Stereochemistry in Palladium-Catalyzed Cyclization Forming a Vinyldihydrofuran via a ?-Allylpalladium Intermediate

Full text of DOI:10.1021/jo9603901

204
J . Org. Chem. 1997, 62, 204-207
Sch em e 1
Ster eoch em istr y in P a lla d iu m -Ca ta lyzed
Cycliza tion F or m in g a Vin yld ih yd r ofu r a n
via a π-Allylp a lla d iu m In ter m ed ia te
Tamio Hayashi,* Masaki Yamane, and Akira Ohno
Department of Chemistry, Faculty of Science,
Kyoto University, Sakyo, Kyoto 606-01, J apan
Received February 26, 1996 (Revised Manuscript Received
October 28, 1996 )
We have previously reported that the reaction of
dimethyl (Z)-2-butenylene dicarbonate (1) with acetylac-
etone (2a ) or methyl acetylacetate (2b) in the presence
of a palladium catalyst coordinated with a chiral ferro-
cenylbisphosphine or ruthenocenylbisphosphine ligand
forms optically active vinyldihydrofuran 3 in up to 86%
ee1,2 (Scheme 1). The cyclization proceeds successively
through two π-allylpalladium(II) intermediates 4 and 6.
Thus, oxidative addition of dicarbonate 1 to a palladium-
(0) species forms the first π-allylpalladium intermediate
4, which undergoes nucleophilic attack of the enolate
anion of 2 to give the carbon-carbon bond formation
product 5. Cyclization by the intramolecular attack of
enolate oxygen on the π-allyl takes place on the second
π-allylpalladium intermediate 6, which is formed by the
oxidative addition of monocarbonate 5 to palladium(0).
The stereochemical pathway of the palladium-cata-
lyzed allylic substitution reactions has been studied in
reactions with several kinds of nucleophiles.3,4 The
oxidative addition forming π-allylpalladium usually pro-
ceeds with inversion of configuration at the stereogenic
allylic carbon,3-5 while the stereochemistry at the nu-
cleophilic substitution of the π-allylpalladium is depend-
ent upon the nature of the nucleophile.3,6 Here we report
that the intramolecular attack of enolate oxygen on the
π-allylpalladium, which is the second nucleophilic attack
forming 3 from 6 in Scheme 1, proceeds with inversion
of configuration at the π-allyl carbon.
Sch em e 2a
a
(a) Ph3PdCHCO2Me, MeOH, 0 °C, 7.5 h; (b) DIBALH, CH2Cl2,
rt, 14 h; (c) ClCO2Me, pyridine, DMAP, THF, rt, 17 h; (d)
Pd2(dba)3‚CHCl3, dppf, acetylacetone, rt, 2.5 h; (e) 46% HF aq,
MeCN, rt, 3.5 h; (f) ClCO2Me, pyridine, DMAP, CH2Cl2, rt, 40 h.
does not undergo racemization under usual reaction
conditions.3,4
The optically active allylic carbonate (S)-7 was pre-
pared from (S)-2-((tert-butyldimethylsilyl)oxy)propanal7
(8) (>99% ee) by a sequence of reactions shown in Scheme
2. Thus, the Wittig olefination of aldehyde (S)-8 with
((methoxycarbonyl)methylene)triphenylphosphorane fol-
lowed by reduction of the ester with diisobutylaluminum
hydride gave allylic alcohol (S)-9. Treatment of (S)-9
with methyl chloroformate and pyridine followed by
palladium-catalyzed allylic alkylation of the resulting
carbonate (S)-10 with acetylacetone gave alkylation
product (S)-11, where the carbon-carbon double bond is
trans. Silyl ether was converted into carbonate by
deprotection of the silyl ether with hydrofluoric acid in
acetonitrile followed by esterification with methyl chlo-
roformate to give allylic monocarbonate (S)-7.
