The synthesis of deoxyfusapyrone. 2. Preparation of the bis-trisubstituted olefin fragment and its attachment to the pyrone moiety

Article abstract of DOI:10.1021/jo034371k

A convergent and modular synthesis has been devised to construct the eight diastereoisomers of deoxyfusapyrone (1). In this paper the synthesis of the complex polyene chain is reported as is its connection to the pyrone moiety that is in the middle of the

Full text of DOI:10.1021/jo034371k

Th e Syn th esis of Deoxyfu sa p yr on e. 2. P r ep a r a tion of th e
Bis-Tr isu bstitu ted Olefin F r a gm en t a n d Its Atta ch m en t to th e
P yr on e Moiety
Michael G. Organ* and J unquan Wang
Department of Chemistry, York University, 4700 Keele Street, Toronto, Ontario, Canada M3J 1P3
organ@yorku.ca
Received March 21, 2003
A convergent and modular synthesis has been devised to construct the eight diastereoisomers of
deoxyfusapyrone (1). In this paper the synthesis of the complex polyene chain is reported as is its
connection to the pyrone moiety that is in the middle of the structure of the final target molecule.
This route has been fully worked out for one of the isomers and will now be applied in a parallel
synthesis format to make all the stereoisomers of 1.
In tr od u ction
allow us to use existing chirality and build it into the
structure. While building blocks 6 and 7 appear different,
in fact, we can use 8 that is commercially available in
both enantiomeric forms to make both compounds, there-
fore maximally exploiting the synthetic methods devel-
oped to modify 8. This modular approach offers the
further advantage of only having to prepare 6 as one
enantiomer. That is, groups X and Y are electronically
differentiated such that one will always be the most
reactive of the two (e.g., I vs Cl) in oxidative addition
reactions involving metals such as Pd.4 Thus, simply
changing the order in which 4 and 7 are added to 6 will,
by design, change the chirality of C13 from (R) to (S)
because 6 is pseudo-C2 symmetrical. However, first as a
proof of principle we opted to deal with the couplings to
4 and 7 one step at a time to ensure that they work
independently and in doing so have generated one
optically pure isomer of 3.
Deoxyfusapyrone (1) is a secondary metabolite isolated
from rice cultures of Fusarium semitectum which has
demonstrated pronounced antifungal activity against
plant pathogenic and/or mycotoxigenic filamentous fungi.1
Compound 1 is a candidate for biotechnology applications
and has potential as a natural and safe herbicide to
suppress parasite seed germination.2 Structurally, 1 can
be divided into three components: a 4-deoxy glucose
moiety, a pyrone component, and a long-chain polyene
fragment. Synthetically, there are a number of challenges
to consider when planning a route for the preparation of
1, not the least of which is that three of the seven
stereocenters in 1 remain undetermined. Any proposed
synthetic route would have to be general enough to
facilitate the preparation all possible diastereomers of 1
to confirm its relative and absolute stereochemistry. Our
approach (Figure 1, X and Y ) halogen, M1 and M2 )
metal) is modular and allows for the parallel synthesis
of all eight diastereomers that arise from unassigned
stereocenters 8, 13, and 17 (i.e., the deoxy glucose stereo-
chemistry has been assigned unambiguously). The dis-
connections outlined in Figure 1 require the synthesis
of 2, 4, and 5 as the principal building blocks. We have
already completed the synthesis of the alkyne precursor
of 43 and now wish to report on the preparation of 5 and
its coupling with 4.
Resu lts a n d Discu ssion
Compound 8 was protected as the PMB ether and then
the ester converted to the corresponding aldehyde (11,
Scheme 1).5 The Corey-Fuchs procedure6 gave the
requisite alkyne (13) that was regioselectively hydrozir-
conated7 and quenched with iodine to give optically pure
14.
In a related series of transformations compound 8 was
protected, reduced,9 and converted to the corresponding
The two chiral centers in 5 are quite challenging to
build into the structure. The C13 position is bis allylic,
thus there is concern over epimerization of this position
while the C17 position is remote from any functional
group that could be used to direct a stereoselective
reaction, such as the reduction of an olefin precursor.
With this in mind, we opted for a strategy that would
(3) Organ, M. G.; Wang, J . J . Org. Chem. 2002, 67, 7847-7851.
(4) (a) Organ, M. G.; Cooper, J . T.; Rogers, L. R.; Soleymanzadeh,
F.; Paul, T. J . Org. Chem. 2000, 65, 7959-7970. (b) Zeng, F.; Negishi,
E.-i. Org. Lett. 2001, 3, 719-722.
(5) (a) Shimizu, S.; Nakamura, S.; Nakada, M.; Shibasaki, M.
Tetrahedron 1996, 52, 13363-13408. (b) Walkup, R. D.; Kahl, J . D.;
Hane, R. R. J . Org. Chem. 1998, 63, 9113-9116. (c) Walkup, R. D.;
Boatman, P. D.; Kane, R. R.; Cunningham, R. T. Tetrahedron Lett.
1991, 32, 3937-3940.
(1) Evidente, A.; Conti, L.; Altomare, C. Nat. Toxins 1994, 2, 4-13.
(2) (a) Altomare, C.; Perrone, G.; Zonno, M. C. J . Nat. Prod. 2000,
63, 1131-1135. (b) Altomare, C.; Perrone, G.; Zonno, M. C. Cereal Res.
Commun. 1997, 25, 349-351. (c) Zonno, M. C.; Vurro, M. Weed Res.
1999, 39, 15-20.
(6) Corey, E. J .; Fuchs, P. L. Tetrahedron Lett. 1972, 36, 3769-3772.
(7) Panek, J . S.; Hu, T. J . Org. Chem. 1997, 62, 4912-4913.
(8) (a) Hart, D. W.; Blackburn, T. F.; Schwartz, J . J . Am. Chem.
Soc. 1975, 97, 679. For a review, see: (b) Wipf, P.; J ahn, H. Tetrahedron
1996, 52, 12853-12910.
10.1021/jo034371k CCC: $25.00 © 2003 American Chemical Society
Published on Web 06/06/2003
5568
J . Org. Chem. 2003, 68, 5568-5574

Synthesis of Deoxyfusapyrone
F IGURE 1. Retrosynthetic analysis of deoxyfusapyrone.
SCHEME 1a
SCHEME 2a
a
Reagents and conditions: (a) TBDMSCl, imidazole, DMF, rt
(15, 86%); (b) DIBAL-H (1.1 equiv), -50 °C (16, 79%); (c) TsCl
(1.35 equiv), pyridine, rt, 5 h (used crude in the next step); (d)
n-C5H9MgBr (5 equiv), Li2CuCl4 (5 mol %), THF, rt, 48 h (18, 90%
from 16); (e) TBAF (1.5 equiv), THF, rt, 3 h (92%); (f) TsCl,
pyridine, rt (20, 80%); (g) NaI, acetone, reflux (97%).
a
Reagents and conditions: (a) PMBOC(dNH)CCl3, PPTS,
CH2Cl2, rt (9, 96%); (b) LAH, ether, 0 °C (10, 99%); (c) ClCOCOCl,
DMSO, Et3N, CH2Cl2, -78 °C (used crude in the next step); (d)
CBr4, PPh3, CH2Cl2 (12, used crude in the next step); (e) (i) n-BuLi
(2 equiv), THF, -78 °C to rt, (ii) CH3I (3 equiv) (75% from 10);
(f) (i) Schwartz’s reagent8 (2.5 equiv), THF, rt, 20 h, (ii) I2, rt
(63%).
ceeded smoothly with Pd catalyst (Scheme 3).13 Depro-
tection of 22 and elaboration with similar chemistry to
that outlined in Scheme 1 provided the oxidative addition
partner (27) to be coupled with organometallic 4.
