and its regioisomer 140,23 changing the solvent from ether to
toluene/hexane (1:1) significantly increased the ratio to 3.2:1,
providing the desired isomer 14 in 73% isolated yield.24,25 To obtain
bicyclic intermediate 18, the alcohol 14 was first oxidized to olefinic
ketone 15, the ozonolysis of which afforded 16. Z-Selective iodo-
methylenation of the aldehyde 16 followed by intramolecular
NozakieHiyamaeKishi coupling of the resulting iodo ketone 17
furnished 18.26,27 Compound 18 was also prepared much more ef-
ficiently in two steps from 15 by its exposure to vinyllithium in THF
at ꢁ78 ꢂC to form allylic alcohol 19 as the exclusive diastereomer
and subsequent ring-closing metathesis of the diene product 19.28
It is worth mentioning that the reaction of 15 with vinylmagnesium
chloride (instead of vinyllithium) in THF was very sluggish at low
temperatures (ꢁ78 to ꢁ50 ꢂC) presumably due to steric congestion
around the ketone functionality, and a substantial amount of the
corresponding epimeric alcohol (1-epi-19) was also produced when
the reaction temperature was raised to room temperature.
Scheme 1 outlines our retrosynthetic analysis of 2. Compound 2
was traced back to olefinic carboxylate 3 with the intention of in-
stalling the
g-lactone and the double bond in 2 by halolactonization
of 3 and subsequent dehydrohalogenation. The
g,d-unsaturated
carboxylate 3 would be obtainable by SN20-type introduction of an
acetate unit into 4. For the construction of the bicyclic allylic alcohol
4, we envisaged a two-step sequence comprising the addition of
a vinyl group to ketone 5 from its bottom face and ring-closing
metathesis (RCM) of the resulting diene product. The ketone 5
would be prepared by regioselective ring opening of epoxide 6,
which in turn should be derived from optically active cyclohexenol
derivative 7 by hydroxyl-directed epoxidation.
Scheme 1. Retrosynthetic analysis of 2.
Our first task for the synthesis of 2 was the preparation of 7 in
high enantiomeric purity (Scheme 2). Although compound 7 was
known to be preparable by a Noyori asymmetric reduction of the
corresponding enone, the enantiomeric excess (ee) of the alcoholic
product 7 was reported to be only 47%.16,17 We, therefore, adopted
an alternative route via iodine-substituted cyclohexenol derivative
11, the (R)-enantiomer of which had previously been synthesized in
98% ee by a modified CoreyeBakshieShibata (CBS) reduction using
diethylaniline$BH3 and a catalytic amount of (S)-2-methoxy-CBS-
oxazaborolidine.18 The reduction of 9 using (R)-2-methoxy-CBS
oxazaborolidine as catalyst proceeded smoothly, providing 11 in
92% yield;18c,19 the iodo enone 9 in turn was readily prepared from
enone 8 almost quantitatively according to the literature (I2, DMAP,
K2CO3, THFeH2O).20 Hydrogenolytic removal of the iodine atom in
11 was best performed with 5% Pd/C in MeOH in the presence of
Et3N as catalyst poison,21 furnishing 7 in a satisfactory overall yield
of 76% from 8. Diastereoselective epoxidation of 12 with MCPBA in
the presence of solid NaHCO3 afforded 12 as an inseparable 93:7 cis/
trans mixture. Finally, protection of the alcohol as its TBS ether
provided 13.
Scheme 3. Preparation of bicyclic allylic alcohol 18.
The installation of an acetate unit at the C2 position of 18 was
first attempted by applying the JohnsoneClaisen rearrangement to
the cyclic allylic alcohol (Scheme 5, a). Treatment of 18 with triethyl
or trimethyl orthoacetate in the presence of an acid catalyst (pro-
pionic acid, p-anisic acid, or o-nitrophenol) at high temperatures
ranging from 135 to 180 ꢂC, however, gave no desired product 20,
With the protected cis-epoxy alcohol 13 in hand, we next pro-
ceeded to its epoxide ring opening with allylmagnesium bromide
(Scheme 3). Although the epoxide 13, upon exposure to

6636
A. Takahashi et al. / Tetrahedron 72 (2016) 6634e6639
resulting in the formation of complex mixtures.29 The Eschenmo-
sereClaisen rearrangement of 18 to 21 was also unsuccessful (b).
The IrelandeClaisen rearrangement of acetate 22, obtained by
acetylation of 18, was also attempted by treating 22 with a base
(MNR02¼LDA or KHMDS) and a silylating agent (TMSCl or TBSCl) in
THF, THF/HMPA, or toluene, and then stirring the mixture at tem-
peratures ranging from ꢁ78 to 110 ꢂC (c). However, neither the
desired product 23 nor the corresponding carboxylic acid was
detected in the reaction mixture. The introduction of a malonate
unit into 22 by the TsujieTrost reaction was next examined (d).30
Although the reaction of 22 with dimethyl malonate was con-
ducted under various conditions (base: NaH, K2CO3, or Cs2CO3;
Pd(0) species: Pd(PPh3)3 or Pd2(dba)3; ligand: Ph3P, n-Bu3P, or
dppe), none of the conditions gave the desired product 24, resulting
in the recovery of the starting material 22 in most cases. The in-
stallation of an acetate unit onto 22 was eventually achieved by
modification of the procedure developed by Mukaiyama and co-
workers which had rarely been documented in the literature.31
When a mixture of 22 and silyl ketene acetal 25 in CH2Cl2 was
treated with BF3$OEt2 at ꢁ78 ꢂC, a quick reaction took place to give
an inseparable mixture of 26 and 260 in 86% yield, albeit with
a modest selectivity of 2:1. The stereochemistry of each epimer was
assigned later at the stage of 29/290 (see Scheme 5) on the basis of
their NOESY spectra (vide infra).
