Nickel-catalyzed coupling producing (2Z)-2,4-alkadien-1-ols, conversion to (E)-3-alkene-1,2,5-triol derivatives, and synthesis of decarestrictine D

Article abstract of DOI:10.1021/jo0623890

The 3-alkene-1,2,5-triol structure is not only a major framework of biologically important molecules but also a new functional-group-rich unit for synthesis of polyols and sugars. A method furnishing such triol derivatives 8 was developed and successfully applied to synthesis of decarestrictine D (18). First, coupling reaction of the unprotected alcohols 2 with borates 4 was investigated to produce the dienyl alcohols 6 with NiCl₂(dppf) in Et₂O/THF (5:1) at room temperature. The hydroxyl-group-directed epoxidation of 6 followed by palladium-catalyzed reaction with AcOH (Scheme 1) furnished 3-alkene-1,2,5-triol derivatives 8. Since each step proceeded with high stereo- and regioselectivities, the stereochemistry of 8 has been correlated with the olefin geometry of 6. With the above transformation in mind, synthesis of the full carbon skeleton of decarestrictine D (18) could be designed easily and was completed successfully. Furthermore, a new seco acid 19b with the MOM protective group for the three hydroxyl groups was found to afford macrolide 48 in a yield higher than those reported previously.

Full text of DOI:10.1021/jo0623890

Nickel-Catalyzed Coupling Producing (2Z)-2,4-Alkadien-1-ols,
Conversion to (E)-3-Alkene-1,2,5-triol Derivatives, and Synthesis of
Decarestrictine D
Yuichi Kobayashi,* Shinya Yoshida, Moriteru Asano, Akira Takeuchi,
and Hukum P. Acharya
Department of Biomolecular Engineering, Tokyo Institute of Technology, 4259 Nagatsuta-cho,
Midori-ku, Yokohama 226-8501, Japan
ykobayas@bio.titech.ac.jp
ReceiVed NoVember 21, 2006
The 3-alkene-1,2,5-triol structure is not only a major framework of biologically important molecules but
also a new functional-group-rich unit for synthesis of polyols and sugars. A method furnishing such triol
derivatives 8 was developed and successfully applied to synthesis of decarestrictine D (18). First, coupling
reaction of the unprotected alcohols 2 with borates 4 was investigated to produce the dienyl alcohols 6
with NiCl2(dppf) in Et2O/THF (5:1) at room temperature. The hydroxyl-group-directed epoxidation of 6
followed by palladium-catalyzed reaction with AcOH (Scheme 1) furnished 3-alkene-1,2,5-triol derivatives
8. Since each step proceeded with high stereo- and regioselectivities, the stereochemistry of 8 has been
correlated with the olefin geometry of 6. With the above transformation in mind, synthesis of the full
carbon skeleton of decarestrictine D (18) could be designed easily and was completed successfully.
Furthermore, a new seco acid 19b with the MOM protective group for the three hydroxyl groups was
found to afford macrolide 48 in a yield higher than those reported previously.
Introduction
optically active forms by using several methods.5 Later, this
coupling reaction has been utilized in the synthesis of the
dihydroleukotrienes B4 family6 and korormicin,7 in which the
dienyl alcohol unit is seen in their core structures.
Through these investigations, we have reconfirmed the
advantages mentioned above. We then turned our attention to
transformation of 5 or unprotected dienyl alcohols 6 to highly
functionalized compounds of specific interest.
Lithium borates 4 (in E and Z forms) shown in eq 1 are among
the highly reactive organometallics for coupling reactions with
organic substrates such as allylic esters,1 aryl mesylates,2 and
alkenyl halides3 to produce compounds that had previously been
inaccessible because of steric and/or electronic reasons.4 For
example, dienyl alcohol derivatives 5 are synthesized by
coupling with cis bromides 1, which are available easily as
We envisioned synthesis of triol derivatives 8 shown in
Scheme 1. The first step is a hydroxyl-group-directed epoxi-
dation of dienyl alcohols 6 with m-CPBA, and the second step
(1) (a) Kobayashi, Y.; Mizojiri, R.; Ikeda, E. J. Org. Chem. 1996, 61,
5391-5399. (b) Kobayashi, Y.; Murugesh, M. G.; Nakano, M.; Takahisa,
E.; Usmani, S. B.; Ainai, T. J. Org. Chem. 2002, 67, 7110-7123.
(2) Kobayashi, Y.; William, A. D.; Mizojiri, R. J. Organomet. Chem.
2002, 653, 91-97.
(3) (a) Kobayashi, Y.; Nakayama, Y.; Mizojiri, R. Tetrahedron 1996,
54, 1053-1062. (b) Kobayashi, Y.; William, A. D. AdV. Synth. Cat. 2004,
346, 1749-1757.
(4) (a) Kobayashi, Y. J. Synth. Org. Chem. 1999, 55, 845-855.
(b) Kobayashi, Y. Recent Res. DeV. Org. Chem. 1999, 3, 61-77.
(5) (a) Okamoto, S.; Shimazaki, T.; Kobayashi, Y.; Sato, F. Tetrahedron
Lett. 1987, 28, 2033-2036. (b) Stork, G.; Zhao, K. Tetrahedron Lett. 1989,
30, 2173-2174. (c) Zhang, X.; Schlosser, M. Tetrahedron Lett. 1993, 34,
1925-1928.
(6) Nakayama, Y.; Kumar, G. B.; Kobayashi, Y. J. Org. Chem. 2000,
65, 707-715.
(7) Kobayashi, Y.; Yoshida, S.; Nakayama, Y. Eur. J. Org. Chem. 2001,
1873-1881.
10.1021/jo0623890 CCC: $37.00 © 2007 American Chemical Society
Published on Web 01/25/2007
J. Org. Chem. 2007, 72, 1707-1716
1707

Kobayshi et al.
SCHEME 1. An Approach to Triol Derivatives 8
borates 4 to produce dienyl alcohol derivatives 5. Since
unprotected alcohol 6 is required to attain high stereoselectivity
in the next epoxidation according to the literature,13 coupling
reaction between alcohols 2 and borates 4 was investigated first.
Alcohol 2a (R1 ) C5H11, R ) H) (1 equiv) was added to a
mixture of borate (E)-4a (R2 ) H, R3 ) C5H11) and a Ni(0)
species generated from the corresponding boronate ester (E)-
3a (1.5 equiv) and NiCl2(PPh3)2 (10 mol %) with MeLi (1.6
equiv) at 0 °C for 15 min, and the reaction was conducted under
the original conditions (THF/Et2O (5:1), rt, overnight) to furnish
the cis,trans dienyl alcohol 6a (R1 ) R3 ) C5H11, R2 ) R )
H) in 49% yield. Although the yield is moderate, the production
of 6a clearly indicates that the borate is compatible with the
free hydroxyl group present in 2a. In order to increase the yield
of the coupling, nickel ligands and solvents were examined with
the same quantity (1.5 equiv) of (E)-3a. We found that reaction
with NiCl2(dppf) as a catalyst in an Et2O-rich solvent (Et2O/
THF ) 5:1) at room temperature produced 6a in 72% yield
with 95% stereoselectivity (ss) over the trans,trans isomer
(Table 1, entry 1).
The optimized conditions were applied to other combinations
of substrates and borates. As summarized in entries 2-7 of
Table 1, cis,cis isomer 6b (R1 ) R2 ) C5H11, R3 ) H) and
other cis,trans dienyl alcohols 6c-g (R1 and R3 ) alkyl, R2 )
H) were synthesized in good yields with >90% ss. Among these
entries, especially noteworthy is entry 4, where substrate 2 even
with the bulky t-Bu group as R1 produced 6d with similar
efficiency to others. On the other hand, 6h was produced with
86% ss (entry 8). Conjugation of the cis,trans diene moiety with
the phenyl ring in 6h is probably a reason for the partial
isomerization of 6h to the trans,trans isomer during routine
purification by chromatography on silica gel.14
is palladium-assisted reaction of the resulting epoxy alcohols 7
with the acetate anion. The triol structure is seen as such or as
a masked form in biologically active molecules such as the
lipoxygenase metabolites of fatty acids,8 decarestrictine D,9 and
acetogenins.10 To date, several methods have been reported to
construct such triol units.11 In contrast, our approach is quite
simple and hence would be an attractive complement to the
reported methods. Herein, we present the results of this
transformation and a synthesis of decarestrictine D.12
Epoxidation of the cis,trans dienyl alcohol 6a of 95% purity
with m-CPBA under the standard conditions (NaHCO3, CH2-
Cl2, 0 °C) furnished 7a in 77% isolated yield (Table 1, entry
1). The cis,cis isomer 6b was also converted into epoxide 7b
in good yield (entry 2). Epoxides 7a and 7b were fairly stable
during chromatography on silica gel using hexane/EtOAc with
Et3N (trace). The stereochemistries of 7a and 7b were assigned
by analogy as drawn in Scheme 1 and confirmed later by
derivation to the known compounds.
Palladium-catalyzed reaction of epoxide 7a with AcOH in
the presence of Pd(PPh3)4 (10 mol %) at 0 °C for 30 min
provided acetate 8a in 71% yield (Table 1, entry 1). The trans
Results and Discussion
In the original coupling reaction,3 silyl ethers 1 derived from
alcohols 2 were used as substrates for the coupling reaction with
(12) (a) Kobayashi, Y.; Asano, M.; Yoshida, S.; Takeuchi, A. Org. Lett.
2005, 7, 1533-1536. (b) Yoshida, S.; Asano, M.; Kobayashi, Y. Tetrahe-
dron Lett. 2005, 46, 7243-7246.
(13) (a) Rossiter, B. E.; Verhoeven, T. R.; Sharpless, K. B. Tetrahedron
Lett. 1979, 4733-4736. (b) Narula, A. S. Tetrahedron Lett. 1981, 22, 2017-
2020. (c) Tomioka, H.; Suzuki, T.; Oshima, K.; Nozaki, H. Tetrahedron
Lett. 1982, 23, 3387-3390.