What was left to do now was to produce 4 and couple
it to 27. In light of the value of optically pure 4, we
decided to work out the hydrometalation/cross-coupling
sequence on a model system (Scheme 4). Attempts to
hydroborate 28 with pinacol borane,14 dibromoborane,
tosylate (17) as depicted in Scheme 2. The alkyl chain
was elongated by using dipentyl cuprate to provide 18.10
Deprotection and conversion to the corresponding iodide10b
provided the organozinc precursor 21.
The one-pot lithium/halogen exchange11-zinc lithium
exchange-Negishi coupling12 between 21 and 14 pro-
(9) (a) J ones, T. K.; Reamer, R. A.; Desmond, R.; Mills, S. G. J . Am
Chem. Soc. 1990, 112, 2998-3017. (b) Mulzer, J .; Mantoulidis, A.;
Ohler. E. J . Org. Chem. 2000, 65, 7456-7467. (c) White, J . D.;
Hanselmann, R.; J ackson, R. W.; Porter, W. J .; Ohba, Y.; Tiller, T.;
Wang, S. J . Org. Chem. 2001, 66, 5217-5231. (d) Nakamura, Y.; Mori,
K. Eur. J . Org. Chem. 2000, 2745-2753.
(10) (a) Fouquet, G.; Schlosser, M. Angew. Chem., Int. Ed. 1974,
13, 82-83. (b) Shirai, Y.; Sekei, M.; Mori, K. Eur. J . Org. Chem. 1999,
3139-3145.
(11) Applequist, D. E.; O’Brien, D. F. J . Am. Chem. Soc. 1963, 85,
743-748.
(12) (a) Negishi, E.-i.; Valente, L. F.; Kobayashi, M. J . Am. Chem.
Soc. 1980, 102, 3298-3299. (b) Arefolov, A.; Langille, N. F.; Panek, J .
S. Org. Lett. 2001, 3, 3281-3284. For reviews, see: (c) Knochel, P.;
Perea, J . J . A.; J ones, P. Tetrahedron 1998, 54, 8275-8317. (d) Erdik,
E. Tetrahedron 1992, 48, 9577-9648.
(13) The corresponding reduction product was produced in a ratio
of desired product (22) to reduction product of 12:1.
J . Org. Chem, Vol. 68, No. 14, 2003 5569

Organ and Wang
SCHEME 3a
a
Reagents and conditions: (a) (i) t-BuLi (2.1 equiv), ether, -78 °C, (ii) ZnCl2 (1.1 equiv) in ether, -78 °C to rt, (iii) 14, (0.67 equiv),
Pd(PPh3)4 (5 mol %), THF, rt (66%); (b) DDQ (1.1 equiv), CH2Cl2, rt, 40 min (23, 90%); (c) ClCOCOCl, DMSO, Et3N, CH2Cl2, -78 °C
(98%); (d) CBr4/PPh3, CH2Cl2, 0 °C to rt (25, used crude in the next step); (e) (i) n-BuLi (2 equiv), THF, -78 °C to rt, (ii) MeI (2 equiv)
(99%); (f) (i) Schwartz’s reagent (2.1 equiv), THF, rt, 20 h, (ii) I2, rt.
SCHEME 4a
a
Reagents and conditions: (a) dicyclohexylborane, DME, 0°C to rt; (b) trimethylamine N-oxide (TMANO), rt; (c) pinacol, rt; (d) 27,
KOH (aq), Pd(PPh3)4 (8 mol %), THF reflux.
SCHEME 5a
catecholborane, and 9-BBN15 all failed as did hydrozir-
conation with Schwartz reagent.7 It is not clear whether
the propargyllic OTBDMS substituent and/or the gem
dimethyl groups made the alkyne too sterically hindered
or if the allylic oxygen was exerting an unfavorable
electronic effect. In any case we tried the reaction with
dicyclohexylborane and this time the reaction proceeded
smoothly providing 29.16 Oxidation (30) and borate
esterification provided the corresponding pinacolborane
(31), which was then smoothly coupled with 27 to give
32.
With this last hydrometalation/coupling sequence
worked out, we tried it on the chiral substrate 33 (Scheme
5).3 After the hydroxy group was capped as a methyl
ether, hydroboration, oxidation, and esterification pro-
ceeded smoothly to provide borate ester 37. All of these
steps and the subsequent cross-coupling step were con-
ducted on unpurified material providing the desired
protected compound 38 in 57% yield over these four steps.
For compound 1, deprotection of the two hydroxyl groups
would take place following addition to the pyrone moiety
to the epoxy glycal 2.
a
Reagents and conditions: (a) Me2SO4 (2.8 equiv), Na2CO3,
acetone, reflux (34, 83%); (b) dicyclohexylborane (1.2 equiv), DME,
0°C to rt (35, used crude in the next step); (c) TMANO (2.4 equiv),
rt (36, used crude in the next step); (d) pinacol (1.0 equiv), rt (used
crude in the next step); (e) 28 (1.2 equiv), KOH (aq) (2 equiv),
Pd(PPh3)4 (8 mol %), THF reflux (57% from 34).
ported preparation of compound 33,3 the middle and
right-hand pieces of the final target have been completed
for one of the eight stereoisomers of 38. We are exploring
currently the construction and utilization of the pseudo-
symmetric building block 6 for the one-pot, parallel
synthesis of all the isomers and their addition to 2 to
complete the work.
In summary, we have developed a convergent, modular
approach toward the synthesis of the eight possible
stereoisomers of deoxyfusapyrone. Building on our re-
(14) Tucker, C. E.; Davidson, J .; Knochel, P. J . Org. Chem. 1992,
57, 3482-3485.
(15) Scheidt, K. A.; Bannister, T. D.; Tasaka, A.; Wendt, M. D.;
Savall, B. M.; Fegley, G. J .; Roush, W. R. J . Am. Chem. Soc. 2002,
124, 6981-6990.
Exp er im en ta l Section
(16) (a) Hoffmann, R. W.; Dresely, S. Synthesis 1988, 103-106. (b)
Zhang, A.; Kan, Y.; Zhao, G.-L.; J iang, B. Tetrahedron 2000, 56, 965-
970.
All solvents used were dry and reactions were run under a
blanket of dry nitrogen unless indicated otherwise.