Scheme 5. Completion of the synthesis of 2.
stereochemistries as depicted in Scheme 5 (see Supplementary
data). The mixture of 29 and 290 was treated with DBU in toluene to
afford, after silica gel column chromatographic separation, olefinic
lactone 31 together with recovered 290; the recovery of 290 sup-
ported our stereochemical assignment to the tricyclic g-lactones in
light of the anti elimination mechanism in E2 reactions.34 Finally,
removal of the TBS group in 31 furnished the target molecule 2, the
1H and 13C NMR spectra of which showed good agreement with
those reported.12a,b,35 The melting point and the specific rotation of
25
2 [mp¼104e106 ꢂC, [
a
]
¼ þ8.24 (c¼1.25, CHCl3)] were also vir-
D
25
tually identical with authentic data [mp¼103e104 ꢂC, [
a
]
¼ þ8.28
D
(c¼1.3, CHCl3)].12a Since compound 2 was previously transformed
into (þ)-strigol (1), albeit in non-diastereoselective manner,12aec
the present synthesis constitutes a formal total synthesis of 1.36
3. Conclusion
In conclusion, an enantioselective synthesis of the tricyclic core
structure (2) of (þ)-strigol (1) has been achieved from 2-iodo-4,4-
dimethyl-2-cyclohexen-1-one 9 by a 14-step sequence that fea-
tures: (1) preparation of cyclohexenol derivative 7 of high enan-
tiomeric excess (98% ee) by a modified CBS reduction of 9 coupled
with hydrogenolysis of the resulting allylic alcohol 11; (2) regio-
selective epoxide ring opening of intermediate 13 with allylmag-
nesium bromide in a solvent of low polarity (13/14); (3) highly
diastereoselective formation of bicyclic allylic alcohol 18 in two
steps (15/19/18); and (4) Lewis acid-promoted introduction of
an acetate unit into allyl acetate 22 (22/26). Efforts to improve the
efficiency of the transformation of 22 into 2 are now in progress and
will be reported in due course along with diastereoselective con-
version of 2 into (þ)-strigol (1).
Scheme 4. Installation of an acetate unit onto 18.
The final stage of our synthesis of 2 is shown in Scheme 5. The
2:1 mixture of 26 and 260 obtained in Scheme 4 was subjected to
alkaline hydrolysis to afford carboxylic acid 27 (dr¼2:1), which was
then exposed to NBS in CHCl3 in the presence of guanidine de-
rivative 28.32 This bromolactonization reaction provided a mixture
4. Experimental section
4.1. General
containing diastereomeric g d-lactone 30
-lactones 29 and 290, and
in a ratio of ca. 1:1:1, which was easily separated by silica gel col-
umn chromatography into a mixture of 29 and 290, and 30. By re-
peating the separation of the mixture (29/290), each diastereomer
could be isolated in a pure state,33 and the analysis of the NOESY
spectra of 29 and 290 enabled the determination of their
IR spectra were recorded by a Jasco FT/IR-4100 spectrometer
using an ATR (ZnSe) attachment. NMR spectra were recorded with
TMS as an internal standard in CDCl3 by a Varian 400-MRTT spec-
trometer (400 MHz for 1H and 100 MHz for 13C) unless otherwise
stated. Optical rotation values were measured with a Jasco P-2200

A. Takahashi et al. / Tetrahedron 72 (2016) 6634e6639
6637
polarimeter, and mass spectra were obtained with Jeol JMS-700
spectrometer operated in the EI or FAB mode. Melting points
were determined with a Yanaco MP-J3 apparatus and are un-
corrected. Merck silica gel 60 (70e230 mesh) was used for column
chromatography. Analytical thin-layer chromatography was per-
formed using Merck silica gel 60 F254 plates (0.25 mm thick). Sol-
vents for reactions were distilled prior to use: THF from Na and
benzophenone; CH2Cl2 and DMF from CaH2; toluene, hexane, and
ether from LiAlH4. All air- or moisture-sensitive reactions were
conducted under a nitrogen atmosphere unless otherwise stated.
overnight. The mixture was quenched with saturated aqueous
NaHCO3 at 0 ꢂC and extracted with Et2O. The extract was succes-
sively washed with water and brine, dried (MgSO4), and concen-
trated in vacuo. The residue was purified by silica gel column
chromatography (hexane/EtOAc, 20:1) to give 13 (3.32 g, 92%) as
19
a colorless oil. [
a
]
¼ ꢁ26.0 (c¼2.00, CHCl3). IR: ¼1110 (w), 913
n
(s), 744 (s) cmꢁ1. 1DH NMR:
d
¼0.10 (s, 3H), 0.11 (s, 3H), 0.91 (s, 9H),
1.01 (s, 3H), 1.07 (s, 3H), 1.04e1.12 (m, 1H), 1.29e1.35 (m, 1H),
1.38e1.45 (m, 1H), 1.50e1.58 (m, 1H), 2.82 (dd, J¼4.0, 1.6 Hz, 1H),
3.16e3.18 (m, 1H), 4.00 (ddd, J¼9.6, 5.6, 2.0 Hz, 1H) ppm. 13C NMR:
d
¼ꢁ4.6, e4.5, 18.3, 24.7, 25.7, 25.9 (3C), 28.6, 28.8, 35.7, 57.2, 62.6,
4.1.1. (S)-2-Iodo-4,4-dimethylcyclohex-2-en-1-ol (11). To a stirred
solution of 10 (203 mg, 0.801 mmol) in THF (12 mL) was added
70.1 ppm. HRMS (EI): calcd for C14H28O2Si [M]þ 256.1858; found
256.1859.