(14) Easy isomerization of the cis,trans,trans conjugated trienyl alcohol
during chromatography to the all-trans isomer is reported: Kobayashi, Y.;
Shimazaki, T.; Taguchi, H.; Sato, F. J. Org. Chem. 1990, 55, 5324-5335.
(15) In the 13C NMR spectra of 9 and 10, the carbons circled in the
structure appear at 74.6, 74.9, and 75.7 ppm for 9, and 74.5, 75.2, and 75.7
ppm for 10.
(8) (a) Pace-Asciak, C. R.; Martin. J. M.; Corey, E. J.; Su, W.-G.
Biochem. Biophys. Res. Commun. 1985, 128, 942-946. (b) Hamberg, M.;
Hamberg, G. Plant Physiol. 1996, 110, 807-815. (c) Grechkin, A. N.;
Mukhtarova, L. S.; Hamberg, M. Biochem. J. 2000, 352, 501-509.
(9) (a) Grabley, S.; Granzer, E.; Hu¨tter, K.; Ludwig, D.; Mayer, M.;
Thiericke, R.; Till, G.; Wink, J.; Philipps, S.; Zeeck, A. J. Antibiot. 1992,
45, 56-65. (b) Go¨hrt, A.; Zeeck, A.; Hu¨tter, K.; Kirsch, R.; Kluge, H.;
Thiericke, R, J. Antibiot. 1992, 45, 66-73. (c) Ayer, W. A.; Sun, M.;
Browne, L. M.; Brinen, L. S.; Clardy, J. J. Nat. Prod. 1992, 55, 649-653.
(10) Alali, F. Q.; Liu, X.-X.; McLaughlin, J. L. J. Nat. Prod. 1999, 62,
504-540.
(11) (a) For syntheses of decarestrictine D, see ref 22. (b) Suemune, H.;
Harabe, T.; Sakai, K. Chem. Pharm. Bull. 1988, 36, 3632-3637. (c) Gosse´-
Kobo, B.; Mosset, P.; Gre´e, R. Tetrahedron Lett. 1989, 30, 4235-4236.
(d) Yadav, J. S.; Vadapalli, P. Tetrahedron Lett. 1994, 35, 641-644. (e)
Motoyoshi, H.; Ishigami, K.; Kitahara, T. Tetrahedron 2001, 57, 3899-
3908. (f) Pilli, R. A.; Victor, M. M.; de Meijere, A. J. Org. Chem. 2000,
65, 5910-5916. (g) Sabino, A. A.; Pilli, R. A. Tetrahedron Lett. 2002, 43,
2819-2821. (h) Taber, D. F.; Pan, Y.; Zhao, X. J. Org. Chem. 2004, 69,
7234-7240. (i) Taber, D. F.; Zhang, Z. J. Org. Chem. 2006, 71, 926-933.
(j) Conrow, R. E. Org. Lett. 2006, 8, 2441-2443.
(16) The 1H NMR spectra of 9 and 10 were superimposed and hence
useless for the determination.
1708 J. Org. Chem., Vol. 72, No. 5, 2007

Synthesis of Decarestrictine D
TABLE 1. Results of the Transformation to 8
R1, R2, and R3 for 6-8
compound numbers, yields,a and stereoselectivitiesb
dienyl alcohol 6 epoxide 7 acetate 8
77%
entry
R1
C5H11
C5H11
c-C6H11
t-Bu
(CH2)2OBn
C5H11
C5H11
R2
R3
1
2
3
4
5
6
7
8
H
C5H11
6a
6b
6c
6d
6e
6f
72%, 95% ss
86%, 92% ss
73%, 93% ss
83%, 90% ss
74%, 92% ss
76%, 96% ss
76%, 95% ss
76%, 86% ss
7a
7b
7c
7d
7e
7f
8a
8b
8c
8d
8e
8f
71%
88%
77%
49%
48%d
78%
52%e
93% ds
93% ds
95% ds
91% ds
92% ds
94% ds
>90% ds
C5H11
H
H
C5H11
69%
64%
62%c
H
C5H11
H
C5H11
H
H
H
(CH2)4OTBS
CH(n-Bu)2
Ph
76%
83%
6g
6h
7g
7h
8g
8h
C5H11
a Isolated yields. b ss represents stereoselectivities of the cis olefin moiety of 6 over the trans; ds represents diastereoselectivities of 8 and C(5) isomers.
c Diastereomer of 7d was produced in 16% yield and was separated by chromatography. d Two-step yield from 6e. e Corresponding regioisomer with the
AcO group at C(3) position was obtained in 8% yield.
SCHEME 2. Conversion of 8a to Diastereomers 9 and 10
for Calculation of the Diastereoselectivity and for
Determination of the Olefin Geometry
SCHEME 3. Determination of the Stereochemistry of 8a
Derived from (R)-2a
stereochemistry of the olefin moiety was determined by the
coupling constant (JHa-Hb ) 16 Hz) of the bis-TES ether 9
derived by silylation (Et3SiCl, 90%) (Scheme 2), whereas the
diastereoselectivity (ds) of the reaction was determined by
calculating the height of the 13C NMR signals for 9 and for its
diastereomer 10 at 74.9 and 75.2 ppm, respectively.15,16 The
latter isomer was synthesized from 9 through the Mitsunobu
reaction.
AcOH under similar reaction conditions to produce 8b, the C(5)
diastereomer of 8a, in 88% yield with 93% ds (Table 1, entry
2). The trans olefin geometry of 8b was determined by 1H NMR
spectroscopy of the derived silyl ether (JHa-Hb ) 16 Hz), which
was identical by spectroscopy with 10 prepared through
Mitsunobu inversion of 9 (Scheme 2). These facts indicate that
the three steps to produce 8b take place sequentially: (1)
oxidative addition to produce the anti,syn π-allylpalladium
complex; (2) conversion to the more stable syn,syn isomer via
σ-allyl complex; and (3) reaction with the acetoxy anion
(Scheme 4).
The relative stereochemistry of 8a was assigned unambigu-
ously by using the homochiral alcohol (R)-2a (>99% ee),5a
which was transformed to (R,R,R)-8a through dienyl alcohol
(R)-6a (Scheme 3). Ozonolysis of the derived bis-TBS ether
11 followed by reductive workup with Me2S afforded a mixture
of two aldehydes 12 and 13. After separation of the two
aldehydes by chromatography, the former was reduced to
1
alcohol 14. The H NMR spectrum of 14 was identical with
that of the syn isomer,17 thus allowing assignment of the
stereocenter of epoxide 7a as depicted in the structure. Further
evidence for the determination was provided by comparison of
In order to expand the synthetic advantage of the transforma-
tion, we explored a variation of the method to produce triol
derivatives with the differently protected hydroxyl groups.
Epoxy alcohol 7a was converted to TES ether 15, which upon
palladium-catalyzed reaction with AcOH furnished 16 in 67%
yield with 94% ds (Scheme 5). No migration of the TES group
to the next C(2)-OH was confirmed by 1H NMR spectroscopy
of 16 and by exclusive production of acetate 17 from 16. The
proton at the C(2) position of 17 appears at 5.17-5.28 ppm.
The stereochemistry of 16 was determined by converting it into
the specific rotations: 14 synthesized, [R]26 +33 (c 0.48,
D
CHCl3); (2S,3S)-14 in the literature,17 [R]25 -33.2 (c 1.0,
D
CHCl3). Similarly, the stereochemistry of the acetoxy-carbon
of 8a was determined as depicted: 13 synthesized, [R]26D +31
(c 0.10, CHCl3); (S)-13 in the literature,18 [R]20D -37.8 (c 0.5,
CHCl3).
Next, epoxide 7b prepared from the cis,cis dienyl alcohol
6b was submitted to the palladium-catalyzed reaction with
1
bis-TES ether 9, which showed H and 13C NMR spectra and
(17) Nicolaou, K. C.; Webber, S. E. Synthesis 1986, 453-461.
(18) Noyori, R.; Tomino, I.; Yamada, M.; Nishizawa, M. J. Am. Chem.
Soc. 1984, 106, 6717-6725.
Rf value on TLC identical with those synthesized above from
8a. It should be noted that differentiation of the hydroxyl groups
J. Org. Chem, Vol. 72, No. 5, 2007 1709

Kobayshi et al.
SCHEME 4. Three Steps to 8b
SCHEME 5. Synthesis of 1,2,5-Triol Derivative 16 with the
Three Hydroxyl Groups Being Differentiated
in the vicinal diols is usually difficult to attain without an
additional functional group at a proximal position of the diol
moiety.19,20
As mentioned in the Introduction, the structural pattern of 8
(Scheme 1) is seen in decarestrictine D (18), isolated from
Penicillium corylophilum and Polyporus tuberaster, which
shows inhibitory activity toward HMG-CoA reductase.9a Before
the publication of our synthesis of 18 as a Letter,12a two
syntheses were reported by Andrus22a and Pilli.22b,c Quite
recently, another synthesis was reported by Krishna,22d who
prepared a seco acid similar to our newly designed seco acid.
However, some of the chiral centers in the previous syntheses
are prepared by chiral induction from the pre-existing chiral
center(s) with rather low efficiency, and the lactone ring
formation suffers from low yields and/or excess use of the toxic
reagent.
Based on the stereochemical correlation summarized in
Scheme 1, a synthesis of 18 was deduced as depicted in Scheme
6, in which a precursor is seco acid 19 with properly protected
hydroxyl groups at C(3), C(4), and C(7). Preparation of the
C(3)-C(7) structure in 19 and its precursor 20 requires the
cis,trans dienyl alcohol 21, which in turn was disconnected to
the borate derived from boronate ester 22 and cis bromide 23.