Allylic carbonate (S)-7 was subjected to the palladium-
catalyzed intramolecular substitution reaction (Scheme
3). Thus, (S)-7 was treated with 2 mol % of a palladium-
(0) catalyst generated from tris(dibenzylideneacetone)-
dipalladium(0) and 1,1′-bis(diphenylphosphino)ferrocene
(dppf)8 in THF at 60 °C for 15 h. Evaporation of the
solvent followed by silica gel column chromatography
gave 98% yield of 2-(1-propenyl)-4-acetyl-5-methyl-2,3-
dihydrofuran (13) which consists of (E)- and (Z)-isomers
For the stereochemical studies on the intramolecular
allylic substitution reaction, we have designed an enan-
tiomeric system. Enantiomerically pure allylic mono-
carbonate (S)-7, which is similar to the intermediate 5a
but has a stereogenic carbon center at the R-position, was
used as a starting substrate. The π-allylpalladium
intermediate formed from (S)-7 should contain two dif-
ferent substituents at the 1 and 3 positions and hence
(1) Hayashi, T.; Yamamoto, A.; Ito, Y. Tetrahedron Lett. 1988, 29,
669.
(2) Hayashi, T.; Ohno, A.; Lu, S.-J .; Matsumoto, Y.; Fukuyo, E.;
Yanagi, K. J . Am. Chem. Soc. 1994, 116, 4221.
(3) For reviews, see: (a) Frost, C. G.; Howarth, J .; Williams, J . M.
J . Tetrahedron Asymmetry 1992, 3, 1089. (b) Consiglio, G.; Waymouth,
R. M. Chem. Rev. 1989, 89, 257. (c) Trost, B. M.; Verhoeven, T. R. In
Comprehensive Organometallic Chemistry; Wilkinson, G., Stone, F. G.
A., Abel, E. W., Eds.; Pergamon: Oxford, 1982; Vol. 8, p 799.
(4) For a review on stereochemistry of palladium-catalyzed cycliza-
tions, see: Heumann, A.; Re´glier, M. Tetrahedron 1995, 51, 975.
(5) Hayashi, T.; Hagihara, T.; Konishi, M.; Kumada, M. J . Am.
Chem. Soc. 1983, 105, 7767 and references cited therein.
(6) Hayashi, T.; Konishi, M.; Kumada, M. J . Chem. Soc., Chem.
Commun. 1984, 107 and references cited therein.
(7) Massad, S. K.; Hawkins, L. D.; Baker, D. C. J . Org. Chem. 1983,
48, 5180.
(8) (a) Bishop, J . J .; Davidson, A.; Katcher, M. L.; Lichtenberg, D.
W.; Merrill, R. E.; Smert, J . C. J . Organomet. Chem. 1971, 27, 241. (b)
Hayashi, T.; Konishi, M.; Kobori, Y.; Kumada, M.; Higuchi, T.; Hirotsu,
K. J . Am. Chem. Soc. 1984, 106, 158.
S0022-3263(96)00390-8 CCC: $14.00 © 1997 American Chemical Society

Notes
J . Org. Chem., Vol. 62, No. 1, 1997 205
Sch em e 3
Sch em e 5
Sch em e 4a
together with a minor amount of its (Z)-isomer and
regioisomers. The 1,3-rearrangement is known to pro-
ceed with net retention of configuration, the incoming
nucleophile, pivalate in this case, attacking the π-al-
lylpalladium intermediate from the same side as the
leaving group.10 The authentic sample of (S)-(-)-17
([R]20 ) -22.2 (c 1.8, chloroform)) was obtained by
D
deacetylation of (S)-12 followed by pivalate ester forma-
tion. The enantiomeric purity (97% ee) of (R)-(E)-13 and
(S)-(Z)-13 indicates that the palladium-catalyzed cycliza-
tion of (S)-7 proceeded with high stereoselectivity. Al-
most the same stereochemical outcome was observed in
cyclization catalyzed by a palladium complex coordinated
with 1,2-bis(diphenylphosphino)butane (dppb), which
gave (R)-(E)-13 of 97% ee and (S)-(Z)-13 of 97% ee in a
ratio of 4 to 1 (80% yield).
The stereochemical outcome observed here can be
visualized by the mechanism shown in Scheme 5, where
the π-allylpalladium intermediate syn,syn-18, formed by
oxidative addition of allylic carbonate (S)-7 to palladium-
(0) with inversion,3-5 undergoes nucleophilic attack of
enolate oxygen with inversion at the π-allyl carbon11 to
result in dihydrofuran (R)-(E)-13 with net retention of
configuration. Thus, the intramolecular attack of enolate
oxygen on π-allylpalladium was demonstrated to take
place from the side opposite to palladium. The isomer-
ization of π-allylpalladium intermediate from syn,syn-18
to anti,syn-18 by the π-σ-π mechanism, where pal-
ladium transfers from R-face to â-face, followed by
nucleophilic attack of enolate oxygen from the side
opposite to palladium gives (S)-(Z)-13 as a minor product.