B(OMe)3 (89
mL, 0.80 mmol) at room temperature. After 1 h of
stirring, PhNMe2$BH3 (1.6 mL, 9.0 mmol) and a solution of 9 (2.00 g,
8.00 mmol) in THF (15 mL) were successively added, and the stir-
ring was continued for 1 h. The mixture was quenched with MeOH,
diluted with saturated aqueous NH4Cl, and extracted with Et2O. The
extract was successively washed with water and brine, dried
(MgSO4), and concentrated in vacuo. The residue was purified by
4.1.5. (1S,5S,6S)-6-Allyl-5-[(tert-butyldimethylsilyl)oxy]-2,2-
dimethylcyclohexan-1-ol (14) and (1R,2S,6S)-2-Allyl-6-[(tert-bu-
tyldimethylsilyl)oxy]-3,3-dimethylcyclohexan-1-ol (140). A solution
of allylmagnesium bromide in Et2O (1.0 m, 19.4 mL, 19.4 mmol) was
placed in a flask. The solvent was removed in vacuo and then the
residue was diluted with hexane (32 mL). To the resulting sus-
pension was added a solution of 13 (3.32 g, 12.9 mmol) in toluene
(32 mL) at room temperature. After 5 h of stirring at 40 ꢂC, the
mixture was quenched with saturated aqueous NH4Cl at 0 ꢂC and
extracted with Et2O. The extract was successively washed with
water and brine, dried (MgSO4), and concentrated in vacuo. The
residue was purified by silica gel column chromatography (hexane/
EtOAc, 50:1) to give 14 (2.83 g, 73%) as a colorless oil. Data for 14:
silica gel column chromatography (hexane/EtOAc, 30:1) to give 11
17
(1.85 g, 92%) as a colorless oil. [
n
a
]
¼ ꢁ42.5 (c¼0.900, CH2Cl2). IR:
D
¼3446 (br w), 1669 (w) cmꢁ1. 1H NMR:
¼1.00 (s, 3H), 1.04 (s, 3H),
d
1.50 (ddd, J¼13.6, 8.4, 3.2 Hz, 1H), 1.63 (ddd, J¼13.6, 9.8, 3.2 Hz, 1H),
1.82e1.91 (m,1H), 2.01 (d, J¼4.8 Hz,1H, OH), 2.02e2.10 (m,1H), 4.13
(br q, J¼5.0 Hz, 1H), 6.24 (s, 1H) ppm. 13C NMR:
¼28.0, 28.8 (2C),
d
32.2, 37.4, 72.0, 102.5, 150.3 ppm. HRMS (EI): calcd for C8H13OI [M]þ
252.0011; found 252.0010.
Rf¼0.36 (hexane/EtOAc, 10:1; Merck silica gel 60 F254, 0.25 mm
19
thick). [
a
]
¼ þ29.7 (c¼2.00, CHCl3). IR: ¼3503 (m), 3075 (w),
n
D
4.1.2. (S)-4,4-Dimethylcyclohex-2-en-1-ol (7). A mixture of 11
(8.95 g, 35.5 mmol), Et3N (5.90 mL, 42.3 mmol), and 5% Pd/C
(4.88 g) in MeOH (170 mL) was stirred at room temperature for 1 h
under a hydrogen atmosphere. The mixture was filtered through
a pad of Celite, and the filtrate was concentrated in vacuo. The
residue was diluted with water and extracted with EtOAc. The ex-
tract was successively washed with water and brine, dried (MgSO4),
1253 (m), 1100 (m), 837 (m) cmꢁ1. 1H NMR:
d¼0.06 (s, 6H), 0.89 (s,
9H), 0.90 (s, 3H), 0.96 (s, 3H), 1.13 (ddd, J¼13.8, 13.8, 3.6 Hz, 1H),
1.35e1.72 (m, 5H), 2.28e2.37 (m, 1H), 2.48e2.56 (m, 1H), 3.06 (dd,
J¼10.4, 5.2 Hz, 1H), 3.32 (ddd, J¼10.4, 10.4, 4.6 Hz, 1H), 5.05 (dm,
J¼10.2 Hz, 1H), 5.15 (dm, J¼17.2 Hz, 1H), 5.95 (ddt, J¼17.2, 10.2,
7.2 Hz, 1H) ppm. 13C NMR:
d
¼ꢁ4.7, e3.7, 18.1, 25.9 (4C), 28.9, 31.2,
32.6, 35.1, 35.2, 47.1, 72.3, 78.8, 116.4, 137.4 ppm. HRMS (FAB): calcd
and concentrated in vacuo to give 7 (3.87 g, 86%) as a colorless oil,
for C17H35O2Si [MþH]þ 299.2506; found 299.2409. Data for 140:
21
which was pure enough to be used for the next step. [
a
]
¼ ꢁ104
Rf¼0.53 (hexane/EtOAc, 10:1; Merck silica gel 60 F254, 0.25 mm
D
18
(c¼0.700, CHCl3). IR:
n
¼3346 (m), 3020 (w), 1056 (s), 746 (m) cmꢁ1
.
thick). [
a
]
¼ þ45.7 (c¼0.88, CHCl3). IR: ¼3575 (w), 3075 (w), 1637
n
D
1H NMR:
d
¼0.97 (s, 3H), 1.02 (s, 3H), 1.39e1.47 (m, 2H), 1.54e1.67
(w), 1254 (m), 1083 (s), 837 (s), 775 (m) cmꢁ1. 1H NMR:
d
¼0.08 (s,
(m, 2H), 1.87e1.96 (m, 1H), 4.15 (br s, 1H), 5.53 (d, J¼10.0 Hz, 1H),
6H), 0.81 (s, 3H), 0.92 (s, 9H), 0.95 (s, 3H),1.01e1.10 (m,1H), 1.50 (dt,
J¼10.4, 5.2 Hz, 1H), 1.56e1.67 (m, 3H), 1.76 (d, J¼10.4 Hz, 1H, OH),
2.15e2.28 (m, 2H), 3.34 (ddd, J¼10.4, 10.4, 2.8 Hz, 1H), 3.92e3.95
(m, 1H), 4.91 (dm, J¼10.4 Hz, 1H), 5.01 (dq, J¼16.8, 1.9 Hz, 1H), 5.97
5.60 (dd, J¼10.0, 2.8 Hz, 1H) ppm. 13C NMR:
¼29.0, 29.1, 29.2, 31.9,
d
33.6, 65.9, 127.3, 140.7 ppm. HRMS (EI): calcd for C8H14O [M]þ
126.1045; found 126.1043.
