Total synthesis of (-)-ircinianin and (+)-wistarin

Article abstract of DOI:10.1021/jo961993f

(-)-Ircinianin (1), a cyclic furanosesterterpenetetronic acid isolated from a marine sponge (genus Ircinia), is synthesized in 17 steps from (S)-2-methylpropane-1,3-diol mono THP ether 10 and 3-furfural. The key step involves a NiCl₂-CrCl₂-mediated coupling reaction of iodotriene 9 with chiral aldehyde 8 in DMSO and subsequent intramolecular Diels-Alder reaction in one pot. Both reactions proceed very smoothly at room temperature and eventually give the cyclic product 30A possessing the desired cyclic skeleton of 1 in 60% yield. The structure of 30A is determined by X-ray crystallographic analysis. The stereochemistry of Diels-Alder reactions of 7A and another acyclic precursor 7B are discussed. The first total synthesis of (+)-wistarin (2) is accomplished in 55% yield by iodoether ring formation of 1 and hydrogenolysis of the iodide 33A. Based on the coupling constant in the proton NMR spectrum of 33A, the reported structure 2A is revised to 2B.

Full text of DOI:10.1021/jo961993f

J . Org. Chem. 1997, 62, 1691 1701
1691
Tota l Syn th esis of ( )-Ir cin ia n in a n d ( )-Wista r in †
J un’ichi Uenishi,* Reiko Kawahama, and Osamu Yonemitsu
Department of Chemistry, Okayama University of Science, Ridaicho, Okayama 700, J apan
Received October 24, 1996X
( )-Ircinianin (1), a cyclic furanosesterterpenetetronic acid isolated from a marine sponge (genus
Ircinia), is synthesized in 17 steps from (S)-2-methylpropane-1,3-diol mono THP ether 10 and
3-furfural. The key step involves a NiCl2 CrCl2-mediated coupling reaction of iodotriene 9 with
chiral aldehyde 8 in DMSO and subsequent intramolecular Diels Alder reaction in one pot. Both
reactions proceed very smoothly at room temperature and eventually give the cyclic product 30A
possessing the desired cyclic skeleton of 1 in 60% yield. The structure of 30A is determined by
X-ray crystallographic analysis. The stereochemistry of Diels Alder reactions of 7A and another
acyclic precursor 7B are discussed. The first total synthesis of ( )-wistarin (2) is accomplished in
55% yield by iodoether ring formation of 1 and hydrogenolysis of the iodide 33A. Based on the
coupling constant in the proton NMR spectrum of 33A, the reported structure 2A is revised to 2B.
In tr od u ction
( )-Ircinianin (1) was isolated from the marine sponge,
genus Ircinia, by Hofheinz et al. in 1977,1 and its cyclic
isomer ( )-wistarin (2) was obtained from the marine
sponge, Ircinia wistarii, by Gregson et al. in 1982.2 They
are both structurally unique cyclic furanosesterterpene-
tetronic acids, as shown in Figure 1. The relative
structure of 1 was determined by X-ray crystallographic
analysis, and that of 2 was assumed on the basis of
spectroscopic data. Although a number of furanosester-
terpenetetronic acids,3 e.g. fasciculatin (3),4 variabilin
(4),5 and ircinic acid (5),6 have been reported, the absolute
stereochemistries of this family including 1 and 2 have
not been determined except in the case of 3.4 Because
most furanosesterterpenetetronic acids exist in a linear
form, the cyclic structures of 1 and 2 are particularly
interesting. Biogenetically, 1 is assumed to be produced
enzymatically or thermally by intramolecular Diels
Alder reaction from acyclic 8,11,13,20-tetraene precursor
6 in nature.7 The thermal transformation of 6 to ircini-
anin was achieved in racemic form by Yoshii and Take-
da.8 However, a lack of absolute structure determination
and not enough biological and chemical studies,1,9 for both
compounds prompted us to synthesize 1 and 2 in optically
active forms. In this paper, we report the first enanti-
oselective total synthesis of ( )-ircinianin and ( )-wist-
† This paper is dedicated to Professor Yoshito Kishi on the occasion
of his 60th birthday.
X Abstract published in Advance ACS Abstracts, March 1, 1997.
(1) Hofheinz, W.; Scho¨nholzer, P. Helv. Chim. Acta 1977, 60, 1367.
(2) Gregson, R. P.; Ouvrier, D. J . Nat. Prod. 1982, 45, 412.
(3) (a) Krebs, H. C. In Fortschritte der Chemie Organischer Natur-
stoffe; Herz, W., Grisebach, H., Kirby, G. W., Tamm, C., Eds.; Springer-
Verlag: New York, 1986; Vol. 49, pp 151 363. (b) Crews, P.; Naylor,
S. In Fortschritte der Chemie Organischer Naturstoffe; Herz, W.,
Grisebach, H., Kirby, G. W., Tamm, C., Eds.; Springer-Verlag: New
York, 1985, Vol. 48, pp 203 269.
F igu r e 1. Furanosesterterpenetetronic acids.
(4) Cafieri, F.; Fattorusso, E.; Santacroce, C.; Minale, L. Tetrahedron
1972, 28, 1579.
arin, including a minor stereochemical revision of the
(5) Faulkner, D. J . Tetrahedron Lett. 1973, 3821.
(6) Manes, L. V.; Crews, P.; Ksebati M. B.; Schmitz, F. J . J . Nat.
Prod. 1986, 49, 787.
(7) Ichihara, A. In Studies in Natural Products Chemistry, Stereo-
selective Synthesis (Part C); Atta-ur-Rahman, Ed.; Elsevier: New York,
1989; Vol. 4, pp 570 624.
(8) The elegant total synthesis of racemic 1 was achieved by Yoshii
et al. See Takeda, K.; Sato, M.; Yoshii, E. Tetrahedron Lett. 1986, 27,
3903.
(9) Endo, M.; Nakagawa, M.; Hamamoto, Y.; Ishihama, M. Pure
Appl. Chem. 1986, 58, 387.
proposed wistarin structure 2A to 2B.
Our synthetic plan of 1 and 2 is outlined in Figure 2.
The tricyclic ring is constructed by an intramolecular
Diels Alder reaction of tetraene 7, which may be ob-
tained by a NiCl2 CrCl2-promoted coupling reaction of
iodo triene 9 with aldehyde 8. The (R)- or (S)-chiral
carbogenic center of 8 will be derived from commercially
available (S)-( )- or (R)-( )-3-hydroxy-2-methylpropionic
S0022-3263(96)01993-7 CCC: $14.00 © 1997 American Chemical Society

1692 J . Org. Chem., Vol. 62, No. 6, 1997
Uenishi et al.
Sch em e 2
F igu r e 2. Retrosynthesis of 1 and 2.
Sch em e 1
yield via the following steps: (i) tosylation of 10 by
p-toluenesulfonyl chloride in pyridine; (ii) cyanation with
sodium cyanide in 90% yield (over two steps, 10 f 12 f
13); (iii) reduction of cyanide to the aldehyde by DIBAL-
H; (iv) reduction of aldehyde with NaBH4 in 60% yield
(over two steps, 13 f CHO f 14). After protection of
the alcohol as a tert-butyldiphenylsilyl ether and depro-
tection of THP ether with Bu2Sn(SMe)2 in the presence
of BF3 OEt2,12 the primary alcohol was oxidized to chiral
aldehyde 17 under the Swern oxidation condition in 86%
yield (over three steps, 14 f 15 f 16 f 17). Treatment
of the lithium salt of methyl 2-methyltetronate13 with 17
gave aldol adducts 18 as three diasteromers. Mesylation
of aldol 18 with methanesufonyl chloride followed by
elimination of the mesylate with DBU afforded 20 as a
2:1 mixture of Z and E isomers in 84% yield (over three
steps, 17 f 18 f 19 f 20). After deprotection of the
TBDPS group with tetrabutylammonium fluoride, the
geometric isomers were separated by silica gel flash
chromatography and the desired Z isomer 21 was isolated
as a major product in 62% yield.14 This was subject to
PCC oxidation to give 8 in 68% yield.
acid methyl ester through the optically active alcohol 10.
Iodo triene 9 is prepared from furanopentyne 11.
Tota l Syn th esis of ( )-Ir cin ia n in
Synthesis of 9 started from 3-furfural via 11 in 12 steps
as shown in Scheme 2. Compound 11 was prepared by
standard carbon chain extension reactions and function-
alizations in the following five steps: (i) Wittig Horner
Emmons reaction of 3-furfural with the sodium salt of
The synthetic route to 8 is described in Scheme 1. The
starting optically pure alcohol 10 was derived from (R)-
( )-3-hydroxy-2-methylpropionic acid methyl ester11 in
78% yield with a slight modification of Mori’s method10.
A one-carbon extension of 10 to 14 was performed in 54%
(12) Sato, T.; Otera, J .; Nozaki, H. J . Org. Chem. 1990, 55, 4770.
(13) Wengel, A. S.; Reffstrup, T.; Boll, P. M. Tetrahedron 1979, 35,
2181.
(14) The geometries and stereochemistries were confirmed after
leading to the final product 1 ultimately.
(10) Mori, K. Tetrahedron 1983, 39, 3107.
(11) The (R)-enantiomer was initially taken as a chiral pool, and
later it was found that this was a proper choice to build up the correct
stereochemistry for 1 and 2.

Total Synthesis of ( )-Ircinianin and ( )-Wistarin
J . Org. Chem., Vol. 62, No. 6, 1997 1693
Sch em e 3
triethyl phosphonoacetate, (ii) Pd-catalyzed reduction of
the ,â-unsaturated ester under H2 atmosphere, (iii)
LiAlH4 reduction of the ester to primary alcohol 22 in
88% yield (over three steps, 3-furfuralf f f22), (iv)
bromination with carbon tetrabromide and triphenylphos-
phine in 96% yield (22 f 2315), (v) coupling reaction with
sodium acetylide in 90% yield (23 f 11).
A key functional transformation for terminal alkyne
11, and dienyne 29 at a later stage, to trisubstituted
iodoolefin was performed by a regioselective syn addition
of MeMgSnBu3.16 Thus, the alkyne 11 was treated with
17
MeMgSnBu3 in the presence of a catalytic amount of
CuCN followed by methylation with iodomethane to give
the 1-(tributylstannyl)-2-methylalkene which was then
treated with iodine to afford (E)-1-iodo-2-methylalkenyl
function of 24 in 62% yield. The improved Heck reac-
tion18 of 24 with methyl acrylate in the presence of Pd-
(OAc)2 catalyst provided dienyl acid methyl ester 25 in
95% yield. Manipulation of the ester to the terminal
alkyne (25 f 29) was carried out by standard procedures
in 51% overall yield; thus, (i) DIBAL-H reduction of the
ester to alcohol (25 f 26) in 88% yield; (ii) BaMnO4
oxidation of alcohol to aldehyde (26 f 27) in 95% yield;
(iii) dibromoolefin formation by CBr4 and Ph3P; (iv)
transformation of the dibromoalkene to alkyne by treat-
ing with 2.2 equiv of LDA in 61% yield (over two steps,
27 f 28 f 29). Stereospecific conversion of the terminal
acetylene 29 to the (E)-1-iodo-2-methylalkene was carried
out using by the same procedure described for 11 and
afforded 9 in 75% yield.19,20
Since Kishi used 0.1% NiCl2 CrCl2-promoted addition
of iodoalkenes and iodoalkynes to aldehydes,21 the reac-
tion has been successfully adopted as an important key
coupling reaction in natural product syntheses.22 Thus,
the coupling of 9 with 8 using this method proceeded
smoothly in DMSO at room temperature (Scheme 3). This
is the first successful case of a NiCl2 CrCl2-promoted
coupling reaction of an iodotriene with an aldehyde. The
reaction afforded the desired alcohols 7A and 7B at the
initial stage of the reaction. However, surprisingly, one
of the two isomers, presumably 7A, started to undergo
Diels Alder cyclization during the reaction at room
temperature, and eventually gave the single cyclized
product 30A among four possible stereoisomers.23 The
other isomer, 7B, did not cyclize and remained in the
reaction mixture. This reaction is discussed later in this
paper. After the mixture was allowed to react at room
temperature for 18 h, purification of the reaction mixture
gave the desired cyclized product 30A in 60% yield along
with the uncyclized coupling product 7B in 20% yield.
