Total synthesis of (-)-invictolide

Article abstract of DOI:10.1055/s-0032-1316561

A convergent approach to the total synthesis of (-)-invictolide, a component of the queen recognition pheromone of Solenopsis invicta, is described. Key steps involve the desymmetrization of a bicyclic olefin with Brown's chiral hydroboration, C-C bond fo

Full text of DOI:10.1055/s-0032-1316561

PAPER
▌2595
paper
Total Synthesis of (–)-Invictolide
Total Synthesis of (–)-Invictolide
Jhillu S. Yadav,* K. Anantha Lakshmi, N. Mallikarjuna Reddy, Attaluri R. Prasad, Ahmad Al Khazim Al Ghamdi
Natural Product Chemistry Division, Pheromone Group, CSIR - Indian Institute of Chemical Technology, Hyderabad, 500 607, India
Fax +91(40)27160387; E-mail: yadavpub@iict.res.in
Received: 11.04.2012; Accepted after revision: 22.05.2012
Abstract: A convergent approach to the total synthesis of (–)-invic-
tolide, a component of the queen recognition pheromone of
O
O
O
O
Solenopsis invicta, is described. Key steps involve the desymmetri-
zation of a bicyclic olefin with Brown’s chiral hydroboration, C–C
bond formation, 1,3-syn reduction, and oxidative lactonization of a
1,3,5-triol with TEMPO/PhI(OAc)2.
1
21
Key words: pheromones, desymmetrization strategy, syn-1,3-re-
OH OH OH
duction, oxidative lactonization
19
Invictolide (1) is a component of the queen recognition
pheromone of the red fire ant, Solenopsis invicta. Invic-
tolide, exhibits pheromone activity in both the laevorota-
tory and racemic forms in surrogate queen field tests.1 (–)-
Invictolide [(–)-1] is isolated from the red fire ant queen,
Solenopsis invicta Buren (Figure 1).2a Its relative stereo-
chemistry was proposed by Rocca et al.2b and its absolute
stereochemistry was established by Mori’s group3 to have
the (3R,5R,6S,1′R)-configuration. The significant stereo-
chemistry and the fascinating biosynthetic pathways in-
volving δ-lactone compounds have driven many groups to
attempt the synthesis of invictolide and several synthetic
approaches have been reported.4 In fact, ongoing research
studies at our group on the synthesis of polyketide natural
products exploring a desymmetrization strategy6 has giv-
en impetus to attempt the synthesis of invictolide in a hith-
erto unreported approach. The present work depicts a
radically different, novel strategy for total synthesis of
(–)-invictolide [(–)-1] and efforts are mainly centered on
the construction of a Prelog–Djerassi-type lactone unit as
a key intermediate.5
O
O
O
O
OBn
OBn
8
4
Scheme 1
triol 9. Bicyclic lactone 8 could be obtained from bicyclic
olefin 46f as shown in Scheme 2.
O
O
O
a
c
b
HO
O
OBn
OBn
OBn
4
5
6
O
O
e
d
O
O
O
O
OBn
OH
OBn
OH
OH
OBn
7
8
9
O
Scheme 2 Reagents and conditions: (a) (–)-Ipc2BH, –23 °C, 24 h, 3
M NaOH, 30% H2O2, 0 °C–r.t., 6 h; (b) PCC, CH2Cl2, r.t., 3 h; (c)
MCPBA, NaHCO3, CH2Cl2, 0 °C–r.t., 10 h, 97%; (d) LDA, MeI,
THF, –78 °C, 99%; (e) LiAlH4, THF, 0 °C–r.t., 5 h, 97%.
O
O
O
O
O
(–)-1
2
3
Figure 1 Fire ant queen pheromone components: (–)-invictolide
[(–)-1]; (E)-6-pent-1-enyl-2H-pyran-2-one (2); dihydroactinidiolide (3)
The synthesis commenced with precursor 4, the com-
pound synthesized in our group and utilized for the syn-
thesis of several natural products. The desymmetrization
approach is explored to create five stereogenic centers at
once.6 The bicyclic olefin 4 was subjected to the key de-
symmetrization reaction using the enantioselective hy-
droboration reaction of Brown et al.7 [(–)-Ipc2BH, THF, 0
°C, NaOH, H2O2] to afford the required alcohol 5 with
97% ee in 95% yield. Alcohol 5 was converted into the bi-
cyclic lactone 7 in 97% yield by pyridinium chlorochro-
mate oxidation followed by Baeyer–Villiger oxidation
(MCPBA, NaHCO3, CH2Cl2). The thus-formed bicyclic
Accordingly, the envisaged retrosynthetic strategy for (–)-
invictolide [(–)-1] is shown in Scheme 1. (–)-Invictolide
[(–)-1] can be prepared by short sequential manipulations
of triol 19 embedded with all the required stereocenters,
which in turn can be generated from bicyclic lactone 8 via
SYNTHESIS 2012, 44, 2595–2600
Advanced online publication: 06.07.2012
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0032-1316561; Art ID: SS-2012-Z0353-OP
© Georg Thieme Verlag Stuttgart · New York

2596
J. S. Yadav et al.
PAPER
a,b
c
OH
OBn OBn
11
O
O
OBn OBn OH OH
OH
OBn
9
OH
12
g
d,e
f
OBn OBn OTBS
OTBS OTs
OBn OBn
14
15
h
i
OBn OBn
17
O
OBn OBn OH
OBn OBn OH
16
18
OH
j
k
l
OH OH OH
O
O
19
20
m
O
O
O
O
21
1
Scheme 3 Reagents and conditions: (a) 2,2-dimethoxypropane, CSA, anhyd CH2Cl2, 0 °C–r.t., 5 h, 89%; (b) NaH, BnBr, TBAI (cat.), anhyd
THF, 0 °C–reflux, 3 h, 93%; (c) CSA, MeOH, r.t., 3 h, 96%; (d) TsCl, Et3N, Bu2SnO (cat.), anhyd CH2Cl2, 0 °C–r.t., 12 h, 92%; (e) TBSOTf,
2,6-lutidine, anhyd CH2Cl2, 0 °C–r.t., 1 h, 94%; (f) EtMgBr, CuBr·Me2S, anhyd THF, –20 °C to r.t., 5 h, 83%; (g) PTSA, MeOH, 0 °C–r.t., 2
h, 92%; (h) Dess–Martin periodinane, NaHCO3, anhyd CH2Cl2, r.t., 1 h, 96%; (i) DIBAL-H, anhyd CH2Cl2, –78 °C, 1 h, 94%; (j) Li/naphtha-
lene, anhyd THF, –20 °C, 93%; (k) PhI(OAc)2, TEMPO, anhyd CH2Cl2, r.t., 3 h, 83%; (l) (i) MsCl, Et3N, 0 °C to r.t., 1 h; (ii) DBU, anhyd THF,
r.t., 2 h, 88%; (m) H2, 10% Pd/C, EtOAc, 6 h, 80%.