(ddt, J¼16.8,10.4, 6.8 Hz,1H) ppm. 13C NMR:
¼ꢁ4.9, e4.4,18.1, 25.8
d
4.1.3. (1S,2S,6R)-5,5-Dimethyl-7-oxabicyclo[4.1.0]heptan-2-ol
(12). To a stirred mixture of 7 (1.01 g, 8.00 mmol) and NaHCO3
(739 mg, 8.80 mmol) in CH2Cl2 (50 mL) was added MCPBA (70%
purity, 2.17 g, 8.80 mmol) at 0 ꢂC. After 6 h, the mixture was con-
centrated in vacuo to a half of its original volume and filtered
through a short column of alumina. The filtrate was concentrated in
vacuo and the residue was purified by silica gel column chroma-
(4C), 28.1, 30.6, 32.5, 34.7, 34.8, 47.4, 71.0, 74.1, 113.7, 141.2 ppm.
HRMS (FAB): calcd for
299.2405.
C
17H35O2Si [MþH]þ 299.2506; found
4.1.6. (5S,6R)-6-Allyl-5-[(tert-butyldimethylsilyl)oxy]-2,2-
dimethylcyclohexan-1-one (15). To a stirred solution of 14 (80.0 mg,
0.268 mmol) in CH2Cl2 (1.0 mL) were added successively iPr2NEt
tography (hexane/EtOAc, 2:1e1:1) to give 12 (cis/trans¼93:7, 1.13 g,
(233 mL, 1.34 mmol), DMSO (95 mL, 1.1234 mmol), and SO3$Py
18
99%) as a colorless oil. [
a
]
¼ ꢁ37.9 (c¼1.00, CHCl3). IR:
n
¼3420 (m),
(128 mg, 0.804 mmol) at 0 ꢂC. After 3 h of stirring at ambient
temperature, the mixture was quenched with water and extracted
with CH2Cl2. The extract was successively washed with water and
brine, dried (MgSO4), and concentrated in vacuo. The residue was
D
1064 (w), 912 (w) cmꢁ1. 1H NMR:
d
¼1.02 (s, 3H), 1.06 (s, 1H, OH),
1.08 (s, 3H), 1.36 (ddd, J¼13.8, 9.2, 3.2 Hz, 1H), 1.42e1.51 (m, 1H),
1.53e1.62 (m, 1H), 1.99e2.04 (m, 1H), 2.93 (d, J¼3.6 Hz, 1H), 3.36 (t,
J¼3.6 Hz, 1H), 3.97e4.04 (m, 1H) ppm. 13C NMR:
d
¼25.9, 26.3, 26.4,
purified by silica gel column chromatography (hexane/EtOAc, 50:1)
19
29.1, 32.0, 56.4, 63.6, 66.3 ppm. HRMS (EI): calcd for C8H14O2 [M]þ
142.0994; found 142.0989.
to give 15 (73.0 mg, 92%) as a colorless oil. [
a
]
D
¼ ꢁ2.9 (c¼2.00,
CHCl3). IR:
n
¼3080 (w), 1711 (vs), 1254 (m), 1097 (s), 838 (s) cmꢁ1
.
1H NMR:
d
¼0.06 (s, 3H), 0.07 (s, 3H), 0.91 (s, 9H), 1.03 (s, 3H), 1.18 (s,
4.1.4. tert-Butyl{[(1R,2S,6R)-5,5-dimethyl-7-oxabicyclo[4.1.0]heptan-
2-yl]oxy}dimethylsilane (13). To a stirred solution of 12 (2.00 g,
14.1 mmol) in DMF (45 mL) were added successively imidazole
(2.80 g, 41.1 mmol) and TBSCl (4.10 g, 27.2 mmol) at 0 ꢂC. The
mixture was gradually warmed to room temperature and stirred
3H), 1.37 (ddd, J¼14.0, 12.0, 5.6 Hz, 1H), 1.67 (dt, J¼14.0, 3.8 Hz, 1H),
1.82e1.95 (m, 2H), 2.32e2.44 (m, 2H), 2.68 (ddd, J¼10.0, 7.6, 4.0 Hz,
1H), 3.47 (ddd, J¼10.0, 10.0, 5.2 Hz, 1H), 4.95 (dm, J¼10.0 Hz, 1H),
5.02 (dm, J¼17.2 Hz, 1H), 5.82 (ddt, J¼17.2, 10.0, 6.8 Hz, 1H) ppm. 13
C
NMR:
d
¼ꢁ4.8, e4.0, 18.0, 24.9, 25.1, 25.8 (3C), 29.8, 31.3, 35.0, 44.3,

6638
A. Takahashi et al. / Tetrahedron 72 (2016) 6634e6639
55.5, 74.6, 115.6, 137.3, 213.6 ppm. HRMS (EI): calcd for C17H32O2Si
[M]þ 296.2172; found 296.2172.
33.6, 36.3, 38.3, 49.6, 79.1, 79.4, 119.1, 160.3, 171.2 ppm. HRMS (EI):
calcd for C19H34O3Si [M]þ 338.2277; found 338.2279.