Phenoxythionoformylation of 30A with phenyl chlo-
rothionoformate in the presence of DMAP followed by
AIBN-catalyzed deoxygenation with Bu3SnH24 provided
ircinianin methyl ether 32 in 64% overall yield (30A f
31 f 32). Deprotection of the methyl ether with PrSNa25
completed the total synthesis of 1 in 90% yield. Spec-
troscopic data for synthetic 1 were identical to those
reported in the literature.1 In particular, the specific
rotation, [ ]24
235° (c 0.3, CHCl3) was in accordance
D
with the reported value, [ ]25
232° (c 0.5, CHCl3),
D
confirming the correct absolute structure of 1 including
the S-configuration at the C-18 chiral center, originally
provided from (R)-( )-3-hydroxy-2-methylpropionic acid
methyl ester.
(15) Magatti, C. V.; Kaminski, J . J .; Rothberg, I. J . Org. Chem. 1991,
56, 3102.
(16) Uenishi, J .; Kawahama, R.; Tanio, A.; Wakabayashi, S. J . Chem.
Soc., Chem. Commun. 1993, 1438.
Ch em ica l Tr a n sfor m a tion of ( )-Ir cin ia n in to
(
)-Wista r in
(17) Matsubara, S.; Hibino, J .; Morizawa, Y.; Oshima, K.; Nozaki,
H. J . Organomet. Chem. 1985, 285, 163.
(18) J effery, T. Tetrahedron Lett. 1985, 26, 2667.
(19) This compound is unstable, and so it is better to be used
subsequently.
(20) The use of Negishi’s carbometalation reaction by Cp2ZrCl2 with
Me3Al also worked well to give the same product in similar yield.
(21) (a) J in, H.; Uenishi, J .; Christ, W. J .; Kishi, Y. J . Am. Chem.
Soc. 1986, 108, 5644. (b) Aicher, T. D.; Kishi, Y. Tetrahedron Lett. 1987,
28, 3463. (c) Rowley, M.; Kishi, Y. Tetrahedron Lett. 1988, 29, 4909.
(22) Recent examples for total syntheses of natural products using
this coupling. (a) Aicher, T. D.; Buszek, K. R.; Fang, F. G.; Forsyth, C.
J .; J ung, S. H.; Kishi, Y.; Matelich, M. C.; Scola, P. M.; Spero, D. M.;
Yoon, S. K. J . Am. Chem. Soc. 1992, 114, 3162. (b) Roush, W. R.;
Brown,.B. B. J . Am. Chem. Soc. 1993, 115, 2268. (c) Nerenberg, J . B.;
Hung, D. T.; Somers, P. K.; Schreiber, S. L. J . Am. Chem. Soc. 1993,
115, 12621.
Gregson reported that attempts of an acid-promoted
transformation of 1 to 2 were unsuccessful.2 However,
as shown in Scheme 4, when 1 was treated with iodine
in the presence of K2CO3, cyclic iodo ether 33A was
formed very cleanly as a single product in 71% yield.
Chemical shifts in 1H and 13C NMR spectra of 33A
indicated that the cyclization occurred in 6-endo-trigonal
fashion, in which the methine (C-10) proton appeared at
4.13 ppm, and the corresponding carbon (C-10) and the
next quaternary carbon (C-8) appeared at 38.4 and 79.7
ppm, respectively.26 Hydrogenolysis of the iodide 33A
(23) The stereoisomers are due to the hydroxy center, the ring
juncture, and exo- and/or endo-adducts.
(24) Robins, M. J .; Wilson, J . S. J . Am. Chem. Soc. 1981, 103, 932.
(25) Feutrill, G. I.; Mirrington, R. N. Tetrahedron Lett. 1970, 1327.

1694 J . Org. Chem., Vol. 62, No. 6, 1997
Uenishi et al.
Sch em e 4. Ch em ica l Tr a n sfor m a tion s of
Ir cin ia n in to Wista r in
stereocenter of 33A was confirmed by proton NMR, in
which a 11.7 Hz coupling constant between C-10 and
C-11 protons was clearly observed as a typical axial
axial coupling. Therefore, the C-9 methyl group is
located at an axial position and the 3-furylpropyl group
is placed at an equatorial position. Consequently the
reported structure 2A conflicts stereochemically with (R)-
configuration at the C-8 quaternary center, and therefore,
we revise the structure of ( )-wistarin to 2B.
Diels Ald er Rea ction s of th e Tetr a en e
In ter m ed ia tes
As noted in the above total synthesis of 1, the NiCl2
CrCl2-mediated coupling reaction of 8 and 9, and suc-
cessive Diels Alder cyclization gave a mixture of 30A
and 7B in a combined yield of 80% after 18 h at room
temperature. However, when the reaction was stopped
after 1 h, aldehyde 8 was consumed in the reaction, and
a mixture of 30A, 7B, and another acyclic isomer 7A was
obtained in a total yield of 89% in a 1:2:2 ratio. Based
on this ratio, the diastereoface selectivity of the addition
was found to be 3:2 ( :â). Although the acyclic precursor
7A underwent the intramolecular Diels Alder reaction
to give 30A quite smoothly under the coupling condi-
tions,28 alternative diastereoisomer 7B did not cyclize
easily under the conditions at room temperature, and its
decomposition proceeded gradually. Interestingly the
Diels Alder cyclization of 7A surely took place at room
temperature in the presence of CrCl2, however, it did not
in the absence of CrCl2. This fact indicated that the
CrCl2 certainly mediated the Diels Alder cyclization by
acting as an appropriate Lewis acid. Nevertheless, when
7B was heated in xylene at 150 °C (bath temperature)
for 15 min, the Diels Alder products 30B, 30B′, and
30B′′ (Scheme 5) were formed in 27, 18, and 14% yields,
respectively.29 All were cyclic stereoisomers with the
same molecular weight (m/z 426) characterized by mass
spectrometry. Deoxygenation of the major isomer 30B
led to 32 confirming that 30B was a diastereomer of 30A.
Fortunately, 30A was crystallized from methanol, and
the relative stereochemistry was determined by X-ray
crystallographic analysis34 which clearly indicated the
(S)-configuration of the C-16 chiral center. Therefore, we
were able to determine all the structures of 30A, 30B,
and 32 at this stage. The structure of 32 was also
confirmed by proton NMR. The coupling constants of
F igu r e 3. Cyclic iodo ether formation of 1 6-endo-trigonal
fashion.
under radical conditions by Bu3SnH and a catalytic
amount of Et3B proceeded at 7 °C in benzene to give ( )-
wistarin 2B in 77% yield. The specific rotation, [ ]27
D
132° (c 0.3, CH2Cl2) and other spectroscopic data for
the synthetic material confirmed the total synthesis of
( )-wistarin, lit. [ ]20
130° (c 0.25, CH2Cl2).2
D
1
2
H2
H3
J H
and J H
in 32 were observed as 11.0 and 11.0
In this cyclization, differentiation of the two diaste-
reotopic faces of the trisubstituted olefin is possible, and
is shown in Figure 3. In one case, the enol oxygen attacks
from the re-face of the C-8 olefin plane, in which the
iodonium intermediate is located on the side in A. This
reaction path goes through a chair transition state
leading to 33A. In the other case, the enol oxygen attacks
from the si-face of the C-8 olefin plane, in which the
iodonium intermediate is located on the side, shown
in the structure B. This path affords 33B via a boat
transition state. The former can be considered preferred
because the chair transition state smoothly proceeds to
the end product 33A. However, in the latter case the
resulting boat product requires a ring inversion leading
to the stable chair conformation 33B. Furthermore,
based on MM2 calculations, the structure of 33A was 2.93
kcal/mol more stable than that of 33B.27 The C-10
Hz, respectively. These values were nearly equal to the
corresponding coupling constants (12.1 and 10.5 Hz),
calculated with PM3 (Spartan version 4.1). The com-
pound 32′ was obtained by deoxygenation of 30B′ and
was identified as a diastereoisomer of 32 by NMR. The
coupling constant between H1 and H2 protons was 12.4
Hz, indicating a trans relationship in the bicyclo[4.3.0]-
nonane system.30 The coupling constant between H2 and
H3 was observed as 6.6 Hz. Calculated values of the
corresponding protons showing 12.5 and 6.4 Hz, respec-
(27) The calculations were performed by Macro Model program
(version 5.1).
(28) The matching combination of 16R and 18S26 chiral centers in
7A may allow the intramolecular exo-Diels Alder reaction occurring
quite smoothly to provide the cyclized product 30A under the condi-
tions.
(29) Formation of a [4.3.0] ring system by intramolecular Diels
Alder reaction of -chiral dienes at high temerature was reported by
Roush et al. See (a) Roush, W. R. J . Org. Chem. 1979, 44, 4008. (b)
Roush, W. R. J . Am. Chem. Soc. 1980, 102, 1390.
(26) A numbering of carbons is based on the acyclic furanosester-
terpenetetronic acid.3

Total Synthesis of ( )-Ircinianin and ( )-Wistarin
J . Org. Chem., Vol. 62, No. 6, 1997 1695
Sch em e 5. Diels Ald er Cycliza tion of 7B a n d Deoxygen a tion of th e Cyclized P r od u cts
Sch em e 6. All P ossible Ster eoisom er s a n d th e Tr a n sition Sta tes in th e Diels Ald er Cycliza tion
tively, also supported the structure of 32′. Deoxygenation
of 30B′′ led to the other isomer 32′′. The coupling
constant between H1 and H2 was observed as 9.5 Hz,
which indicated a cis-fused ring system in the bicy-
clo[4.3.0]nonane. Clear NOE enhancement (9%) between
H2 and C-19 methyl protons suggested that the H2 and
H3 protons possess a trans relationship. All the values
obtained here were in good accordance with previous data
for bicyclo[4.3.0]nonane systems reported in the litera-
ture.30
to IV, in two exo and two endo modes, are possible in the
transition state. The experimental results indicate that
trans-fused products are formed in preference to the
corresponding cis products. Particularly the reaction of
7A gave 30A via IA exclusively among four possible
stereoisomers, 30A to 30A′′′. On the other hand, the
reaction of 7B provided 30B via IB as a major product
along with the alternative trans ring fused isomer 30B′
via IIB, and a cis isomer 30B′′ via IIIB. The steric effect
of an -oxy group and a 2-bromo or 2-methyldienyl group
was previously discussed by Roush.31 In comparing the
transition state IA with IB, the C-16 OH group com-
The transition state of the Diels Alder reaction is
considered in Scheme 6. Four possible conformations I
(30) (a) Kozikowski, A. P.; Tu¨ckmantel, W. J . Org. Chem. 1991, 56,
2826. (b) Kurth, M. J .; O’Brien, M. J .; Hope, H.; Yanuck, M. J . Org.
