Enantioselective tandem formation and [2,3]-sigmatropic rearrangement of cyclic propargylic oxonium ylides catalyzed by dirhodium(II) tetrakis[N-phthaloyl-(S)-tert-leucinate]

Article abstract of DOI:10.1560/E7M9-EM8U-TP1B-41HB

This paper describes the first examples of catalyst-dependent asymmetric induction in the periselective [2,3]-sigmatropic rearrangement of propargylic oxonium ylides generated by catalytic diazo decomposition. Catalysis of α-diazo-β-keto esters 4a-g using

Full text of DOI:10.1560/E7M9-EM8U-TP1B-41HB

Enantioselective Tandem Formation and [2,3]-Sigmatropic Rearrangement of
Cyclic Propargylic Oxonium Ylides Catalyzed by Dirhodium(II) Tetrakis[N-
phthaloyl-(S)-tert-leucinate]
HIDEYUKI TSUTSUI, MAYA MATSUURA, KAZUISHI MAKINO, SEIICHI NAKAMURA, MAKOTO NAKAJIMA,
SHINJI KITAGAKI, AND SHUNICHI HASHIMOTO*
Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
(Received 8 February 2002)
Abstract. This paper describes the first examples of catalyst-dependent asym-
metric induction in the periselective [2,3]-sigmatropic rearrangement of propargylic
oxonium ylides generated by catalytic diazo decomposition. Catalysis of α-diazo-β-
keto esters 4a–g using dirhodium(II) tetrakis[N-phthaloyl-(S)-tert-leucinate] in tolu-
ene has led to the virtually exclusive formation of benzofuran-3-ones bearing an
allenic group with up to 79% ee.
INTRODUCTION
ee together with [1,2]-Stevens rearrangement products
The dirhodium(II) or copper(I) complex-catalyzed reac- 3b–d of up to 66% ee as side-products. These findings
tion of diazocarbonyl compounds with the lone pairs of suggest that both rearrangements proceed through a chiral
an ether oxygen atom represents one of the most effec- rhodium(II)-bound oxonium ylide, as it is generally be-
tive methods for the generation of oxonium ylides lieved that the energy barriers to configurational inversion
because they are not amenable to formation by de- of chiral, nonracemic, free oxonium ylides detached
protonation or desilylation of appropriate oxonium from the chiral catalyst are very small compared to their
salts.1 The tandem cyclic oxonium ylide generation and sulfonium counterparts.9 Despite a reasonable level of
rearrangement methodology, developed independently
by Pirrung2 and Johnson3, is rapidly being recognized as
a powerful means for constructing substituted cyclic
ethers and carbocycles. Consequently, the development
of a catalytic enantioselective version of this sequence
would be a significant addition to the field of asymmet-
ric synthesis.4–7 To reach this goal, we recently found
that the tandem formation and [2,3]-sigmatropic rear-
rangement of cyclic allylic oxonium ylide from α-diazo-
β-keto ester 1a under the influence of dirhodium(II)
tetrakis[N-phthaloyl-(S)-tert-leucinate], Rh2(S-PTTL)4,
gave benzofuran-3-one 2a in 76% ee,8 representing the
highest enantioselectivity to date reported with this re-
action system (Scheme 1).6a–c,g On the other hand, we
have observed that catalysis of 1b–d furnished [2,3]-
sigmatropic rearrangement products 2b–d in up to 72%
Scheme 1
This paper is dedicated with admiration and respect to Prof.
Ryoji Noyori, in celebration of the awards of the 2001 Wolf *Authortowhomcorrespondenceshouldbeaddressed. E-mail:
Prize and the 2001 Nobel Prize in Chemistry.
hsmt@pharm.hokudai.ac.jp
Israel Journal of Chemistry
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284
asymmetric induction, however, the lack of peri- and [1,2]-Stevens rearrangement product 6a via a radical
diastereoselectivity with a crotyl substituent precluded dissociation–recombination pathway could be detected.