4.1.7. (1S,5S,6R)-6-Allyl-5-((tert-butyldimethylsilyl)oxy)-2,2-
dimethyl-1-vinylcyclohexan-1-ol (19). To a stirred solution of tet-
ravinyltin (1.7 mL, 9.34 mmol) in THF (40 mL) was added a solution
of nBuLi (1.6 m in hexane, 23 mL, 36.8 mmol) at ꢁ78 ꢂC. After
30 min of stirring at the same temperature, the mixture was further
stirred at ambient temperature for 15 min. To the resulting mixture
was added a solution of 15 (6.95 g, 23.4 mmol) in THF (60 mL) while
stirring at ꢁ78 ꢂC. After 40 min, the mixture was quenched with
saturated aqueous NH4Cl and extracted with Et2O. The extract was
successively washed with water and brine, dried (MgSO4), and
concentrated in vacuo. The residue was purified by silica gel column
4.1.10. (3aR,5S,8bS)-5-[(tert-Butyldimethylsilyl)oxy]-8,8-dimethyl-
3,3a,4,5,6,7,8,8b-octahydro-2H-indeno[1,2-b]furan-2-one
(31). To
a stirred solution of 22 (115 mg, 0.340 mmol) in CH2Cl2 (3.4 mL)
were successively added 25 (148
mL, 0.678 mmol) and BF3$OEt2
(51
m
L, 0.41 mmol) at ꢁ78 ꢂC. After 1 h, the mixture was quenched
with saturated aqueous NaHCO3 and extracted with Et2O. The ex-
tract was successively washed with water and brine, dried (MgSO4),
and concentrated in vacuo. The residue was purified by silica gel
column chromatography (hexane/EtOAc, 70:1) to give a 2:1 mix-
ture of 26 and 260 (103 mg, 86%) as a colorless oil. To a stirred so-
lution of the mixture (100 mg, 0.284 mmol) in MeOH/hexane (1:1,
chromatography (SiO2 containing 10 w/w % K2CO3; hexane/EtOAc,
1.3 mL) was added 5 m aqueous NaOH (630 mL, 3.15 mmol) at room
24
70:1) to give 19 (7.52 g, 99%) as a colorless oil. [
a
]
¼ ꢁ1.5 (c¼2.00,
temperature. After 2 h, the mixture was neutralized with 2 m
aqueous HCl at 0 ꢂC and extracted with Et2O. The extract was
successively washed with water and brine, dried (MgSO4), and
concentrated in vacuo. The residue was purified by silica gel column
chromatography (hexane/EtOAc, 8:1) to give 27 (91 mg, 95%, dr 2:1)
as a colorless oil. To a stirred solution of 27 (95.0 mg, 0.281 mmol)
in CHCl3 (1.4 mL) were successively added NBS (50.0 mg,
D
CHCl3). IR:
n
¼3566 (m), 3070 (w),1254 (m),1077 (m), 837 (m) cmꢁ1
.
1H NMR (600 MHz, DMSO-d6):
d¼0.00 (s, 3H), 0.02 (s, 3H), 0.69 (s,
3H), 0.83 (s, 9H), 0.93 (s, 3H), 1.20e1.27 (m, 1H), 1.39e1.48 (m, 2H),
1.60 (dt, J¼10.3, 5.2 Hz, 1H), 1.65e1.69 (m, 1H), 1.79e1.85 (m, 1H),
2.13e2.19 (m, 1H), 3.42e3.47 (m, 1H), 3.94 (s, 1H, OH), 4.74 (dm,
J¼10.2 Hz, 1H), 4.81 (dm, J¼17.1 Hz, 1H), 5.12 (dd, J¼10.9, 2.5 Hz,
1H), 5.26 (dd, J¼16.9, 2.5 Hz, 1H), 5.90e5.98 (m, 2H) ppm. 13C NMR
0.281 mmol) and 28 (4.0 mL, 0.032 mmol) at room temperature.
(150 MHz, DMSO-d6):
d
¼ꢁ4.3, e3.5, 18.1, 22.6, 26.26 (3C), 26.32,
After 5 min, the mixture was quenched with saturated aqueous
Na2S2O3 and extracted with Et2O. The extract was successively
washed with water and brine, dried (MgSO4), and concentrated in
vacuo. The residue was purified by silica gel column chromatog-
raphy (hexane/EtOAc, 30:1) to give a mixture of 29, 290, and 30
which was taken up in toluene (2.7 mL). To the solution was added
32.1, 32.8, 34.7, 37.8, 49.9, 74.5, 79.3, 113.4, 114.9, 139.4, 142.1 ppm.
HRMS (EI): calcd for C19H36O2Si [M]þ 324.2485; found 324.2488.
4.1.8. (3aS,7S,7aR)-7-[(tert-Butyldimethylsilyl)oxy]-4,4-dimethyl-
1,4,5,6,7,7a-hexahydro-3aH-inden-3a-ol (18). A mixture of 19
(400 mg, 1.23 mmol) and the second generation Grubbs catalyst
(104 mg, 0.123 mmol) in CH2Cl2 (12 mL) was heated under reflux
for 1.5 h and then cooled to room temperature. To the mixture was
DBU (61 mL, 0.41 mmol) and the resulting solution was stirred at
80 ꢂC for 26 h. The mixture was cooled to room temperature and
concentrated in vacuo. The residue was purified by silica gel column
added DMSO (438
stirred overnight. The mixture was concentrated in vacuo and the
residue was purified by silica gel column chromatography (hexane/
EtOAc, 30:1) to give 18 (358 mg, 98%) as a colorless oil. [
(c¼0.515, CHCl3). IR:
1005 (m) cmꢁ1. 1H NMR:
m
L, 6.17 mmol) and the resulting mixture was
chromatography (hexane/EtOAc, 30:1) to give 31 (24.0 mg, 25%
24
from 27) as a colorless oil. [
a]
¼ ꢁ11 (c¼0.520, CHCl3). IR:
n
¼1776
D
(s), 1254 (m), 1167 (m), 1090 (m), 839 (m) cmꢁ1. 1H NMR:
d
¼0.068
24
a
]
¼ þ75.8
(s, 3H), 0.074 (s, 3H), 0.90 (s, 9H), 1.08 (s, 3H), 1.15 (s, 3H), 1.42 (ddd,
J¼13.0, 13.0, 3.0 Hz, 1H), 1.54 (ddd, J¼13.0, 5.6, 3.0 Hz, 1H), 1.70
(dddd, J¼13.0, 13.0, 9.0, 3.0 Hz, 1H), 1.82e1.90 (m, 1H), 2.35 (dd,
J¼18.4, 5.8 Hz, 1H), 2.43 (br d, J¼16.8 Hz, 1H), 2.51 (dd, J¼16.8,
8.0 Hz, 1H), 2.79 (dd, J¼18.4, 10.4 Hz, 1H), 2.98e3.08 (m, 1H), 4.12
(br t, J¼7.0 Hz, 1H), 5.46 (dt, J¼7.6, 2.0 Hz, 1H) ppm. 13C NMR:
D
n
¼3480 (br w), 3046 (w), 1255 (m), 1094 (s),
d
¼0.03 (s, 6H), 0.88 (s, 9H), 1.01 (s, 3H),
1.06 (s, 3H), 1.11 (ddd, J¼14.0, 8.8, 7.6 Hz, 1H), 1.24e1.32 (br s, 1H,
OH), 1.40 (dt, J¼14.0, 4.0 Hz, 1H), 1.53e1.62 (m, 2H), 2.04 (dd, J¼8.4,
5.2 Hz,1H), 2.21 (d, J¼16.8 Hz,1H), 2.66 (dd, J¼16.8, 5.2 Hz,1H), 3.12
(ddd, J¼8.4, 8.4, 7.2 Hz, 1H), 5.98e6.02 (m, 2H) ppm. 13C NMR:
d
¼ꢁ4.9, e4.3, 18.1, 25.8 (3C), 27.3, 27.9, 30.0, 32.2, 34.4, 36.0, 37.6,
d
¼ꢁ4.6, e3.8, 18.0, 24.0, 25.8, 25.9 (3C), 29.7, 35.1, 35.3, 35.7, 53.0,
38.8, 68.3, 89.9, 141.4, 143.5, 177.4 ppm. HRMS (EI): calcd for
75.3, 88.3, 135.7, 136.1 ppm. HRMS (EI): calcd for C17H32O2Si [M]þ
296.2171; found 296.2173.