a
(a) 50% KOH aq, MeOH, reflux, 2.5 h; (b) (R)-MTPA chloride,
pyridine, DMAP, CH2Cl2, rt, 45 h; (c) ClCO2Me, pyridine, DMAP,
CH2Cl2, rt, 4 h; (d) [PdCl(π-C3H5)]2, dppf, Hex4NBr, Me3CCOONa,
THF, 60 °C, 1 h; (e) NaOMe, MeOH, reflux, 1.5 h; (f) Me3CCOCl,
pyridine, CH2Cl2, rt, 1.5 h.
in a ratio of 3 to 1. Both isomers, (E)-13 and (Z)-13, were
determined to have 97% enantiomeric purity by GLC
analysis with a chiral stationary phase column. The
absolute configurations of (E)-13 and (Z)-13 were as-
signed to be (R) and (S), respectively, by Mosher’s
method9 using 2-methoxy-2-phenyl-2-(trifluoromethyl)-
acetic acid (MTPA) esters. Thus, alkaline hydrolysis and
deacetylation of (E)-13 and (Z)-13 by treatment with
aqueous potassium hydroxide in methanol followed by
esterification of the resulting allylic alcohols 14 with (R)-
MTPA chloride gave (R)-(E)-15 and (S)-(Z)-15 (see Ex-
perimental Section). The absolute configurations of 13
were confirmed by converting them into (S)-7-((2,2-
Exp er im en ta l Section
(S)-4-((ter t-Bu tyld im eth ylsilyl)oxy)-(Z)-2-p en ten -1-ol (9).
To a solution of 8.04 g (44.6 mmol) of (S)-2-((tert-butyldimeth-
ylsilyl)oxy)propanal (8)7 in 160 mL of methanol was added at 0
°C 22.4 g (66.9 mmol) of ((methoxycarbonyl)methylene)tri-
phenylphosphorane, and the mixture was stirred at the same
temperature for 7.5 h. Evaporation of the solvent followed by
silica gel column chromatography (hexane/ethyl acetate ) 10/
1) gave 10.7 g (43.9 mmol) of crude methyl (S)-4-((tert-butyldi-
methylsilyl)oxy)-(Z)-2-pentenoate, which was used for the
subsequent reduction without further purification. 1H NMR
(CDCl3): δ 0.03 (s, 3 H), 0.05 (s, 3 H), 0.88 (s, 9 H), 1.25 (d, J )
6.7 Hz, 3 H), 3.71 (s, 3 H), 5.44 (dqd, J ) 1.3, 6.7, 7.6 Hz, 1 H),
5.67 (dd, J ) 1.3, 11.9 Hz, 1 H), 6.22 (dd, J ) 7.6, 11.9 Hz, 1 H).
To a dichloromethane (100 mL) solution of the methyl ester
obtained above was added at 0 °C a solution of 129 mmol of
diisobutylaluminum hydride in hexane (1.01 M, 128 mL). After
dimethylpropanoyl)oxy)-(E)-5-octen-2-one (17) ([R]20
)
D
-19.0 (c 0.3, chloroform)) (Scheme 4). Thus, the alcohols
14 were esterified into methyl carbonate 16, which was
then subjected to allylic transposition with sodium piv-
alate catalyzed by palladium(0)10 to give (-)-(E)-17
(9) Ohtani, I.; Kusumi, T.; Kashman, Y.; Kakisawa, H. J . Am. Chem.
Soc. 1991, 113, 4092 and references cited therein.
(10) (a) Trost, B. M.; Organ, M. G. J . Am. Chem. Soc. 1994, 116,
10320 and references cited therein. (b) DearDorff, D. R.; Myles, D. C.;
Mac Ferrin, K. D. Tetrahedron Lett. 1985, 26, 5615.
(11) Oxygen nucleophiles of alcohol and carbamate have been
reported to attack π-allylpalladium with inversion of configuration: (a)
Suzuki, T.; Sato, O.; Hirama, M. Tetrahedron Lett. 1990, 31, 4747. (b)
Spears, G. W.; Nakanishi, K.; Ohfune, Y. Tetrahedron Lett. 1990, 31,
5339.