lactone 7 was then subjected to enolization using lithium Inversion of the configuration of the secondary hydroxy
diisopropylamide in tetrahydrofuran at –78 °C followed group in the intermediate 16 was achieved by an oxida-
by treatment with iodomethane to furnish the methylated tion–reduction strategy. Thus, oxidation of 16 with Dess–
lactone 8 as a single diastereomer in 99% yield. Reductive Martin periodinane in dichloromethane yielded ketone 17
cleavage of bicyclic lactone 8 with lithium aluminum hy- in 96% yield, followed by reduction of 17 with diisobutyl-
dride in tetrahydrofuran at room temperature furnished aluminum hydride in dichloromethane at –78 °C to afford
triol 9 in 97% yield, which is the key intermediate in the exclusively alcohol 18 in 94% yield, as a result of 1,3-syn
desymmetrization strategy with five stereogenic centers reduction.10 Deprotection of the benzyl ethers of com-
as shown in Scheme 3.6
pound 18 was achieved using lithium/naphthalene in an-
hydrous tetrahydrofuran at –20 °C to yield the triol 19 in
93% yield.11 The resulting triol is subjected to oxidative
lactonization in the presence of (diacetoxyiodo)benzene/
2,2,6,6-tetramethylpiperdin-1-oxyl to obtain Prelog–
Djerassi-type lactone 20 in 83% yield.12 Epimerization of
lactone 20 at C3 was carried out by mesylation, elimina-
tion with DBU, followed by catalytic reduction with 10%
palladium on carbon to provide (–)-invictolide [(–)-1] and
its 3-epimer in the ratio of 3:1. Pure (–)-invictolide [(–)-1]
was separated from its 3-epimer by crystallization from n-
hexane at –78 °C. The spectroscopic data (1H and 13C
NMR) and specific rotation of the synthetic (–)-invic-
tolide [(–)-1] is in good agreement with those of the re-
ported data.3
The 1,3-diol functionality of triol 9 is protected by using
2,2-dimethoxypropane and a catalytic amount of 10-cam-
phorsulfonic acid to give acetonide compound 10 fol-
lowed by protection of the free hydroxy group as benzyl
ether 11 using sodium hydride, benzyl bromide, and a cat-
alytic amount of tetrabutylammonium iodide in 93%
yield. Deprotection of the acetonide group using catalytic
10-camphorsulfonic acid in methanol afforded diol 12 in
96% yield. Selective protection of the primary hydroxy
group with tosyl chloride, triethylamine, and catalytic di-
butyltin oxide gave tosylate 13 in 92% yield. Protection of
the secondary hydroxy group as its tert-butyldimethylsilyl
ether with tert-butyldimethylsilyl triflate and 2,6-lutidine
in dichloromethane afforded 14 in 94% yield.8 The C–C
bond formation occurred by treating 14 with ethylmagne- In conclusion total synthesis of (–)-invictolide is present-
sium bromide in tetrahydrofuran with copper(I) bromide– ed with an overall yield of 23%. The stereogenic centers
dimethyl sulfide complex to provide 15 in 83% yield.9 De- are all obtained through a desymmetrization strategy and
protection of the silyl ether with 4-toluenesulfonic acid in 1,3-syn reduction.
methanol provided 16 in 92% yield.
Synthesis 2012, 44, 2595–2600
© Georg Thieme Verlag Stuttgart · New York

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Total Synthesis of (–)-Invictolide
2597
All reactions were conducted under N2 in anhydrous solvents such
as CH2Cl2, THF, EtOAc, and Et2O. Preparative chromatographic
separations were performed on silica gel (35–75 μm); reactions
were monitored by TLC analysis using silica plates with fluorescent
indicator (254 nm) and visualized with a UV lamp, anisaldehyde or
β-naphthol soln or alkaline KMnO4 soln. All commercially avail-
able reagents were purchased and were typically used as supplied.
HRMS (ESI): m/z [M + Na]+ calcd for C17H22O4Na: 313.1407;
found: 313.1410.
(2R,3R,4S,5R,6R)-5-(Benzyloxy)-2,4,6-trimethylheptane-1,3,7-
triol (9)
To an ice-cooled suspension of LiAlH4 (5.7 g, 150 mmol) in THF
(100 mL) was added a soln of lactone 8 (14.5 g, 50 mmol) in THF
(50 mL) under a N2 atmosphere. The mixture was stirred for 5 h at
r.t. After completion of the reaction, the mixture was quenched with
H2O (6 mL) and 5 M NaOH (6 mL) and H2O (18 mL), and the thus-
formed precipitate was filtered through a Celite pad using EtOAc.
The filtrate was dried (anhyd Na2SO4), the solvent was evaporated,
and the residue was purified by column chromatography to afford
pure 9 as a pale-yellow liquid; yield: 14.5 g (97%); Rf = 0.1 (50%
EtOAc–hexane); [α]D25 +0.26 (c 1.0, CHCl3).
Optical rotations were measured at r.t. (25 °C) on CHCl3 solns with
a polarimeter using a 2-mL capacity cell with a 100-mm path length.
Infrared spectra were recorded using a thin film between NaCl
plates or as a solid embedded in a KBr disc. 1H (300 MHz) and 13
C
NMR (75 MHz) spectra were recorded in Fourier transform mode
on a Bruker UXNMR FT-300 MHz (Avance). Spectra were ob-
tained on CDCl3 solns in 5-mm diameter tubes, and signals are re-
ported relative to the residual signals of CHCl3 (δH = 7.25 or δC =
77.0).
IR (neat): 3403, 3032, 2967, 1458, 1061 cm–1.