synthetic application of the enantioselective tandem proto- While a sharp drop in enantioselectivity was observed at
col to natural products such as (+)-griseofulvin.10 To avoid room temperature (entry 2), lowering the reaction tem-
this issue, it is reasonable to expect that the [2,3]- perature to –10 °C had little effect on the degree of
sigmatropic rearrangement of cyclic propargylic oxo- asymmetric induction, yet produced a marked decrease
nium ylides2,3,11 would lead to cyclic ethers bearing an in product yield (entry 3). The solvent survey revealed
allenic substituent that would act as a useful moiety for a that toluene was also the optimal solvent in this system
wide range of transformations.12 Thus, our interest is (entries 1 and 2 vs. 4–7). At this stage, we evaluated the
now centered on illuminating the mechanistic pathway abilities of two classes of dirhodium(II) carboxylate
for asymmetric induction, as well as on the rearrange- catalysts that incorporate N-phthaloyl- and N-benzene-
ment mode followed by the propargylic counterparts.
fused-phthaloyl-(S)-amino acids as bridging ligands, as
shown in Fig. 1.13 While a uniform sense of asymmetric
induction was observed in all cases, ee values were
highly dependent on the catalyst. Investigation of the
RESULTS AND DISCUSSION
At the outset of this work, we explored the tandem former class of dirhodium(II) catalysts provided confir-
cyclic ylide formation and rearrangement of α-diazo-β- mation that Rh2(S-PTTL)4, characterized by a bulky
keto ester 4a under the previously optimized conditions, tert-butyl group, proved to be by far the best choice
i.e., using 2 mol% of Rh2(S-PTTL)4 in toluene at 0 °C. (entries 1 vs. 8–11). It is worth noting that the latter class
The reaction proceeded smoothly to give benzofuran-3- of catalysts, characterized by an extension of the
one 5a via a symmetry-allowed [2,3]-sigmatropic rear- phthalimido wall with one additional benzene ring, with
rangement in similar levels of product yield and asym- the exception of Rh2(S-BPTTL)4, noticeably improved
metric induction as found with its allylic counterpart the enantioselectivity observed with the respective par-
(70% yield, 78% ee) (Table 1, entry 1). No trace of the ent dirhodium(II) catalyst (entries 12–15). Disappoint-
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6g was formed in the case of 4g bearing a bulky tert-
butyldimethylsilyl substituent (entry 7). These results
stand in contrast to those from the allylic oxonium
ylides derived from 1b–d. Although the stereochemical
course of the [2,3]-sigmatropic rearrangement of
propargylic oxonium ylides has received little attention,
the five-membered allenic transition state appears to be
geometrically unfavorable because of severe strain rela-
tive to its allylic counterpart.14 Thus, this outcome may
be attributed to a smaller steric interaction encountered
during the concerted [2,3]-sigmatropic rearrangement
of propargylic oxonium ylides in comparison with
allylic oxonium ylides. No explanation for the virtual
exclusion of [1,2]-Stevens rearrangement products,
however, can presently be offered.
Fig. 1. Dirhodium(II) carboxylates incorporating N-phthaloyl-
or N-benzene-fused phthaloyl-(S)-amino acids as bridging
ligands.
The preferred absolute configuration of product 5a
was established as S by its transformation to the now
known (S)-dihydrobenzofuran 7, which also determined
the preferred absolute configuration of 1a to be S
(Scheme 2).15 For the other products 5b–g, the same
ingly, Rh2(S-BPTTL)4 displayed virtually the same
enantioselectivity as Rh2(S-PTTL)4 (entry 12).
We then investigated the tandem reaction of α-diazo-
β-keto esters 4b–g containing methyl, ethyl, metho-
xymethyl, silyloxymethyl, and trialkylsilyl substituents,
instead of the acetylenic hydrogen moiety (Table 2).
Rh2(S-PTTL)4-catalyzed reactions of 4b–g in toluene
were found to give [2,3]-sigmatropic rearrangement
products 5b–g in approximately the same enantio-
selectivities as found with 4a. To our delighted surprise,
no sign of [1,2]-Stevens rearrangement was observed
with the reactions of 4b–f as in the case of 4a, though a
small amount of [1,2]-Stevens rearrangement product
Scheme 2
Tsutsui et al. / Enantioselective [2,3]-Sigmatropic Rearrangement

286
Fig. 2. Crystal structure of bis(4-tert-butylpyridine) adduct of Fig. 3. C2-symmetric model of dirhodium(II) carboxylates.