206 J . Org. Chem., Vol. 62, No. 1, 1997
Notes
the mixture was stirred at rt for 14 h, it was diluted with ether
and the reaction was quenched with methanol. Filtration
through a pad of Celite, evaporation of the solvent, and silica
gel column chromatography (hexane/ethyl acetate ) 1/1) gave
6.84 g (71%) of (S)-4-((tert-butyldimethylsilyl)oxy)-(Z)-2-penten-
extracts were washed with saturated cupric(II) sulfate solution
and brine and dried over anhydrous sodium sulfate, and the
solvent was removed under reduced pressure. The crude product
was purified by preparative thin layer silica gel chromatography
(hexane/ethyl acetate ) 1/1) to give 50.6 mg (84%) of methyl
(S)-3-acetyl-2-oxo-(E)-5-octen-7-yl carbonate (7). [R]20D ) -59.3
(c 0.70, chloroform). 1H NMR shows that 7 exists as keto and
enol forms (keto/enol ) 7/5) in CDCl3. 1H NMR: δ 1.32 (d, J )
6.9 Hz, 1/2 × 3 H), 1.35 (d, J ) 6.9 Hz, 1/2 × 3 H), 2.09 (s, 1/2 ×
1-ol (9). [R]20 ) +47.4 (c 0.3, chloroform). 1H NMR: δ 0.06 (s,
D
3 H), 0.07 (s, 3 H), 0.88 (s, 9 H), 1.22 (d, J ) 6.3 Hz, 3 H), 1.83
(bs, 1 H), 4.09-4.31 (m, 2 H), 4.58 (quint, J ) 6.3 Hz, 1 H), 5.47-
5.60 (m, 2 H). Anal. Calcd for C11H24O2Si: C, 61.06; H, 11.18.
Found: C, 61.00; H, 11.39.
1
1
6 H), 2.17 (s, /2 × 6 H), 2.57 (t, J ) 6.6 Hz, /2 × 2 H), 2.98 (d,
1
1
1
J ) 4.6 Hz, /2 × 2 H), 3.70 (t, J ) 7.4 Hz, /2 × 1 H), 3.76 (s, /2
× 3 H), 3.76 (s, 1/2 × 3 H), 5.11 (quint, J ) 6.9 Hz, 1/2 × 1 H),
5.19 (quint, J ) 6.9 Hz, 1/2 × 1 H), 5.46 (dd, J ) 15.5, 6.9 Hz, 1/2
Met h yl (S)-4-((ter t-Bu t yld im et h ylsilyl)oxy)-(Z)-2-p en -
ten yl Ca r bon a te (10). To a solution of 6.84 g (31.6 mmol) of
(S)-9 in 40 mL of THF were added successively at 0 °C 4.0 mL
(49 mmol) of pyridine, a catalytic amount of DMAP, and 3.0 mL
(39 mmol) of methyl chloroformate. The mixture was stirred at
rt for 17 h. Saturated sodium bicarbonate solution was added,
and it was extracted with ether. The organic phase was washed
with aqueous cupric sulfate and water, dried over anhydrous
sodium sulfate, and evaporated. The crude product was purified
by silica gel column chromatography (hexane/ethyl acetate )
5/1) to give 6.56 g (76%) of methyl (S)-4-((tert-butyldimethylsilyl)-
oxy)-(Z)-2-pentenyl carbonate (10). 1H NMR: δ 0.04 (s, 3 H),
0.05 (s, 3 H), 0.87 (s, 9 H), 1.21 (d, J ) 6.3 Hz, 3 H), 3.79 (s, 3
H), 4.60-4.78 (m, 2 H), 4.71 (dqd, J ) 1.3, 6.3, 6.9 Hz, 1 H),
5.45 (tdd, J ) 1.0, 6.9, 11.2 Hz, 1 H), 5.67 (dtd, J ) 1.3, 7.9,
11.2 Hz, 1 H). Anal. Calcd for C13H26O4Si: C, 56.90; H, 9.55.
Found: C, 57.11; H, 9.68.