5570 J . Org. Chem., Vol. 68, No. 14, 2003

Synthesis of Deoxyfusapyrone
(R)-Meth yl 3-(4-Meth oxy-ben zyloxy)-2-m eth yl-p r op i-
on a te (9). To a suspension of NaH (90 mg, 3.75 mmol, 60%
suspension in mineral oil) in ether (25 mL) at rt was added a
solution of 4-methoxybenzyl alcohol (5.18 g, 37.5 mmol) in
ether (20 mL) via cannula. The resulting suspension was
stirred for 1 h and cooled to 0 °C, and trichloroacetonitrile (3.76
mL, 5.42 g, 37.5 mmol) was added. The mixture was stirred
for 5 min and then for an additional 20 min at rt. Ether (50
mL) was added and the solution was washed successively with
saturated NaHCO3 and brine. After drying over anhydrous
MgSO4, the suspension was filtered and concentrated in vacuo
to give the intermediate as a yellow oil. This crude intermedi-
ate was dissolved in CH2Cl2 (50 mL) at rt and (R)-methyl
3-hydroxy-2-methylpropionate (8, 2.77 mL, 2.95 g, 25.0 mmol)
and PPTS (276 mg, 0.044 mmol) were added. The mixture was
stirred for 22 h during which time a white solid formed. After
washing with saturated NaHCO3 and brine, the solution was
dried over anhydrous MgSO4 and subsequently filtered. The
solvent was removed in vacuo and the resulting semisolid
mixture was triturated with 1:1 hexane/CH2Cl2. The triturant
solution was concentrated to an oil that was purified by flash
chromatography on silica gel (hexane/ethyl acetate, 5:1) to
warmed to rt and diluted with ether. The mixture was then
filtered and the brown solid was washed with ether. Hexane
was added to the filtrate leading to the formation of additional
precipitate. After filtration and removal of the solvent in vacuo,
the residue was chromatographed on silica gel (20:1 hexane/
ethyl acetate) to give 12 as a light yellow oil (2.6 g, 75% from
10). [R]24 +13.13 (c 9.13, CHCl3); 1H NMR (400 MHz, CDCl3)
D
δ 7.29 (d, J ) 8.2 Hz, 2H), 6.92 (d, J ) 8.3 Hz, 2H), 6.35 (d, J
) 9.1 Hz, 1H), 4.49 (s, 2H), 3.84 (s, 3H), 3.42-3.37 (m, 2H),
2.85-2.78 (m, 1H), 1.09 (d, J ) 6.9 Hz, 3H); 13C NMR (100.6
MHz, CDCl3) APT δ 159.3 (+), 141.3 (-), 130.4 (+), 129.2 (-),
113.9 (-), 88.8 (+), 72.8 (+), 55.3 (-), 38.8 (-), 38.3 (+), 15.9
(-); IR (neat) 1613 cm-1; HRMS m/z calcd for C13H16Br2O2 (M+)
361.9467, found 361.9517.
(R)-1-Meth oxy-4-(2-m eth yl-bu t-3-en yloxym eth yl)-ben -
zen e (13). To a stirred solution of 12 (4.94 g, 13.64 mmol) in
THF (50 mL) at -78 °C was added dropwise a solution of
n-BuLi (17.5 mL, 28.0 mmol, 2.05 equiv, 1.6 M in hexane).
The mixture was allowed to reach rt over a period of 2 h and
then it was cooled back to -78 °C. Methyl iodide (2.55 mL,
5.81 g, 41 mmol) was added dropwise and the mixture was
allowed to reach rt slowly where it was stirred for 16 h. The
reaction was quenched with saturated NH4Cl, and then
extracted with ether (2×). The combined organic extracts were
washed with brine, dried over anhydrous MgSO4, and filtered.
The solvent was removed in vacuo to give crude product that
was chromatographed on silica gel (hexane/ethyl acetate, 60:
provide 9 (5.7 g, 96%) as a yellow oil. [R]24 -9.23 (c 8.38,
D
CHCl3); 1H NMR (400 MHz, CDCl3) δ 7.26 (d, J ) 8.6 Hz, 2H),
6.90 (d, J ) 8.6 Hz, 2H), 4.47 (s, 2H), 3.83 (s, 3H), 3.71 (s,
3H), 3.67-3.63 (m, 1H), 3.50-3.46 (m, 1H), 2.82-2.77 (m, 1H),
1.19 (d, J ) 7.2 Hz, 3H). All spectral data compare well with
the literature.5
1) to give 13 (2.3 g, 78%) as a yellow oil. [R]24 -2.32 (c 2.50,
D
(S)-3-(4-Meth oxy-ben zyloxy)-2-m eth yl-pr opan -1-ol (10).
To a solution of 9 (2.374 g, 9,98 mmol) in ether (50 mL) at 0
°C was added LAH (0.38 g, 10 mmol) in one portion. The
mixture was stirred for 4 h and quenched with cold water (5
mL) in small portions. The clear solution was decanted and
the residue was washed with ether. The combined ethereal
solution was washed with brine, dried over anhydrous MgSO4,
and filtered. The filtrate was concentrated in vacuo to give
crude 10 (2.0 g, 99%) as a yellow oil that was used in the next
step without further purification. An analytical sample was
CHCl3); 1H NMR (400 MHz, CDCl3) δ 7.28 (d, J ) 8.4 Hz, 2H),
6.90 (d, J ) 8.4 Hz, 2H), 4.51 (d, J ) 2.1 Hz, 2H), 3.82 (s, 3H),
3.49 (dd, J ) 8.9, 6.0 Hz, 1H), 3.32 (t, J ) 8.7 Hz, 1H), 2.82-
2.81 (m, 1H), 1.81 (d, J ) 1.9 Hz, 3H), 1.19 (d, J ) 6.9 Hz,
3H); 13C NMR (100.6 MHz, CDCl3) APT δ 159.2 (+), 130.5 (+),
129.2 (-), 113.8 (-), 81.2 (+), 77.4 (+), 74.2 (+), 72.6 (+), 55.2
(-), 26.7 (-), 18.1 (-), 3.6 (-); IR (neat) 2049, 1696, 1613 cm-1
;
HRMS m/z calcd for C14H18O2 (M+) 218.1307, found 218.1297.