Synthesis of the boronate ester 22 was accomplished by a
sequence delineated in Scheme 7 starting with epichlorohydrin
24 of 98.9% ee. The first step was reaction with TMS acetylene,
and the resulting chlorohydrin was reduced to 25 in 82% yield
from 24. Protection of 25 with PMBCl (p-MeOC6H4CH2Cl)
under the standard conditions (NaH and NaI in THF)23 resulted
in concomitant removal of the TMS group, though incompletely,
to afford a mixture of 26 and PMB ether of 25 in a 1:2 ratio.
Without separation, the mixture was treated with K2CO3 in
MeOH to produce 26 in 81% from 25. The reverse sequence,
i.e., removal of the TMS group from 25 followed by PMB
protection, was less productive since most of the volatile alcohol
produced in the first step was lost during isolation. Finally, the
acetylene part of 26 was converted to the vinyl boronate ester
moiety of 22 by hydroboration with (Ipc)2BH, ligand exchange
with CH3CHO,24 and transesterification with diol 29.
The above transformation established for the cis,trans dienyl
alcohol 6a (Table 1, entry 1) was applied to other cis,trans
analogues 6c-h in order to examine efficiency of the transfor-
mation (Scheme 1).21 Epoxidation of 6c,e-g with m-CPBA
afforded the corresponding epoxides in good yields with
exclusive ds. However, 6d produced 7d only with 80% ds, and
6h gave a mixture of products. Epoxides 7c,d,f,g were fairly
stable to allow chromatography on silica gel, whereas 7e was
somewhat unstable and was hence submitted to the next step
after short-path chromatography. The stereochemistries of
epoxides 7c-g depicted in Scheme 1 are speculated from that
of 7a. Palladium-catalyzed reaction of epoxide 7c (R1
)
c-C6H11) with AcOH afforded 8c with similar efficiency (Table
1, entry 3), whereas 7d with t-Bu produced 8d with somewhat
lower efficiency (entry 4), probably because of steric reasons.
The steric obstruction by the other side chain (R3) was also
observed in the case of 7g with CH(n-Bu)2, which furnished
acetate 8g as a major product (52%) and the regioisomer (8%)
with the AcO group installed at C(3) (structure not shown) (entry
7). However, easy separation by chromatography compensates
for the moderate regioselectivity. The alkoxy groups (OBn,
OTBS) at the end of the R1 or R3 group were compatible with
this transformation, thus producing 8e and 8f in moderate to
good yields (entries 5 and 6).
(19) Kolb, H. C.; VanNieuwenhze, M. S.; Sharpless, K. B. Chem. ReV.
1994, 94, 2483-2547.
(20) See Tables 53 and 54 of ref 19.
(21) The bis-TES ethers i-v and their diastereomers vi-x were prepared
from 8c-g as in the cases of 8a and 8b in order to establish the trans
olefin geometry and to calculate diastereomeric ratio of 8c-g by 1H NMR
and 13C NMR spectroscopy. See the experimental details in Supporting
Information.
(22) (a) Andrus, M. B.; Shih, T.-L. J. Org. Chem. 1996, 61, 8780-
8785. (b) Pilli, R. A.; Victor, M. M. Tetrahedron Lett. 1998, 39,
4421-4424. (c) Pilli, R. A.; Victor, M. M. J. Braz. Chem. Soc. 2001, 12,
373-385. (d) Krishna, P. R.; Reddy, P. V. N. Tetrahedron Lett. 2006, 47,
7473-7476.
(23) Paquette, L. A.; Barriault, L.; Pissarnitski, D.; Johnston, J. N.
J. Am. Chem. Soc. 2000, 122, 619-631.
(24) Kamabuchi, A.; Moriya, T.; Miyaura, N.; Suzuki, A. Synth.
Commun. 1993, 23, 2851-2859.
1710 J. Org. Chem., Vol. 72, No. 5, 2007

Synthesis of Decarestrictine D
SCHEME 6. Retrosynthesis of Decarestrictine Da
SCHEME 8. Preparation of the C(1)-C(5) Fragment 23
a OH groups at C(3), C(4), and C(7) of 19 and 20 should be protected
for the transformation. We found that the choice of the protective groups
was crucial for the successful macrolactonization.
SCHEME 7. Preparation of the C(6)-C(10) Intermediate
22
afforded 34, which was free of the diastereomeric acetate derived
1
from 33 (Ac2O, pyridine) by H NMR spectroscopy. Reaction
of 34 with MgBr2 proceeded cleanly at the carbon bearing the
TMS, and bromohydrin 35 thus formed was subjected to
mesylation and reaction with Bu4NF to produce 36 in 77% yield
from 34. Finally, methanolysis with K2CO3 in MeOH produced
1
23. The yield from 33 was 60%. The H NMR and 13C NMR
spectra of each 23 synthesized by the two routes were clean,
and the signals corresponding to the trans isomer were not
detected.
As presented in Scheme 9, nickel-catalyzed coupling reaction
of alcohol 23 (1 equiv) and borate 37 derived in situ from
boronate 22 (1.5 equiv) proceeded successfully to afford dienyl
alcohol 21 in 76% yield as the sole product. Epoxidation with
m-CPBA followed by palladium-catalyzed reaction of 38 with
AcOH furnished 39, which comprises the full carbon skeleton
of 18 and the necessary functional groups. The 13C NMR spectra
of 39 and its bis-TES ether showed no signals corresponding
to the diastereomer at C(7) (structure not shown). The stereo-
chemistry of 39 tentatively assigned as drawn at this stage was
proved by the transformation to the known compounds (see the
next paragraph).
The remaining tasks for completion of the synthesis were
functional group manipulation and macrocyclization. First, 39
was converted to the Andrus acetonide 42.22a Protection of 39
as the acetonide followed by hydrolysis afforded alcohol 41,
which on reaction with MOMCl furnished the advanced
intermediate 20a of our strategy. Removal of the TBDPS
protection from 20a and Swern oxidation produced 42 in good
yield. The 1H NMR and 13C NMR spectra of synthetic 42 were
Another key intermediate 23 was synthesized by taking
advantage of the reactivity of the vinyl silane (Scheme 8). Thus,
reaction of aldehyde 30 with the lithium anion derived from 31
and n-BuLi afforded racemic alcohol rac-32. Sharpless asym-
metric epoxidation25 of rac-32 afforded allylic alcohol (S)-32
and epoxy alcohol 33, which were separated easily by chro-
matography. As expected from the epoxidation of similar γ-TMS
allylic alcohols,26 both of the products were of high ee
(confirmed by the MTPA method) and consequently were
transformed to 23. Bromination of (S)-32 with Br2 at -78 °C
took place without injuring the TBDPS group, and subsequent
treatment of the bromine adduct with Bu4NF at -78 °C afforded
23 in 77% yield. As for 33, the Mitsunobu inversion with AcOH
(25) (a) Martin, V. S.; Woodard, S. S.; Katsuki, T.; Yamada, Y.; Ikeda,
M.; Sharpless, K. B. J. Am. Chem. Soc. 1981, 103, 6237-6240. (b) Gao,
Y.; Hanson, R. M.; Klunder, J. M.; Ko, S. Y.; Masamune, H.; Sharpless,
K. B. J. Am. Chem. Soc. 1987, 109, 5765-5780.
(26) Kinetic resolution of γ-silylallylic alcohols: Kitano, Y.; Matsumoto,
T.; Sato, F. Tetrahedron 1988, 44, 4073-4086.
J. Org. Chem, Vol. 72, No. 5, 2007 1711

Kobayshi et al.
SCHEME 9. Synthesis of Triol Derivative 20a and Its Further Conversion to the Known Intermediate 42
SCHEME 10. Macrolactonization of 19a
projection of the two reaction sites (CO2H and OH) into the
opposite spaces divided by the acetonide plane, thus increasing
the energy barrier for the lactonization (Figure 1). This simple
hypothesis led us to examine another seco acid, which is free
of such an obstacle.
A new seco acid 19b was prepared from 39 by a sequence
presented in Scheme 11. Toward this end, the acetyl (Ac) group
was removed, and the resulting triol 44 was converted to MOM
ether 20b. After removal of the TBDPS protective group, the
C(1) carbon of the resulting alcohol 45 was oxidized to the
methoxycarbonyl moiety (CO2Me) by the standard method in
75% yield. The PMB group of 46 thus prepared was removed
with DDQ, and the ester group was hydrolyzed to afford 19b.
Yamaguchi lactonization of 19b furnished 48 in 40% yield.31,32
1
The H NMR and 13C NMR spectra of lactone 48 are clean
and indicate existence of a single conformational isomer.33
Deprotection of the MOM group of 48, the last step, under
the standard conditions such as CF3CO2H/CH2Cl2, Dowex-50/
MeOH, and BF3‚OEt2/(CH2SH)2/CH2Cl2 provided a mixture of
products. Fortunately, PPTS34 in refluxing n-BuOH was found
to proceed well to afford decarestrictine D (18) in 81% yield
consistent with the data reported, and thus the chiral centers at
C(4) and C(7) of 39 created by the key transformation were
established unambiguously.
Previously, macrolactonization of seco acid 19a derived from
42 was achieved by using the Corey-Nicolaou reagent ((2-
PyS)2, PPh3, AgClO4) to produce lactone 43 in 33% yield,27
whereas the Keck reagent (DCC, DMAP, H+) and Yamaguchi
reagent (Cl3C6H2COCl, DMAP) did not afford the lactone
(Scheme 10).22a In order to improve the yield, the same seco
acid 19a was prepared from aldehyde 42 (NaClO2 then DDQ),
and the lactonization was studied with the Yamaguchi reagent,28
since we were especially familiar with this reagent through
synthesis of other macrolides.29 The procedure improved by
Yonemitsu30 did furnish 43 in 17% yield, though it is practically
quite low. A reason for the failure by Andrus (0%) and for the
low yield observed by us (17%) would probably be the undesired
(27) Professor T.-L. Shih, a co-author of ref 22a, communicated privately
that lactonization repeated after their publication produced 43 and two other
products, which were probably the corresponding diol- and monool-lactones.