Chem. 1985, 50, 2626. (c) Parker, K. A.; Iqbal, T. J . Org. Chem. 1987,
52, 4369.
(31) (a) Roush, W. R.; Kageyama, M.; Riva, R.; Brown, B. B.;
Warmus, J . S.; Moriarty, K. J . J . Org. Chem. 1991, 56, 1192. (b) Roush,
W. R.; Koyama, K.; Curtin, M. L.; Moriarty, K. J . J . Am. Chem. Soc.
1996, 118, 7502.

1696 J . Org. Chem., Vol. 62, No. 6, 1997
Uenishi et al.
added sodium cyanide (5.4 g, 111 mmol) and heated at 60 °C
for 30 min. The mixture was quenched with ice water and
extracted with 20% ether in pentane. The crude product was
distilled to give 13 (9.16 g) in 90% (two steps). Colorless oil;
pletely eclipses the C-14 Me group in IB, but not in IA.
The steric interaction of the OH and Me groups desta-
bilizes the overlap of the C-11 and C-15 carbons in the
diene with the C-20 and C-21 carbons in the dienophile.
In fact, the Diels Alder reaction of 7B required heating
at 150 °C to give the major isomer 30B along with some
formation of other stereoisomers 30B′ and 30B′′ via
unfavorable transition states, IIB and IIIB. In the case
of IA, the lack of steric interaction between OH and Me
groups as well as a perfect overlapping conformation of
diene and dienophile accelerate the cyclization of 7A
which occurs very smoothly even at room temperature.32
bp 85 87 °C/1.8 mmHg; Rf
0.34 (20% EtOAc in hexane);
[ ]29
31.0° (c 1.00, Et2O), lit. [ ]21.5
27.8° (c 1.41, Et2O)10;
D
D
IR (neat) 2245 cm 1; 1H NMR (400 MHz, CDCl3) δ 1.09 (3/2H,
d, J
2H, m), 1.64 1.76 (2/2H, m), 1.76 1.86 (2/2H, m), 2.16 (2/2H,
qm, J 6.8 Hz), 2.36 (1/2H, dd, J 16.6 and 7.3 Hz) and 2.39
6.8 Hz) and 1.10 (3/2H, d, J
6.8 Hz), 1.48 1.62 (8/
(1/2H, dd, J
5.2 Hz) and 2.53 (1/2H, dd, J
dd, J
16.6 and 6.9 Hz), 2.49 (1/2H, dd, J
16.6 and
16.6 and 5.4 Hz), 3.21 (1/2H,
9.8 and 8.0 Hz) and 3.58 (1/2H, dd, J 9.8 and 7.8
Hz), 3.38 (1/2H, dd, J
9.8 and 4.7 Hz) and 3.75 (1/2H, dd, J
9.8 and 4.8 Hz), 3.48 3.56 (2/2H, m), 3.78 3.88 (2/2H, m),
4.54 4.62 (2/2H, dm, J 10.3 Hz); 13C NMR (100 MHz, CDCl3)
δ 16.1 and 16.2, 19.2 and 19.4, 21.3 and 21.3, 25.3, 30.4 and
30.4, 30.9 and 31.0, 62.0 and 62.3, 70.1 and 70.5, 98.5 and 99.2,
Con clu sion
The total syntheses of 1 and 2 were accomplished in
optically active forms. The absolute structures were
determined by asymmetric synthesis, and the C-8 ste-
reocenter of 2 was revised based on the proton NMR
studies and the mechanistic considerations. The meth-
odology for preparation of a trisubstituted iodotriene and
its Ni Cr-promoted addition to an aldehyde was found
to be useful for the preparation of Diels Alder interme-
diates in the synthesis of complicated natural products.
In addition, the availability of synthetic 1 and 2 will
permit the further pharmacological studies.
118.5 and 118.6. MS (EI) m/z 183 (M ). HRMS Calcd for C10
H17NO2: M , 183.1259. Found: m/z 183.1249.
-
(S)-( )-3-Met h yl-4-[(2-t et r a h yd r op yr a n yl)oxy]b u t a n -
ol (14). To a solution of 13 (12.0 g, 65 mmol) in CH2Cl2 (100
mL) at 78 °C was added dropwise DIBAL-H (0.93 M in
hexane solution; 78 mL). The reaction mixture was stirred
for 5 min at the same temperature and quenched with
saturated ammonium chloride (200 mL). The mixture was
stirred vigorously at room temperature for 30 min and then
filtered though a Celite pad. The filtrate was extracted with
ether (300 mL), and the extract was condensed to 150 mL of
the volume and diluted with methanol (25 mL). NaBH4 (2.5
g, 66 mmol) was added to the extract solution at room
temperature. The reaction was completed in 5 min. After an
excess of NaBH4 was decomposed with 2 mL of acetone, the
mixture was diluted with ether and washed with water. The
crude product was purified by flash column chromatography
on silica gel eluted with 20% EtOAc in hexane to give 14 (7.44
Exp er im en ta l Section
Gen er a l P r oced u r es. All air- or moisture-sensitive reac-
tions were carried out in flame-dried glassware under Ar
atmosphere. Solvents were distilled freshly over sodium/
benzophenone ketyl for THF, ether, and benzene, over P2O5
for CH2Cl2, and over CaH2 for hexane, toluene, DMSO, and
DMF under nitrogen atmosphere. Unless otherwise stated,
organic extracts were washed with water and brine, dried over
anhydrous MgSO4, filtered, and concentrated with a rotary
evaporator under reduced pressure (30 40 mmHg). Thin
layer chromatography (TLC) was performed with Merck
60F254-precoated silica gel plates. Column chromatography
was carried out using Merck silica gel 60 (70 230 mesh) for
gravity column, silica gel 60 (230 400 mesh) for flash column,
and Wako neutral alumina (200 mesh).
(R)-( )-2-Met h yl-3-[(2-t et r a h yd r op yr a n yl)oxy]p r op yl
p-Tolu en esu lfon a te (12).10 A mixture of 10 (9.68 g, 55.6
mmol) and p-toluenesulfonyl chloride (15.9 g, 83.3 mmol) was
stirred for 3 h in pyridine (90 mL) at 0 °C. The reaction
mixture was poured into ice water and extracted with 20%
ether in pentane. The crude product was used for the next
reaction without further purification, but for analytical pur-
poses, a part of the product was purified by column chroma-
tography on silica gel eluted with 7.5% EtOAc in hexane to
give 12 as a diastereomeric mixture. Colorless oil; Rf 0.33
g) in 60% yield (two steps). Colorless oil; Rf 0.22 (30% EtOAc
1
in hexane); [ ]29
12.8° (c 1.00, CHCl3); IR (neat) 3400 cm
;
D
1H NMR (400 MHz, CDCl3) δ 0.88 (3/2H, d, J
0.88 (3/2H, d, J 7.0 Hz), 1.39 1.68 (14/2H, m), 1.68 1.78
(2/2H, m), 1.79 1.88 (2/2H, m), 2.90 (2/2H, br s), 3.16 (1/2H,
dd, J 9.5 and 7.0 Hz) and 3.19 (1/2H, dd, J 9.5 and 5.1
Hz), 3.41 3.48 (2/2H, m), 3.50 3.69 (6/2H, m), 3.74 3.83 (2/
2H, m), 4.52 (2/2H, dd, J
6.6 and 3.7 Hz); 13C NMR (100
6.6 Hz) and
MHz, CDCl3) δ 17.4 and 17.4, 19.3 and 19.4, 25.3, 30.4 and
30.4, 30.8 and 30.9, 37.5 and 37.5, 60.8, 62.1, 73.0 and 73.1,
98.8 and 98.9; MS (FAB) m/z 189 (MH ). HRMS Calcd for
C10H21O3: MH , 189.1491. Found: m/z 189.1463.
(S)-( )-3-Meth yl-4-[(2-tetr ah ydr opyr an yl)oxy]bu tyl ter t-
Bu tyld ip h en ylsilyl Eth er (15). tert-Butylchlorodiphenylsi-
lane (6.6 mL, 25.4 mmol) was dropped into a mixture of 14
(3.97 g, 21.1 mmol) and DMAP (2.58 g, 21.1 mmol) in CH2Cl2
(30 mL) at room temperature. The mixture was stirred for 5
min and diluted with ether. The mixture was washed with
water. The crude product was chromatographed on silica gel
eluted with
quantitatively. Colorless oil; Rf 0.31 (5% EtOAc in hexane);
[ ]28 1.8° (c 1.00, CHCl3); IR (neat) 1110 cm 1; 1H NMR (400
MHz, CDCl3) δ 0.90 (3/2H, d, J 6.2 Hz) and 0.91 (3/2H, d, J
6.4 Hz), 1.04 (18/2H, s), 1.33 1.44 (2/2H, m), 1.46 1.60 (8/
1 2% EtOAc in hexane to give 15 (9.0 g)
(20% EtOAc in hexane); [ ]29
8.9° (c 1.00, Et2O); IR (neat)
D
1361, 1177 cm 1; H NMR (400 MHz, CDCl3) δ 0.93 (3/2H, d,
1
D
J
6.9 Hz) and 0.94 (3/2H, d, J
m), 1.66 1.78 (2/2H, m), 2.03 2.14 (2/2H, m), 2.45 (6/2H, s),
3.20 (1/2H, dd, J 9.7 and 7.4 Hz) and 3.58 (1/2H, dd, J 9.8
and 6.9 Hz), 3.26 (1/2H, dd, J 9.8 and 5.0 Hz) and 3.60 (1/
2H, dd, J 9.8 and 5.4 Hz), 3.42 3.49 (2/2H, m), 3.70 3.78
(2/2H, m), 3.94 (1/2H, dd, J 9.3 and 5.9 Hz), 3.97 4.04 (2/
2H, dm, J 5.5 Hz), 4.07 (1/2H, dd, J 9.3 and 6.0 Hz), 4.42
4.48 (2/2H, dm, J 11.8 Hz), 7.34 (4/2H, d, J 8.2 Hz), 7.79
(4/2H, d, J
8.2 Hz); 13C NMR (100 MHz, CDCl3) δ 13.5 and
6.9 Hz), 1.42 1.65 (10/2H,
2H, m), 1.63 1.86 (6/2H, m), 1.89 1.99 (2/2H, qm, J
Hz), 3.16 (1/2H, dd, J 9.4 and 6.4 Hz), 3.22 (1/2H, dd, J
9.4 and 5.8 Hz), 3.44 3.53 (3/2H, m), 3.58 (1/2H, dd, J
and 6.4 Hz), 3.73 (4/2H, t, J
8.5 Hz), 4.51 4.56 (2/2H, dd, J
6.4
9.4
6.4 Hz), 3.79 3.86 (2/2H, br t,
3.1 and 3.5 Hz), 7.35
J
7.45 (6H, m), 7.65 7.73 (4H, m); 13C NMR (100 MHz, CDCl3)
δ 17.1 and 17.2, 19.2, 19.5 and 19.5, 25.5, 26.8 and 26.9, 30.3
and 30.3, 30.7, 36.6 and 36.6, 62.1, 62.2, 72.9, 98.7 and 98.8,
127.6, 129.5, 134.1, 135.5; MS (EI) m/z (rel intensity) 325 (M
13.6, 19.2 and 19.4, 21.5 and 21.6, 25.3, 30.4, 33.4 and 33.6,
61.9 and 62.1, 67.9 and 68.4, 72.1 and 72.2, 98.5 and 99.0,
127.9, 129.7, 133.1, 144.5.