C
19H32O3Si [M]þ 336.2121; found 336.2119. The intermediates 29
and 290 could be separated by repeated silica gel column chroma-
tography (hexane/EtOAc, 30:1) and exhibited the following physi-
23
4.1.9. (3aS,7S,7aR)-7-[(tert-Butyldimethylsilyl)oxy]-4,4-dimethyl-
1,4,5,6,7,7a-hexahydro-3aH-inden-3a-yl acetate (22). To a stirred
solution of 18 (350 mg, 1.18 mmol) in toluene (14 mL) were suc-
cessively added Et3N (1.60 mL, 11.5 mmol), DMAP (29 mg,
0.24 mmol) and Ac2O (1.10 mL, 11.6 mmol) at room temperature.
The mixture was heated under reflux for 33 h and then cooled to
room temperature before being quenched with water and extracted
with ether. The extract was successively washed with water and
brine, dried (MgSO4), and concentrated in vacuo. The residue was
cochemical properties. Data for 29: mp 107e109 ꢂC. [
a
]
¼ þ8.4
D
(c¼0.500, CHCl3). IR:
n
¼1789 (vs),1157 (m),1100 (m) cmꢁ1. 1H NMR:
d
¼0.05 (s, 3H), 0.06 (s, 3H), 0.88 (s, 9H), 1.26 (s, 3H), 1.36 (s, 3H),
1.29e1.36 (m, 1H), 1.48e1.60 (m, 1H), 1.69e1.78 (m, 2H), 1.99e2.09
(m, 2H), 2.20 (dt, J¼13.2, 10.6 Hz, 1H), 2.36 (dd, J¼18.4, 1.8 Hz, 1H),
2.80 (dd, J¼18.4, 10.0 Hz, 1H), 3.17e3.26 (m, 1H), 3.87 (ddd, J¼10.6,
9.0, 5.2 Hz, 1H), 5.19 (d, J¼5.6 Hz, 1H) ppm. 13C NMR:
¼ꢁ4.7, e4.2,
d
18.0, 24.9, 25.8 (3C), 28.7, 31.9, 35.7, 36.2, 36.7, 39.0, 39.2, 47.6, 74.5,
89.8, 95.9, 176.8 ppm. HRMS (EI): calcd for C19H33O3BrSi [M]þ
23
purified by silica gel column chromatography (hexane/EtOAc, 50:1)
416.1383; found 416.1382. Data for 290: mp 70e72 ꢂC. [
a
]
¼ ꢁ7.1
D
23
to give 22 (291 mg, 73%) as a colorless oil. [
a
]
D
¼ ꢁ89.9 (c¼1.50,
(c¼0.500, CHCl3). IR:
n
¼1787 (s), 1253 (m), 1155 (m), 1092 (m), 836
CHCl3). IR:
n
¼1733 (s), 1245 (s), 1095 (m), 838 (m) cmꢁ1. 1H NMR:
(m) cmꢁ1. 1H NMR (600 MHz):
d
¼0.04 (s, 3H), 0.05 (s, 3H), 0.87 (s,
d
¼0.05 (s, 6H), 0.89 (s, 9H), 1.09 (s, 3H), 1.13 (s, 3H), 1.19 (ddd,
9H), 1.20 (s, 3H), 1.36 (s, 3H), 1.51e1.61 (m, 2H), 1.66 (dd, J¼14.4,
3.2 Hz,1H),1.69e1.74 (m,1H), 2.00e2.07 (m,1H), 2.38 (d, J¼18.4 Hz,
1H), 2.48 (br t, J¼8.9 Hz,1H), 2.74 (ddd, J¼14.4,11.3, 7.7 Hz,1H), 2.85
(dd, J¼18.4, 10.2 Hz, 1H), 3.28 (ddd, J¼10.6, 10.6, 4.7 Hz, 1H),
J¼13.6, 13.6, 4.4 Hz, 1H), 1.46 (dt, J¼13.6, 3.4 Hz, 1H), 1.58e1.64 (m,
1H), 1.65e1.73 (m, 1H), 1.97 (ddd, J¼15.0, 7.6, 5.2 Hz, 1H), 2.01 (s,
3H), 2.10 (ddd, J¼15.0, 7.6, 2.0 Hz, 1H), 2.74e2.82 (m, 1H), 3.05 (ddd,
J¼10.4, 10.4, 4.8 Hz, 1H), 5.42 (t, J¼2.4 Hz, 1H), 5.57e5.61 (m, 1H)
3.31e3.37 (m, 1H), 5.12 (d, J¼6.0 Hz, 1H) ppm. 13C NMR:
¼ꢁ4.7,
d
ppm. 13C NMR:
d
¼ꢁ4.6, e3.9, 18.0, 21.4, 25.75, 25.82 (3C), 28.2, 31.8,
e3.8, 17.9, 25.5, 25.8 (3C), 30.5, 31.1, 35.5, 36.3, 37.0, 37.3, 37.7, 55.1,

A. Takahashi et al. / Tetrahedron 72 (2016) 6634e6639
6639
73.6, 91.2, 91.6, 176.8 ppm. HRMS (EI): calcd for C19H33O3BrSi [M]þ
416.1383; found 416.1382.