1H NMR (300 MHz, CDCl3): δ = 0.69 (d, J = 7.1 Hz, 3 H), 0.94 (d,
J = 7.1 Hz, 3 H), 1.10 (d, J = 7.1 Hz, 3 H), 1.81–1.86 (m, 2 H), 2.25
(m, 1 H), 3.48–3.50 (dd, J = 2.0 Hz, 6.1 Hz, 1 H), 3.55–3.62 (m, 2
H), 3.63–3.66 (dd, J = 5.0, 6.1 Hz, 1 H), 3.70–3.72 (m, 1 H), 3.82
(d, J = 10.0 Hz, 1 H), 4.61–4.66 (q, J = 11.0, 5.1 Hz, 2 H), 7.25–7.32
(m, 5 H).
13C NMR (75 MHz, CDCl3): δ = 11.5, 13.2, 14.6, 35.5, 37.2, 37.8,
65.1, 69.0, 76.4, 88.4, 127.8, 128.1, 128.6, 137.4.
LC-MS: m/z = 319 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C17H28O4Na: 319.1885;
7-(Benzyloxy)-6,8-dimethyl-2,9-dioxabicyclo[3.3.1]nonan-3-
one (7)
To a stirred soln of NaHCO3 (13.56 g, 161 mmol) and ketone 6 (14
g, 53.8 mmol) in CH2Cl2 (150 mL) was added anhyd MCPBA
(18.57 g, 107 mmol) at 0 °C. The mixture was stirred for 10 h at r.t.
After completion of the reaction, the mixture was diluted with
CH2Cl2 (100 mL) and quenched with sat. NaHCO3 soln (50 mL) at
0 °C. The organic layer was separated and washed with sodium
metabisulfite soln (50 mL) followed by brine (50 mL). The organic
layer was dried (anhyd Na2SO4) and the solvent was removed in
vacuo. The residue was purified by column chromatography to af-
ford pure 7 as a pale-yellow liquid; yield: 14 g (97%); Rf = 0.5 (30%
EtOAc–hexane); [α]D25 –46.5 (c 2.0, CHCl3).
found: 319.1901.
(2R,3R,4R)-3-(Benzyloxy)-2-methyl-4-[(4R,5R)-2,2,5-trimethyl-
1,3-dioxan-4-yl]pentan-1-ol (10)
IR (neat): 2963, 2882, 1742, 1225, 1064, 970 cm–1.
To a stirred soln of triol 9 (11 g, 37 mmol) in anhyd CH2Cl2 (100
mL) was added 2,2-dimethoxypropane (9.12 mL, 74.3 mmol) and
CSA (1.5 g); the mixture was stirred at r.t. for 5 h. The mixture was
quenched with solid NaHCO3 (2 g) and it was filtered through a
small Celite pad. Solvent was evaporated in vacuo and the residue
was purified by column chromatography to afford pure 10 as a col-
orless solid; yield: 11.2 g (89%); Rf = 0.3 (30% EtOAc–hexane);
[α]D25 –40.0 (c 1.0, CHCl3).
1H NMR (300 MHz, CDCl3): δ = 0.95 (d, J = 7.5 Hz, 3 H), 1.15 (d,
J = 7.5 Hz, 3 H), 2.01–2.11 (m, 1 H), 2.20–2.30 (m, 1 H), 2.71–2.73
(m, 2 H), 3.58–3.60 (m, 1 H), 4.06–4.12 (m, 1 H), 4.48–4.52 (m, 1
H), 4.65–4.69 (m, 1 H), 5.43–5.44 (d, J = 2.3 Hz, 1 H), 7.23–7.36
(m, 5 H).
13C NMR (75 MHz, CDCl3): δ = 13.1, 13.7, 31.0, 37.5, 39.6, 70.1,
76.7, 79.3, 99.8, 127.4, 128.2, 137.6, 166.2.
LC-MS: m/z = 299 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C16H20O4Na: 219.1250;
IR (neat): 3480, 2964, 2929, 2879, 1458, 1382, 1198, 1060, 1033
cm–1.
found: 299.1253.
1H NMR (300 MHz, CDCl3): δ = 0.72 (d, J = 6.8 Hz, 3 H), 0.87 (d,
J = 6.8 Hz, 3 H), 1.22 (d, J = 6.8 Hz, 3 H), 1.36 (s, 3 H), 1.37 (s, 3
H), 1.83–2.06 (m, 3 H), 2.92 (br s, OH), 3.46–3.54 (m, 3 H), 3.66–
3.72 (m, 1 H), 3.88–3.92 (m, 2 H), 4.6–4.71 (q, J = 10.5, 11.3 Hz, 2
H), 7.27–7.37 (m, 5 H).
13C NMR (75 MHz, CDCl3): δ = 9.8, 12.4, 16.3, 19.4, 29.8, 30.2,
36.0, 37.4, 64.2, 66.1, 73.3, 75.4, 85.5, 97.9, 126.9, 127.5, 128.4,
138.3.
(4S)-7-(Benzyloxy)-4,6,8-trimethyl-2,9-dioxabicyclo[3.3.1]non-
an-3-one (8)
LDA [prepared by the addition of 1.6 M BuLi in hexane (52 mL, 82
mmol) to a cooled soln of i-Pr2NH (10.5 g, 15 mmol) at –10 °C in
THF (100 mL)] was added to a soln of lactone 7 (14.3 g, 52 mmol)
in THF (50 mL) at –78 °C. The lithium enolate thus generated was
alkylated with MeI (6.5 mL, 103.5 mmol) after 1 h. Stirring was
continued for a further 2 h and the reaction was quenched with sat.
NH4Cl (100 mL). The mixture was extracted with EtOAc (3 × 100
mL), the solvent was evaporated, and the residue was purified by
column chromatography to afford pure 8 as a pale-yellow liquid;
LC-MS: m/z = 359 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C20H32O4Na: 359.2198;
found: 359.2210.
25
yield: 15 g (99%); Rf = 0.4 (30% EtOAc–hexane); [α]D –54.7 (c
3.0, CHCl3).