101, 9), 285 (73), 199 (34), 85 (base). HRMS Calcd for C26
H38O3SiNa: M Na, 449.2488. Found: m/z 449.2483.
-
(S)-( )-3-Meth yl-4-[(2-tetr ah ydr opyr an yl)oxy]bu tyr on i-
tr ile (13).10 To a DMSO solution (50 mL) of the crude 12 was
(S)-( )-2-Meth yl-4-[(ter t-bu tyld ip h en ylsilyl)oxy]bu ta n -
ol (16). To an ice-cooled CH2Cl2 solution (100 mL) of 15 (5.12
g, 12.0 mmol) and Bu2Sn(SMe)2 (4.71 g, 14.4 mmol) was added
a CH2Cl2 (5 mL) solution of BF3 OEt (1.77 mL, 14.4 mmol)
dropwise. The reaction was stirred for 5 min at 0 °C, EtOAc
(32) Due to a lack of reliable parameters for the tetronic acid part,
we have failed to calculate the transition state for the Diels Alder
reactions using the Macro Model.

Total Synthesis of ( )-Ircinianin and ( )-Wistarin
J . Org. Chem., Vol. 62, No. 6, 1997 1697
57, base), 267 (55), 149 (45), 128 (41). HRMS Calcd for C27
(200 mL) and saturated NaHCO3 (100 mL) were added to the
mixture, and precipitates were filtered through a Celite pad
under reduced pressure. The organic filtrate was isolated and
washed with water. The oily product was purified by flash
column chromatography on silica gel eluted with 7.5% EtOAc
in hexane to give 16 (3.76 g) in 91% yield. Colorless oil; Rf
-
H35O4Si: MH , 451.2305. Found: m/z 451.2325. 4E-Isomer:
colorless oil; Rf 0.28 (15% EtOAc in hexane); [ ]22
5.4° (c
D
1.00, CHCl3); IR (neat) 1760, 1632, 1111 cm 1; H NMR (400
1
MHz, CDCl3) δ 1.02 (3H, d, J
7.0 Hz), 1.04 (9H, s), 1.50
6.2
Hz), 4.00 (3H, s), 5.38 (1H, d, J 11.0 Hz), 7.33 7.44 (6H,
1.69 (2H, m), 2.07 (3H, s), 3.27 (1H, m), 3.64 (2H, t, J
0.37 (20% EtOAc in hexane); [ ]28
7.5° (c 1.00, CHCl3); IR
(neat) 3360, 1100 cm 1; 1H NMR (400 MHz, CDCl3) δ 0.90 (3H,
d, J 6.9 Hz), 1.05 (9H, s), 1.48 (1H, m), 1.63 (1H, m), 1.84
(1H, qm, J 6.4 Hz), 2.42 (1H, br s), 3.44 3.56 (2H, br m),
3.66 3.80 (2H, m), 7.36 7.45 (6H, m), 7.66 7.68 (4H, m); 13
D
m), 7.61 7.66 (4H, m); 13C NMR (100 MHz, CDCl3) δ 8.9, 19.0,
21.3, 26.6, 26.7, 40.1, 58.7, 61.7, 101.2, 120.0, 127.5, 129.5,
133.7, 135.4, 142.1, 162.9, 170.5; MS (EI) m/z (rel intensity)
C
393 (M
57, 27), 285 (50), 212 (46), 167 (base). HRMS Calcd
NMR (100 MHz, CDCl3) δ 17.1, 19.1, 26.8, 33.8, 36.7, 62.5,
68.2, 127.7, 129.7, 133.5, 135.6; MS (FAB) m/z 343 (MH ).
HRMS Calcd for C21H31O2Si: MH , 343.2093. Found: m/z
343.2097.
for C27H35O4Si: MH , 451.2305. Found: m/z 451.2314.
Dep r otection of TBDP S Gr ou p of 20. P r ep a r a tion of
21. A mixture of 20 (4.0 g, 8.88 mmol) in THF (40 mL) and
tetrabutylammonium fluoride (1 M THF solution; 10.6 mL)
was stirred for 30 min. The reaction mixture was diluted with
EtOAc (150 mL) and washed with brine. The crude product
was chromatographed on silica gel eluted with 30% EtOAc in
hexane to give 21 (1.16 g) in 62% yield and its E-isomer (112
mg) in 6% yield.33 21: Colorless crystals; mp 64.8 65.2 °C
(S)-( )-2-Meth yl-4-[(ter t-bu tyld ip h en ylsilyl)oxy]bu ta -
n a l (17). To a solution of oxalyl chloride (0.76 mL, 8.71 mmol)
in CH2Cl2 (30 mL) was added DMSO (1.24 mL, 17.5 mmol) at
78 °C. The mixture was stirred for 20 min at the same
temperature, and then a CH2Cl2 solution (10 mL) of 16 (2.0 g,
5.84 mmol) was dropped during 5 min at 78 °C. The stirring
was continued for 20 min, and triethylamine (4.1 mL, 29.4
mmol) was dropped. The whole mixture was stirred for 20
min at the same temperature and an additional 30 min on an
ice bath. Saturated ammonium chloride (50 mL) was added
to the mixture and extracted with EtOAc. The crude aldehyde
was purified by column chromatography on silica gel eluted
with 1 2.5% EtOAc in hexane to afford pure aldehyde 17 (1.88
(30% Et2O in hexane); Rf 0.27 (40% EtOAc in hexane); [ ]26
D
5.7° (c 1.00, CHCl3); IR (KBr) 3482, 1737, 1627 cm 1; 1H NMR
(400 MHz, CDCl3) δ 1.06 (3H, d, J
1.70 (1H, m), 1.91 (1H, br s), 2.03 (3H, s), 2.88 (1H, m), 3.57
(2H, t, J 6.6 Hz), 4.10 (3H, s), 5.16 (1H, d, J
10.1 Hz); 13
6.8 Hz), 1.54 (1H, m),
C
NMR (100 MHz, CDCl3) δ 8.5, 20.7, 27.6, 39.7, 58.8, 60.8, 99.0,
114.0, 142.9, 161.9, 170.8; MS (EI) m/z (rel intensity) 212 (M ,
66), 167 (78), 151 (74), 78 (base). HRMS Calcd for C11H16O4:
M , 212.1049. Found: m/z 212.1031. Anal. Calcd for
C11H16O4: C, 62.25; H, 7.60. Found: C, 62.35; H, 7.70. 4E-
g) in 95% yield. Colorless oil; Rf 0.31 (5% EtOAc in hexane);
1
[ ]28
8.9° (c 1.00, CHCl3); IR (neat) 1715, 1100 cm
;
1H
D
Isomer: Colorless oil; Rf 0.17 (40% EtOAc in hexane); [ ]22
NMR (400 MHz, CDCl3) δ 1.04 (9H, s), 1.09 (3H, d, J
Hz), 1.62 (1H, ddt, J
13.9, 7.0 and 6.6 Hz), 2.58 (1H, qtd, J
Hz), 3.65 3.78 (2H, m), 7.36 7.46 (6H, m), 7.63 7.67 (4H,
m), 9.67 (1H, d, J
7.0
D
41.8° (c 0.41, CHCl3); IR (neat) 3432, 1761, 1628 cm 1; H
1
13.9, 6.6 and 5.5 Hz), 2.01 (1H, dtd, J
7.0, 6.6 and 1.7
NMR (400 MHz, CDCl3) δ 1.08 (3H, d, J
(2H, m), 1.71 (1H, m), 2.09 (3H, s), 3.20 (1H, m), 3.54 3.67
(2H, m), 4.15 (3H, s), 5.38 (1H, d, J
11.0 Hz); 13C NMR (100
6.7 Hz), 1.46 1.55
1.7 Hz); 13C NMR (100 MHz, CDCl3) δ
13.1, 19.1, 26.8, 33.4, 43.5, 61.1, 127.6, 129.6, 133.5, 135.5,
MHz, CDCl3) δ 9.0, 21.7, 26.7, 40.4, 59.1, 60.8, 102.2, 119.4,
142.5, 162.8, 170.4; MS (EI) m/z (rel intensity) 212 (M , 59),
167 (base), 151 (76). HRMS Calcd for C11H16O4: M , 212.1049.
Found: m/z 212.1067.
204.7; MS (FAB) m/z 341 (MH ). HRMS Calcd for C21H28O2-
SiNa: M
Na, 363.1756. Found: m/z 363.1746.
Cou p lin g Rea ction of 17 w ith Meth yl 2-Meth yltetr on -
a t e a n d E lim in a t ion R ea ct ion . P r ep a r a t ion of 20.
Lithium diisopropylamide (8.27 mmol) in THF (12 mL) and
HMPA (5 mL) solution was prepared from diisopropylamine
(1.23 mL, 9.38 mmol) and BuLi (1.56 M in hexane solution;
5.3 mL) by the standard procedure. To this solution was added
methyl 2-methyltetronate (1.06 g, 8.27 mmol) in THF (8 mL)
at 78 °C and stirred for 30 min. Aldehyde 17 (1.88 g, 5.52
mmol) dissolved in a mixture of THF (8 mL) and HMPA (2
mL) was dropped to the mixture at 78 °C, and the whole
was stirred for 20 min. The bath was removed, and the
mixture was quenched with saturated ammonium chloride (20
mL) and extracted with EtOAc. The obtained crude product
was purified by flash column chromatography on silica gel
eluted with 40% EtOAc in hexane to give oily product 18 as
diastereomeric mixtures. This mixture was subjected to the
next mesylation. To a mixture of 18, triethylamine (1.4 mL,
10.0 mmol), and DMAP (406 mg, 3.32 mmol) in CH2Cl2 (20
mL) was added methanesulfonyl chloride (0.43 mL, 5.56 mmol)
at 0 °C. The reaction mixture was stirred for 5 min at the
same temperature to form mesylate 19, and then DBU (1 mL,
6.69 mmol) was added to the reaction mixture. After stirring
for 10 min at room temperature, saturated ammonium chloride
(10 mL) was added and the whole mixture was extracted with
20% EtOAc in hexane. The product was purified by flash
column chromatography on silica gel eluted with 10% EtOAc
in hexane to give a 2:1 geometrical mixture of 20 and its
E-isomer (2.08 g) in 84% yield in three steps. The isomers
were separable by HPLC, but for practical purposes, the
separation was much easier in the next step. Colorless oil; Rf
P r ep a r a tion of 8. PCC (191 mg, 0.89 mmol) was added
to a stirred solution of 21 (126 mg, 0.59 mmol) in CH2Cl2 (10
mL), and the reaction was continued at room temperature for
1 h. The mixture was passed through a florisil column eluted
with CH2Cl2 and condensed. The residue was purified by silica
gel flash column chromatography eluted with 20% EtOAc in
hexane. Pure aldehyde 8 (85 mg) was obtained in 68% yield.