(28) Inanaga, J.; Hirata, K.; Saeki, H.; Katsuki, T.; Yamaguchi, M. Bull.
Chem. Soc. Jpn. 1979, 52, 1989-1993.
(29) (a) Kobayashi, Y.; Nakano, M.; Kumar, G. B.; Kishihara, K. J. Org.
Chem. 1998, 63, 7505-7515. (b) Kobayashi, Y.; Okui, H. J. Org. Chem.
2000, 65, 612-615. (c) Kobayashi, Y.; Matsuumi, M. J. Org. Chem. 2000,
65, 7221-7224. (d) Kobayashi, Y.; Kumar, G. B.; Kurachi, T.; Acharya,
H. P.; Yamazaki, T.; Kitazume, T. J. Org. Chem. 2001, 66, 2011-2018.
(e) Kobayashi, Y.; Wang, Y.-G. Tetrahedron Lett. 2002, 43, 4381-4384.
(30) (a) Hikota, M.; Sakurai, Y.; Horita, K.; Yonemitsu, O. Tetrahedron
Lett. 1990, 31, 6367-6370. (b) Makino, K.; Nakajima, N.; Hashimoto, S.;
Yonemitsu, O. Tetrahedron Lett. 1996, 37, 9077-9080.
(31) Perhaps lactonization of 19b with (2-PyS)2, PPh3, and AgClO4 may
furnish a better yield of 48 based on the results summarized in Scheme 10.
However, this possibility was not studied partly because of the explosive
nature of AgClO4: (a) Brinkley, S. R., Jr. J. Am. Chem. Soc. 1940, 62,
3524. (b) Hein, F. Chem. Tech. (Berlin) 1957, 9, 97; Chem. Abstr. 1957,
51, 54429.
(32) Difficulty in formation of medium ring lactones: Rousseau, G.
Tetrahedron 1995, 51, 2777-2849.
(33) On the other hand, lactone 43 derived from 19a (Scheme 10) exists
as a mixture of the three conformational isomers according to Andrus.22a
(34) Miyashita, M.; Yoshida, A.; Grieco, P. A. J. Org. Chem. 1977, 42,
3772-3774.
FIGURE 1. Plausible 3D structure of 19a.
1712 J. Org. Chem., Vol. 72, No. 5, 2007

Synthesis of Decarestrictine D
TABLE 2. Specific Rotations of Synthetic and Natural Decarestrictine D
[R]D
source of the data
in MeOH
in CHCl3
our data (synthetic)
[R]24D -68 (c 0.066)a
[R]24D -99 (c 0.156)b
[R]D -67 (c 0.26)
Andrus (ref 22a) (synthetic)
Krishna (ref 22d) (synthetic)
data cited by Andrus and Krishna for identification
Pilli (ref 22b,c) (synthetic)
Wink and Zeeck (ref 9a) (natural)
Ayer (ref 9c) (natural)
[R]25D -60.3 (c 0.4)
[R]D -62 (c 0.4) (incorrect)c
[R]D -70.9 (c 1.0 or 0.24)
[R]20D -62 (c 1.0)
[R]25D -31 (c 0.4)
a After recrystallization from CH2Cl2/hexane. b The rotation was measured again in CHCl3: [R]24 -102 (c 0.066). c This value (-62) was originally
D
measured in MeOH (c 1.0) by Wink and Zeeck.9a
SCHEME 11. Synthesis of Decarestrictine D (18) through a
New Seco Acid 19b
Conclusion
We have shown a transformation of dienyl alcohols 6 to trans
3-alkene-1,2,5-triol derivatives 8 (Scheme 1) and clarified the
stereochemical relationship between the olefin moiety of 6 and
the chiral centers of 8. A variation of the method for synthesizing
the triol derivatives with the differentiated hydroxyl groups was
examined as delineated in Scheme 5, which is an additional
synthetic advantage of this method.
With the above relationship in mind, synthesis of decarestric-
tine D (18) was designed easily and executed with minimum
effort in differentiating the hydroxyl groups since the hydroxyl
group of the cis bromo alcohol 23 was compatible with the
coupling partner (borate 37), which is formally a hard anion.
Moreover, examination of the negative factor for the lacton-
ization of the seco acid 19a with the acetonide group led us to
design a new seco acid 19b, which furnished a better yield of
lactone 48 using the Yamaguchi reagent. We think that the
present synthesis of decarestrictine D would be applicable to
that of analogues as well.
Experimental Section
(7Z,9E)-7,9-Pentadecadien-6-ol (6a). To an ice-cold mixture
of boronate ester (E)-3a (R2 ) H, R3 ) C5H11) (158 mg, 0.752
mmol) and NiCl2(dppf) (34 mg, 0.050 mmol) in Et2O (1.0 mL)
and THF (0.2 mL) was added MeLi (0.57 mL, 1.41 M in Et2O,
0.804 mmol) slowly. After 15 min of stirring at 0 °C, bromoalcohol
2a (R1 ) C5H11) (104 mg, 0.502 mmol) was added. The resulting
mixture was stirred at room temperature overnight and diluted with
Et2O and saturated NaHCO3. The layers were separated, and the
aqueous layer was extracted with Et2O three times. The combined
extracts were dried (MgSO4) and concentrated to give a residue,
which was purified by chromatography on silica gel (hexane/EtOAc/
Et3N (trace)) to give 6a (81 mg) in 72% yield: IR (neat) 3338,
1654 cm-1; 1H NMR δ 0.88 (t, J ) 6 Hz, 6 H), 1.16-1.72 (m, 15
H), 2.09 (q, J ) 7 Hz, 2 H), 4.51-4.63 (m, 1 H), 5.27 (t, J ) 10
Hz, 1 H), 5.74 (dt, J ) 15, 7 Hz, 1 H), 6.02 (t, J ) 11 Hz, 1 H),
6.31 (dd, J ) 15, 11 Hz, 1 H); 13C NMR δ 137.4, 131.4, 130.5,
125.1, 68.1, 37.6, 33.0, 32.0, 31.6, 29.0, 25.2, 22.8, 22.7, 14.2. Anal.
Calcd for C15H28O: C, 80.29; H, 12.58. Found: C, 80.18; H, 12.33.
(6R*,7R*,8R*,9E)-7,8-Epoxy-9-pentadecen-6-ol (7a). To an
ice-cold mixture of 6a (213 mg, 0.950 mmol) and NaHCO3 (181
mg, 2.13 mmol) in CH2Cl2 (4.8 mL) was added m-CPBA (246 mg,
80% purity, 1.14 mmol). After 40 min of stirring at 0 °C, Me2S
(0.030 mL, 0.423 mmol) was added to the resulting mixture at the
same temperature. The mixture was stirred at 0 °C for 5 min and
diluted with Et2O and saturated NaHCO3. The layers were separated,
and the water layer was extracted with Et2O three times. The
combined extracts were dried (MgSO4) and concentrated to give a
mixture of an oil and a white precipitate, which was purified by
short-path chromatography on silica gel (hexane/EtOAc/Et3N
(trace)) to give 7a (175 mg) in 77% yield: IR (neat) 3429, 968
1
after chromatography. The H NMR and 13C NMR spectra of
synthetic 1835 measured in CDCl3 and in CD3OD were identical
with those reported.9c,22a-c
In addition, we would like to comment on the specific rotation
of 18 ([R]24 -68 (c 0.066, MeOH); [R]24 -99 to -102 (c
D
D
0.156-0.066, CHCl3)). The value in MeOH was in agreement
with that reported for natural 18 by Wink and Zeeck ([R]20
D
-62 (c 1.0)).9a On the contrary, the rotation in CHCl3 was not
consistent with that reported by Andrus ([R]D -67 (c 0.26,
CHCl3)).22a Values similar to that of Andrus have been reported
later by Pilli22b,c and quite recently by Krishna.22d Fortunately,
the coauthor (T.-L. Shih) of ref 22a informed us (Y.K.) that
the data (-67) was actually measured in MeOH and not in
CHCl3. The [R]D values measured by us and others are
summarized in Table 2.36
(35) Mp (121-123 °C (recrystallized from CH2Cl2/hexane)) was also
in good agreement with the reported values: 118-120 °C (synthetic);22a,d
116 °C (natural);9b 114-115 °C (natural).9c
(36) Note that the value (-62) in MeOH measured by Wink and Zeeck9a
and that (-68) by us have been used incorrectly as measured in CHCl3 by
the authors of ref 22a,d. The lower value reported by Ayer9c is probably
due to incomplete purification from a natural source.
J. Org. Chem, Vol. 72, No. 5, 2007 1713

Kobayshi et al.
1
cm-1; H NMR δ 0.88 (t, J ) 6 Hz, 6 H), 1.13-1.71 (m, 14 H),
1 H), 5.77 (dd, J ) 16, 5 Hz, 1 H); 13C NMR δ 170.2, 132.3,
128.9, 75.7, 75.2, 74.5, 34.6, 32.2, 31.7, 31.4, 25.8, 25.0, 22.8, 22.7,
21.5, 14.26, 14.19, 7.2, 7.0, 5.3, 5.1.
2.00-2.12 (m, 3 H), 3.02 (dd, J ) 8, 4 Hz, 1 H), 3.46-3.56 (m,
2 H), 5.29 (ddt, J ) 16, 8, 1 Hz, 1 H), 5.94 (dt, J ) 16, 7 Hz, 1
H); 13C NMR δ 138.8, 123.6, 70.1, 62.4, 58.2, 33.8, 32.6, 31.9,
31.4, 28.7, 24.8, 22.71, 22.66, 14.2.