(4R,5R)-4-[(2R,3R,4R)-3,5-Bis(benzyloxy)-4-methylpentan-2-
yl]-2,2,5-trimethyl-1,3-dioxane (11)
To an ice-cooled suspension of NaH (2 g, 83.3 mmol, 60% in min-
eral oil) in anhyd THF (100 mL) was added a soln of alcohol 10
(11.1 g, 33 mmol) in THF (50 mL) under a N2 atmosphere. After
stirring for 10 min, BnBr (5.89 mL, 49.5 mmol) in THF (10 mL)
was added slowly; TBAI (cat.) was then added at the same temper-
ature. The resulting mixture was heated to reflux for 3 h. After com-
pletion of the reaction, it was cooled to 0 °C and the excess hydride
was quenched with sat. NH4Cl soln (25 mL). The mixture was ex-
tracted with EtOAc (3 × 60 mL), and the combined extracts were
washed with brine (50 mL), dried (anhyd Na2SO4), and evaporated.
The residue was purified by column chromatography to afford pure
IR (neat): 2970, 2937, 2881, 1742, 1457, 1392, 1210, 1073, 977,
739 cm–1.
1H NMR (300 MHz, CDCl3): δ = 0.96 (d, J = 8.0 Hz, 3 H), 1.16 (d,
J = 8.0 Hz, 3 H), 1.42 (d, J = 5.0 Hz, 3 H), 2.06–2.08 (m, 1 H), 2.24–
2.26 (m, 1 H), 2.76–2.81 (m, 1 H), 3.57–3.60 (m, 1 H), 3.69–3.71
(m, 1 H), 4.49–4.70 (m, 2 H), 5.43 (s, 1 H), 7.27–7.34 (m, 5 H).
13C NMR (75 MHz, CDCl3): δ = 13.1, 13.5, 20.4, 35.8, 37.6, 39.7,
76.6, 77.4, 79.2, 100.0, 127.4, 128.1, 137.7, 170.5.
LC-MS: m/z = 313 [M + Na]+.
© Georg Thieme Verlag Stuttgart · New York
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J. S. Yadav et al.
PAPER
11 as a pale-yellow liquid; yield: 13.1 g (93%); Rf = 0.8 (30%
EtOAc–hexane); [α]D25 –35.6 (c 1.0, CHCl3).
(2R,3R,4S,5R,6R)-5,7-Bis(benzyloxy)-3-(tert-butyldimethylsil-
oxy)-2,4,6-trimethylheptyl 4-Methylbenzenesulfonate (14)
To a stirred soln of 13 (13.2 g, 24.4 mmol) in anhyd CH2Cl2 (130
mL) was added 2,6-lutidine (5.6 mL, 48.8 mmol), the mixture was
cooled to 0 °C and TBSOTf (8.4 mL, 36.6 mmol) was added. The
mixture was stirred at r.t. for 1 h. After completion of the reaction,
H2O (50 mL) was added and the mixture was extracted with CH2Cl2
(3 × 75 mL). The combined extracts were dried (Na2SO4) and evap-
orated and the residue was purified by column chromatography to
afford pure 14 as a pale-yellow liquid; yield: 15.1 g (94%); Rf = 0.6
(10% EtOAc–hexane); [α]D25 +16.1 (c 0.5, CHCl3).
IR (neat): 3060, 3031, 2965, 1602, 1457, 1382, 1198, 1101, 735
cm–1.
1H NMR (300 MHz, CDCl3): δ = 0.64 (d, J = 6.7 Hz, 3 H), 0.86 (d,
J = 6.7 Hz, 3 H), 1.12 (d, J = 7.5 Hz, 3 H), 1.35 (s, 3 H), 1.37 (s, 3
H), 1.78–1.96 (m, 2 H), 2.14–2.21 (m, 1 H), 3.34–3.51 (m, 3 H),
3.62–3.70 (m, 2 H), 3.84–3.88 (m, 1 H), 4.43–4.51 (m, 2 H), 4.56–
4.65 (q, J = 11.3, 5.2 Hz, 2 H), 7.22–7.31 (m, 10 H).
13C NMR (75 MHz, CDCl3): δ = 11.6, 13.3, 14.9, 26.5, 34.7, 36.7,
37.2, 69.1, 72.1, 73.1, 76.0, 76.8, 87.2, 127.3, 127.5, 127.6, 127.9,
128.3, 128.5, 137.7, 138.3.
IR (neat): 3060, 3032, 2958, 1600, 1458, 1364, 1178, 1095, 967,
836 cm–1.
LC-MS: m/z = 449 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C27H38O4Na: 449.2667;
1H NMR (300 MHz, CDCl3): δ = 0.12 (s, 3 H), 0.19 (s, 3 H), 0.98
(d, J = 4.5 Hz, 3 H), 1.0 (s, 9 H), 1.02–1.05 (d, J = 6.8 Hz, 3 H), 1.28
(d, J = 6.8 Hz, 3 H), 1.98–2.16 (m, 2 H), 2.29–2.34 (m, 1 H), 2.6 (s,
3 H), 3.46–3.50 (dd, J = 3.7, 5.3 Hz, 1 H), 3.55–3.6 (t, J = 9.1, 7.5
Hz, 1 H), 3.75–3.79 (m, 1 H), 3.95–4.01 (m, 2 H), 4.28–4.32 (m, 1
H), 4.61–4.83 (m, 4 H), 7.45–7.52 (m, 12 H), 7.90–7.92 (d, J = 8.3
Hz, 2 H).
13C NMR (75 MHz, CDCl3): δ = –4.2, –3.2, 12.1, 14.4, 16.0, 18.6,
25.7, 26.1, 35.7, 39.0, 39.4, 72.2, 72.9, 73.1, 73.7, 74.0, 84.5, 127.2,
127.4, 127.5, 127.7, 127.7, 127.9, 128.3, 128.5, 129.7, 138.7, 138.9,
144.5.
found: 449.2667.
(2R,3R,4S,5R,6R)-5,7-Bis(benzyloxy)-2,4,6-trimethylheptane-
1,3-diol (12)
Compound 11 (13 g, 30.5 mmol) was dissolved in MeOH (100 mL),
CSA (cat.) was added and the mixture was stirred at r.t. for 3 h. Af-
ter completion of the reaction, it was quenched with solid NaHCO3
(2 g). The solvent was evaporated, and the residue was purified by
column chromatography to afford pure 12 as a pale-yellow liquid;
yield: 11.3 g (96%); Rf = 0.2 (30% EtOAc–hexane); [α]D25 +22.0 (c
0.5, CHCl3).