Rh2(S-PTPA)4. All hydrogen atoms except those attached to
the stereogenic centers are omitted.
sense of asymmetric induction in each series was sup- dominant formation of the observed (S)-benzofuran-3-
ported by CD curve comparison with 5a. This observa- ones 5. Although no explanation for the beneficial effect
tion, together with the similar levels of asymmetric of an exceptionally bulky tert-butyl group in Rh2(S-
induction found, suggests that the present [2,3]- PTTL)4 and Rh2(S-BPTTL)4 can presently be offered,
sigmatropic rearrangement has also proceeded through this operational model suggests that the presence of a
a chiral rhodium(II)-associated oxonium ylide. Based benzene ring connected to an ether oxygen and an α-
on the mechanistic hypothesis proposed in the allylic diazo-β-keto ester moiety is responsible for the reason-
oxonium studies,8 it appears likely that this rearrange- able levels of asymmetric induction that were observed.
ment takes place with the inversion of configuration at Indeed, it was found that the tandem reaction of aliphatic
the rhodium-bound carbon, in which propargylic sub-
stituents extend outward to avoid intrusion into the
rhodium framework and migrate in concert with disso-
ciation of the carbon–rhodium bond.
The direction of asymmetric induction observed here
can be rationalized based on a structural model of our
dirhodium(II) catalysts, which has been patterned after
the solid state structure of Rh2(S-PTPA)4, established as
the bis(4-tert-butylpyridine) adduct by single-crystal
X-ray structural analysis (Fig. 2).16 This structural
model adopts a C2-symmetric conformation with the
phthalimido or benzene-fused-phthalimido groups
aligned in a “down-down-up-up” arrangement (Fig. 3).17
Provided that the catalysts function in a C2-symmetry-
like fashion in solution, two rhodium(II)-bound oxo-
nium ylide intermediates, A and B, can be presented in
which the benzofuran–oxonium moiety is accommo-
dated in the less crowded first or fourth quadrants
(Fig. 4). The reactive intermediate A is favored over the
reactive intermediate B because of severe steric repul-
sion between the benzene ring and the phthalimido
group in B. Thus the reactive intermediate A provides a
lower energy transition state, which leads to the pre-
Fig. 4. Proposed model for asymmetric induction.
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phomolybdic acid. Purification of products was performed by
column chromatography on silica gel (Kanto Chemical Co.,
Inc., Silica Gel 60N, 63–210 µm).
Reagents and solvents were purified by standard means.
CH2Cl2 was distilled from P2O5 and then CaH2. Toluene, ben-
zene, hexane, and Et2O were distilled from Na/benzophenone
ketyl. Dehydrated stabilizer-free THF was purchased from
Kanto Chemical Co., Inc. Methanesulfonyl azide was pre-
pared according to Danheiser’s procedure.18
Preparation of Diazo Substrates
Diazo substrates 4a–g and 8a,b were prepared as shown in
Scheme 4.
Scheme 3
substrates 8a,b with Rh2(S-PTTL)4 in toluene proceeded
smoothly even at –30 °C to give [2,3]-sigmatropic rear-
rangement products 9a,b in good yields, but with sig-
nificantly lower enantioselectivities (Scheme 3).
Methyl 3-methyl-2-(2-propynyloxy)benzoate (11a)
A mixture of methyl 3-methyl-2-hydroxybenzoate (10)19
(1.0 g, 6.02 mmol), propargyl bromide (785 mg, 6.60 mmol),
and K2CO3 (1.66 g, 12.0 mmol) in acetone (25 mL) was heated
at reflux for 16 h. After cooling to room temperature, the
mixture was filtered and the filtrate was concentrated in vacuo
to give the crude product, which was purified by column
chromatography on silica gel (25 g, 30:1 hexane/EtOAc) to
CONCLUSION
We have demonstrated the first examples of asymmetric
induction (up to 79% ee) in the periselective [2,3]-
sigmatropic rearrangement of cyclic propargylic oxo-
nium ylides derived from the diazo decomposition of α-
diazo-β-keto esters under the influence of Rh2(S-
PTTL)4. Exploitation of the present protocol for the
synthesis of natural products is currently in progress.