Colorless crystals; mp 59.5 60.0 °C (20% Et2O in hexane); Rf
0.27 (30% EtOAc in hexane); [ ]28
12.9° (c 1.00, CHCl3);
D
IR (neat) 1760, 1680, 1640 cm 1; H NMR (400 MHz, CDCl3)
1
δ 1.16 (3H, d, J
and 2.0 Hz), 3.32 (1H, m), 4.12 (3H, s), 5.22 (1H, d, J
Hz), 9.70 (1H, t, J
6.8 Hz), 2.07 (3H, s), 2.52 (2H, dd, J
6.9
9.6
2.0 Hz); 13C NMR (100 MHz, CDCl3) δ
8.4, 20.3, 25.8, 50.0, 58.8, 99.2, 111.6, 142.9, 161.7, 170.4, 201.0;
MS (FAB) m/z 211 (MH ). HRMS Calcd for C11H15O4: MH ,
211.0971. Found: m/z 211.0957. Anal. Calcd for C11H14O4:
C, 62.85; H, 6.71. Found: C, 62.84; H, 6.81.
3-(3-F u r yl)p r op a n ol (22).15 To a THF solution (300 mL)
of sodium triethyl phosphonoacetate (0.25 mol) prepared from
triethyl phosphonoacetate (50 mL, 0.25 mol) and sodium
hydride (60% dispersion in mineral oil; 10.1 g, 0.25 mol) by
the standard method in text was added 3-furfural (22.0 g, 0.23
mol) dropwise during 10 min at room temperature and stirred
for 5 min. The reaction mixture was poured into ice water
(100 mL) and extracted with ether. The aqueous layer was
reextracted with ether (100 mL × 2). After the combined
extracts were washed with water and brine, the mixture was
condensed to 300 mL of the volume. To this solution, pal-
ladium charcoal (10%, 1.0 g) was added and stirred under
hydrogen atmosphere for 5 h. After the removal of palladium
0.28 (15% EtOAc in hexane); [ ]29
36.2° (c 1.00, CHCl3);
D
1
IR (neat) 1768, 1643, 1110 cm 1; H NMR (400 MHz, CDCl3)
δ 1.03 (3H, d, J
6.6 Hz), 1.03 (9H, s), 1.55 1.74 (2H, m),
6.2 and 1.8 Hz),
10.3 Hz), 7.33 7.44 (6H, m),
(33) The 4Z isomer gave cyclized products by Michael addition
during the deprotection with tetrabutylammonium fluoride.
(34) The author has deposited atomic coordinates for this structure
with the Cambridge Crystallographic Data Centre. The coordinates
can be obtained, on request, from the Director, Cambridge Crystal-
lographic Data Centre, 12 Union Road, Cambridge, CB2 1EZ, UK.
2.06 (3H, s), 2.95 (1H, m), 3.65 (2H, td, J
4.08 (3H, s), 5.19 (1H, d, J
7.62 7.67 (4H, m); 13C NMR (100 MHz, CDCl3) δ 8.9, 19.0,
21.3, 26.6, 28.1, 40.1, 58.7, 61.7, 99.0, 114.8, 127.5, 129.5, 133.7,
135.4, 142.1, 162.9, 170.5; MS (EI) m/z (rel intensity) 393 (M

1698 J . Org. Chem., Vol. 62, No. 6, 1997
Uenishi et al.
charcoal by filtration, the filtrate was dropped to a suspension
of LiAlH4 (5 g, 0.13 mol) in ether (100 mL) at 0 °C. The whole
was stirred for 30 min, and then the excess of LiAlH4 was
decomposed by adding acetone (5 mL) and quenching with
water (100 mL). The mixture was diluted with ether and
filtered through a Celite pad under reduced pressure. The
aqueous layer was reextracted with ether, and the extracts
were combined in the organic layer. The crude product was
distilled in vacuo to give 22 (25.4 g) in 88% yield. Colorless
oil; bp 62 65 °C/2 mmHg; Rf 0.30 (30% EtOAc in hexane);
(2H, t, J
7.6 Hz), 2.39 (2H, t, J
7.5 Hz), 5.88 (1H, d, J
0.8 Hz), 6.25 (1H, br s), 7.20 (1H, br s), 7.35 (1H, t, J
1.5
Hz); 13C NMR (100 MHz, CDCl3) δ 23.7, 24.0, 27.8, 38.9, 74.8,
110.8, 124.4, 138.8, 142.7, 147.5; MS (EI) m/z (rel intensity)
276 (M , 16), 149 (M
OI: M , 276.0011. Found: m/z 276.0021.
127, base). HRMS Calcd for C10H13-
Met h yl (2E,4E)-8-(3-F u r yl)-5-m et h yl-2,4-oct a d ien a t e
(25). To a mixture of 24 (6.27 g, 22.71 mmol) and methyl
acrylate (3.91 g, 45.42 mmol), in anhydrous degassed DMF
(40 mL) were added successively tetrabutylammonium chloride
(6.31 g, 22.71 mmol), anhydrous K2CO3 (7.85 g, 56.78 mmol),
and Pd(OAc)2 (255 mg, 1.14 mmol), and the whole was stirred
for 3 h under an argon atmosphere. Water (20 mL) was added,
and the mixture was extracted with 20% EtOAc in hexane.
The crude product was chromatographed on silica gel eluted
with 5% EtOAc in hexane to give 25 (5.04 g) in 95% yield.
Colorless oil; Rf 0.33 (10% EtOAc in hexane); IR (neat) 1725,
1
IR (neat) 3352 cm 1; H NMR (400 MHz, CDCl3) δ 1.43 (1H,
br s), 1.83 (2H, m), 2.53 (2H, t, J
7.6 Hz), 3.69 (2H, t, J
1.5 Hz);
6.5 Hz), 6.28 (1H, br s), 7.23 (1H, s), 7.35 (1H, t, J
13C NMR (100 MHz, CDCl3) δ 20.8, 32.6, 61.6, 110.8, 124.3,
138.7, 142.6; MS (EI) m/z (rel intensity) 126 (M , 44), 108 (51),
97 (19), 81 (base). HRMS Calcd for C7H10O2: M , 126.0681.
Found: m/z 126.0676.
3-(3-F u r yl)p r op yl Br om id e (23).15 To a mixture of 22
(9.77 g, 77.5 mmol) and carbon tetrabromide (26.0 g, 78.4
mmol) in CH2Cl2 (200 mL) was added Ph3P (20.6 g, 78.4 mmol)
at 0 °C by 20 portions for 20 min. The reaction was completed
after the addition, and pentane (2 L) was added to the mixture.
Upon cooling, Ph3PO was formed as a crystal. After removal
of the precipitates by filtration, the filtrate was condensed
under reduced pressure, and the residue was distilled to give
23 (14.0 g) in 96% yield. Colorless oil; bp 61 62 °C/5 mmHg;
1630, 1610 cm 1; H NMR (400 MHz, CDCl3) δ 1.73 (2H, m),
1.89 (3H, s), 2.17 (2H, t, J
3.74 (3H, s), 5.79 (1H, d, J
1
7.6 Hz), 2.41 (2H, t, J
15.2 Hz), 5.99 (1H, d, J
7.6 Hz),
11.6
Hz), 6.26 (1H, br s), 7.21 (1H, br s), 7.35 (1H, br s), 7.58 (1H,
dd, J
15.2 and 11.6 Hz); 13C NMR (100 MHz, CDCl3) δ 17.3,
24.3, 27.8, 39.6, 51.3, 110.8, 118.6, 123.4, 124.5, 138.9, 141.0,
142.8, 149.5, 168.0; MS(EI) m/z (rel intensity) 234 (M , 26),
219 (34), 135 (55), 93 (48), 82 (base); MS (FAB) m/z 235 (MH ).
HRMS Calcd for C14H19O3: MH , 235.1334. Found: m/z
235.1325.
1
Rf 0.36 (hexane); IR (neat) 1163 cm 1; H NMR (400 MHz,
CDCl3) δ 2.10 (2H, m), 2.60 (2H, t, J
7.2 Hz), 3.41 (2H, t, J
1.5
(2E,4E)-8-(3-F u r yl)-5-m eth yl-2,4-octa d ien -1-ol (26). To
a CH2Cl2 (40 mL) solution of 25 (2.60 g, 11.1 mmol) was
dropped DIBAL-H (0.93 M hexane solution; 24 mL) at 78 °C
during 20 min. After the addition, the reaction was completed.
Saturated ammonium chloride (100 mL) was added to the
mixture, which was then stirred vigorously for 10 min. The
precipitate was filtered through a Celite pad, and the filtrate
was extracted with EtOAc. The crude product was purified
by flash column chromatography on silica gel eluted with 15%
EtOAc in hexane to give 26 (2.01 g) in 88% yield. A pale yellow
6.6 Hz), 6.27 (1H, br s), 7.26 (1H, s), 7.36 (1H, t, J
Hz); 13C NMR (100 MHz, CDCl3) δ 23.1, 32.8, 33.0, 110.8,
123.1, 139.3, 143.0; MS (EI) m/z (rel intensity) 190 and 188
(M , 16 and 16), 82 (base), 81 (98). HRMS Calcd for C7H9-
OBr: M , 189.9816 and 187.9837. Found: m/z 189.9835 and
187.9858.
5-(3-F u r yl)p en tyn e (11). Sodium acetylide (purchased
from Aldrich Co. in mineral oil; 8.0 g, 166.6 mmol) was washed
with hexane (10 mL × 2) and suspended in HMPA (50 mL).
To the suspension was added an HMPA (10 mL) solution of
23 (10.5 g, 55.54 mmol) at 15 °C, and it was stirred for 2 h at
the same temperature. The mixture was poured into ice
water (100 mL), acidified with 20% HCl, and extracted with
pentane. The crude product was roughly purified by column
chromatography on silica gel eluted with 5% ether in pentane
and distilled in vacuo to give 11 (6.71 g) in 90% yield. Colorless
oil; bp 55 °C/7 mmHg; Rf 0.28 (hexane); IR (neat) 3290, 2110
oil; Rf
0.23 (20% EtOAc in hexane); IR (neat) 3300, 1660
1
cm 1; H NMR (400 MHz, CDCl3) δ 1.30 (1H, br s), 1.70 (2H,
m), 1.76 (3H, s), 2.10 (2H, t, J
7.7 Hz), 2.40 (2H, t, J
7.6
Hz), 4.19 (2H, br s), 5.74 (1H, dt, J
(1H, d, J
11.0 and 1.3 Hz), 7.21 (1H, br s), 7.35 (1H, t, J
NMR (100 MHz, CDCl3) δ 16.5, 24.2, 28.0, 39.2, 63.6, 110.9,
124.1, 124.8, 128.1, 129.5, 138.8, 139.3, 142.6; MS (EI) m/z (rel
intensity) 206 (M , 54), 191 (74), 149 (53), 94 (76), 81 (base).
HRMS Calcd for C13H18O2: M , 206.1307. Found: m/z
206.1328.
15.1 and 6.1 Hz), 5.85
11.0 Hz), 6.26 (1H, br s), 6.48 (1H, ddt, J
15.1,
1.5 Hz); 13
C
1
cm 1; H NMR (400 MHz, CDCl3) δ 1.78 (2H, m), 1.97 (1H, t,
J
2.6 Hz), 2.21 (2H, td, J
7.5 Hz), 6.27 (1H, br s), 7.23 (1H, br s), 7.35 (1H, t, J
7.1 and 2.6 Hz), 2.55 (2H, t, J
1.6
Hz); 13C NMR (100 MHz, CDCl3) δ 17.8, 23.6, 28.7, 68.6, 84.0,
110.9, 124.0, 139.1, 142.8; MS (EI) m/z (rel intensity) 134 (M ,
68), 105 (40), 91 (54), 82 (base). HRMS Calcd for C9H10O: M ,
134.0732. Found: m/z 134.0710.
(2E,4E)-8-(3-Fu r yl)-5-m eth yl-2,4-octa dien a l (27). A mix-
ture of 26 (1.85 g, 8.97 mmol) and BaMnO4 (6.9 g, 26.93 mmol)
was stirred in CH2Cl2 (25 mL) for 6 h at room temperature.