LC-MS: m/z = 677 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C37H54O6SSiNa: 677.1724;
IR (neat): 3441, 3060, 3032, 2968, 1457, 1091, 738, 699 cm–1
.
found: 677.1723.
1H NMR (300 MHz, CDCl3): δ = 0.75 (d, J = 6.9 Hz, 3 H), 1.04 (d,
J = 6.9 Hz, 3 H), 1.16 (d, J = 6.9 Hz, 3 H), 1.86–1.93 (m, 2 H), 2.13–
2.20 (m, 1 H), 3.52–3.74 (m, 4 H), 3.88 (d, J = 9.6 Hz, 1 H), 4.14 (s,
1 H), 4.54–4.66 (m, 4 H), 7.26–7.37 (m, 10 H).
13C NMR (75 MHz, CDCl3): δ = 11.7, 13.3, 14.9, 34.7, 36.8, 37.3,
69.1, 72.2, 73.2, 76.1, 76.8, 87.3, 127.6, 127.6, 127.7, 127.9, 128.3,
128.5, 137.8, 138.4.
[(2R,3R,4R,5R,6R)-1,3-Bis(benzyloxy)-2,4,6-trimethylnonan-5-
yloxy]-tert-butyldimethylsilane (15)
To a stirred soln of CuBr·Me2S (12.6 g, 87 mmol) in anhyd THF
(130 mL) was added 1 M EtMgBr in THF (150 mL), the mixture
was stirred for 1 h; it was then cooled to –20 °C and 14 (15 g, 29.2
mmol) dissolved in anhyd THF (50 mL) was added and the mixture
was for 5 h at r.t. After completion of the reaction, it was quenched
with sat. NH4Cl soln (100 mL) and extracted with EtOAc (3 × 100
mL). The combined extracts were dried (Na2SO4) and the solvent
was evaporated. The residue was purified by column chromatogra-
phy to afford pure 15 as a pale-yellow liquid; yield: 9.8 g (83%);
Rf = 0.5 (10% EtOAc–hexane); [α]D25 +3.83 (c 0.5, CHCl3).
LC-MS: m/z = 409 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C24H34O4Na : 409.2354;
found: 409.2366.
(2R,3R,4S,5R,6R)-5,7-Bis(benzyloxy)-3-hydroxy-2,4,6-trimeth-
ylheptyl 4-Methylbenzenesulfonate (13)
IR (neat): 3065, 3031, 2957, 1459, 1252, 1068, 835 cm–1.
To a stirred soln of 12 (11 g, 28.5 mmol) in anhyd CH2Cl2 (100 mL)
was added Et3N (8.72 mL, 62 mmol) and Bu2SnO (cat.), the mixture
was stirred for 15 min, and then cooled to 0 °C; TsCl (8.86 g, 47
mmol) was added and the mixture was stirred overnight. After com-
pletion of the reaction, H2O (50 mL) was added and the mixture was
extracted with CH2Cl2 (3 × 80 mL). The combined extracts were
dried (Na2SO4), the solvent was evaporated in vacuo, and the resi-
due was purified by column chromatography to afford pure 13 as a
pale-yellow liquid; yield: 14.3 g (92%); Rf = 0.5 (20% EtOAc–hex-
ane); [α]D25 +18.43 (c 1.0, CHCl3).
1H NMR (300 MHz, CDCl3): δ = 0.03 (s, 3 H), 0.04 (s, 3 H), 0.80–
0.85 (m, 6 H), 0.87 (d, J = 2.3 Hz, 3 H), 0.91 (s, 9 H), 1.12 (d, J =
7.6 Hz, 3 H), 1.25–1.40 (m, 4 H), 1.47–1.61 (m, 1 H), 1.83–1.95 (m,
1 H), 2.07–2.22 (m, 1 H), 3.22–3.28 (dd, J = 3.0, 5.3 Hz, 1 H), 3.34–
3.42 (m, 1 H), 3.58–3.64 (m, 1 H), 3.79–3.82 (m, 1 H), 4.46 (s, 2 H),
4.53–4.66 (m, 2 H), 7.20–7.32 (m, 10 H).
13C NMR (75 MHz, CDCl3): δ = –3.7, 12.3, 14.3, 15.7, 16.5, 20.7,
26.1, 35.0, 35.7, 38.0, 39.6, 72.3, 73.0, 74.3, 75.3, 85.2, 127.2,
127.3, 127.4, 128.1, 128.2, 138.8, 139.1.
IR (neat): 3482, 3032, 2970, 1599, 1457, 1358, 1176, 1081, 963
cm–1.
LC-MS: m/z = 535 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C32H52O3NaSi: 535.35855;
1H NMR (300 MHz, CDCl3): δ = 0.84 (d, J = 6.9 Hz, 3 H), 0.96 (d,
J = 6.9 Hz, 3 H), 1.00 (d, J = 7.9 Hz, 3 H), 1.83–1.85 (m, 2 H), 2.01–
2.05 (m, 1 H), 2.37 (s, 3 H), 3.45–3.48 (dd, J = 3.0, 5.9 Hz, 1 H),
3.50–3.53 (dd, J = 2.0, 8.8 Hz, 1 H), 3.56–3.59 (m, 2 H), 3.97–4.01
(m, 1 H), 4.07–4.10 (dd, J = 2.9, 5.9 Hz, 1 H), 4.45–4.55 (m, 4 H),
7.17 (d, J = 7.9 Hz, 2 H), 7.24–7.31 (m, 10 H), 7.74 (d, J = 7.9 Hz,
2 H).
13C NMR (75 MHz, CDCl3): δ = 11.5, 13.4, 15.3, 21.9, 34.2, 36.5,
37.0, 70.8, 72.4, 73.5, 73.6, 76.4, 87.3, 127.9, 128.0, 128.1, 128.2,
128.3, 128.7, 128.8, 130.0, 133.4, 138.1.
found: 535.35779.