EXPERIMENTAL
General Methods
Melting points were determined on a Büchi 535 digital
melting point apparatus and were uncorrected. Infrared spec-
tra were recorded on a JASCO FT/IR-5300 spectrophotom-
1
eter. H NMR spectra were recorded in CDCl3 using a JEOL
JNM-EX 270 (270 MHz) or AL 400 (400 MHz) with tetra-
methylsilane as an internal standard. 13C NMR spectra were
recorded in CDCl3 using a JEOL JNM-EX 270 (67.8 MHz)
with CDCl3 as an internal standard. Abbreviations are as fol-
lows: s, singlet, d, doublet, t, triplet, q, quartet, m, multiplet,
br, broad. Data were presented as follow: chemical shift, inte-
gration, multiplicity, and coupling constant. Mass spectra were
obtained at the Center for Instrumental Analysis, Hokkaido
University. EI mass spectra were measured with a JEOL JMS-
DX303 or JEOL FABmate spectrometer. FAB mass spectra
were measured with a JEOL JMS-HX110. Optical rotations
were obtained on a JASCO P-1030 digital polarimeter. Chiral
HPLC was performed on Daicel Chemical Industries Chiralcel
OD, OD-H, OJ-H and Chiralpak AD, AD-H, AS columns,
with a flow rate of 1.0 mL/min, using a UV detector set at 254
or 225 nm. Retention time (tR) and peak ratios were deter-
mined with a Shimadzu Chromatopac C-R6A. Hexane and 2- Scheme 4. Reagents and conditions: (a) propargyl bromide,
propanol for HPLC were of HPLC grade and filtered and K2CO3, acetone, reflux; (b) propargylic alcohol, DIAD, Ph3 P,
degassed before use. CD spectra were measured with a THF; (c) aq KOH, THF–MeOH; (d) CDI, THF, then methyl
JASCO J-720 spectropolarimeter. Analytical thin layer chro- lithioacetate, THF, –78 °C; (e) MsN3, Et3N, MeCN; (f)
matography was carried out on Merck Kieselgel 60 F254 plates LiHMDS, HMPA, THF, then NCCO2Me, –78 °C; (g)
with visualization by UV (254 nm) and anisaldehyde or phos- propargylic alcohol, Triton B, 50 °C; (h) TFA, CH2Cl2, reflux.
Tsutsui et al. / Enantioselective [2,3]-Sigmatropic Rearrangement

288
provide 11a (1.22 g, 99%) as a colorless oil: TLC Rf 0.40 (5:1 (C); enol tautomer: δ 16.6 (CH3), 51.4 (CH3), 60.6 (CH2), 75.4
hexane/EtOAc); IR (film) ν 3291, 2951, 2124, 1725 cm–1; (CH), 78.7 (C), 91.6 (CH), 124.5 (CH), 127.2 (CH), 132.79
1H NMR δ 2.37 (3H, s), 2.51 (1H, t, J = 2.7 Hz), 3.91 (3H, s), (CH), 132.83 (C), 135.4 (C), 154.6 (C), 170.2 (C), 173.7 (C);
4.66 (2H, d, J = 2.7 Hz), 7.08 (1H, t, J = 7.6 Hz), 7.34–7.37 LRMS (EI) m/z 246 (M+); HRMS (EI) Calcd for C14H14O4 (M+):
(1H, m), 7.65–7.69 (1H, m); 13C NMR δ 16.4 (CH3), 52.1 246.0892. Found: 246.0892.