The mixture was filtered through a Celite pad under reduced
pressure, and the filtrate was concentrated. The crude product
was purified by flash column chromatography on silica gel
eluted with 10% EtOAc in hexane to give 27 (1.74 g) in 95%
yield. A pale yellow oil; Rf 0.37 (15% EtOAc in hexane); IR
(E)-5-(3-F u r yl)-1-iod o-2-m eth ylp en ten e (24). To a sus-
pension of anhydrous SnCl2 (2.1 g, 11.1 mmol) in THF (30 mL)
was added BuLi (1.56 M solution in hexane; 21 mL, 33.3 mmol)
dropwise at 0 °C and stirred for 20 min. To this solution was
dropped methylmagnesium bromide (1.02 M solution in THF;
11 mL, 11.1 mmol) during 10 min, and it was stirred for an
additional 15 min. Cuprous cyanide (40 mg, 0.4 mmol) was
added, and 11 (500 mg, 3.7 mmol) in THF (5 mL) was dropped
slowly. After stirring for 15 min, methyl iodide (3.2 mL, 51.4
mmol) was dropped and stirred for 20 min. To the reaction
mixture, anhydrous hexane (300 mL) was added and stirred
vigorously for 15 min. After the mixture separated into two
layers, the upper layer was transferred via cannula to an ice-
cooled flask to which iodine in CH2Cl2 solution (iodine (20 g)
and anhydrous Na2CO3 (10 g) in 200 mL of CH2Cl2) was
dropped carefully by monitoring with TLC. Up to this stage,
all the reactions were handled at 0 °C. Then, the ice bath was
removed, and the mixture was diluted with ether (200 mL)
and washed with sodium thiosulfate (30 mL), water, and brine.
The organic extract was dried over MgSO4 and condensed. The
residual oil was purified by column chromatography on
alumina eluted with 1% ether in pentane to give 24 (630 mg)
in 62% yield. Colorless oil; Rf 0.43 (hexane); 1H NMR (400
(neat) 1680, 1665, 1620 cm 1; H NMR (400 MHz, CDCl3) δ
1.76 (2H, quint, J
(2H, t, J
15.1 and 8.0 Hz), 6.14 (1H, d, J
7.22 (1H, br s), 7.35 (1H, t, J
and 11.4 Hz), 9.57 (1H, d, J
CDCl3) δ 17.5, 24.2, 27.8, 39.8, 110.8, 123.8, 124.4, 130.0, 138.8,
142.8, 148.3, 152.5, 193.9; MS (EI) m/z (rel intensity) 163 (M
1
7.5 Hz), 1.94 (3H, d, J
7.5 Hz), 2.43 (2H, t, J
0.6 Hz), 2.22
7.5 Hz), 6.08 (1H, dd, J
11.4 Hz), 6.26 (1H, br s),
1.5 Hz), 7.39 (1H, dd, J
15.1
8.0 Hz); 13C NMR (100 MHz,
41, 3), 149 (M
55, base), 81 (36); MS(FAB) m/z 205 (MH ).
HRMS Calcd for C13H17O2: MH , 205.1229. Found: m/z
205.1246.
(3E,5E)-9-(3-F u r yl)-6-m eth yl-3,5-n on a d ien -1-yn e (29).
To a mixture of dienal 27 (1.60 g, 7.83 mmol) and carbon
tetrabromide (5.20 g, 15.66 mmol) in CH2Cl2 (30 mL) was
added PPh3 (4.11 g, 15.66 mmol) by 10 portions during a 10
min at 0 °C. The reaction completed soon after the addition,
and the mixture was diluted with hexane (200 mL). The
mixture was then subjected to silica gel flash chromatography,
quickly eluted with hexane. Evaporation of the fractions in
MHz, CDCl3) δ 1.70 (2H, m), 1.83 (3H, d, J
0.6 Hz), 2.24

Total Synthesis of ( )-Ircinianin and ( )-Wistarin
J . Org. Chem., Vol. 62, No. 6, 1997 1699
vacuo gave pure dibromotriene 28 as a pale yellow oil, which
was not very stable and subjected to the next reaction
successively. Rf 0.42 (hexane); 1H NMR (400 MHz, CDCl3)
0.85 (3H, d, J
(4H, m), 1.72 1.89 (2H, m), 1.85 (3H, d, J
2.07 (3H, m), 1.98 (3H, s), 2.40 (2H, t, J
br m), 3.06 (1H, dm, J
4.96 5.04 (2H, dm, J
7.21 (1H, br s), 7.35 (1H, t, J
CDCl3) δ 8.7, 16.1, 19.7, 20.4, 24.4, 28.4, 29.7, 39.3, 43.7, 47.5,
47.7, 51.5, 57.9, 72.8, 84.6, 97.3, 110.9, 123.2, 123.6, 124.9,
134.3, 134.4, 138.8, 142.7, 174.2, 175.1; MS (FAB) m/z 427
(MH ). HRMS Calcd for C26H35O5: MH , 427.2485. Found:
m/z 427.2494. Anal. Calcd for C26H34O5: C, 73.21; H, 8.03.
Found: C, 73.33; H, 8.12. 7B: Colorless oil; Rf 0.28 (30%
EtOAc in hexane); IR (KBr) 3437, 1760, 1638 cm 1; UV (EtOH)
6.5 Hz), 1.58 (3H, d, J
1.3 Hz), 1.54 1.72
1.3 Hz), 1.90
7.6 Hz), 2.49 (1H,
10.3 Hz), 3.93 (3H, s), 4.07 (1H, m),
δ 1.70 (2H, m), 1.76 (3H, s), 2.10 (2H, t, J
t, J 7.5 Hz), 5.91 (1H, d, J 11.3 Hz), 6.11 (1H, dd, J
14.9 and 10.5 Hz), 6.24 (1H, br s), 6.58 (1H, dd, J 14.9 and
11.3 Hz), 6.96 (1H, d, J 10.5 Hz), 7.19 (1H, br s), 7.33 (1H,
t, J
1.5 Hz); 13C NMR (100 MHz, CDCl3) δ 17.0, 24.3, 27.9,
7.7 Hz), 2.39 (2H,
10.3 Hz), 6.26 (1H, d, J
0.8 Hz),
1.6 Hz); 13C NMR (100 MHz,
39.6, 89.3, 110.9, 124.7, 124.9, 126.6, 132.5, 137.5, 138.8, 142.7,
143.1. To a THF (20 mL) solution of 28 was dropped freshly
prepared LDA (0.7 M THF solution; 22.4 mL) at 0 °C during
30 min. After the addition, the mixture was diluted with
hexane (200 mL) and quenched with water (20 mL). After the
general workup, the crude product was purified by column
chromatography on silica gel eluted with hexane to give 29
(949 mg) in 61% yield in the two steps. A pale yellow oil; Rf
0.20 (hexane); IR (neat) 3280, 2070, 1620 cm 1; UV (hexane)
λ
max 292 (ꢀ 11600, sh), 278 (18700, sh), 269 (22100), 258 (16400,
sh), 200 nm (5500); 1H NMR (400 MHz, CDCl3) δ 1.08 (3H, d,
7.0 Hz), 1.47 (1H, ddd, J 13.9, 9.5, and 5.5 Hz), 1.64
1.82 (4H, m), 1.79 (3H, s), 1.80 (3H, d, J
J
1.1 Hz), 2.05 (3H,
7.7 Hz), 2.95 (1H,
s), 2.11 (2H, t, J
m), 4.11 (3H, s), 4.46 (1H, ddd, J
7.7 Hz), 2.39 (2H, t, J
λ
max 282 (ꢀ 25300, sh), 268 (35500), 258 (27700, sh), 207 (9200),
205 (9300), 201 nm (8800). 1H NMR (400 MHz, CDCl3) δ 1.70
(2H, m), 1.79 (3H, s), 2.12 (2H, t, J 7.7 Hz), 2.39 (2H, t, J
2.2 Hz), 5.46 (1H, dd, J 15.5 and
11.3 Hz), 6.25 (1H, br s), 6.93 (1H,
13.9, 8.8 and 5.5 Hz), 5.17
8.8 Hz), 5.89 (1H, d, J
15.4 Hz), 6.26 (1H, br d, J
(1H, d, J
10.3 Hz), 5.40 (1H, d, J
10.6 Hz), 6.12 (1H, d, J
Hz), 6.41 (1H, dd, J
0.7 Hz), 7.35 (1H, t, J
δ 8.6, 12.9, 16.7, 21.1, 24.3, 27.8, 28.1, 39.5, 44.6, 58.8, 66.9,
99.1, 110.9, 114.1, 124.9, 124.9, 125.4, 133.2, 134.7, 135.7,
138.8, 139.0, 142.7, 143.0, 161.8, 170.7; MS (EI) m/z (rel
intensity) 426 (M , 3), 279 (52), 181 (46), 167 (base), 149 (94).
HRMS Calcd for C26H34O5: M , 426.2401. Found: m/z
426.2385.
1.1
7.3 Hz), 3.00 (1H, d, J
2.2 Hz), 5.89 (1H, d, J
15.4 and 10.6 Hz), 7.21 (1H, br d, J
1.5 Hz); 13C NMR (100 MHz, CDCl3)
dd, J
15.5 and 11.3 Hz), 7.20 (1H, br s), 7.35 (1H, t, J
1.5
Hz); 13C NMR (100 MHz, CDCl3) δ 16.9, 24.2, 27.9, 39.4, 78.6,
83.7, 107.3, 110.9, 124.3, 124.7, 138.8, 140.0, 142.7, 143.1; MS
(EI) m/z (rel intensity) 200 (M , 10), 149 (M
51, 52), 81
(29), 44 (base). HRMS Calcd for C14H16O: M , 200.1201.
Found: m/z 200.1181.
(1E,3E,5E)-9-(3-F u r yl)-1-iod o-2,6-d im et h yl-1,3,5-n on -
a tr ien e (9). To a suspension of anhydrous SnCl2 (682 mg,
3.60 mmol) in THF (8 mL) was added BuLi (1.56 M solution
in hexane; 6.9 mL, 10.8 mmol) dropwise at 20 °C, and it was
stirred for 20 min. To this solution was dropped methylmag-
nesium bromide (0.99 M solution in THF; 3.64 mL, 3.60 mmol)
during 10 min, and it was stirred for an additional 15 min.