(2R,3R,4S,5R,6R)-1,3-Bis(benzyloxy)-2,4,6-trimethylnonan-5-
ol (16)
To a stirred soln of 15 (9.7 g, 18.9 mmol) in MeOH (100 mL) was
added PTSA at 0 °C; the mixture was stirred at r.t. for 2 h. After
completion of the reaction, it was quenched with solid NaHCO3 (3
g), the solvent was evaporated, and the residue was purified by col-
umn chromatography to afford pure 16 as a pale-yellow liquid;
yield: 6.9 g (92%); Rf = 0.4 (10% EtOAc–hexane); [α]D25 +40.1 (c
0.5, CHCl3).
LC-MS: m/z = 563 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C31H40O6NaS: 563.2432;
IR (neat): 3501, 3064, 3031, 2961, 1456, 1074, 736 cm–1.
found: 563.2437.
Synthesis 2012, 44, 2595–2600
© Georg Thieme Verlag Stuttgart · New York

PAPER
Total Synthesis of (–)-Invictolide
2599
1H NMR (300 MHz, CDCl3): δ = 0.68 (d, J = 6.0 Hz, 3 H), 0.79 (t,
J = 7.0 Hz, 3 H), 0.92 (d, J = 6.0 Hz, 3 H), 0.98–0.99 (d, J = 7.0 Hz,
3 H), 1.09–1.17 (m, 2 H), 1.31–1.38 (m, 2 H), 1.42–1.47 (m, 1 H),
1.62–1.68 (m, 1 H), 1.83–1.87 (m, 1 H), 2.02–2.07 (br s, OH), 3.41–
3.48 (m, 3 H), 3.56–3.59 (m, 1 H), 4.40–4.43 (m, 4 H), 7.14–7.25
(m, 10 H).
13C NMR (75 MHz, CDCl3): δ = 11.3, 14.4, 14.9, 15.0, 19.8, 34.3,
35.1, 35.7, 36.7, 72.2, 73.0, 74.2, 76.0, 87.2, 127.5, 127.6, 127.7,
128.2, 128.3, 137.8, 138.4.
HRMS (ESI): m/z [M + Na]+ calcd for C26H38O3Na: 421.2709;
found: 421.2713.
(2R,3R,4S,5S,6R)-2,4,6-Trimethylnonane-1,3,5-triol (19)
To a stirred soln of naphthalene powder (17.36 g, 135.6 mmol) in
anhyd THF (30 mL) was added Li metal (0.5 g, 67.7 mmol). The
mixture was stirred for 3 h at r.t. then cooled to –20 °C and 18 (2.7
g, 6.78 mmol) in anhyd THF (10 mL) was added. After stirring the
mixture for 2 h at –20 °C, it was quenched with sat. aq NH4Cl soln
(20 mL), extracted with Et2O (3 × 20 mL) and dried (Na2SO4). The
solvent was evaporated, and the residue was purified by column
chromatography to afford pure 19 colorless oil; yield: 1.37 g (93%);
Rf = 0.1 (40% EtOAc–hexane); [α]D25 –4.37 (c 1.0, CHCl3).
LC-MS: m/z = 421 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C26H38O3Na: 421.2709;
found: 421.2712.
IR (neat): 3334, 2961, 1455, 976 cm–1.
(2R,3R,4R,6R)-1,3-Bis(benzyloxy)-2,4,6-trimethylnonan-5-one
(17)
1H NMR (300 MHz, CDCl3): δ = 0.74 (d, J = 6.0 Hz, 3 H), 0.84 (d,
J = 7.0 Hz, 3 H), 0.87–0.90 (t, J = 7.0 Hz, 3 H), 1.14 (d, J = 7.0 Hz,
3 H), 1.21–1.35 (m, 4 H), 1.66–1.70 (m, 1 H), 1.82–1.89 (m, 2 H),
3.34 (br s, OH), 3.45 (br s, OH), 3.55–3.61 (m, 3 H), 3.95 (d, J =
11.0 Hz, 1 H), 4.98 (br s, OH).
13C NMR (75 MHz, CDCl3): δ = 11.8, 13.4, 14.2, 15.3, 20.4, 34.5,
35.4, 36.3, 38.7, 64.6, 80.0, 83.1.
To a soln of 16 (3 g, 7.53 mmol) in CH2Cl2 (40 mL) at 0 °C was add-
ed NaHCO3 (1.89 g, 22.5 mmol) and then Dess–Martin periodinane
(4.79 g, 11.3 mmol) and the mixture was stirred at r.t. for 1 h. After
completion of the reaction, hexane (50 mL) was added. A white pre-
cipitate separated, it was filtered, and the filtrate was concentrated
under reduced pressure to a viscous oil, which was purified by col-
umn chromatography to afford pure 17 as a colorless oil; yield: 2.87
LC-MS: m/z = 241 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C12H26O3Na: 241.1781;
25
g (96%); Rf = 0.8 (10% EtOAc–hexane); [α]D –28.63 (c 0.5,
CHCl3).
found: 241.1774.
IR (neat): 3065, 3032, 2963, 1713, 1455, 1090, 735 cm–1.
1H NMR (300 MHz, CDCl3): δ = 0.78–0.83 (t, J = 7.5, 6.7 Hz, 3 H),
0.86 (d, J = 6.8 Hz, 3 H), 0.93 (d, J = 6.8 Hz, 3 H), 1.03 (d, J = 6.8
Hz, 3 H), 1.14–1.22 (m, 2 H), 1.53–1.60 (m, 2 H), 2.05–2.12 (m, 1
H), 2.49–2.56 (m, 1 H), 3.03–3.13 (m, 1 H), 3.30–3.35 (m, 1 H),
3.60–3.66 (m, 2 H), 4.33–4.44 (m, 4 H), 7.14–7.29 (m, 10 H).
13C NMR (75 MHz, CDCl3): δ = 14.0, 14.1, 15.1, 16.0, 20.4, 34.3,
35.6, 46.9, 47.4, 71.7, 73.0, 74.8, 84.4, 127.2, 127.3, 127.4, 128.0,
128.2, 138.5, 138.7, 217.3.