(CH3), 61.4 (CH2), 75.2 (CH), 79.0 (C), 124.1 (CH), 124.7 (C),
Methyl 2-diazo-3-[3-methyl-2-(2-propynyloxy)phenyl]-3-
oxopropionate (4a)
To a solution of 13a (815 mg, 3.31 mmol) and triethy-
lamine (670 mg, 6.60 mmol) in MeCN (15 mL) at 0 °C was
129.2 (CH), 133.3 (C), 135.1 (CH), 156.1 (C), 166.5 (C);
LRMS (EI) m/z 204 (M+); HRMS (EI) Calcd for C12H12O3
(M+): 204.0786. Found: 204.0790.
added methanesulfonyl azide (480 mg, 3.97 mmol). After
stirring at room temperature for 1 h, the mixture was parti-
tioned between EtOAc (60 mL) and water (40 mL). The
organic layer was washed successively with 10% aqueous
NaOH and brine, and dried over Na2SO4. Filtration and con-
centration in vacuo gave the crude product, which was purified
by column chromatography on silica gel (20 g, 15:1 hexane/
EtOAc) to provide 4a (806 mg, 90%) as a yellow oil: TLC Rf
0.43 (2:1 hexane/EtOAc); IR (film) ν 3269, 2955, 2135, 1732,
1634 cm–1; 1H NMR δ 2.35 (3H, s), 2.51 (1H, t, J = 2.7 Hz),
3.75 (3H, s), 4.53 (2H, d, J = 2.7 Hz), 7.11 (1H, t, J = 7.6 Hz),
7.17–7.21 (1H, m), 7.30–7.33 (1H, m); 13C NMR δ 16.2 (CH3),
52.3 (CH3), 62.1 (CH2), 75.8 (CH), 78.5 (C), 124.6 (CH),
126.2 (CH), 131.8 (C), 132.6 (C), 134.1 (CH), 153.8 (C),
161.2 (C), 186.0 (C); LRMS (EI) m/z 272 (M+); HRMS (EI)
Calcd for C14H12N2O4 (M+): 272.0797. Found: 272.0794. Anal.
Calcd for C14H12N2O4: C, 61.76; H, 4.44; N, 10.29. Found: C,
61.45; H, 4.56; N, 10.56.
3-Methyl-2-(2-propynyloxy)benzoic acid (12a)
A solution of 11a (1.0 g, 4.90 mmol) and 15% aqueous
NaOH (3 mL) in THF–MeOH (15 mL–5 mL) was stirred at
room temperature for 2 h. The solution was concentrated in
vacuo and the residue was dissolved in water (10 mL) and
acidified with 10% aqueous HCl (5 mL). The resulting pre-
cipitate was filtered, washed with water, and dried in vacuo to
give 12a (923 mg, 99%) as a white powder. This product was
used without further purification for the next reaction. The
analytical sample was obtained by recrystallization from hex-
ane as colorless needles: mp 98.0–98.5 °C; IR (CHCl3) ν 3308,
1
3021, 1740, 1699, 1372 cm–1; H NMR δ 2.40 (3H, s), 2.57
(1H, t, J = 2.7 Hz), 4.73 (2H, d, J = 2.7 Hz), 7.18 (1H, t, J = 7.8
Hz), 7.43–7.46 (1H, m), 7.90–7.93 (1H, m); 13C NMR δ 16.5
(CH3), 61.9 (CH2), 77.3 (CH), 77.6 (C), 123.2 (C), 125.0 (CH),
130.4 (CH), 132.6 (C), 136.6 (CH), 155.8 (C), 168.4 (C);
LRMS (EI) m/z 190 (M+); HRMS (EI) Calcd for C11H10O3
(M+): 190.0630. Found: 190.0646. Anal. Calcd for C11H10O3:
C, 69.46; H, 5.30. Found: C, 69.48; H, 5.46.