Cuprous cyanide (16 mg, 0.18 mmol) was added, and 29 (120
mg, 0.60 mmol) in THF (4 mL) was dropped slowly. After
stirring for 15 min, methyl iodide (0.75 mL, 12.0 mmol) was
dropped and stirred for 20 min. To the reaction mixture,
anhydrous hexane (40 mL) was added and stirred vigorously
for 15 min. After the mixture separated to two layers, the
upper layer was transferred via cannula to the ice-cooled flask,
to which iodine solution in CH2Cl2 (iodine (2 g) and anhydrous
Na2CO3 in 20 mL of CH2Cl2) was dropped carefully by
monitoring on TLC. Up to this stage, all the reactions were
carried out at 20 °C. The ice bath was then removed, and
the mixture was diluted with hexane (30 mL) containing Et3N
in 5% of the volume and washed with sodium thiosulfate (2
mL), water, and brine. The organic extract was dried over
MgSO4 and condensed. The residual oil was purified by
column chromatography on alumina eluted with 5% Et3N in
hexane to give 9 (153 mg) in 75% yield. A pale yellow oil; Rf
0.33 (hexane); UV (hexane) λmax 341 (ꢀ 180, sh), 302 (34600),
289 (43300), 279 (38400), 267 (24000, sh), 208 (10800), 196
nm (7800). 1H NMR (400 MHz, CDCl3) δ 1.71 (2H, quint, J
Syn th esis of Ir cin ia n in Meth yl Eth er (32). To a mixture
of 30A (260 mg, 0.61 mmol), DMAP (37 mg, 0.3 mmol), and
pyridine (0.15 mL, 1.83 mmol) in CH2Cl2 (6 mL) was added
phenyl chlorothionoformate (0.13 mL, 0.92 mmol) at room
temperature, and then it was stirred for 1 h. The mixture was
diluted with ether and washed with water and brine. The
crude extract was roughly purified by column chromatography
on silica gel eluted with 30% EtOAc in hexane to give
thionoformate 31 (295 mg) in 89% yield. Colorless oil; Rf
0.41 (30% EtOAc in hexane); 1H NMR (400 MHz, CDCl3) δ
0.89 (3H, d, J
(3H, m), 1.75 (3H, d, J 1.2 Hz), 1.96 2.10 (5H, m), 1.99 (3H,
s), 2.41 (2H, t, J 7.6 Hz), 2.98 (1H, br t, J 11.3 Hz), 3.08
(1H, dm, J 10.3 Hz), 3.94 (3H, s), 5.00 (1H, dd, J 10.3 and
0.8 Hz), 5.05 (1H, m), 5.43 (1H, m), 6.26 (1H, br s), 7.08 (2H,
d, J 7.7 Hz), 7.21 (1H, br s), 7.29 (1H, d, J 7.4 Hz), 7.36
(1H, t, J 1.5 Hz), 7.41 (2H, dd, J 7.7 and 7.4 Hz).
5.6 Hz), 1.59 (3H, d, J
0.9 Hz), 1.62 1.80
A
mixture of 31 (295 mg, 0.52 mmol), Bu3SnH (0.21 mL, 0.78
mmol), and AIBN (15 mg, 0.09 mmol) was dissolved in benzene
(6 mL) and degassed. The mixture was heated at refluxing
temperature for 30 min. After cooling, the mixture was diluted
with ether (60 mL) and washed with saturated sodium
bicarbonate (1 mL), water, and brine. The crude extract was
purified by column chromatography on alumina eluted with
10% EtOAc in hexane to give 32 (155 mg) in 72% yield.
Colorless crystals, mp 50 52 °C (hexane); Rf
0.23 (15%
EtOAc in hexane); [ ]24
167.7° (c 0.47, CHCl3); IR (neat)
D
7.5 Hz), 1.78 (3H, s), 2.00 (3H, s), 2.10 (2H, t, J
2.40 (2H, t, J 7.5 Hz), 5.85 (1H, d, J 10.9 Hz), 6.22 (1H,
d, J 15.1 and
7.5 Hz),
1
1747, 1660 cm 1; H NMR (400 MHz, CDCl3) δ 0.88 (3H, d, J
6.6 Hz), 1.21 1.37 (2H, m), 1.51 (1H, t, J
(3H, d, J 1.2 Hz), 1.62 1.78 (3H, m), 1.68 (3H, d, J
Hz), 1.85 (1H, m), 1.92 2.06 (3H, m), 1.98 (3H, s), 2.40 (2H, t,
11.0 Hz), 1.58
15.1 Hz), 6.27 (2H, br s), 6.51 (1H, dd, J
1.2
10.9 Hz), 7.21 (1H, br s), 7.35 (1H, br s); 13C NMR (100 MHz,
CDCl3) δ 16.9, 20.1, 24.3, 28.0, 39.6, 82.1, 110.9, 124.8, 125.0,
125.9, 131.2, 138.8, 140.9, 142.7, 145.6; MS (EI) m/z (rel
J
7.6 Hz), 2.45 (1H, br m), 3.06 (1H, dm, J
10.3 Hz), 3.94
10.3 and 0.8 Hz), 6.27
1.4 Hz); 13C NMR
(3H, s), 4.98 (1H, m), 5.04 (1H, dd, J
(1H, br s), 7.21 (1H, br s), 7.35 (1H, t, J
intensity) 342 (M , 53), 328 (28), 215 (M
127, 34), 133 (83),
120 (64), 105 (base), 81 (73). HRMS Calcd for C15H19OI: M ,
342.0481. Found: m/z 342.0507.
(100 MHz, CDCl3) δ 8.7, 16.1, 20.2, 20.4, 24.4, 26.1, 28.4, 31.5,
32.3, 39.4, 44.6, 47.8, 50.5, 57.9, 84.9, 96.1, 110.9, 121.9, 124.2,
125.0, 134.0, 135.9, 138.8, 142.7, 174.4, 175.7; MS (FAB) m/z
411 (MH ). HRMS Calcd for C26H35O4: MH , 411.2536.
Found: m/z 411.2508.
Syn th esis of ( )-Ir cin ia n in (1). To a DMF (5 mL)
solution of 32 (120 mg, 0.29 mmol) was added sodium salt of
propanethiol (1.1 M DMF solution; 1.33 mL, 1.46 mmol)
(sodium salt of propanethiol was prepared as follows: pro-
panethiol (0.2 mL, 2.21 mmol) was added dropwise slowly to
a suspension of NaH (60% dispersion in mineral oil, 88 mg,
2.21 mmol) in DMF (1.8 mL) at room temperature, resulting
Cou p lin g Rea ction of Iod otr ien e 9 w ith Ald eh yd e 8.
To a degassed DMSO solution (30 mL) of 8 (600 mg, 2.85
mmol) and 9 (1.67 g, 4.89 mmol) was added CrCl2 containing
0.1% NiCl2 (1.3 g, 10.6 mmol), and the whole mixture was
stirred for 18 h at room temperature. Water (10 mL) was then
added, and the mixture was extracted with EtOAc. Purifica-
tion of the crude mixture by silica gel flash chromatography
gave cyclized product 30A (737 mg) in 60% yield and â-alcohol
7B (244 mg) in 20% yield. 30A: Colorless crystals; mp 128.0
129.8 °C (methanol); Rf
(KBr) 3460, 1734, 1654 cm
0.18 (30% EtOAc in hexane); IR
;
1
1H NMR (400 MHz, CDCl3) δ
in a clear solution and was used for the next reaction

1700 J . Org. Chem., Vol. 62, No. 6, 1997
Uenishi et al.
successively), and then the mixture was stirred for 40 min at
room temperature. Aqueous sodium hydroxide (1 M solution,
0.1 mL) was added and diluted with EtOAc (50 mL). The
organic layer was taken and washed with water and brine.
The solvent was removed under reduced pressure (20 mmHg
and then 5 mmHg), and the residue was chromatographed on
silica gel eluted with 30% EtOAc in hexane to give 1 (104 mg)
0.96 (3H, d, J
6.4 Hz), 1.58 (3H, d, J
6.7 Hz), 1.22 1.30 (2H, ddm, J
14.6 and
1.1 Hz), 1.61 1.74 (3H, m), 1.79 (3H,
d, J
1.3 Hz), 1.98 2.08 (2H, m), 1.99 (3H, s), 2.19 (1H, dd,
J
12.3 and 10.4 Hz), 2.32 2.42 (4H, m), 3.05 (1H, dm, J
10.3 Hz), 3.95 (3H, s), 4.36 (1H, t, J
4.5 Hz), 5.09 (1H, dd,
J
10.3 and 1.0 Hz), 5.15 (1H, m), 6.26 (1H, br s), 7.21 (1H,
br s), 7.35 (1H, t, J
1.5 Hz); 13C NMR (100 MHz, CDCl3) δ
8.7, 16.1, 19.9, 20.6, 24.5, 28.5, 30.4, 39.4, 43.8, 45.1, 47.8, 50.6,
58.0, 70.3, 85.0, 97.2, 110.9, 123.8, 124.9, 125.5, 131.7, 134.2,
138.8, 142.7, 174.3, 175.5; MS (EI) m/z (rel intensity) 426 (M ,
34), 408 (15), 241 (27), 167 (35), 135 (77), 44 (base). HRMS
Calcd for C26H34O5: M , 426.2407. Found: m/z 426.2390.
30B′: Colorless oil; Rf 0.17 (30% EtOAc in hexane); 1H NMR
in 90% yield. Colorless crystals; mp 153 156 °C; Rf
0.27
(40% EtOAc in hexane); [ ]24 235° (c 0.28, CHCl3), lit. [ ]25
D
D
232° (c 0.5, CHCl3);1 IR (KBr) 3437, 1720, 1652, 1118 cm
1H NMR (400 MHz, CDCl3) δ 0.88 (3H, d, J
6.6 Hz), 1.20
1.38 (2H, m), 1.45 (1H, t, J 11.0 Hz), 1.65 (3H, d, J 0.7
Hz), 1.70 (3H, d, J 1.2 Hz), 1.52 1.74 (3H, m), 1.71 (3H, s),
1.90 (1H, m), 2.00 (1H, m), 2.06 2.19 (2H, m), 2.43 (2H, t, J
7.5 Hz), 2.54 (1H, br m), 3.16 (1H, dm, J 10.2 Hz), 5.04
(1H, m), 5.09 (1H, dd, J 10.2 and 0.8 Hz), 6.06 (1H, br s),
;
1
(400 MHz, CDCl3) δ 0.90 (3H, d, J
14.1 Hz), 1.58 (3H, d, J 1.2 Hz), 1.50 1.72 (3H, m), 1.87
(3H, s), 1.94 2.10 (4H, m), 1.98 (3H, s), 2.40 (2H, t, J 7.7
Hz), 2.51 (1H, dt, J 14.1 and 9.0 Hz), 2.67 (1H, br t, J
10.7 Hz), 2.95 (1H, m), 3.97 (3H, s), 4.00 (1H, m), 4.95 (1H, d,
10.2 Hz), 5.03 (1H, br s), 6.26 (1H, br s), 7.21 (1H, br s),
7.35 (1H, t, J 1.5 Hz); MS (EI) m/z (rel intensity) 426 (M ,
7.1 Hz), 1.19 (1H, dm, J
6.28 (1H, br s), 7.23 (1H, br s), 7.37 (1H, br s); 13C NMR (75
MHz, CDCl3) δ 5.8, 16.7, 20.0, 20.5, 24.4, 26.2, 28.3, 31.4, 32.0,
39.4, 45.1, 46.0, 50.7, 84.0, 100.0, 110.9, 121.1, 122.3, 124.5,
136.6, 138.9, 142.8, 143.3, 174.1, 174.5; MS (EI) m/z (rel
intensity) 396 (M , 27), 287 (52), 135 (base); MS (FAB) m/z
397 (MH ). HRMS Calcd for C25H33O4: MH , 397.2379.
Found: m/z 397.2402.
J
4), 408 (6), 241 (19), 167 (27), 149 (base). HRMS Calcd for
C26H34O5: M , 426.2407. Found: m/z 426.2403. 30B′′: Color-
less oil; Rf 0.19 (30% EtOAc in hexane); 1H NMR (400 MHz,
CDCl3) δ 0.99 (3H, d, J
9.2 Hz), 1.58 (3H, d, J
7.0 Hz), 1.17 (1H, dt, J
1.0 Hz), 1.45 1.75 (3H, m), 1.87 (3H,
12.3 and
Iod o Eth er F or m a tion Rea ction of 1. Syn th esis of 33A.