9. Heather, J. B.; Mittal, R. S. D.; Sih, C. J. J. Am. Chem. Soc. 1974, 96, 1976e1977.
10. (a) Boyer, F.-D.; de Saint Germain, A.; Pillot, J.-P.; Pouvreau, J.-B.; Chen, V. X.;
ꢀ
Ramos, S.; Stevenin, A.; Simier, P.; Delavault, P.; Beau, J.-M.; Rameau, C. Plant
Physiol. 2012, 159, 1524e1544; (b) Lachia, M.; Wolf, H. C.; Jung, P. J. M.; Scre-
panti, C.; De Mesmaeker, A. Bioorg. Med. Chem. Lett. 2015, 25, 2184e2188; (c)
Zwanenburg, B.; Regeling, H.; van Tilburg-Joukema, C. W.; van Oss, B.; Mo-
lenveld, P.; de Gelder, R.; Tinnemans, P. Eur. J. Org. Chem. 2016, 2163e2169; (d)
Takahashi, I.; Fukui, K.; Asami, T. Pest Manag. Sci. [Online early access]. doi: 10.
1002/ps.4265.
4.1.11. (3aR,5S,8bS)-5-Hydroxy-8,8-dimethyl-3,3a,4,5,6,7,8,8b-octa-
hydro-2H-indeno[1,2-b]furan-2-one (2). To
(20.0 mg, 0.0594 mmol) in THF (110 L) was added a solution of
TBAF (1.0 m in THF, 118 L, 0.12 mmol) at room temperature. After
a
solution of 31
m
m
11. For a review, see Zwanenburg, B.; Zeljkovic, S. C.; Pospísil, T. Pest Manag. Sci.
10 min, the mixture was quenched with saturated aqueous NaHCO3
and extracted with EtOAc. The extract was successively washed
with saturated water and brine, dried (MgSO4), and concentrated in
vacuo. The residue was purified by silica gel column chromatog-
raphy (hexane/EtOAc, 5:1e2:1) and recrystallization (hexane/
CH2Cl2) to give 2 (10.0 mg, 76%) as a white solid. Mp 104e106 ꢂC
2016, 72, 15e29.
12. (a) Heather, J. B.; Mittal, R. S. D.; Sih, C. J. J. Am. Chem. Soc. 1976, 98, 3661e3669;
(b) Samson, E.; Frischmuth, K.; Berlage, U.; Heinz, U.; Hobert, K.; Welzel, P.
Tetrahedron 1991, 47, 1411e1416; (c) Hirayama, K.; Mori, K. Eur. J. Org. Chem.
1999, 2211e2217; (d) Chen, V. X.; Boyer, F.-D.; Rameau, C.; Retailleau, P.; Vors,
J.-P.; Beau, J.-M. Chem.dEur. J. 2010, 16, 13941e13945.
13. (a) Berlage, U.; Schmidt, J.; Milkova, Z.; Welzel, P. Tetrahedron Lett. 1987, 28,
3095e3098; (b) Matsui, J.; Bando, M.; Kido, M.; Takeuchi, Y.; Mori, K. Eur. J. Org.
Chem. 1999, 2183e2194.
25
25
(lit.11a mp 103e106 ꢂC). [
þ8.28 (c¼1.3, CHCl3)]. IR:
743 (m) cmꢁ1. 1H NMR:
a]
¼ þ8.24 (c¼1.25, CHCl3) [lit.11a
[
a
]
¼
D
D
n
¼3445 (m), 1769 (s), 1168 (m), 913 (m),
14. Sugimoto, Y.; Wigchert, S. C. M.; Thuring, J. W. J. F.; Zwanenburg, B. J. Org. Chem.
d
¼1.09 (s, 3H), 1.16 (s. 3H), 1.43 (d, J¼6.4 Hz,
1998, 63, 1259e1267.
15. Lachia, M.; Dakas, P. Y.; De Mesmaeker, A. Tetrahedron Lett. 2014, 55,
6577e6581.
1H, OH), 1.46 (ddd, J¼13.6, 11.2, 3.0 Hz, 1H), 1.59 (ddd, J¼13.6, 6.8,
2.8 Hz, 1H), 1.66e1.76 (m, 1H), 1.95e2.04 (m, 1H), 2.37 (dd, J¼18.4,
5.0 Hz, 1H), 2.50 (br d, J¼16.8 Hz, 1H), 2.63 (dd, J¼16.8, 8.0 Hz, 1H),
2.82 (dd, J¼18.4, 10.4 Hz, 1H), 3.03e3.13 (m, 1H), 4.14 (q, J¼6.4 Hz,
16. Ohkuma, T.; Ikehira, H.; Ikariya, T.; Noyori, R. Synlett 1997, 467e468.
17. For an alternative method to obtain 7 (96% ee) from rac-7 via multiple enzy-
matic treatments, see Winska, K.; Grudniewska, A.; Chojnacka, A.; Biolonska, A.;
Wawrzenczyk, C. Tetrahedron: Asymmetry 2010, 21, 670e678.
18. (a) Masui, M.; Shioiri, T. Synlett 1997, 273e274; (b) Salunkhe, S. M.; Burkhardt,
E. R. Tetrahedron Lett. 1997, 38, 1523e1526; (c) Soorukram, D.; Knochel, P. Org.
Lett. 2004, 6, 2409e2411; (d) Fujioka, H.; Matsuda, S.; Horai, M.; Fujii, E.;
Morishita, M.; Nishiguchi, N.; Hara, K.; Kita, Y. Chem.dEur. J. 2007, 13,
5238e5248.