Methyl 2-(2-butynyloxy)-3-methylbenzoate (11b)
To a solution of 10 (2.0 g, 12.0 mmol), 2-butyn-1-ol (1.27 g,
18.1 mmol) and triphenylphosphine (4.74 g, 18.1 mmol) in
THF (50 mL) was added diisopropyl azodicarboxylate
(DIAD) (3.84 g, 18.1 mmol) at 0 °C. The mixture was stirred
for 5 h and the solvent was removed in vacuo. Et2O (15 mL)
was added and the resulting precipitate was filtered off. The
filtrate was concentrated in vacuo and the residue was purified
by column chromatography on silica gel (50 g, 10:1 hexane/
EtOAc) to provide 11b (2.10 g, 80%) as a colorless oil: TLC Rf
0.64 (2 : 1 hexane/EtOAc); IR (film) ν 2951, 2234, 1727 cm–1;
1H NMR δ 1.85 (3H, t, J = 2.2 Hz), 2.36 (3H, s), 3.91 (3H, s),
4.59 (2H, q, J = 2.2 Hz), 7.07 (1H, t, J = 7.6 Hz), 7.33–7.37
(1H, m), 7.63–7.67 (1H, m); 13C NMR δ 3.6 (CH3), 16.3 (CH3),
52.0 (CH3), 62.1 (CH2), 74.5 (C), 83.5 (C), 123.9 (CH), 125.1
(C), 129.1 (CH), 133.3 (C), 135.0 (CH), 156.1 (C), 166.7 (C);
LRMS (EI) m/z 218 (M+); HRMS (EI) Calcd for C13H14O3
(M+): 218.0943. Found: 218.0926.
Methyl 3-[3-methyl-2-(2-propynyloxy)phenyl]-3-
oxopropionate (13a)
To a suspension of 1,1′-carbonylbis-1H-imidazole (CDI)
(750 mg, 4.63 mmol) in THF (10 mL) at 0 °C was added 12a
(800 mg, 4.21 mmol) and the mixture was stirred at room
temperature for 1 h. To a solution of diisopropylamine (3.07 mL,
21.9 mmol) in THF (30 mL) at –78 °C was added n-BuLi
(2.47 M in hexane, 8.5 mL, 21.0 mmol) and the mixture was
stirred for 30 min. To this mixture at –78 °C was added methyl
acetate (1.67 mL, 21.0 mmol) and the mixture was stirred for
1 h. The solution of acid imidazolide obtained above was added
and the mixture was stirred at –78 °C for 10 min. The reaction
was quenched with saturated aqueous NH4Cl (30 mL). The
whole was extracted with EtOAc (100 mL), and the organic
extract was successively washed with water and brine, and
dried over anhydrous Na2SO4. Filtration and evaporation in
vacuo furnish the crude product, which was purified by col-
umn chromatography on silica gel (30 g, 15:1 hexane/EtOAc) 2-(2-Butynyloxy)-3-methylbenzoic acid (12b)
to provide 13a (900 mg, 87%) as a pale yellow oil; TLC Rf
Following the procedure for the preparation of 12a, start-
0.49 (2:1 hexane/EtOAc); IR (film) ν 3287, 2955, 2124, 1746, ing from 11b (2.06 g, 9.44 mmol), 12b (1.78 g, 92%, colorless
1684 cm–1; 1H NMR keto tautomer: δ 2.36 (3H, s), 2.52 (1H, t, needles) was obtained: mp 107.0–108.0 °C (hexane); IR
J = 2.7 Hz), 3.74 (3H, s), 4.10 (2H, s), 4.59 (2H, d, J = 2.7 Hz), (CHCl3) ν 3246, 2240, 1738, 1375 cm–1; 1H NMR δ 1.84 (3H, t,
7.07–7.16 (1H, m), 7.36–7.40 (1H, m), 7.50–7.54 (1H, m); J = 2.2 Hz), 2.38 (3H, s), 4.67 (2H, q, J = 2.2 Hz), 7.20 (1H, t, J
enol tautomer: δ 2.37 (3H, s), 2.48 (1H, t, J = 2.7 Hz), 3.80 = 7.8 Hz), 7.41–7.44 (1H, m), 7.94–7.98 (1H, m);
(3H, s), 4.54 (2H, d, J = 2.7 Hz), 5.87 (1H, s), 7.07–7.16 (1H, 13C NMR δ 3.6 (CH3), 16.2 (CH3), 63.0 (CH2), 72.4 (C), 87.0
m), 7.36–7.40 (1H, m), 7.50–7.54 (1H, m), 12.52 (1H, s); 13
C
(C), 123.5 (C), 125.3 (CH), 130.5 (CH), 131.9 (C), 136.7 (CH),
NMR keto tautomer: δ 16.3 (CH3), 49.1 (CH2), 52.2 (CH3), 155.3 (C), 166.3 (C); LRMS (EI) m/z 204 (M+); HRMS (EI)
61.6 (CH2), 76.9 (CH), 77.8 (C), 124.9 (CH), 128.0 (CH), Calcd for C12H12O3 (M+): 204.0786. Found: 204.0799. Anal.