To an ice-cooled mixture of 1 (18.9 mg, 0.05 mmol) and
anhydrous K2CO3 (41.5 mg, 0.3 mmol) in CHCl3 (1 mL) was
added a CHCl3 (0.5 mL) solution of iodine (13.3 mg, 0.05
mmol). After being stirred for 30 min at the same tempera-
ture, the whole mixture was directly purified by silica gel
column chromatography and eluted with 10% EtOAc in hexane
s), 1.95 (3H, d, J
2.26 (2H, m), 2.32 (2H, t, J
1.6 Hz), 1.98 (2H, t, J
7.1 Hz), 2.18
7.7 Hz), 2.35 2.50 (2H, m), 3.32
(1H, dm, J
10.1 Hz), 4.02 (3H, s), 4.18 (1H, br m), 4.90 (1H,
d, J 10.1 Hz), 5.06 (1H, br s), 6.25 (1H, br s), 7.20 (1H, br s),
7.34 (1H, br s); MS (EI) m/z (rel intensity) 426 (M , 24), 408
(12), 241 (39), 167 (42), 135 (base), 91 (42). HRMS Calcd for
C26H34O5: M , 426.2407. Found: m/z 426.2413.
Deoxygen a tion of 30B, 30B′, a n d 30B′′. These deoxy-
genation reactions were performed using an identical proce-
dure as described for ircinianin methyl ether 32 from 30A.
30B gave 32 in 65% yield. The physical and spectroscopic data
was noted in the experiment for 32. 30B′ afforded 32′ in 67%
to give 33A (17.7 mg) in 71% yield. Colorless oil; Rf
(10% EtOAc in hexane); [ ]29
44.9° (c 1.00, CHCl3); IR (neat)
1768, 1695, 1275, 1167, 1028 cm 1; 1H NMR (400 MHz, CDCl3)
δ 0.84 (3H, d, J 6.5 Hz), 1.22 1.38 (2H, m), 1.48 (1H, dd, J
11.0 Hz), 1.53 (3H, s), 1.63 (1H, m), 1.73 (3H, s), 1.74 (3H,
0.26
D
d, J
1.0 Hz), 1.70 1.80 (2H, m), 1.89 (1H, m), 1.94 2.04
(2H, m), 2.11 (1H, m), 2.44 2.58 (3H, m), 2.67 (1H, dm, J
yield. 32′: Colorless oil; Rf
[ ]21
124° (c 0.27, CHCl3); IR (KBr) 1749, 1664 cm
7.1 Hz), 1.11 1.34
0.20 (15% EtOAc in hexane);
11.7 Hz), 4.13 (1H, d, J
br d, J
11.7 Hz), 5.55 (1H, br m), 6.29 (1H,
1
;
1H
D
0.7 Hz), 7.26 (1H, br s), 7.37 (1H, br m); 13C NMR
NMR (400 MHz, CDCl3) δ 0.76 (3H, d, J
(100 MHz, CDCl3); δ 6.2, 20.7, 20.8, 22.1, 22.6, 24.5, 26.5, 30.6,
32.0, 38.4, 40.3, 45.6, 47.9, 52.1, 79.7, 88.5, 108.3, 110.8, 122.0,
124.4, 138.9, 140.6, 142.9, 173.3, 173.4; MS (FAB) m/z 523
(MH ). HRMS Calcd for C25H32O4I: MH , 523.1346. Found:
m/z 523.1328.
(2H, m), 1.58 (3H, d, J
0.9 Hz), 1.86 (1H, dd, J
1.0 Hz), 1.66 (2H, m), 1.70 (3H, d, J
12.4 and 6.6 Hz), 1.92 2.06 (4H,
m), 1.98 (3H, s), 2.14 (1H, m), 2.39 (2H, t, J
(1H, br m), 2.94 (1H, dm, J 10.3 Hz), 3.97 (3H, s), 5.00 (1H,
dm, J 10.3 Hz), 5.01 (1H, br s), 6.26 (1H, br s), 7.21 (1H, br
s), 7.35 (1H, t, J
1.5 Hz); 13C NMR (100 MHz, CDCl3) δ 8.6,
7.3 Hz), 2.60
Syn th esis of ( )-Wista r in (2B). A freshly prepared
benzene solution of Bu3SnH (0.9 M, 277 µL, 249 µmol)
containing a catalytic amount of Et3B (Bu3SnH (0.37 mmol)
and Et3B (0.124 mmol) in 3 mL of benzene) was added to a
benzene (0.3 mL) solution of 33A (13 mg, 24.9 µmol) at 10 °C.
After being stirred for 20 min, the whole mixture was directly
purified by column chomatography on silica gel eluted with
20% EtOAc in hexane to give ( )-wistarin (7.6 mg) in 77%
16.2, 18.1, 20.9, 24.4, 26.8, 28.4, 31.8, 32.6, 39.4, 39.8, 45.3,
50.0, 58.5, 85.7, 97.9, 110.9, 121.8, 124.0, 125.0, 134.6, 136.2,
138.8, 142.7, 174.2, 175.9; MS (FAB) m/z 411 (MH ). HRMS
Calcd for C26H35O4: MH , 411.2536. Found: m/z 411.2534.
32′′ was obtained form 30B′′ in 60% yield. 32′′; Colorless oil;
Rf 0.30 (15% EtOAc in hexane); [ ]21
45° (c 0.15, CHCl3);
D
IR (KBr) 1748, 1670 cm 1; H NMR (400 MHz, CDCl3) δ 0.93
1
yield. Colorless oil; Rf 0.27 (15% EtOAc in hexane); [ ]28
D
(3H, d, J
6.9 Hz), 1.06 (1H, m), 1.42 1.62 (4H, m),1.59 (3H,
132° (c 0.34, CH2Cl2), lit. [ ]20
130° (c 0.25, CH2Cl2);2 IR
D
d, J 1.3 Hz), 1.72 (3H, s), 1.85 1.93 (2H, m), 1.96 (3H, s),
1.98 (2H, t, J
2.32 (2H, t, J
(neat) 1757, 1693, 1275, 1171, 1028 cm 1; 1H NMR (400 MHz,
7.5 Hz), 2.08 (1H, dd, J
7.6 Hz), 2.48 (1H, br m), 3.33 (1H, dm, J
10.2 and 0.9 Hz), 5.00
9.5 and 5.4 Hz),
CDCl3) δ 0.84 (3H, d, J
6.4 Hz), 1.21 (3H, s), 1.21 1.36 (2H,
11.0 Hz), 1.65 (1H, m), 1.68 (3H, d, J
m), 1.56 (1H, dd, J
10.2 Hz), 4.02 (3H, s), 4.92 (1H, dd, J
1.0 Hz), 1.72 (3H, s), 1.70 1.80 (6H, m), 1.87 (1H, m), 1.97
(1H, m), 2.44 2.59 (4H, m), 5.12 (1H, br m), 6.28 (1H, br s),
(1H, br d, J
(1H, t, J
1.5 Hz), 6.24 (1H, br s), 7.19 (1H, br s), 7.33
1.6 Hz); 13C NMR (100 MHz, CDCl3) δ 8.5, 16.0,
7.23 (1H, br s), 7.37 (1H, t, J
1.5 Hz); 13C NMR (100 MHz,
21.9 (2C), 24.0, 28.4, 31.8, 33.1, 35.0, 39.2, 40.2, 44.7, 48.3,
58.3, 84.6, 98.8, 110.9, 121.2, 122.5, 124.9, 136.4, 137.6, 138.8,
142.7, 173.9, 174.9; MS (FAB) m/z 411 (MH ). HRMS Calcd
for C26H35O4: MH , 411.2536. Found: m/z 411.2536.
CDCl3) δ 6.2, 20.6, 20.7, 23.4, 23.8, 24.9, 26.7, 30.4, 32.0, 39.9,
40.8, 42.0, 44.8, 51.3, 80.7, 86.2, 107.1, 110.8, 121.2, 124.5,
138.5, 138.9, 142.9, 174.1, 175.1; MS (EI) m/z 396 (M , 73),
246 (18), 135 (base); MS (FAB) m/z 397 (MH ). HRMS Calcd
for C25H33O4: MH , 397.2379. Found: m/z 397.2395.
Alter n a tive Ad d ition Rea ction of Iod otr ien e 9 to
Ald eh yd e 8. The reaction of aldehyde 8 (70 mg, 0.33 mmol)
and iodotriene 9 (333 mg, 0.97 mmol) was carried out under
the same condition described for the precedent synthesis for
30A and 7B except for reaction time. The reaction was
stopped after 1 h, when the starting aldehyde 8 was consumed.
After the same workup, the crude mixture was roughly
purified by flash column chromatography on silica gel eluted
with 25% EtOAc in hexane to give a mixture of three isomers
(126 mg) in 89% yield. This mixture contained 7A, 7B, and
30A in a 2:2:1 ratio determined by 1H NMR. They were
unseparable by chromatography. 7A was particularly un-
Diels Ald er Rea ction of 7B. A xylene (4 mL) solution
of 7B (77 mg, 0.18 mmol) was heated at the refluxing
temperature for 15 min. After being cooled to room temper-
ature, the mixture was chromatographed directly on silica gel
and carefully eluted with 20% EtOAc in hexane to give three
stereoisomers. The first fraction gave 30B (20.8 mg) in 27%
yield, the second portion gave 30B′′ (10.8 mg) in 14% yield,
and 30B′ (13.9 mg) was obtained in 18% yield from the last
portion. 30B: Colorless oil; Rf 0.28 (30% EtOAc in hexane);
IR (KBr) 3469, 1745, 1658 cm 1; 1H NMR (400 MHz, CDCl3) δ

Total Synthesis of ( )-Ircinianin and ( )-Wistarin
J . Org. Chem., Vol. 62, No. 6, 1997 1701
stable and decomposed within a day. 1H NMR of 7A was
assigned from the chart consisting of the mixtures. 7A: 1H
late Mr. Arifumi Tanio for his devoted efforts at the
initial stage of this project. This research was supported
by a Grant-in-Aid for Scientific Research from the
Ministry of Education, Science and Culture, J apan.
NMR (400 MHz, CDCl3) δ 1.08 (3H, d, J
7.0 Hz), 1.47 (1H,
m), 1.64 1.82 (4H, m), 1.79 (3H, s), 1.80 (3H, s), 2.05 (3H, s),
2.11 (2H, t, J
4.12 (3H, s), 4.46 (1H, m), 5.24 (1H, d, J
d, J 8.9 Hz), 5.89 (1H, d, J
7.7 Hz), 2.39 (2H, t, J
7.7 Hz), 2.82 (1H, m),
10.1 Hz), 5.37 (1H,
Su p p or tin g In for m a tion Ava ila ble: Copies of 13C-NMR
spectra for the 26 new compounds and the ORTEP drawing
for 30A (29 pages). This material is contained in libraries on
microfiche, immediately follows this article in the microfilm
version of the journal, and can be ordered from the ACS; see
any current masthead page for ordering information.
10.9 Hz), 6.13 (1H, d, J
15.2
Hz), 6.26 (1H, br s), 6.45 (1H, dd, J
15.2 and 10.9 Hz), 7.21
(1H, br s), 7.35 (1H, m).
Ack n ow led gm en t. The authors wish to acknowl-
edge Messrs. Tatsuya Yamazaki and Takahiro Imakoga
for performing the X-ray crystallography. We thank the
J O961993F