(R)-1-(4-Iod o-2-m eth yl-p en t-3-en yloxym eth yl)-4-m eth -
oxy-ben zen e (14). To a stirred suspension of Schwartz’s
reagent (Cp2Zr(H)Cl, 6.82 g, 26.45 mmol) in THF (25 mL) at
rt was added a solution of 13 (2.31 g, 10.58 mmol) in THF (25
mL). The mixture was stirred for 24 h and cooled to 0 °C, and
a solution of iodine (5.38 g, 21.16 mmol) in THF (10 mL) was
added dropwise. The reaction was warmed to rt and quenched
with a dilute solution of Na2S2O3. The mixture was extracted
with ether (3×) and the combined organic layers were washed
with a dilute solution of Na2S2O3. After being washed with
brine, the organic layer was dried over anhydrous MgSO4 and
filtered. The solvent was removed in vacuo to give a semisolid
residue that was extracted with pentane (3×). Following
pentane removal in vacuo, the crude product was chromato-
obtained by chromatography on silica gel (hexane/ethyl ac-
1
etate, 5:1). [R]24 -10.62 (c 4.87, CHCl3); H NMR (400 MHz,
D
CDCl3) δ 7.26 (d, J ) 7.0 Hz, 2H), 6.89 (d, J ) 7.0 Hz, 2H),
4.46 (s, 2H), 3.82 (s, 3H), 3.63-3.59 (m, 2H), 3.53 (dd, J ) 9.0,
4.7 Hz, 2H), 3.40 (t, J ) 8.8 Hz, 1H), 2.70 (br s, 1H), 2.10-
2.02 (m, 1H), 0.89 (d, J ) 5.4 Hz, 3H); 13C NMR (100.6 MHz,
CDCl3) APT δ: 159.3 (+), 130.3 (+), 129.2 (-), 113.9 (-), 74.7
(+), 73.0 (+), 67.3 (+), 55.2 (-), 35.7 (-), 13.6 (-). All spectral
data compare well with the literature.5
(R)-3-(4-Met h oxy-b en zyloxy)-2-m et h yl-p r op ion a ld e-
h yd e (11). To a stirred solution of oxalyl chloride (0.92 mL,
1.34 g, 10.58 mmol) in CH2Cl2 (40 mL) at -78 °C was added
DMSO dropwise (1.65 mL, 1.804 g, 23.1 mmol). After 0.5 h, a
solution of 10 (2.02 g, 9.62 mmol) in CH2Cl2 (25 mL) was added
via cannula. The mixture was stirred for 40 min after which
triethylamine (0.87 mL, 0.63 g, 6.24 mmol) was added. The
mixture was allowed to reach rt slowly and then it was
quenched with water (30 mL). The separated organic layer was
washed with brine (2×), dried over anhydrous MgSO4, and
filtered. The solvent was removed in vacuo to give crude 11
(2.00 g, quantitative) as a yellow oil that was used in the next
graphed on silica gel (hexane/ethyl acetate, 60:1) to give 14
1
(2.31 g, 63%) as a yellow oil. [R]24 -11.77 (c 7.0, CHCl3); H
D
NMR (400 MHz, CDCl3) δ 7.27 (d, J ) 8.3 Hz, 2H), 6.92 (d, J
) 8.3 Hz, 2H), 6.03 (d, J ) 9.4 Hz, 1H), 4.46 (s, 2H), 3.83 (s,
3H), 3.29 (dd, J ) 6.7, 2.8 Hz, 2H), 2.78-2.73 (m, 1H), 2.43 (s,
3H), 1.02 (d, J ) 6.7 Hz, 3H); 13C NMR (100.6 MHz, CDCl3)
APT δ 159.2 (+), 143.9 (-), 130.5 (+), 129.1 (-), 113.8 (-),
94.5 (+), 73.9 (+), 72.7 (+), 55.3 (-), 36.2 (-), 28.0 (-), 17.1
(-); IR (neat) 1611 cm-1; HRMS m/z calcd for C14H19IO2 (M+)
346.0430, found 346.0430.
1
step without further purification. H NMR (400 MHz, CDCl3)
δ 9.73 (s, 1H), 7.26 (d, J ) 8.1 Hz, 2H), 6.90 (d, J ) 8.1 Hz,
2H), 4.47 (s, 2H), 3.82 (s, 3H), 3.67-3.63 (m, 2H), 2.68-2.64
(m, 1H), 1.13 (d, J ) 6.9 Hz, 3H); 13C NMR (100.6 MHz, CDCl3)
APT δ 203.9 (-), 159.3 (+), 130.0 (+), 129.3 (-), 113.9 (-),
73.0 (+), 69.8 (+), 55.3 (-), 46.8 (-), 10.7 (-). All spectral data
compare well with the literature.5
(R)-1-(4,4-Dibr om o-2-m et h yl-b u t -3-en yloxym et h yl)-4-
m eth oxy-ben zen e (12). To a stirred brown suspension of
triphenylphosphine (10.09 g, 38.48 mmol) and carbon tetra-
bromide (6.38 g, 19.24 mmol) in CH2Cl2 (55 mL) at 0 °C was
added a solution of crude aldehyde 11 (2.00 g, 9.62 mmol) in
CH2Cl2 (20 mL). After being stirred for 0.5 h, the mixture was
(S)-Meth yl 3-(ter t-bu tyl-d im eth yl-sila n yloxy)-2-m eth -
ylp r op ion a te (15). To a solution of (S)-(+)-3-hydroxy-2-
methylpropionate (8, 4.02 g, 34.03 mmol) and imidazole (6.50
g, 95.28 mmol) in DMF (80 mL) at rt was added TBDMSCl
(5.4 g, 35.73 mmol) in three portions. The mixture was stirred
for 5 h, poured into a dilute solution of NaHCO3, and extracted
with ether (3×). The combined organic extracts were washed
successively with a dilute solution of NaHCO3 and brine
followed by drying over anhydrous MgSO4. Following filtration,
the solvent was removed in vacuo to give crude product that
was purified by chromatography on silica gel (hexane/ethyl
acetate 15:1) to give 15 (6.8 g, 86%) as a colorless oil. 1H NMR
J . Org. Chem, Vol. 68, No. 14, 2003 5571

Organ and Wang
(400 MHz, CDCl3) δ 3.80 (dd, J ) 9.7, 7.0 Hz, 1H), 3.70 (s,
3H), 3.67 (dd, J ) 9.7, 6.2 Hz, 1H), 2.70-2.65 (m, 1H), 1.16
(d, J ) 7.1 Hz, 3H), 0.90 (s, 3H), 0.06 (s, 6H). All spectral data
compare well with the literature data.9b
product was purified by chromatography on silica gel (hexane/
ethyl acetate 10:1) to afford 19 (1.632 g, 92%) as a yellow oil.
1H NMR (400 MHz, CDCl3) δ 3.55 (dd, J ) 10.5, 5.5 Hz, 1H),
3.40 (dd, J ) 10.5, 6.0 Hz, 1H), 1.81-1.09 (m, 12H), 1.06-
0.78 (m, 6H). All spectral data compare well with the literature
data.10b
(R)-3-(ter t-Bu tyl-dim eth yl-silan yloxy)-2-m eth yl-pr opan -
1-ol (16). To a stirred solution of 15 (6.84 g, 29.47 mmol) in
THF (70 mL) at -50 °C was added dropwise a solution of
DIBAL-H (89 mL, 88.41 mmol, 1.0 M in toluene). The mixture
was stirred for 3 h and then quenched carefully at 0 °C with
MeOH (5 mL). A saturated solution of sodium/potassium
tartrate (Roschelle’s salt, 50 mL) was added and after 10 min
of stirring the mixture was extracted with ether. The combined
organic extracts were washed with brine, dried over anhydrous
MgSO4, and filtered. The solvent was removed in vacuo to give
crude 16 (4.75 g, 79%) as a yellow oil that was used in the
next step without further purification. 1H NMR (400 MHz,
CDCl3) δ 3.67 (dd, J ) 9.9, 4.6 Hz, 1H), 3.59-3.50 (m, 3H),
2.99 (s, 1H), 1.92-1.85 (m, 1H), 0.88 (s, 9H), 0.82 (d, J ) 6.9
Hz, 3H), 0.04 (s, 6H); 13C NMR (100.6 MHz, CDCl3) APT δ
68.2 (+), 67.6 (+), 37.2 (-), 25.8 (-), 18.1 (+), 13.1 (-), -5.6
(-). All spectral data compare well with the literature data.9b
(R)-2-Meth yl-octyl Tolu en e-4-su lfon a te (20). A mixture
of 19 (1.63 g, 11.33 mmol) and tosyl chloride (2.81 g, 14.73
mmol) in pyridine (8 mL) was stirred for 0.5 h at 0 °C, then
additionally for 5 h at rt. Cold water (20 mL) was added, and
the solution was stirred for 15 min and then extracted with
ether (3×). The combined organic extracts were washed
successively with a dilute solution of HCl, saturated NaHCO3,
and brine. After drying over anhydrous MgSO4, the suspension
was filtered and the solvent was removed in vacuo. The crude
product was purified by chromatography on silica gel (hexane/
ethyl acetate 20:1) to afford 20 (2.67 g, 80%) as a colorless oil.