(1R,2E,4R,5R)-4,5-Bis[(tert-butyldimethylsilyl)oxy]-1-pentyl-
2-decenyl Acetate ((R,R,R)-11). Alcohol (R)-2a (2 of R1 ) C5H11)
1
(1R*,2E,4R*,5R*)-4,5-Dihydroxy-1-pentyl-2-decenyl Acetate
(8a). To an ice-cold mixture of Pd(PPh3)4 (87 mg, 0.075 mmol)
and AcOH (0.062 mL, 1.09 mmol) in THF (2 mL) was added a
solution of 7a (175 mg, 0.728 mmol) in THF (1.0 mL + 0.50 mL
× 2) slowly. After 35 min of stirring at 0 °C, H2O2 (0.11 mL, 3.6
mmol) was added to the resulting mixture with vigorous stirring.
To the mixture were added EtOAc and saturated NaHCO3 with
stirring. The layers were separated, and the aqueous layer was
extracted with EtOAc three times. The combined extracts were dried
(MgSO4) and concentrated to give a yellow oil, which was purified
by silica gel chromatography (hexane/EtOAc) to afford 8a (156
of >99% ee (by H NMR spectroscopy of the MTPA ester) was
prepared according to the literature method5a,26 and transformed
into acetate (R,R,R)-8a in yields similar to those obtained with the
racemic alcohol 2a.
A solution of (R,R,R)-8a (159 mg, 0.529 mmol), TBSCl (191
mg, 1.27 mmol), and imidazole (108 mg, 1.59 mmol) in DMF (1.2
mL) was stirred at room temperature overnight and diluted with
Et2O and saturated NaHCO3 with stirring. The layers were
separated, and the aqueous layer was extracted with Et2O three
times. The combined extracts were dried (MgSO4) and concentrated
to leave an oil, which was purified by chromatography on silica
gel (hexane/EtOAc) to give TBS ether (R,R,R)-11 (230 mg) in 82%
yield: IR (neat) 1742, 1239, 1097 cm-1; 1H NMR δ 0.02 (s, 3 H),
0.03 (s, 3 H), 0.045 (s, 3 H), 0.050 (s, 3 H), 0.89 (br s, 24 H),
1.10-1.70 (m, 16 H), 2.03 (s, 3 H), 3.47-3.62 (m, 1 H), 4.02-
4.16 (m, 1 H), 5.26 (q, J ) 7 Hz, 1 H), 5.58 (ddd, J ) 16, 7, 1.5
Hz, 1 H), 5.78 (dd, J ) 16, 5 Hz, 1 H); 13C NMR δ 170.2, 132.0,
128.7, 75.4, 75.0, 74.6, 34.6, 32.1, 31.7, 31.0, 26.03, 26.01, 25.85,
25.0, 22.79, 22.75, 21.5, 18.4, 18.2, 14.25, 14.21, -4.0, -4.36,
mg) in 71% yield: IR (neat) 3421, 1739, 1241 cm-1; H NMR δ
1
0.87 (t, J ) 7 Hz, 3 H), 0.88 (t, J ) 7 Hz, 3 H), 1.15-1.74 (m, 16
H), 2.04 (s, 3 H), 2.40 (br s, 1 H), 2.49 (br s, 1 H), 3.39-3.50 (m,
1 H), 3.88-3.96 (m, 1 H), 5.18-5.27 (m, 1 H), 5.63-5.80 (m, 2
H); 13C NMR δ 170.4, 131.8, 131.4, 75.3, 74.6, 74.1, 34.4, 33.0,
32.0, 31.7, 25.4, 24.9, 22.73, 22.68, 21.4, 14.22, 14.17; HRMS-CI
m/z ([M + 1]+): calcd for C17H33O4 301.2379, found 301.2368.
(1R*,2E,4R*,5R*)-4,5-Bis[(triethylsilyl)oxy]-1-pentyl-2-dece-
nyl Acetate (9). To an ice-cold solution of 8a (156 mg, 0.519 mmol)
and imidazole (106 mg, 1.56 mmol) in DMF (2 mL) was added
triethylsilyl chloride (0.209 mL, 1.25 mmol) slowly, and the
resulting solution was stirred at room temperature for 6 h. Hexane
and saturated NaHCO3 were added with stirring. The layers were
separated, and the aqueous layer was extracted with hexane three
times. The combined extracts were dried (MgSO4) and concentrated
to give an oil, which was subjected to chromatography on silica
gel (hexane/EtOAc) to afford 9 (248 mg) in 90% yield: IR (neat)
1742, 1239, 1016 cm-1; 1H NMR δ 0.57 (q, J ) 8 Hz, 6 H), 0.59
(q, J ) 8 Hz, 6 H), 0.87 (t, J ) 7 Hz, 3 H), 0.88 (t, J ) 7 Hz, 3
H), 0.94 (t, J ) 8 Hz, 9 H), 0.96 (t, J ) 8 Hz, 9 H), 1.14-1.70 (m,
16 H), 2.02 (s, 3 H), 3.52-3.61 (m, 1 H), 4.12 (dt, J ) 1.5, 5 Hz,
1 H), 5.26 (q, J ) 7 Hz, 1 H), 5.60 (ddd, J ) 16, 7, 2 Hz, 1 H),
5.80 (ddd, J ) 16, 5, 1 Hz, 1 H); 13C NMR δ 170.2, 132.2, 128.8,
75.7, 74.9, 74.6, 34.7, 32.2, 31.8, 31.5, 25.8, 25.0, 22.8, 22.7, 21.5,
14.3, 14.2, 7.2, 7.0, 5.3, 5.1. Anal. Calcd for C29H60O4Si2: C, 65.85;
H, 11.43. Found: C, 65.89; H, 11.41.
-4.40, -4.6; [R]25 +59.4 (c 1.19, CHCl3). Anal. Calcd for
D
C29H60O4Si2: C, 65.85; H, 11.43. Found: C, 65.78; H, 11.17.
Ozonolysis of the Above TBS Ether (R,R,R)-11. Ozone was
introduced into a solution of TBS ether (R,R,R)-11 (78 mg, 0.147
mmol) in CH2Cl2 (3 mL) at -78 °C for 30 min. Argon was bubbled
gently through the solution for 20 min at -78 °C to purge excess
ozone, and then Me2S (0.156 mL, 2.13 mmol) was added. The
solution was allowed to warm to room temperature overnight and
concentrated to give an oil, which was subjected to chromatography
on silica gel (hexane/Et2O) to give aldehyde (2R,3R)-12 with a small
quantity of an unidentified compound(s) (46 mg, ca. 80%) and pure
R-acetyloxy aldehyde (R)-13 (16 mg, 64% yield). (2R,3R)-12: IR
and 1H NMR spectra were identical with those reported;17 13C NMR
δ 203.7, 80.1, 74.7, 32.8, 31.9, 25.92, 25.90, 25.7, 22.7, 18.4, 18.2,
14.2, -4.26, -4.30, -4.32, -4.9. (R)-13: 1H NMR δ 0.89 (t, J )
7 Hz, 3 H), 1.24-1.47 (m, 6 H), 1.65-1.89 (m, 2 H), 2.17 (s, 3
H), 4.98 (dd, J ) 8, 5 Hz, 1 H), 9.51 (s, 1 H); [R]26D +31 (c 0.10,
CHCl3). Compare (S)-13 of 100% ee, [R]20D -37.8 (c 0.5, CHCl3).18
(2R,3R)-2,3-Bis[(tert-butyldimethylsilyl)oxy]-1-octanol ((2R,3R)-
14). To an ice-cold solution of the above aldehyde (2R,3R)-12 in
MeOH (0.65 mL) and THF (0.01 mL) was added NaBH4 (4.4 mg,
0.12 mmol), and the resulting mixture was stirred for 4 h at 0 °C.
The solution was diluted with Et2O and H2O. After 10 min of
stirring, the layers were separated, and the aqueous layer was
extracted with EtOAc four times. The combined extracts were dried
(MgSO4) and concentrated to leave a residue, which was purified
by short-path chromatography on silica gel (hexane/Et2O) to afford
(2R,3R)-14 (24 mg) in 42% yield from (R,R,R)-11 (2 steps): IR
and 1H NMR spectra were identical with those reported;17 13C NMR
δ 75.5, 73.8, 63.3, 32.0, 30.5, 26.4, 26.0, 25.9, 22.8, 18.2, 18.1,
(1S*,2E,4R*,5R*)-4,5-Bis[(triethylsilyl)oxy]-1-pentyl-2-dece-
nyl Acetate (10) from 9. A mixture of acetate 9 (15 mg, 0.028
mmol) and K2CO3 (20 mg, 0.145 mmol) in MeOH (0.8 mL) was
stirred at room temperature for 8 h and diluted with brine and
EtOAc. The layers were separated, and the aqueous layer was
extracted with EtOAc three times. The combined organic layers
were dried (MgSO4) and concentrated to afford a residue, which
was purified by chromatography on silica gel to furnish the
corresponding alcohol (10 mg) in 73% yield: 1H NMR δ 0.58 (q,
J ) 8 Hz, 6 H), 0.61 (q, J ) 8 Hz, 6 H), 0.8-1.1 (m, 21 H),
1.1-1.7 (m, 17 H), 3.54-3.62 (m, 1 H), 4.08-4.19 (m, 2 H), 5.69
(dd, J ) 16, 5 Hz, 1 H), 5.76 (dd, J ) 16, 4.5 Hz, 1 H).