(S)-7-((ter t-Bu tyld im eth ylsilyl)oxy)-3-a cetyl-(E)-5-octen -
2-on e (11). A solution of 174 mg (0.168 mmol) of tris-
(dibenzylideneacetone)dipalladium‚CHCl3 and 223 mg (0.402
mmol) of 1,1′-bis(diphenylphosphino)ferrocene (dppf) in 20 mL
of THF was kept stirring at rt for 20 min. To the resulting
yellow solution were added 1.70 mL (16.5 mmol) of acetylacetone
and 2.05 g (7.47 mmol) of (S)-10, and the mixture was stirred
at rt for 2.5 h. Water was added, and the aqueous layer was
extracted with ether. The ether extracts were dried over
anhydrous magnesium sulfate, and the solvent was removed
under reduced pressure. The crude product was purified by
silica gel column chromatography (hexane/ethyl acetate ) 1/1)
to give 1.00 g (43%) of (S)-7-((tert-butyldimethylsilyl)oxy)-3-
acetyl-(E)-5-octen-2-one (11). [R]20D ) -13.9 (c 0.29, chloroform).
1H NMR shows that 11 exists as keto and enol forms (keto/enol
1
× 1 H), 5.55 (dd, J ) 6.9, 15.5 Hz, /2 × 1 H), 5.63 (td, J ) 6.9,
1
1
15.5 Hz, /2 × 1 H), 5.76 (td, J ) 4.6, 15.5 Hz, /2 × 1 H). Anal.
Calcd for C7H12O4: C, 52.49; H, 7.55. Found: C, 52.53; H, 7.48.
2-(1-P r op en yl)-4-a cetyl-5-m eth yl-2,3-d ih yd r ofu r a n (13).
A solution of 7.0 mg (0.0068 mmol) of tris(dibenzylideneacetone)-
dipalladium‚CHCl3 and 7.8 mg (0.014 mmol) of 1,1′-bis(di-
phenylphosphino)ferrocene (dppf) in 12 mL of THF was kept
stirring at rt for 10 min. To the resulting yellow solution was
added 153 mg (0.630 mmol) of (S)-7, and the mixture was stirred
at 60 °C for 15 h. The catalyst was removed by short silica gel
column chromatography (THF). Evaporation of the solvent
followed by preparative thin layer silica gel chromatography
(hexane/ethyl acetate ) 3/1) gave 102 mg (98%) of 2-(1-propenyl)-
4-acetyl-5-methyl-2,3-dihydrofuran (13) which consists of (R)-
(E)- and (S)-(Z)-isomers in a ratio of 3 to 1 (for the determina-
tion of absolute configuration, see below). Specific rotation of
the (E) and (Z) mixture: [R]20 ) -82.6 (c 0.4, chloroform). 1H
D
NMR of (E)-13: δ 1.73 (dd, J ) 1.5, 6.5 Hz, 3 H), 2.19 (s, 3 H),
2.21 (t, J ) 1.5 Hz, 3 H), 2.71 (qdd, J ) 1.5, 8.0, 14.0 Hz, 1 H),
3.08 (qdd, J ) 1.5, 10.0, 14.0 Hz, 1 H), 4.99 (td, J ) 8.0, 10.0
Hz, 1 H), 5.58 (qdd, J ) 1.5, 8.0, 15.0 Hz, 1 H), 5.79 (qd, J )
6.5, 15.0 Hz, 1 H). 1H NMR of (Z)-13: δ 1.74 (dd, J ) 2.0, 7.0
Hz, 3 H), 2.20 (s, 3 H), 2.22 (t, J ) 1.5 Hz, 3 H), 2.67 (qdd, J )
1.5, 8.5, 14.0 Hz, 1 H), 3.13 (qdd, J ) 1.5, 10.0, 14.0 Hz, 1 H),
5.39 (ddd, J ) 8.5, 9.0, 10.0 Hz, 1 H), 5.58 (qdd, J ) 2.0, 9.0,
11.0 Hz, 1 H), 5.79 (qd, J ) 7.0, 11.0 Hz, 1 H). Anal. Calcd for
C
10H14O2: C, 72.26; H, 8.49. Found: C, 72.46; H, 8.56. The
enantiomeric purity of (R)-(E)-13 and (S)-(Z)-13 was determined
to be 97% ee by GLC analysis with a chiral stationary phase
column, CP Cyclodex â236Μ.