[R]24 - 2.22 (c 6.93, CHCl3); 1H NMR (400 MHz, CDCl3) δ
D
7.75 (d, J ) 8.0 Hz, 2H), 7.31 (d, J ) 8.0 Hz, 2H), 3.85 (dd, J
) 9.3, 5.9 Hz, 1H), 3.78 (dd, J ) 9.3, 6.2 Hz, 1H), 2.41 (s, 3H),
1.76-1.71 (m, 1H), 1.32-1.05 (m, 10H), 0.86-0.82 (m, 6H);
13C NMR (100.6 MHz, CDCl3) APT δ 144.6 (+), 133.2 (+), 129.8
(-), 127.8 (-), 75.1 (+), 32.8 (-), 32.6 (+), 31.7 (+), 29.3 (+),
26.5 (+), 22.5 (+), 21.5 (-), 16.4 (-), 14.0 (-); IR (neat) 1599,
1466, 1362, 1177, 1097 cm-1. All spectral data compare well
with the literature data.10b
(S)-3-(ter t-Bu t yl-d im et h yl-sila n yloxy)-2-m et h yl-p r o-
p yl Tolu en e-4-su lfa te (17). A mixture of 16 (4.74 g, 23.24
mmol) and tosyl chloride (5.98 g, 31.37 mmol) in dry pyridine
(15 mL) at 0 °C was stirred for 5 h. Cold water (20 mL) was
added and after 15 min the mixture was extracted with ether
(3×). The combined organic extracts were washed successively
with a dilute solution of HCl, saturated NaHCO3, and brine.
Following drying over anhydrous MgSO4, the suspension was
filtered and the solvent removed in vacuo to provide crude 16
(7.86 g, 94%) as a light yellow oil that was used in the next
step without further purification. A small amount of 17 was
purified by chromatography on silica gel (hexane/ethyl acetate
(R)-1-Iod o-2-m eth yl-octa n e (21). A mixture of 20 (2.669
g, 8.96 mmol) and sodium iodide (2.02 g, 13.43 mmol) in dry
acetone (20 mL) was refluxed for 20 h and then cooled to rt.
Water (40 mL) was added and the mixture was extracted with
ether (3×). The combined organic extracts were washed
successively with dilute Na2S2O3 and brine, and then dried
over anhydrous MgSO4. The suspension was filtered and the
solvent was removed in vacuo to give crude product that was
purified by chromatography on silica gel (pentane) to give
10:1) for analysis. [R]24 + 4.44 (c 4.73, CHCl3); 1H NMR (400
D
MHz, CDCl3) δ 7.79 (d, J ) 8.0 Hz, 2H), 7.34 (d, J ) 8.0 Hz,
2H), 4.03 (dd, J ) 9.4, 5.9 Hz, 1H), 3.93 (dd, J ) 9.0, 5.6 Hz,
1H), 3.51 (dd, J ) 9.9, 4.9 Hz, 1H), 3.42 (dd, J ) 9.9, 6.4 Hz,
1H), 2.45 (s, 3H), 1.98-1.94 (m 1H), 0.89 (d, J ) 6.9 Hz, 3H),
0.83 (s, 9H), -0.01 (s, 6H); 13C NMR (100.6 MHz, CDCl3) APT
δ 144.6 (+), 133.2 (+), 129.8 (-), 127.9 (-), 72.1 (+), 63.7 (+),
35.7 (-), 25.8 (-), 21.6 (-), 18.1 (+), 13.2 (-), -5.6 (-); IR
(neat) 1599, 1252, 1189, 1178, 1098 cm-1. All spectral data
compare well with the literature data.9b
1
iodide 21 (2.20 g, 97%) as a colorless oil. H NMR (400 MHz,
CDCl3) δ 3.26 (dd, J ) 9.6, 4.4 Hz, 1H), 3.13 (dd, J ) 9.7, 5.2
Hz, 1H), 1.62-1.11 (m, 11H), 1.06-0.79 (m, 6H). All spectral
data compare well with the literature data.10b
(R)-1-Meth oxy-4-[(2R),(6R)-2,4,6-tr im eth yl-d od ec-3-en -
yloxym eth yl]-ben zen e (22). To a stirred solution of iodide
21 (2.13 g, 8.39 mmol) in ether (30 mL) at -78 °C was added
dropwise a solution of t-BuLi (10.4 mL, 17.61 mmol, 1.7 M in
pentane) via syringe. The resulting light yellow suspension
was stirred for 30 min. after which a solution of ZnCl2 (9.2
mL, 1.0 M in ether) was added dropwise. The mixture was
slowly brought to rt where it was stirred for an additional 30
min. A solution of 14 (2.34 g, 6.76 mmol) and (PPh3)4Pd (0.39
g, 0.338 mmol, 5 mol %) in THF (35 mL) was added via
cannula. The resulting brown suspension was stirred for 19 h
during which time it turned black. The mixture was quenched
carefully with a solution of saturated NH4Cl and then ex-
tracted with ether (3×). The combined organic extracts were
washed successively with saturated NH4Cl and brine. After
drying over anhydrous MgSO4, the suspension was filtered and
the solvent removed in vacuo to give the crude product that
was purified by chromatography on silica gel (hexane/ethyl
(R)-ter t-Bu tyl-dim eth yl-(2-m eth yl-octyloxy)-silan e (18).
To a solution of crude 17 (7.74 g, 21.61 mmol) in THF (20 mL)
at -78 °C was added a solution of Grignard reagent [prepared
in situ from Mg (3.9 g, 162 mmol) and pentyl bromide (13.4
mL, 16.32 g, 108 mmol) in 100 mL of THF] via cannula and
Li2CuCl4 (2.2 mL, 0.22 mmol, 0.1 M in THF). The mixture was
allowed to reach rt slowly and after 36 h was quenched with
saturated NH4Cl. The solution was extracted with ether (3×)
and the combined organic extracts were washed with saturated
NH4Cl and brine and then dried over anhydrous MgSO4.