14.2, -4.0, -4.4, -4.5; [R]26 +33 (c 0.48, CHCl3). Compare
To an ice-cold solution of the above alcohol (117 mg, 0.240
mmol) and PPh3 (126 mg, 0.480 mmol) in THF (1.0 mL) was added
AcOH (0.027 mL, 0.474 mmol). The resulting solution was allowed
to warm to 8 °C over 5 min, and diethyl azodicarboxylate (0.075
mL, 0.476 mmol) was added to it. The resulting solution was stirred
at room temperature overnight and diluted with Et2O and aqueous
NaHCO3 with stirring. The layers were separated, and the aqueous
layer was extracted with Et2O twice. The combined extracts were
dried (MgSO4) and concentrated to afford an oil, which was purified
by silica gel chromatography (hexane/EtOAc) to furnish acetate
D
(2S,3S)-14: [R]25 -33.2 (c 1.0, CHCl3).17
D
(3S,4Z,6E,9R)-1-[(tert-Butyldiphenylsilyl)oxy]-9-[(4-methoxy-
benzyl)oxy]-4,6-decadien-3-ol (21). To an ice-cold suspension of
NiCl2(dppf) (34 mg, 0.05 mmol) and boronate ester 22 (239 mg,
0.751 mmol) in Et2O (1.1 mL) and THF (0.22 mL) was added MeLi
(0.56 mL, 1.43 M in Et2O, 0.801 mmol). After 15 min of stirring
at 0 °C, bromoalcohol 23 (210 mg, 0.501 mL) was added to the
resulting brown suspension. The mixture was stirred at room
temperature overnight and diluted with NaHCO3 and EtOAc with
stirring. The layers were separated, and the aqueous layer was
extracted with EtOAc three times. The combined extracts were dried
(MgSO4) and concentrated to give a brown oil, which was subjected
to chromatography on silica gel (hexane/EtOAc/Et3N (trace)) to
10 (76 mg) in 60% yield: IR (neat) 1741, 1239, 1016 cm-1; H
1
NMR δ 0.56 (q, J ) 8 Hz, 6 H), 0.59 (q, J ) 8 Hz, 6 H), 0.86 (t,
J ) 7 Hz, 6 H), 0.93 (t, J ) 8 Hz, 9 H), 0.95 (t, J ) 8 Hz, 9 H),
1.11-1.69 (m, 16 H), 2.01 (s, 3 H), 3.51-3.61 (m, 1 H), 4.08 (t,
J ) 5 Hz, 1 H), 5.26 (q, J ) 7 Hz, 1 H), 5.59 (dd, J ) 16, 7 Hz,
afford 21 (208 mg) in 76% yield: IR (neat) 3437, 1513, 1248 cm-1
;
1714 J. Org. Chem., Vol. 72, No. 5, 2007

Synthesis of Decarestrictine D
1H NMR δ 1.06 (s, 9 H), 1.17 (d, J ) 6 Hz, 3 H), 1.56-1.73 (m,
1 H), 1.75-1.93 (m, 1 H), 2.19-2.30 (m, 1 H), 2.33-2.44 (m, 1
H), 2.86 (d, J ) 3 Hz, 1 H), 3.49-3.59 (m, 1 H), 3.79 (s, 3 H),
3.74-3.91 (m, 2 H), 4.41 (d, J ) 11 Hz, 1 H), 4.48 (d, J ) 11 Hz,
1 H), 4.85-4.96 (m, 1 H), 5.36 (dd, J ) 11, 9 Hz, 1 H), 5.74 (dt,
J ) 15, 7 Hz, 1 H), 6.01 (t, J ) 11 Hz, 1 H), 6.40 (dd, J ) 15, 11
Hz, 1 H), 6.86 (dm, J ) 9 Hz, 2 H), 7.25 (dm, J ) 9 Hz, 2 H),
7.35-7.47 (m, 6 H), 7.64-7.73 (m, 4 H); 13C NMR δ 159.0,
135.53, 135.51, 133.2, 133.1, 132.7, 131.6, 130.9, 129.79, 129.76,
129.71, 129.1, 127.8, 127.7, 127.3, 113.7, 74.3, 70.2, 67.3, 62.4,
) 5 Hz, 1 H), 3.44-3.66 (m, 2 H), 3.78 (s, 3 H), 3.64-4.01 (m,
4 H), 4.34 (d, J ) 11 Hz, 1 H), 4.38-4.49 (m, 1 H), 4.54 (d, J )
11 Hz, 1 H), 5.72 (dd, J ) 16, 6 Hz, 1 H), 5.81 (dd, J ) 16, 5 Hz,
1 H), 6.87 (d, J ) 9 Hz, 2 H), 7.25 (d, J ) 9 Hz, 2 H), 7.36-7.48
(m, 6 H), 7.57-7.76 (m, 4 H).
A solution of 44 (113 mg, 0.195 mmol), MOMCl (0.083 mL,
1.09 mmol), and (i-Pr)2NEt (0.27 mL, 1.56 mmol) in CH2Cl2 (0.5
mL) was stirred at 40 °C overnight and diluted with EtOAc and
saturated NaHCO3 with stirring at 0 °C. The layers were separated,
and the aqueous layer was extracted with EtOAc three times. The
combined extracts were dried (MgSO4) and concentrated to give
an oil, which was purified by silica gel chromatography (hexane/
EtOAc) to afford 20b (137 mg) in 99% yield: IR (neat) 1106, 1035
55.4, 40.0, 39.3, 27.0, 19.8, 19.3; [R]24 -8.5 (c 0.66, CHCl3).
D
Anal. Calcd for C34H44O4Si: C, 74.96; H, 8.14. Found: C, 74.66;
H, 8.31.
1
cm-1; H NMR δ 1.04 (s, 9 H), 1.22 (d, J ) 6 Hz, 3 H), 1.59-
(3S,4R,5S,6E)-1-[(tert-Butyldiphenylsilyl)oxy]-4,5-epoxy-9-(4-
methoxybenzyloxy)-6-decen-3-ol (38). To an ice-cold mixture of
21 (259 mg, 0.475 mmol) and NaHCO3 (90 mg, 1.07 mmol) in
CH2Cl2 (2 mL) was added m-CPBA (133 mg, 80% purity, 0.617
mmol). After 50 min of stirring at 0 °C, Me2S (0.018 mL, 0.25
mmol) was added. The mixture was stirred at 0 °C for 5 min and
diluted with Et2O and saturated NaHCO3 with stirring. The layers
were separated, and the aqueous layer was extracted with Et2O three
times. The combined extracts were dried (MgSO4) and concentrated.
The residue was purified by short-path chromatography on silica
gel (hexane/EtOAc/Et3N (trace)) to give epoxide 38 (187 mg) in
70% yield: IR (neat) 3421, 1248, 1111 cm-1; 1H NMR δ 1.05 (s,
9 H), 1.15 (d, J ) 6 Hz, 3 H), 1.57-1.84 (m, 2 H), 2.17-2.38 (m,
2 H), 2.74-2.80 (m, 1 H), 3.11 (dd, J ) 8, 4 Hz, 1 H), 3.44-3.62
(m, 2 H), 3.78 (s, 3 H), 3.71-3.92 (m, 3 H), 4.38 (d, J ) 11 Hz,
1 H), 4.47 (d, J ) 11 Hz, 1 H), 5.37 (dd, J ) 15, 8 Hz, 1 H), 5.99
(dt, J ) 15, 7 Hz, 1 H), 6.86 (d, J ) 9 Hz, 2 H), 7.25 (d, J ) 9 Hz,
2 H), 7.34-7.49 (m, 6 H), 7.62-7.72 (m, 4 H); 13C NMR δ 159.0,
135.49, 135.47, 134.9, 133.2, 133.1, 130.8, 129.79, 129.76, 129.1,
127.75, 127.73, 125.9, 113.8, 74.0, 70.2, 68.9, 62.1, 61.1, 57.3,
1.97 (m, 4 H), 3.29 (s, 3 H), 3.32 (s, 3 H), 3.35 (s, 3 H), 3.79 (s,
3 H), 3.72-3.88 (m, 4 H), 4.14 (t, J ) 5 Hz, 1 H), 4.27-4.37 (m,
1 H), 4.36 (d, J ) 11 Hz, 1 H), 4.50 (d, J ) 7 Hz, 1 H), 4.54 (d,
J ) 7 Hz, 1 H), 4.54 (d, J ) 11 Hz, 1 H), 4.63 (d, J ) 7 Hz, 1 H),
4.65 (d, J ) 7 Hz, 1 H), 4.67 (d, J ) 7 Hz, 1 H), 4.68 (d, J ) 7
Hz, 1 H), 5.53-5.71 (m, 2 H), 6.88 (d, J ) 9 Hz, 2 H), 7.23-7.47
(m, 8 H), 7.62-7.71 (m, 4 H); 13C NMR δ 159.0, 135.5, 134.7,
133.79, 133.76, 130.9, 129.6, 129.2, 129.1, 127.6, 113.8, 97.3, 94.3,
94.1, 77.6, 77.0, 73.5, 71.4, 70.4, 60.4, 55.9, 55.8, 55.7, 55.4, 44.0,
34.0, 27.0, 20.1, 19.4; [R]24D -23.2 (c 0.586, CHCl3). Anal. Calcd
for C40H58O9Si: C, 67.57; H, 8.22. Found: C, 67.61; H, 8.25.
(3S,4S,5E,7S,9R)-9-[(4-Methoxybenzyl)oxy]-3,4,7-tri-
[(methoxymethyl)oxy]-5-decen-1-ol (45). A solution of 20b (148
mg, 0.208 mmol) and Bu4NF (0.25 mL, 1.0 M in THF, 0.25 mmol)
in THF (0.25 mL) was stirred at 40 °C for 2 h and diluted with
Et2O and saturated NH4Cl with stirring. The layers were separated,
and the aqueous layer was extracted with EtOAc three times. The
combined mixture was dried (MgSO4) and concentrated to leave
an oil, which was subjected to chromatography on silica gel (CH2-
Cl2/acetone) to give 45 (98 mg) in 100% yield: IR (neat) 3482,
55.4, 39.6, 35.7, 27.0, 19.7, 19.3; [R]24 -7.4 (c 1.02, CHCl3).