7
5
) 7/5) in CDCl3. 1H NMR: δ 0.02 (s, /12 × 3 H), 0.03 (s, /12
×
7
5
7
6 H), 0.04 (s, /12 × 3 H), 0.88 (s, /12 × 9 H), 0.89 (s, /12 × 9 H),
5-Hyd r oxy-6-octen -2-on e (14). To a solution of 82.5 mg
(0.502 mmol) of dihydrofuran 13 (E/ Z ) 3/1) obtained above in
2.5 mL of methanol was added 0.3 mL of 50% aqueous potassium
hydroxide, and the mixture was stirred at reflux for 2.5 h. Water
was added, and the aqueous layer was extracted with chloroform.
The extracts were dried over anhydrous sodium sulfate, and the
solvent was removed under reduced pressure. The crude product
was purified by preparative thin layer silica gel chromatography
(hexane/ethyl acetate ) 2/1) to give 59.8 mg (83%) of 5-hydroxy-
6-octen-2-one (14) which is a mixture of (R)-(E)-14 and (S)-(Z)-
14 in a ratio of 3 to 1. 1H NMR of (E)-14: δ 1.70 (dd, J ) 1.5,
6.5 Hz, 3 H), 1.79 (m, 2 H), 2.16 (s, 3 H), 2.55 (t, J ) 7.0 Hz, 2
H), 4.07 (m, 1 H), 5.47 (qdd, J ) 1.5, 7.0, 15.5 Hz, 1 H), 5.67
(dqd, J ) 1.0, 6.5, 15.5 Hz, 1 H). 1H NMR of (Z)-14: δ 1.67 (dd,
J ) 1.5, 7.0 Hz, 3 H), 1.80 (m, 2H), 2.16 (s, 3 H), 2.56 (t, J ) 6.0
Hz, 2 H), 4.48 (m, 1 H), 5.39 (qdd, J ) 1.5, 8.5, 10.5 Hz, 1 H),
5.58 (dqd, J ) 1.0, 7.0, 10.5 Hz, 1 H). Anal. Calcd for C8H14O2
C, 67.57; H, 9.92. Found: C, 67.38; H, 9.89.
2-Oxo-6-oct en -5-yl (R)-2-Met h oxy-2-p h en yl-2-(t r iflu o-
r om eth yl)a ceta te (MTP A Ester 15). To a solution of 18.1 mg
(0.127 mmol) of the mixture of (R)-(E)-14 and (S)-(Z)-14 (E/Z )
3/1) in 0.2 mL of dichloromethane, 0.03 mL (0.37 mmol) of
pyridine, and 7.6 mg (0.063 mmol) of DMAP was added succes-
sively 0.70 mg (0.26 mmol) of (R)-MTPA chloride at 0 °C, and
the mixture was stirred at rt for 45 h. Saturated sodium
hydrocarbonate solution was added, and the aqueous layer was
extracted with chloroform. The extracts were dried over anhy-
drous sodium sulfate and evaporated under reduced pressure.
The MTPA esters (R)-(E)-15 and (S)-(Z)-15 (E/Z ) 3/1) were
obtained (45 mg, 99%) by preparative thin layer silica gel
chromatography (hexane/ethyl acetate ) 1/1). Comparison of
1H NMR specra of the MTPA esters 15 obtained from racemic
alcohol 14 with the spectra of those from the optically active 14
obtained in the present studies showed that (E)-15 and (Z)-15
have (R) and (S) configurations, respectively. For the determi-
5
7
1.16 (d, J ) 6.5 Hz, /12 × 3 H), 1.18 (d, J ) 6.5 Hz, /12 × 3 H),
7
5
7
2.10 (s, /12 × 6 H), 2.17 (s, /12 × 6 H), 2.56 (t, J ) 7.3 Hz, /12
×
×
5
7
2 H), 2.94 (d, J ) 5.0 Hz, /12 × 2 H), 3.68 (t, J ) 7.5 Hz, /12
7
1 H), 4.22 (quint, J ) 6.5 Hz,
/
× 1 H), 4.28 (quint, J ) 6.5
12
5
7
Hz, /12 × 1 H), 5.44 (dd, J ) 6.5, 15.0 Hz, /12 × 1 H), 5.45 (dd,
5
5
J ) 6.5, 15.0 Hz, /12 × 1 H), 5.56 (td, J ) 5.0, 15.0 Hz, /12 × 1
7
H), 5.57 (td, J ) 7.3, 15.0 Hz,
C
/
× 1 H). Anal. Calcd for
12
16H30O3Si: C, 64.38; H, 10.13. Found: C, 64.00; H, 10.27.