(3S,4S,5R,6R)-4-Hydroxy-3,5-dimethyl-6-[(R)-pentan-2-yl]-
2H-tetrahydropyran-2-one (20)
To a stirred soln of triol 19 (1.37 g, 6.28 mmol) in anhyd CH2Cl2 (20
mL) was added PhI(OAc)2 (7 g, 22 mmol) and TEMPO (0.2 g, 1.28
mmol) at r.t. The mixture was stirred at r.t. for 3 h. After completion
of the reaction, sat. Na2S2O3 soln (20 mL) and Et2O (20 mL) were
added. The organic layer was washed with sat. NaHCO3 (15 mL)
and H2O (15 mL), and dried (Na2SO4). The solvent was evaporated,
and the residue was purified by column chromatography to afford
pure 20 as a colorless solid; yield: 1.1 g (83%); Rf = 0.4 (30%
EtOAc–hexane); [α]D25 –24.36 (c 1.0, CHCl3).
LC-MS: m/z = 419 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C26H36O3Na: 419.2551;
IR (neat): 3445, 2963, 1714, 1461, 1211, 977 cm–1.
found: 419.2556.
1H NMR (300 MHz, CDCl3): δ = 0.85–0.88 (t, J = 7.0, 5.0 Hz, 3 H),
0.89–0.90 (d, J = 7.0 Hz, 3 H), 1.02–1.03 (d, J = 7.0 Hz, 3 H), 1.28
(d, J = 8.0 Hz, 3 H), 1.32–1.43 (m, 2 H), 1.47–1.54 (m, 1 H), 1.61–
1.65 (m, 1 H), 1.91–1.97 (m, 1 H), 2.19–2.36 (m, 1 H), 2.43–2.48
(m, 1 H), 3.82 (s, 1 H), 4.36 (d, J = 10.0 Hz, 1 H).
13C NMR (75 MHz, CDCl3): δ = 12.3, 12.8, 14.2, 20.5, 33.6, 35.9,
36.0, 42.5, 72.9, 83.1, 96.1, 174.0.
(2R,3R,4S,5S,6R)-1,3-Bis(benzyloxy)-2,4,6-trimethylnonan-5-ol
(18)
To a stirred soln of ketone 17 (2.87 g) in anhyd CH2Cl2 (7.24
mmol), was added DIBAL-H (15.6 mL, 26 mmol) dropwise at –78
°C. The reaction was stirred at this temperature for 1 h while moni-
toring the progress of the reaction. After the reaction was complete,
the mixture was quenched by the addition of MeOH at –78 °C and
the mixture was allowed to reach r.t. The solvent was evaporated
under vacuum and the residue was treated with sat. sodium potassi-
um tartrate soln (40 mL). The residue dissolved in the aqueous layer
and the product was extracted with CH2Cl2 (3 × 50 mL). The com-
bined organic layers were washed with brine (50 mL) and then dried
(Na2SO4). The solvent was evaporated and the residue was purified
by column chromatography to afford pure 18 as a pale-yellow liq-
uid; yield: 2.7 g (94%); Rf = 0.4 (10% EtOAc–hexane); [α]D25 –6.3
(c 0.5, CHCl3).
LC-MS: m/z = 237 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C12H22O3Na: 237.1463;
found: 237.1461.
(5R,6S)-3,5-Dimethyl-6-[(R)-pentan-2-yl]-5,6-dihydro-2H-py-
ran-2-one (21)
To a stirred soln of 20 (1 g, 4.67 mmol) in anhyd CH2Cl2 (10 mL)
was added Et3N (3.6 mL, 25 mmol) and MsCl (1 mL, 10 mmol) at
0 °C; the mixture was stirred at r.t. for 1 h. H2O (10 mL) was added
and the mixture was extracted with CH2Cl2 (3 × 20 mL). The com-
bined extracts were dried (Na2SO4) and the solvent was evaporated
in vacuo.
IR (neat): 3499, 3064, 3031, 2925, 1454, 1069, 698 cm–1.
1H NMR (300 MHz, CDCl3): δ = 0.82 (d, J = 3.0 Hz, 3 H), 0.84 (d,
J = 3.0 Hz, 3 H), 0.89–0.91 (t, J = 6.9 Hz, 3 H), 1.11 (d, J = 7.9 Hz,
3 H), 1.25–1.41 (m, 4 H), 1.56–1.60 (m, 1 H), 1.93–1.98 (m, 1 H),
2.18–2.23 (m, 1 H), 3.42–3.47 (m, 2 H), 3.51–3.57 (m, 1 H), 3.60–
3.63 (m, 1 H), 4.45–4.53 (m, 2 H), 4.60–4.65 (m, 2 H), 7.26–7.34
(m, 10 H).
13C NMR (75 MHz, CDCl3): δ = 12.0, 14.3, 15.4, 15.7, 20.6, 34.3,
36.8, 37.6, 38.5, 72.3, 73.0, 74.7, 76.4, 88.0, 127.4, 127.5, 127.7,
128.2, 128.3, 138.0, 138.6.
DBU (2 mL, 14.5 mmol) was added to the crude product dissolved
in anhyd THF (10 mL) at r.t. The mixture was stirred at r.t. for 2 h
and then it was diluted with H2O (50 mL) and extracted with CH2Cl2
(3 × 10 mL). The combined organic layers were washed with brine
(10 mL), dried (Na2SO4), and evaporated to give crude α,β-unsatu-
rated lactone, which was purified by column chromatography to af-
ford pure 19 as a colorless liquid; yield: 0.81 g (88%); Rf = 0.3 (10%
EtOAc–hexane); [α]D25 –26.81 (c 1.0, CHCl3).
LC-MS: m/z = 421 [M + Na]+.
IR (neat): 2961, 1722, 1715, 1456, 1138 cm–1
.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 2595–2600

2600
J. S. Yadav et al.
PAPER
1H NMR (300 MHz, CDCl3): δ = 0.86–0.91 (t, J = 6.8 Hz, 3 H), 0.92
(d, J = 6.8 Hz, 3 H), 1.03 (d, J = 7.5 Hz, 3 H), 1.23–1.51 (m, 4 H),
1.71–1.73 (dd, J = 1.5, 5.3 Hz, 1 H), 1.88 (s, 3 H), 2.54–2.64 (m, 1
H), 3.93–3.97 (dd, J = 2.3, 8.3 Hz, 1 H), 6.32 (s, 1 H).
(2) (a) Rocca, J. R.; Tumlinson, J. H.; Glancy, B. M.; Lofgren,
C. S. Tetrahedron Lett. 1983, 24, 1889. (b) Rocca, J. R.;
Tumlinson, J. H.; Glancy, B. M.; Lofgren, C. S. Tetrahedron
Lett. 1983, 24, 1893.