Following filtration, the solvent was removed in vacuo to give
crude product that was purified by chromatography on silica
gel (hexane/ethyl acetate 50:1) to afford 18 (5.12 g, 92%) as a
colorless oil. [R]24 +1.77 (c 3.33, CHCl3); 1H NMR (400 MHz,
D
CDCl3) δ 3.47 (dd, J ) 9.4, 6.1 Hz, 1H), 3.39 (dd, J ) 9.5, 6.8
Hz, 1H), 1.65-1.55 (m, 1H), 1.45-1.20 (m, 9H), 1.15-1.00 (m,
1H), 0.99-0.80 (m, 15H), 0.07 (s, 6H); 13C NMR (100.6 MHz,
CDCl3) APT δ 68.4 (+), 35.8 (-), 33.2 (+), 31.9 (+), 29.7 (+),
27.0 (+), 26.0 (-), 22.7 (+), 18.3 (+), 16.8 (-), 14.1 (-), -5.4
(-); IR (neat) 1251, 1100 cm-1. Anal. Calcd for C15H34OSi: C,
69.69; H, 13.26. Found: C, 70.20; H, 13.72.
acetate 50:1) to give 70 (1.54 g, 66%) as a light yellow oil. [R]24
D
+13.72 (c 5.13, CHCl3); 1H NMR (400 MHz, CDCl3) δ 7.29 (d,
J ) 8.4 Hz, 2H), 6.90 (d, J ) 8.4 Hz, 2H), 4.94 (d, J ) 9.0 Hz,
1H), 4.50 (d, J ) 11.2 Hz, 1H), 4.45 (d, J ) 11.7 Hz, 1H), 3.83
(s, 3H), 3.33 (dd, J ) 8.9, 6.2 Hz, 1H), 3.25 (t, J ) 8.1 Hz, 1H),
2.78-2.71 (m, 1H), 2.01 (dd, J ) 13.1, 6.1 Hz, 1H), 1.76 (dd,
J ) 12.9, 8.3 Hz, 1H), 1.64 (s, 3H), 1.64-1.58 (m, 1H), 1.31
(br s, 9H), 1.11-1.07 (m, 1H), 1.02 (d, J ) 6.7 Hz, 3H), 0.93 (t,
J ) 6.2 Hz, 3H), 0.84 (d, J ) 6.4 Hz, 3H); 13C NMR (100.6
MHz, CDCl3) APT δ 159.1 (+), 134.6 (+), 131.0 (+), 129.1 (-),
128.9 (-), 113.7 (-), 75.3 (+), 72.6 (+), 55.2 (-), 47.9 (+), 36.9
(+), 33.1 (-), 32.0 (+), 30.6 (-), 29.7 (+), 27.0 (+), 22.7 (+),
(R)-2-Meth yl-octa n -1-ol (19). To a solution of 18 (3.56 g,
13.8 mmol) in THF (20 mL) at rt was added a solution of TBAF
(20.7 mL, 20.7 mmol, 1.0 M in THF). The mixture was stirred
for 20 h and water (20 mL) was added. The mixture was
extracted with ether (3×) and the combined organic extracts
were washed successively with a saturated solution of NH4Cl
and brine. After drying over anhydrous MgSO4, the suspension
was filtered and the solvent removed in vacuo. The crude
19.5 (-), 18.0 (-), 16.2 (-), 14.1 (-); IR (neat) 1613, 1248 cm-1
HRMS m/z calcd for C23H38O2 (M+) 346.2872, found 346.2836.
;
5572 J . Org. Chem., Vol. 68, No. 14, 2003

Synthesis of Deoxyfusapyrone
(2R),(6R)-2,4,6-Tr im et h yl-d od ec-3-en -1-ol (23). To a
stirred solution of 22 (1.17 g, 3.37 mmol) in CH2Cl2 (20 mL)
at rt was added water (1 mL) and DDQ (0.84 g, 3.71 mmol).
The resulting suspension was stirred for 30 min during which
time it turned green, yellow-green, and ultimately, yellow. The
mixture was diluted with ether and washed successively with
saturated NaHCO3 (2×) and brine. After removal of the solvent
in vacuo, the residue was dissolved in pentane and washed
successively with saturated NaHSO3 (2×, to remove the
byproduct, p-anisaldehyde) and brine. The pooled organic
layers were dried over anhydrous MgSO4 and filtered and the
solvent was removed in vacuo. The crude product was purified
by chromatography on silica gel (pentane/ethyl ether, 10:1) to
give 23 (0.68 g, 90%) as a light yellow oil. [R]24D -22.43 (c 4.73,
CHCl3); 1H NMR (400 MHz, CDCl3) δ 4.87 (d, J ) 9.3 Hz, 1H),
3.46 (dd, J ) 10.1, 6.1 Hz, 1H), 3.34 (t, J ) 10.3 Hz, 1H), 2.66-
2.59 (m, 1H), 2.02 (dd, J ) 13.1, 6.2 Hz, 1H), 1.77 (dd, J )
13.0, 8.2 Hz, 1H), 1.65 (br s, 1H), 1.63 (s, 3H), 1.60-1.55 (m,
1H), 1.27 (br s, 9H), 1.10-1.05 (m, 1H), 0.94 (d, J ) 6.7 Hz,
3H), 0.89 (t, J ) 6.3 Hz, 3H), 0.81 (d, J ) 6.7 Hz, 3H); 13C
NMR (100.6 MHz, CDCl3) APT δ 136.8 (+), 128.4 (-), 67.9
(+), 48.0 (+), 36.8 (+), 35.5 (-), 31.9 (+), 30.5 (-), 29.6 (+),
27.0 (+), 22.7 (+), 19.5 (-), 17.0 (-), 16.3 (-), 14.1 (-); IR (neat)
3344 (br) cm-1; HRMS m/z calcd for C15H30O (M+) 226.2297,
found 226.2281
(2S),(6R)-2,4,6-Tr im eth yl-d od ec-3-en a l (24). To a stirred
solution of oxalyl chloride (0.29 mL, 0.42 g, 3.32 mmol) in CH2-
Cl2 (20 mL) at -78 °C was added dropwise DMSO (0.54 mL,
0.59 g, 7.55 mmol). The mixture was stirred for 30 min after
which a solution of 23 (0.683 g, 3.02 mmol) in CH2Cl2 (10 mL)
was added via cannula. After the solution was stirred for 30
min, triethylamine (1.27 mL, 0.924 g, 9.06 mmol) was added
and the mixture was allowed to reach rt slowly. At that time,
the reaction was quenched with water (30 mL) and the phases
separated. The organic layer was washed successively with
saturated NaHCO3 (2×) and brine (2×). After drying over
anhydrous MgSO4, the suspension was filtered and the solvent
was removed in vacuo. The crude product (24) (0.663 g, 98%),
a yellow oil, was used in the next step without further
purification. 1H NMR (400 MHz, CDCl3) δ 9.51 (d, J ) 1.7 Hz,
1H), 4.96 (d, J ) 4.6 Hz, 1H), 3.30-3.28 (m, 1H), 2.08 (dd,
J ) 13.2, 6.1 Hz, 1H), 1.82 (dd, J ) 13.1, 8.3 Hz, 1H), 1.68 (s,
3H), 1.29 (br s, 10H), 1.17 (d, J ) 6.8 Hz, 3H), 1.18-1.05 (m,
1H), 0.91 (t, J ) 6.3 Hz, 3H), 0.83 (d, J ) 6.6 Hz, 3H).