(S)-7-Hyd r oxy-3-a cetyl-(E)-5-octen -2-on e (12). To 4 mL
of an acetonitrile solution of 1.00 g (3.19 mmol) of (S)-11 was
added 0.41 mL of 46% hydrofluoric acid, and the mixture was
stirred at rt for 3.5 h. Saturated sodium hydrocarbonate solution
was added, and the aqueous layer was extracted with ether. The
ether extracts were dried over anhydrous magnesium sulfate,
and the solvent was removed under reduced pressure. The crude
product was purified by silica gel column chromatography
(hexane/ethyl acetate ) 1/1) to give 550 mg (94%) of (S)-7-
hydroxy-3-acetyl-(E)-5-octen-2-one (12). [R]20 ) -21.8 (c 0.2,
D
chloroform). 1H NMR shows that 12 exists as keto and enol
forms (keto/enol ) 7/5) in CDCl3. 1H NMR: δ 1.23 (d, J ) 6.0
9
5
5
Hz, /14 × 3 H), 1.26 (d, J ) 6.0 Hz, /14 × 3 H), 2.11 (s, /14 × 6
9
9
H), 2.18 (s,
/
× 6 H), 2.57 (t, J ) 7.0 Hz,
/
× 2 H), 2.97 (d,
J ) 5.5 Hz, /14 × 2 H), 3.70 (t, J ) 7.0 Hz, /1144 × 1 H), 4.24 (m,
14
5
9
9
5
5
/
× 1 H), 4.31 (m, /14 × 1 H), 5.51 (td, J ) 5.5, 16.0 Hz, /14
×
14
9
1 H), 5.52 (td, J ) 7.0, 16.0 Hz,
/
× 1 H), 5.60 (dd, J ) 5.5,
14
16.0 Hz, 9/14 × 1 H), 5.66 (dd, J ) 5.5, 16.0 Hz, 5/14 × 1 H). Anal.
Calcd for C10H16O3: C, 65.19; H, 8.75. Found: C, 65.01; H, 8.60.
Meth yl (S)-3-Acetyl-2-oxo-(E)-5-octen -7-yl Ca r bon a te (7).
To a dichloromethane solution of 45.3 mg (0.246 mmol) of (S)-
12, 0.065 mL (0.804 mmol) of pyridine, and 8.3 mg (0.068 mmol)
of DMAP was added 0.047 mL (0.53 mmol) of methyl chlorofor-
mate at 0 °C, and the mixture was stirred at rt for 40 h.
Saturated sodium hydrocarbonate solution was added, and the
aqueous layer was extracted with chloroform. The chloroform

Notes
J . Org. Chem., Vol. 62, No. 1, 1997 207
nation, the protons assigned to CH3CO- (s), -COCH2- (t), and
CH3CHd (d) were used. Their chemical shifts for the enantio-
mers of (E)-15 and (Z)-15 are as follows. (R)-(E)-15: 2.04, 2.30,
1.72. (S)-(E)-15: 2.12, 2.44, 1.69. (S)-(Z)-15: 2.12, 2.46, 1.77.
(R)-(Z)-15: 2.06, 2.32, 1.80.
Meth yl 2-Oxo-6-octen -5-yl Ca r bon a te (16). To a solution
of 40.0 mg (0.28 mmol) of a mixture of (R)-(E)-15 and (S)-(Z)-15
(E/Z ) 3/1) in 0.30 mL of dichloromethane were added 0.069
mL (0.85 mmol) of pyridine, 10 mg (0.80 mmol) of DMAP, and
0.054 mL (0.70 mmol) of methyl chloroformate at 0 °C. After
1.25 (d, J ) 6.3 Hz, 3 H), 1.69 (bs, 1 H), 2.15 (s, 3 H), 2.26-2.34
(m, 2 H), 2.53 (t, J ) 7.3 Hz, 2 H), 4.26 (quint, J ) 6.3 Hz, 1 H),
5.50-5.69 (m, 2 H). To the crude alcohol was added successively
1.2 mL of dichloromethane, 0.034 mL (0.42 mmol) of pyridine,
and 0.043 mL (0.35 mmol) of pivaloyl chloride. After the mixture
was stirred at rt for 1.5 h, it was evaporated under reduced
pressure. Column chromatography on silica gel (hexane/ethyl
acetate ) 3/1) gave 71 mg (two steps, 58%) of (S)-7-(2,2-
dimethylpropanoyl)-(E)-5-octen-2-one (15). [R]20D ) -22.2 (c 1.8,
chloroform). 1H NMR: δ 1.18 (s, 9 H), 1.26 (d, J ) 6.3 Hz, 3 H),
2.14 (s, 3 H), 2.30 (ddt, J ) 2.3, 6.6, 7.3 Hz, 2 H), 2.51 (t, J ) 7.3
Hz, 2 H), 5.27 (d quint, J ) 0.7, 6.3 Hz, 1 H), 5.47 (tdd, J ) 2.3,
6.3, 15.3 Hz, 1 H), 5.66 (dtd, J ) 0.7, 6.6, 15.3 Hz, 1 H). Anal.