1H), 5.47 (d, J¼7.6 Hz, 1H) ppm. 13C NMR:
¼27.4, 27.5, 29.6, 32.3,
d
34.5, 35.9, 36.8, 38.6, 67.1, 89.7, 142.4, 142.7, 177.3 ppm. HRMS (EI):
calcd for C13H18O3 [M]þ 222.1256; found 222.1256.
Acknowledgements
19. The enantiomeric excess of 11 (98% ee) was determined by analyzing the 1H
NMR spectra of the corresponding (R)- and (S)-MTPA esters.
20. Liu, H.; Yan, P.; Li, Y.; Liu, J.; Sun, Q.; Wang, X.; Wang, C. Monatsh. Chem. 2012,
143, 1055e1059.
21. Boyd, D. R.; Sharma, N. D.; Malone, J. F.; Allen, C. C. R. Chem. Commun. 2009,
3633e3635.
We are grateful to Ms. Yuka Taguchi (Tohoku University) for her
help in NMR and MS measurements.
22. Nicolai, S.; Swallow, P.; Waser, J. Tetrahedron 2015, 71, 5959e5964.
23. The ratio of 14 and 140 was determined by 1H NMR analysis of the crude re-
action product.
Supplementary data
24. When the reaction was conducted at 40 ꢂC in ether/hexane (1:1), the 14/140
ratio was 1.8:1, while in toluene the ratio was 2.2:1.
Supplementary data (NMR spectra of 2 and key synthetic in-
termediates) associated with this article can be found in the online
version, at http://dx.doi.org/10.1016/j.tet.2016.08.078.
25. For related studies, see: (a) Chini, M.; Crotti, P.; Flippin, L. A.; Gardelli, C.;
Macchia, F. J. Org. Chem. 1992, 57, 1713e1718; (b) Cainelli, G.; Giacomini, D.;
ꢀ
Perciaccante, F.; Trere, A. Tetrahedron: Asymmetry 1994, 5, 1913e1916.
26. Stork, G.; Zhao, K. Tetrahedron Lett. 1989, 30, 2173e2174.
27. Jin, H.; Uenishi, J.; Christ, W. J.; Kishi, Y. J. Am. Chem. Soc. 1986, 108, 5644e5646.
28. Ahn, Y. M.; Yang, K.; Georg, G. I. Org. Lett. 2001, 3, 1411e1413.
29. For a review of Claisen-type rearrangements, see Castro, A. M. M. Chem. Rev.
2004, 104, 2939e3002.
30. Trost, B. M.; Vranken, D. L. V. Chem. Rev. 1996, 96, 395e422 and references cited
therein.
31. (a) Mukaiyama, T.; Nagaoka, H.; Ohshima, M.; Murakami, M. Chem. Lett. 1986,
1009e1012; (b) Musacchio, A. J.; Nguyen, L. Q.; Beard, G. H.; Knowles, R. R. J. Am.
Chem. Soc. 2014, 136, 12217e12220.
References and notes
1. (a) Cook, C. E.; Whichard, L. P.; Turner, B.; Wall, M. E. Science 1966, 154,
1189e1190; (b) Cook, C. E.; Whichard, L. P.; Wall, M. E.; Egley, G. H.; Coggon, P.;
Luhan, P. A.; McPhail, A. T. J. Am. Chem. Soc. 1972, 94, 6198e6199; (c) Brooks, D.
W.; Bevinakatti, H. S.; Powell, D. R. J. Org. Chem. 1985, 50, 3779e3781.
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1993, 41, 1486e1491.
4. For a review, see Cavar, S.; Zwanenburg, B.; Tarkowski, P. Phytochem. Rev. 2015,
14, 691e711.
5. It was reported that synthetic strigolactone analogs could also induce seed ger-
mination of non-parasitic plants. For details, see: (a) Bradow, J. M.; Connick, W. J.,
Jr.; Papperman, A. B.; Wartelle, L. H. J. Plant Growth Regul. 1990, 9, 35e41; (b)
Villedieu-Percherron, E.; Lachia, M.; Jung, P. M. J.; Screpanti, C.; Fonne-Pfister, R.;
Wendeborn, S.; Zurwerra, D.; De Mesmaeker, A. Chimia 2014, 68, 654e663.
6. Akiyama, K.; Matsuzaki, K.; Hayashi, H. Nature 435, 824e827.
32. Ahmad, S. M.; Braddock, D. C.; Cansell, G.; Hermitage, S. A. Tetrahedron Lett.
2007, 48, 915e918.
33. Although the d-lactone 30 was not fully purified, the structure could be de-
duced from its MS, IR and 1H NMR data including NOE correlations. MS (EI): m/
z 416 [C19H3379BrO3Si (Mþ)] and 418 [C19H3381BrO3Si (Mþ)]; IR: nmax 1739 (vs);
ꢀ
1H NMR (600 MHz, CDCl3):
d 0.07 (3H, s), 0.08 (3H, s), 0.88 (9H, s), 1.17 (3H, s), 1.
18 (3H, s), 1.35 (1H, dt, J¼14.4, 3.6 Hz), 1.59e1.64 (1H, m), 1.65e1.70 (1H, m), 2.
09 (1H, dd, J¼14.2, 8.9 Hz), 2.17e2.26 (2H, m), 2.34e2.39 (1H, m), 2.60 (1H, dd,
J¼18.4, 2.1 Hz), 2.69e2.72 (1H, m), 2.90 (1H, ddd, J¼18.4, 4.8, 2.6 Hz), 3.99 (1H,
ddd, J¼11.5, 9.6, 5.3 Hz), 4.22 (1H, br s).
ꢁ
7. (a) Gomez-Roldan, V.; Fermas, S.; Brewer, P. B.; Puech-Pages, V.; Dun, E. A.;
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