The resulting mixture was warmed to rt slowly and quenched
subsequently with saturated NH4Cl. The solution was ex-
tracted with ether (3×) and the combined organic extracts were
washed with brine and dried over anhydrous MgSO4. The
suspension was filtered and the solvent removed in vacuo to
give crude product that was chromatographed on silica gel
(pentane) to give enyne 26 (0.585 g, 99%) as a colorless oil.
[R]24 +56.88 (c 3.53, CHCl3); 1H NMR (400 MHz, CDCl3) δ
D
5.10 (d, J ) 8.8 Hz, 1H), 3.29-3.25 (m, 1H), 1.96 (dd, J ) 13.3,
6.8 Hz, 1H), 1.80 (d, J ) 1.9 Hz, 3H), 1.83-1.74 (m, 1H), 1.61
(s, 3H), 1.28 (br s, 10H), 1.19 (d, J ) 7.0 Hz, 3H), 1.11-1.02
(m, 1H), 0.90 (t, J ) 6.3 Hz, 3H), 0.84 (d, J ) 6.6 Hz, 3H); 13
C
NMR (100.6 MHz, CDCl3) APT δ 133.9 (+), 128.5 (-), 83.1
(+), 74.7 (+), 47.5 (+), 36.6 (+), 31.9 (+), 30.7 (-), 29.6 (+),
26.9 (+), 24.6 (-), 22.7 (+), 22.3 (-), 19.6 (-), 15.9 (-), 14.1
(-), 3.5 (-); IR (neat) 2051, 1689, 1121 cm-1; HRMS m/z calcd
for C17H30 (M+) 234.2348, found 234.2332.
(4S),(8R)-2-Iodo-4,6,8-tr im eth yl-tetr adeca-2,5-dien e (27).
To a stirred suspension of Schwartz’s reagent (Cp2Zr(H)Cl, 1.36
g, 5.26 mmol) in THF (15 mL) at rt was added a solution of 26
(0.585 g, 2.50 mmol) in THF (15 mL). After being stirred for
24 h, the mixture was cooled to 0 °C and a solution of iodine
(1.27 g, 5.0 mmol) in THF (8 mL) was added dropwise. The
resulting mixture was stirred at rt for 30 min, and then
quenched with a dilute solution of Na2S2O3. The mixture was
extracted with ether (3×) and the combined organic extracts
were washed successively with a dilute solution of Na2S2O3
and brine. After drying over anhydrous MgSO4, the suspension
was filtered and the solvent was removed in vacuo to give a
semisolid residue that was extracted with pentane (3×). After
removal of the pentane in vacuo, the crude product was
chromatographed on silica gel (pentane) to give 27 (0.732 g,
81%) as a yellow oil. Some minor impurities could not be
removed so 27 was used for Suzuki coupling without further
purification. 1H NMR (400 MHz, CDCl3) δ 6.04 (d, J ) 8.7 Hz,
1H), 4.96 (d, J ) 8.8 Hz, 1H), 3.31-3.27 (m, 1H), 2.42 (d, J )
1.2 Hz, 3H), 2.00-1.95 (m. 1H), 1.76-1.71 (m, 1H), 1.60 (s,
3H), 1.29 (br s, 10H), 1.15-1.00 (m, 1H), 1.03 (d, J ) 6.8 Hz,
3H), 0.92 (t, J ) 9.5 Hz, 3H), 0.81 (dd, J ) 6.6, 3.0 Hz, 3H);
13C NMR (100.6 MHz, CDCl3) APT δ 145.9 (-), 133.6 (+), 129.1
(-), 92.0 (+), 47.7 (+), 36.7 (+), 34.8 (-), 31.9 (+), 30.7 (-),
29.6 (+), 27.7 (-), 27.0 (+), 22.7 (+), 21.2 (-), 19.5 (-), 16.1
(-), 14.1 (-); IR (neat) 1631, 1456, 1114 cm-1; HRMS m/z calcd
for C17H31I (M+) 362.1471, found 362.1468.
(2S),(6R)-1,1-Dib r om o-3,5,7-t r im et h yl-t r id eca -1,4-d i-
en e (25). To a stirred brown suspension of triphenylphosphine
(3.15 g, 12.0 mmol) and carbon tetrabromide (2.00 g, 6.0 mmol)
in CH2Cl2 (20 mL) at 0 °C was added a solution of crude
aldehyde 24 (0.663 g, 3.0 mmol) in CH2Cl2 (12 mL) via cannula.
The mixture was stirred for 1 h, diluted with pentane, and
filtered. The brown solid was washed with pentane and
combined with the filtrate. The solvent was removed in vacuo
and hexane was added to the residue resulting in additional
precipitation. After filtration and evaporation, the crude
product was chromatographed on silica gel (pentane) to give
(R)-6-(2-Ben zyloxy-1,1-dim eth yl-bu t-3-yn yl)-4-m eth oxy-
p yr a n -2-on e (34). A mixture of 33 (0.35 g, 1.19 mmol), Na2-
CO3 (0.10 g, 0.95 mmol), and Me2SO4 (0.30 mL, 0.40 g, 3.17
mmol) in dry acetone (4 mL) was refluxed for 20 h and then
cooled to rt. After removal of the solvent in vacuo, the residue
was purified by chromatography on silica gel (hexane/ethyl
acetate, 3:1) to furnish 34 (0.313 g, 85%) as a yellow powder.
Mp 99-101 °C (ether/hexane); [R]24 +171.5 (c 0.867, CHCl3);
D
1H NMR (400 MHz, CDCl3) δ 7.33-7.22 (m, 5H), 5.94 (d, J )
1.5 Hz, 1H), 5.42 (d, J ) 1.4 Hz, 1H), 4.79 (d, J ) 11.9 Hz,
1H), 4.46 (d, J ) 11.9 Hz, 1H), 4.41 (d, J ) 1.3 Hz, 1H), 3.79
dibromide 25 (0.952 g, 83% from 23) as a colorless oil. [R]24
(s, 3H), 2.51 (d, J ) 1.4 Hz, 1H), 1.38 (s, 3H), 1.32 (s, 3H); 13
C
D
-20.89 (c 6.93, CHCl3); 1H NMR (400 MHz, CDCl3) δ 6.25 (d,
J ) 9.3 Hz, 1H), 4.97 (d, J ) 8.8 Hz, 1H), 3.39-3.33 (m, 1H),
1.99 (dd, J ) 13.2, 6.3 Hz, 1H), 1.75 (dd, J ) 13.2, 8.2 Hz,
1H), 1.65 (s, 3H), 1.60-1.55 (m, 1H), 1.29 (br s, 10H), 1.08 (d,
J ) 6.7 Hz, 3H), 0.92 (t, J ) 6.4 Hz, 3H), 0.83 (d, J ) 6.7 Hz,
3H); 13C NMR (100.6 MHz, CDCl3) APT δ 142.9 (-), 135.7 (+),
127.2 (-), 86.8 (+), 47.7 (+), 37.6 (-), 36.8 (+), 32.0 (+), 30.6
(-), 29.6 (+), 27.0 (+), 22.7 (+), 20.1 (-), 19.5 (-), 16.6 (-),
14.1 (-); IR (neat) 1618, 1454, 1194, 1114 cm-1; HRMS m/z
calcd for C16H28Br2 (M+) 378.0558, found 378.0536.