D
1
1514 cm-1; H NMR δ 1.22 (d, J ) 6 Hz, 3 H), 1.59-1.90 (m, 4
(1S,2E,4S,5S,2′R)-7-[(tert-Butyldiphenylsilyl)oxy]-4,5-dihydroxy-
1-[2′-[(4-methoxyl-benzyl)oxy]propyl]-2-heptenyl Acetate (39).
To an ice-cold mixture of Pd(PPh3)4 (282 mg, 0.244 mmol) and
AcOH (0.135 mL, 2.37 mmol) in THF (4 mL) was added a solution
of epoxide 38 (664 mg, 1.18 mmol) in THF (2 mL). The reaction
was carried out between 8 and 11 °C for 30 min and quenched by
addition of H2O2 (0.05 mL, 1.64 mmol), EtOAc, and saturated
NaHCO3. The layers were separated, and the aqueous layer was
extracted with EtOAc three times. The combined extracts were dried
(MgSO4) and concentrated to afford a yellow oil, which was purified
by chromatography on silica gel (CH2Cl2/acetone) to afford 39 (497
mg) in 68% yield: IR (neat) 3448, 1737 cm-1; 1H NMR δ 1.05 (s,
9 H), 1.20 (d, J ) 6 Hz, 3 H), 1.59-1.85 (m, 4 H), 1.96 (s, 3 H),
2.72 (d, J ) 4 Hz, 1 H), 3.49-3.61 (m, 2 H), 3.79 (s, 3 H), 3.69-
3.82 (m, 1 H), 3.86 (t, J ) 6 Hz, 2 H), 3.93-4.02 (m, 1 H), 4.29
(d, J ) 11 Hz, 1 H), 4.49 (d, J ) 11 Hz, 1 H), 5.46-5.58 (m, 1
H), 5.63-5.82 (m, 2 H), 6.86 (d, J ) 9 Hz, 2 H), 7.26 (d, J ) 9
Hz, 2 H), 7.34-7.50 (m, 6 H), 7.58-7.75 (m, 4 H); 13C NMR δ
170.1, 159.0, 135.48, 135.46, 132.72, 132.66, 131.6, 131.2, 130.5,
129.90, 129.89, 129.6, 127.8, 113.8, 75.0, 74.2, 71.0, 70.3, 70.2,
62.9, 55.4, 42.2, 34.4, 26.9, 21.4, 19.8, 19.2; [R]27D -38.1 (c 0.41,
CHCl3). Anal. Calcd for C36H48O7Si: C, 69.64; H, 7.79. Found:
C, 69.73; H, 8.11.
H), 2.64 (t, J ) 6 Hz, 1 H), 3.34 (s, 3 H), 3.36 (s, 3 H), 3.42 (s, 3
H), 3.80 (s, 3 H), 3.60-3.87 (m, 4 H), 4.10 (t, J ) 6 Hz, 1 H),
4.27-4.36 (m, 1 H), 4.35 (d, J ) 11 Hz, 1 H), 4.50 (d, J ) 7 Hz,
1 H), 4.53 (d, J ) 7 Hz, 1 H), 4.54 (d, J ) 11 Hz, 1 H), 4.639 (d,
J ) 7 Hz, 1 H), 4.644 (d, J ) 7 Hz, 1 H), 4.69 (d, J ) 7 Hz, 1 H),
4.81 (d, J ) 7 Hz, 1 H), 5.55 (dd, J ) 16, 7 Hz, 1 H), 5.64 (dd,
J ) 16, 7 Hz, 1 H), 6.88 (dm, J ) 8 Hz, 2 H), 7.28 (dm, J ) 8 Hz,
2 H); 13C NMR δ 159.0, 135.6, 130.9, 129.2, 128.3, 113.8, 98.0,
94.5, 93.9, 78.4, 78.2, 73.7, 71.2, 70.3, 59.2, 56.2, 55.7, 55.6, 55.4,
44.0, 33.9, 20.0; [R]30 -45.6 (c 0.838, CHCl3). Anal. Calcd for
D
C24H40O9: C, 61.00; H, 8.53. Found: C, 61.16; H, 8.47.
Methyl (3S,4S,5E,7S,9R)-9-[(4-Methoxybenzyl)oxy]-3,4,7-tri-
[(methoxymethyl)oxy]-5-decenoate (46). According to the syn-
thesis of aldehyde 42, alcohol 45 (181 mg, 0.383 mmol) in CH2Cl2
(2 mL) was converted into the corresponding aldehyde with oxalyl
chloride (0.100 mL, 1.15 mmol), CH2Cl2 (1.5 mL), DMSO (0.17
mL, 2.4 mmol), and Et3N (0.48 mL, 3.45 mmol). The product was
used for the next reaction without further purification.
To a solution of the above aldehyde and 2-methyl-2-butene (0.40
mL, 3.8 mmol) in H2O (0.8 mL) and t-BuOH (3.2 mL) were added
the phosphate buffer (pH ) 3.6) (1.2 mL) and NaClO2 (217 mg,
purity 80%, 1.92 mmol) at room temperature. The mixture was
stirred at room temperature for 2 h and concentrated in vacuo to
afford an oily residue, which was diluted with the phosphate buffer
(pH ) 3.6) and EtOAc. The layers were separated, and the aqueous
layer was extracted with EtOAc. The combined extracts were dried
(MgSO4) and concentrated to give the corresponding acid. A sample
for characterization was purified by chromatography on silica gel
(hexane/EtOAc): IR (neat) 3100 cm-1; 1H NMR δ 1.22 (d, J ) 6
Hz, 3 H), 1.61-1.78 (m, 2 H), 2.52 (dd, J ) 16, 8 Hz, 1 H), 2.71
(dd, J ) 16, 5 Hz, 1 H), 3.35 (s, 3 H), 3.36 (s, 6 H), 3.80 (s, 3 H),
3.70-3.92 (m, 1 H), 4.08 (dt, J ) 8, 5 Hz, 1 H), 4.18-4.28 (m, 1
H), 4.28-4.40 (m, 1 H), 4.36 (d, J ) 11 Hz, 1 H), 4.51 (d, J ) 7
Hz, 1 H), 4.55 (d, J ) 11 Hz, 1 H), 4.56 (d, J ) 7 Hz, 1 H), 4.64
(3S,4S,5E,7S,9R)-1-[(tert-Butyldiphenylsilyl)oxy]-9-[(4-meth-
oxybenzyl)oxy]-3,4,7-tri[(methoxymethyl)oxy]-5-decene (20b).
To an ice-cold solution of 39 (419 mg, 0.675 mmol) in THF (2
mL) was added MeLi (2.58 mL, 1.65 M in Et2O, 4.26 mmol). The
solution was stirred at room temperature for 2 h and poured into
saturated NH4Cl and EtOAc with stirring. The layers were separated,
and the aqueous layer was extracted with EtOAc three times. The
combined extracts were dried (MgSO4) and concentrated to leave
an oil, which was purified by silica gel chromatography (CH2Cl2/
acetone) to give triol 44 (319 mg) in 82% yield: IR (neat) 3420,
1
1249, 1111 cm-1; H NMR δ 1.05 (s, 9 H), 1.24 (d, J ) 6 Hz, 3
H), 1.55-1.90 (m, 4 H), 2.81 (br d, J ) 3 Hz, 1 H), 3.12 (br d, J
J. Org. Chem, Vol. 72, No. 5, 2007 1715

Kobayshi et al.
(d, J ) 7 Hz, 1 H), 4.66 (d, J ) 7 Hz, 1 H), 4.71 (d, J ) 7 Hz, 1
H), 4.73 (d, J ) 7 Hz, 1 H), 5.62 (dd, J ) 16, 6 Hz, 1 H), 5.68
(dd, J ) 16, 6 Hz, 1 H), 6.88 (d, J ) 8 Hz, 2 H), 7.29 (d, J ) 8
Hz, 2 H).
trichlorobenzoyl chloride (0.040 mL, 0.19 mmol). The mixture was
stirred at room temperature for 2 h and diluted with toluene (70
mL). The supernatant was added dropwise over 6 h to a solution
of DMAP (70 mg, 0.57 mmol) in toluene (17 mL) under reflux.