Calcd. for C13H22O3: C, 68.99; H, 9.80. Found: C, 69.01; H,
9.97.
the mixture was stirred at rt for
4 h, saturated sodium
bicarbonate solution was added. The aqueous layer was ex-
tracted with chloroform. The extracts were washed with aque-
ous cupric sulfate and brine, dried over anhydrous sodium
sulfate, and evaporated under reduced pressure. The carbonate
16 (29.7 mg, 52%) was obtained as a mixture of (E) and (Z)
isomers (E/ Z ) 3/1) by silica gel column chromatography
(hexane/ethyl acetate ) 4/1). 1H NMR of (R)-(E)-16: δ 1.75 (dd,
J ) 1.5, 6.5 Hz, 3 H), 1.93 (q, J ) 7.0 Hz, 2 H), 2.14 (s, 3 H),
2.49 (m, 2 H), 3.76 (s, 3 H), 5.02 (q, J ) 7.0 Hz, 1 H), 5.41 (qdd,
Meth od B (F r om 16). To a solution of 1.2 mg (0.0033 mmol)
of [PdCl(π-C3H5)]2, 3.7 mg (0.0067 mmol) of 1,1′-bis(diphen-
ylphosphino)ferrocene, 76 mg (0.17 mmol) of tetrahexylammo-
nium bromide, and 26.9 mg (0.13 mmol) of carbonate 16 in 2.0
mL of THF was added a solution of sodium pivalate (0.22 mmol)
prepared from pivalic acid and sodium hydride in 2.0 mL of THF,
and the mixture stirred at 60 °C for 1 h. The catalyst was
removed by short silica gel column chromatography (THF).
Evaporation of the solvent followed by medium-pressure silica
gel chromatography (hexane/ethyl acetate ) 4/1) gave 12.5 mg
(41%) of (S)-7-(2,2-dimethylpropanoyl)-(E)-5-octen-2-one (17)
1
J ) 1.5, 7.0, 14.0 Hz, 1 H), 5.79 (qd, J ) 6.5, 14.0 Hz, 1 H). H
NMR of (S)-(Z)-16: δ 1.74 (dd, J ) 1.5, 7.0 Hz, 3 H), 1.96 (q, J
) 7.0 Hz, 2 H), 2.15 (s, 3 H), 2.50 (m, 2 H), 3.76 (s, 3 H), 5.35
(qdd, J ) 1.5, 9.0, 10.5 Hz, 1 H), 5.41 (q, J ) 9.0 Hz, 1 H), 5.70
(qd, J ) 7.0, 10.5 Hz, 1 H). Anal. Calcd for C10H16O4: C, 59.99;
H, 8.05. Found: C, 60.18; H, 8.17.
(S)-7-((2,2-Dim eth ylpr opan oyl)oxy)-(E)-5-octen -2-on e (17).
Meth od A (F r om 12). To a solution of 99 mg (0.54 mmol) of
(S)-12 in 5.5 mL of methanol was added 13 mg (0.24 mmol) of
sodium methoxide, and the mixture was heated to reflux for 1.5
h. Water was added, and the aqueous layer was extracted with
ether. The extracts were dried over anhydrous sodium sulfate,
and the solvent was removed under reduced pressure to give 46
mg (60%) of crude (S)-7-hydroxy-(E)-5-octen-2-one. 1H NMR: δ
([R]20 ) -19.0 (c 0.3, chloroform)) and 8.7 mg (29%) of other
D
isomers.
Ack n ow led gm en t. We thank the Ministry of Edu-
cation, J apan for Grant-in-Aid for Scientific Research
for partial financial support of this work.
J O9603901