13C NMR (75 MHz, CDCl3): δ = 13.1, 14.0, 16.1, 16.8, 20.3, 30.9,
33.3, 35.5, 86.0, 127.0, 146.4, 166.3.
LC-MS: m/z = 219 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C12H20O2Na: 219.1354;
(3) Mori, K.; Nakazono, Y. Tetrahedron 1986, 42, 6459.
(4) For the synthesis of racemic invictolide: (a) Hoye, T. R.;
Peck, D. R.; Thrumper, P. K. J. Am. Chem. Soc. 1981, 103,
5618. (b) Hoye, T. R.; Peck, D. R.; Swanson, T. A. J. Am.
Chem. Soc. 1984, 106, 2738. (c) Schreiber, S. L.; Wang, Z.
J. Am. Chem. Soc. 1985, 107, 5303. (d) Yamamoto, Y.;
Taniguchi, K.; Maruyama, K. J. Chem. Soc., Chem.
Commun. 1985, 1429. For the synthesis of optically active
invictolide: (e) Ziegler, F. E.; Stirchak, E. P.; Wester, R. T.
Tetrahedron Lett. 1986, 27, 1229. (f) Mori, K.; Senda, S.
Agric. Biol. Chem. 1987, 51, 1379. (g) Wakamatsu, T.;
Nishikimi, Y.; Kikuiri, H.; Nakamura, H.; Ban, Y.
Heterocycles 1987, 26, 1761. (h) Hoffman, R. W.; Ditrich,
K.; Koster, G.; Sturmer, R. Chem. Ber. 1989, 122, 1783.
(5) (a) Djerassi, C.; Zderic, J. A. J. Am. Chem. Soc. 1956, 78,
6390. (b) Martin, S. F.; Guinn, D. E. Synthesis 1991, 245.
(6) (a) Yadav, J. S.; SrinivasRao, C.; Chandrasekhar, S.;
Ramarao, A. V. Tetrahedron Lett. 1995, 36, 7717.
(b) Yadav, J. S.; Abraham, S.; MuralidharReddy, M.;
Sabitha, G.; Ravisankar, A.; Kunwar, A. C. Tetrahedron
Lett. 2001, 42, 4713. (c) Yadav, J. S.; Ahmed, M. M.
Tetrahedron Lett. 2002, 43, 7147. (d) Yadav, J. S.; Srinivas,
R.; Sathaiah, K. Tetrahedron Lett. 2006, 47, 1603.
(e) Yadav, J. S.; Rajender, V.; Gangadhararao, Y. Org. Lett.
2010, 12, 348. (f) Yadav, J. S.; Hossain, S. S.; Madhu, M.;
Mohapatra, D. K. J. Org. Chem. 2009, 74, 8822. (g) Yadav,
J. S.; Rajender, V. Eur. J. Org. Chem. 2010, 2148.
(7) (a) Brown, H. C.; Varaprasad, J. V. N. J. Am. Chem. Soc.
1986, 108, 2049. (b) Brown, H. C.; Desai, M. C.; Yadav, P.
K. J. Org. Chem. 1982, 47, 5065.
found: 219.1355.
(3R,5R,6S)-3,5-Dimethyl-6-[(R)-pentan-2-yl]-2H-tetrahydropy-
ran-2-one [(–)-Invictolide, (–)-1]
To a stirred soln of 21 (0.1 g, 0.5 mmol) in EtOAc (10 mL), was
added 10% Pd/C (cat.) and the mixture was stirred under H2 atmo-
sphere for 6 h. Then, the mixture was filtered through a small Celite
pad and concentrated in vacuo. The crude residue thus obtained was
a mixture of (–)-invictolide and its 3-epimer (3:1). The pure isomer
1 could be separated by crystallization (n-hexane at –78 °C). The re-
sulting spectral data, specific rotation are in good agreement with
the reported data.3 Colorless oil; yield: 75 mg (80%); Rf = 0.5 (10%
25
EtOAc–hexane); [α]D –93.06 (c 1.0, CHCl3) [Lit.3 [α]D –101 (c
0.45, CHCl3)].
IR (neat): 2963, 1741, 1460, 1193 cm–1.
1H NMR (300 MHz, CDCl3): δ = 0.86–0.96 (m, 6 H), 0.97 (d, J =
6.8 Hz, 3 H), 1.20 (d, J = 6.8 Hz, 3 H), 1.30–1.48 (m, 5 H), 1.62–
1.74 (t, J = 8.3 Hz, 2 H), 1.84–2.04 (m, 1 H), 2.54–2.67 (m, 1 H),
3.86 (dd, J = 2.3, 9.8 Hz, 1 H).
13C NMR (75 MHz, CDCl3): δ = 12.2, 14.0, 16.4, 17.5, 20.3, 28.3,
32.4, 33.5, 35.2, 36.0, 85.6, 176.7.
LC-MS: m/z = 221 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C12H22O2Na: 221.1512;
found: 221.1512.
(8) Chakraborty, T. K.; Das, S. Tetrahedron Lett. 2001, 42,
3387.
(9) (a) Chandrasekhar, S.; Pavankumarreddy, G.; Sathish, K.
Tetrahedron Lett. 2009, 50, 6851. (b) Mori, K. Tetrahedron
1981, 37, 1341.
(10) (a) Yadav, J. S.; Pratap, T. V.; Rajender, V. J. Org. Chem.
2007, 72, 5882. (b) Evans, D. A. J. Org. Chem. 1990, 55,
5190.
(11) Liu, H. J.; Yip, J. Tetrahedron Lett. 1997, 38, 2253.
(12) Hansen, T. M.; Florence, G. J.; Lugo-Mas, P.; Chen, J.;
Abrams, J. N.; Forsyth, C. J. Tetrahedron Lett. 2003, 44, 57.
Acknowledgement
K. A. Lakshmi and N. M. Reddy thank UGC and CSIR, New Delhi,
respectively, for research fellowships.
References
(1) Toshio, H.; Shin-ichi, Y.; Fumihiro, I.; Miho, K.
Tetrahedron 1996, 52, 12177.
Synthesis 2012, 44, 2595–2600
© Georg Thieme Verlag Stuttgart · New York