After the addition, the mixture was refluxed for further 1 h, cooled
to room temperature, and diluted with Et2O. The solution was
washed successively with 1 N HCl, saturated NaHCO3, and H2O,
dried (MgSO4), and concentrated. The residue thus obtained was
purified by chromatography on silica gel (hexane/EtOAc) to furnish
The above acid was treated with an ethereal solution of CH2N2
at 0 °C for 40 min. The solution was concentrated and chroma-
tography of the residue on silica gel (hexane/EtOAc) furnished 46
(144 mg) in 75% yield from alcohol 45 (3 steps): IR (neat) 1739,
1
1033 cm-1; H NMR δ 1.22 (d, J ) 6 Hz, 3 H), 1.61-1.78 (m, 2
1
H), 2.50 (dd, J ) 16, 8 Hz, 1 H), 2.66 (dd, J ) 16, 4.5 Hz, 1 H),
3.349 (s, 3 H), 3.352 (s, 3 H), 3.357 (s, 3 H), 3.69 (s, 3 H), 3.80
(s, 3 H), 3.70-3.88 (m, 1 H), 4.11 (dt, J ) 8, 4.5 Hz, 1 H), 4.18-
4.27 (m, 1 H), 4.28-4.40 (m, 1 H), 4.36 (d, J ) 11 Hz, 1 H), 4.50
(d, J ) 7 Hz, 1 H), 4.54 (d, J ) 11 Hz, 1 H), 4.55 (d, J ) 7 Hz,
1 H), 4.63 (d, J ) 7 Hz, 1 H), 4.66 (d, J ) 7 Hz, 1 H), 4.69 (d,
J ) 7 Hz, 1 H), 4.72 (d, J ) 7 Hz, 1 H), 5.61 (dd, J ) 16, 2.5 Hz,
1 H), 5.67 (dd, J ) 16, 6 Hz, 1 H), 6.88 (d, J ) 9 Hz, 2 H), 7.29
(d, J ) 9 Hz, 2 H); 13C NMR δ 171.8, 159.0, 135.4, 130.9, 129.3,
128.0, 113.8, 97.3, 94.4, 94.2, 76.9, 76.7, 73.5, 71.3, 70.4, 56.0,
lactone 48 (24 mg) in 40% yield: IR (neat) 1732, 1038 cm-1; H
NMR δ 1.22 (d, J ) 6 Hz, 3 H), 1.79 (dd, J ) 14, 11 Hz, 1 H),
1.88 (ddd, J ) 14, 3.5, 2.5 Hz, 1 H), 2.44 (dd, J ) 14, 7 Hz, 1 H),
2.60 (dd, J ) 14, 3 Hz, 1 H), 3.33 (s, 3 H), 3.37 (s, 3 H), 3.44 (s,
3 H), 3.39 (ddd, J ) 7, 5, 3 Hz, 1 H), 4.07-4.17 (m, 1 H), 4.25
(dd, J ) 6, 1.5 Hz, 1 H), 4.49 (d, J ) 7 Hz, 1 H), 4.65 (d, J ) 7
Hz, 1 H), 4.66 (d, J ) 7 Hz, 1 H), 4.69 (d, J ) 7 Hz, 1 H), 4.77
(d, J ) 7 Hz, 1 H), 4.82 (d, J ) 7 Hz, 1 H), 5.12-5.25 (m, 1 H),
5.69-5.81 (m, 2 H); 13C NMR δ 170.3, 134.1, 128.0, 95.7, 95.2,
93.2, 77.1, 75.9, 75.6, 67.9, 55.9, 55.7, 55.4, 41.0, 34.7, 21.7; [R]26
D
55.8, 55.4, 51.8, 44.0. 36.5, 20.1; [R]25 -21.8 (c 1.724, CHCl3).
-8.6 (c 0.266, CHCl3). Anal. Calcd for C16H28O8: C, 55.16; H,
D
Anal. Calcd for C25H40O10: C, 59.98; H, 8.05. Found: C, 60.15;
H, 8.14.
8.10. Found: C, 55.24; H, 8.00.
Decarestrictine D (18). A solution of lactone 48 (20 mg, 0.057
mmol) and PPTS (147 mg, 0.585 mmol) in n-BuOH (1 mL) was
refluxed for 3.5 h and poured into saturated NH4Cl and EtOAc.
The layers were separated, and the aqueous layer was extracted
with EtOAc. The combined extracts were dried (MgSO4) and
concentrated to afford an oil, which was subjected to chromatog-
raphy on silica gel (hexane/EtOAc) to furnish 18 (10 mg) in 81%
yield: IR (CHCl3) 3450, 1696, 1376, 1167 cm-1; 1H NMR (CDCl3)
δ 1.25 (d, J ) 6.5 Hz, 3 H), 1.76-1.98 (m, 3 H), 2.09 (br s, 1 H),
2.40 (dd, J ) 15, 6 Hz, 1 H), 2.62 (dd, J ) 15, 2 Hz, 1 H), 4.00-
4.11 (m, 1 H), 4.15,-4.26 (m, 1 H), 4.43 (br s), 4.64 (d, J ) 8 Hz,
1 H), 5.19-5.31 (m, 1 H), 5.85 (dd, J ) 16, 3 Hz, 1 H), 5.90 (dd,
Methyl (3S,4S,5E,7S,9R)-9-Hydroxyl-3,4,7-tri[(methoxymethyl)-
oxy]-5-decenoate (47). To an ice-cold solution of 46 (105 mg, 0.210
mmol) in CH2Cl2 (3.7 mL) and H2O (0.3 mL) was added DDQ
(123 mg, 0.542 mmol). The resulting solution was stirred at 0 °C
for 2 h and poured into saturated NaHCO3 and CH2Cl2 with stirring.
The layers were separated, and the aqueous layer was extracted
with CH2Cl2 three times. The combined extracts were dried
(MgSO4) and concentrated to afford an oil, which was purified by
chromatography on silica gel (hexane/EtOAc) to furnish 47 (79
mg) in 100% yield: IR (neat) 3482, 1735, 1029 cm-1; 1H NMR δ
1.21 (d, J ) 6 Hz, 3 H), 1.63-1.76 (m, 2 H), 2.50 (dd, J ) 16, 8
Hz, 1 H), 2.59 (d, J ) 4 Hz, 1 H), 2.67 (dd, J ) 16, 5 Hz, 1 H),
3.355 (s, 3 H), 3.363 (s, 3 H), 3.39 (s, 3 H), 3.69 (s, 3 H), 4.12 (dt,
J ) 8, 5 Hz, 1 H), 4.00-4.15 (m, 1 H), 4.25 (t, J ) 5 Hz, 3 H),
4.32-4.41 (m, 1 H), 4.56 (d, J ) 7 Hz, 1 H), 4.58 (d, J ) 7 Hz,
1 H), 4.65 (d, J ) 7 Hz, 1 H), 4.66 (d, J ) 7 Hz, 1 H), 4.69 (d,
1
J ) 16, 8 Hz, 1 H); H NMR (MeOH-d4) δ 1.20 (d, J ) 6.5 Hz,
3 H), 1.71 (dt, J ) 14, 11 Hz, 1 H), 1.85 (ddd, J ) 14, 3.5, 1.5 Hz,
1 H), 2.30 (dd, J ) 14, 7 Hz, 1 H), 2.59 (dd, J ) 14, 2 Hz, 1 H),
3.88-3.97 (m, 1 H), 4.06 (ddd, J ) 11, 9, 4 Hz, 1 H), 4.15-4.24
(m, 1 H), 5.10-5.23 (m, 1 H), 5.73 (dd, J ) 16, 3 Hz, 1 H), 5.82
(dd, J ) 16, 9 Hz, 1 H); 13C NMR (CDCl3) δ 174.8, 133.7, 129.8,
74.0, 72.6, 72.3, 68.3, 43.2, 33.3, 21.4; 13C NMR (MeOH-d4) δ
174.4, 135.7, 129.3, 75.3, 73.5, 73.1, 69.3, 44.2, 35.6, 21.7. The
J ) 7 Hz, 1 H), 4.72 (d, J ) 7 Hz, 1 H), 5.62-5.78 (m, 2 H); 13
C
NMR δ 171.8, 134.2, 128.4, 97.3, 94.5, 94.4, 77.0, 74.4, 64.4, 56.0,
55.9, 55.8, 51.8, 44.3, 36.4, 23.6; [R]25 -53.2 (c 0.724, CHCl3).
D
22a
IR (in CHCl3),9c 1H NMR (in CDCl3 and in CD3OD)9c,22b,c and
Anal. Calcd for C17H32O9: C, 53.67; H, 8.48. Found: C, 53.62; H,
8.32.
22a-c
13C NMR (in CDCl3
and in CD3OD)9c spectra of the product
Lactone 48. A mixture of methyl ester 47 (80 mg, 0.21 mmol)
and 1 N NaOH (0.32 mL) in THF (1 mL) and H2O (1 mL) was
stirred at room temperature for 40 min and diluted with EtOAc
and H2O. The layers were separated, and EtOAc was added to the
aqueous layer. The resulting layers were acidified with 1 N HCl,
and the organic layer was separated. The aqueous layer was
extracted with EtOAc. The combined extracts were dried (MgSO4)
and concentrated to give seco acid 19b (77 mg) in 100% yield:
1H NMR δ 1.19 (d, J ) 6 Hz, 3 H), 1.56-1.77 (m, 2 H), 2.50 (dd,
J ) 16, 8 Hz, 1 H), 2.69 (dd, J ) 16, 5 Hz, 1 H), 3.35 (s, 6 H),
3.38 (s, 3 H), 3.96-4.17 (m, 2 H), 4.25 (t, J ) 5 Hz, 1 H), 4.34
(dt, J ) 7.5, 5 Hz, 1 H), 4.55 (d, J ) 7 Hz, 1 H), 4.58 (d, J ) 7
Hz, 1 H), 4.64 (d, J ) 7 Hz, 1 H), 4.65 (d, J ) 7 Hz, 1 H), 4.68
(d, J ) 7 Hz, 1 H), 4.72 (d, J ) 7 Hz, 1 H), 5.58-5.78 (m, 2 H);
13C NMR δ 175.8, 134.3, 128.3, 97.2, 94.5, 94.4, 76.9, 76.4, 74.4,
64.5, 56.0, 55.84, 55.80, 44.1, 36.3, 23.5.
were identical with those reported. The following physical constants
of 18 were measured after recrystallization from CH2Cl2/hexane:
[R]24D -68 (c 0.066, MeOH), lit. [R]20D -62 (c 1.0, MeOH)9a; mp
121-123 °C, lit. mp 116 °C9b, 118-120 °C.22a
Acknowledgment. Epichlorohydrin 24 was kindly gifted by
Daiso Co. Ltd. This work was supported by a Grant-in-Aid for
Scientific Research from the Ministry of Education, Science,
Sports, and Culture, Japan. We thank Professor T.-L. Shih of
Chemistry Department, Tamkang University, Taiwan, for fruitful
discussion. We also thank Mr. Y. Tashiro of Nippon Chemiphar
for measuring the high-resolution mass spectra.
Supporting Information Available: Full experimental proce-
dures and spectral data for all new compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
To an ice-cold solution of seco acid 19b (63 mg, 0.172 mmol)
and Et3N (0.029 mL, 0.21 mmol) in THF (2 mL) was added 2,4,6-
JO0623890
1716 J. Org. Chem., Vol. 72, No. 5, 2007