(4S),(8R)-3,5,7-Tr im eth yl-dodec-3-en -1-ol (26). To a stirred
solution of dibromide 25 (0.952 g, 2.505 mmol) in THF (15 mL)
at -78 °C was added a solution of n-BuLi (3.2 mL 5.14 mmol,
1.6 M in hexane). The mixture was allowed to reach rt slowly,
where it was stirred for 10 min and then re-cooled to -78 °C.
Methyl iodide (2 equiv, 5.01 mmol, 706 mg) was then added.
NMR (100.6 MHz, CDCl3) APT δ 171.3 (+), 168.4 (+), 164.4
(+), 137.5 (+), 128.4 (-), 127.8 (-), 127.7 (-), 99.7 (-), 87.8
(-), 79.9 (+), 76.0 (+), 73.5 (-), 71.2 (+), 55.9 (-), 44.0 (+),
22.6 (-), 20.3 (-); IR (neat) 1720, 1643, 1093 cm-1. Anal. Calcd
for C19H20O4: C, 73.06; H, 6.45. Found: C, 73.40; H, 6.83.
6-[2-Ben zyloxy-1,1-dim eth yl-4-(4,4,5,5-ter tam eth yl[1,3,2]-
d ioxa b or ola n -2-yl)-b u t -3-en yl]-4-m et h oxy-p yr a n -2-on e
(37). To a solution of borane-dimethyl sulfide complex (0.06
mL, 10.0 M, 0.6 mmol) in DME (1.5 mL) at 0 °C was added
cyclohexene (0.121 mL, 99 mg, 1.2 mmol). After 15 min, the
mixture was allowed to reach rt and the resulting white
suspension was stirred for 1 h and then cooled to 0 °C. Solid
34 (0.156 g, 0.5 mmol) was added in one portion. The mixture
was stirred at rt for 3 h during which time the white solid
gradually dissolved. The reaction was then cooled to 10 °C and
trimethylamino N-oxide (TMANO, 90 mg, 1.2 mmol) was
J . Org. Chem, Vol. 68, No. 14, 2003 5573

Organ and Wang
added in one portion resulting in an exothermic reaction. After
10 min, the cold-water bath was removed and the mixture was
stirred for 2 h at rt. At this time, pinacol (60 mg, 0.5 mmol)
was added and the mixture was stirred for 16 h after which
the solvent was removed in vacuo. The residue was chromato-
graphed on silica gel (hexane/ethyl acetate, 5:1) to afford borate
37 (0.207 g) as a yellow oil that was contaminated with some
impurities, but was suitable to be used directly in the next
reaction (i.e., Suzuki coupling) without further purification.
1H NMR (400 MHz, CDCl3) δ 7.27-7.16 (m, 5H), 6.47 (dd, J
) 18.2, 6.5 Hz, 1H), 5.88 (s, 1H), 5.73 (d, J ) 18.0 Hz, 1H),
5.39 (s, 1H), 4.54 (d, J ) 11.9 Hz, 1H), 4.24 (d, J ) 11.9 Hz,
1H), 4.15 (d, J ) 6.8 Hz, 1H), 3.79 (s, 3H).
7.30-7.18 (m, 5H), 6.23 (d, J ) 15.7 Hz, 1H), 5.90 (d, J ) 1.8
Hz, 1H), 5.45-5.37 (m, 3H), 5.02 (d, J ) 8.8 Hz, 1H), 4.54 (d,
J ) 12.0 Hz, 1H), 4.28 (d, J ) 12.1 Hz, 1H), 4.10 (d, J ) 8.5
Hz, 1H), 3.79 (s, 3H), 3.43-3.37 (m, 1H), 1.98 (dd, J ) 13.2,
6.4 Hz, 1H), 1.78 (s, 3H), 1.77-1.73 (m, 1H), 1.63 (s, 3H), 1.60-
1.52 (m, 1H), 1.32-1.20 (m, 13H), 1.17 (s, 3H), 1.04 (d, J )
6.8 Hz, 3H), 0.91 (t, J ) 6.6 Hz, 3H), 0.82 (d, J ) 6.6 Hz, 3H);
13C NMR (100.6 MHz, CDCl3) APT δ 171.4 (+), 170.5 (+), 164.7
(+), 140.6 (-), 139.1 (-), 138.7 (+), 132.7 (+), 130.6 (+), 130.4
(-), 128.2(-), 127.4 (-), 127.3 (-), 122.1 (-), 99.2 (-), 87.4
(-), 84.2 (-), 70.4 (+), 55.7 (-), 47.8 (+), 44.2 (+), 36.7 (+),
32.1 (-), 31.9 (+), 30.7 (-), 29.6 (+), 26.9 (+), 22.8 (-), 22.7
(+), 21.7 (-), 20.3 (-), 19.5 (-), 16.2 (-), 14.1 (-), 12.7 (-); IR
6-[(2R),(7S),(11R)-2-Ben zyloxy-1,1,5,7,9,11-h exa m eth yl-
h ep ta d eca -3,5,8-tr ien yl]-4-m eth oxy-p yr a n -2-on e (38). To
a solution of crude pinacol borate 37 (0.199 g, 0.452 mmol) in
THF (0.5 mL) at rt was added KOH (0.91 mL, 1.0 M solution).
After 5 min, a solution of 28 (0.197 g, 0.543 mmol) and Pd-
(PPh3)4 (42 mg, 0.036 mmol, 8 mol %) in THF (2 mL) was added
via cannula. The mixture was heated to 65 °C for 70 min,
cooled to rt, and diluted with ether (30 mL). The mixture was
washed with brine (2×), dried over anhydrous MgSO4, and
filtered. The solvent was removed in vacuo and the crude
residue was chromatographed on silica gel (hexane/ethyl
acetate, 5:1) to give 38 (0.156 g, 57% from 34) as a brown oil.
(neat) 2970, 2924, 2857, 1727, 1644, 1570, 1453, 1403 cm-1
;
HRMS m/z calcd for C36H52O4 (M+) 548.3859, found 548.3866.
Ack n ow led gm en t. This work was supported by
funding from NSERC Canada and the Ontario Research
and Development and Challenge Fund.
Su p p or tin g In for m a tion Ava ila ble: Proton and/or car-
bon NMR spectra are included for compounds 14, 22, 23, 24,
25, 26, 27, and 38. This material is available free of charge
via the Internet at http://pubs.acs.org.
[R]24 +21.7 (c 2.53, CHCl3); 1H NMR (400 MHz, CDCl3) δ
J O034371K
D
5574 J . Org. Chem., Vol. 68, No. 14, 2003