132.5 (C), 133.6 (C), 135.8 (CH), 155.1 (C), 168.2 (C), 195.0 Calcd for C12H12O3: C, 70.57; H, 5.92. Found: C, 70.60; H, 6.04.
Israel Journal of Chemistry
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Methyl 3-[2-(2-butynyloxy)-3-methylphenyl]-3-
oxopropionate (13b)
LRMS (EI) m/z 218 (M+); HRMS (EI) Calcd for C13H14O3
(M+): 218.0943. Found: 218.0941. Anal. Calcd for C13H14O3:
Following the procedure for the preparation of 13a, start- C, 71.54; H, 6.47. Found: C, 71.49; H, 6.48.
ing from 12b (1.50 g, 7.35 mmol ), 13b (1.70 g, 90%, colorless
oil) was obtained: TLC Rf 0.56 (2 : 1 hexane/EtOAc); IR (film)
oxopropionate (13c)
Methyl 3-[3-methyl-2-(2-pentynyloxy)phenyl]-3-
ν 2953, 2232, 1746, 1686 cm–1; 1H NMR keto tautomer: δ 1.78
Following the procedure for the preparation of 13a, start-
(3H, t, J = 2.4 Hz), 2.34 (3H, s), 3.73 (3H, s), 4.14 (2H, s), 4.52
ing from acid 12c (1.50 g, 6.87 mmol), 13c (1.70 g, 90%,
(2H, q, J = 2.4 Hz), 7.12 (1H, t, J = 7.6 Hz), 7.36–7.38 (1H, m),
colorless oil) was obtained: TLC Rf 0.57 (2:1 hexane/EtOAc);
7.50–7.53 (1H, m); enol tautomer: δ 1.83 (3H, t, J = 2.4 Hz),
IR (film) ν 2978, 2232, 1748, 1686 cm–1; 1H NMR keto
2.35 (3H, s), 3.79 (3H, s), 4.47 (2H, q, J = 2.4 Hz), 5.91 (1H,
tautomer: δ 1.07 (3H, t, J = 7.6 Hz), 2.11–2.21 (2H, m), 2.34
s), 7.08 (1H, t, J = 7.6 Hz), 7.25–7.28 (1H, m), 7.50–7.53 (1H,
(3H, s), 3.73 (3H, s), 4.15 (2H, s), 4.56 (2H, t, J = 2.2 Hz), 7.12
m), 12.52 (1H, s); 13C NMR keto tautomer: δ 3.5 (CH3), 16.1
(1H, t, J = 7.6 Hz), 7.35–7.39 (1H, m), 7.51–7.55 (1H, m);
(CH3), 49.2 (CH2), 52.0 (CH3), 62.3 (CH2), 73.5 (C), 86.0 (C),
enol tautomer: δ 1.10 (3H, t, J = 7.6 Hz), 2.11–2.21 (2H, m),
124.6 (CH), 127.8 (CH), 132.3 (C), 133.5 (C), 135.6 (CH),
2.36 (3H, s), 3.79 (3H, s), 4.50 (2H, t, J = 2.4 Hz), 5.93 (1H, s),
155.1 (C), 168.3 (C), 195.0 (C); enol tautomer: δ 3.5 (CH3),
7.08 (1H, t, J = 7.6 Hz), 7.25–7.27 (1H, m), 7.51–7.55 (1H,
16.4 (CH3), 51.3 (CH3), 61.4 (CH2), 74.3 (C), 83.7 (C), 91.4
m), 12.52 (1H, s); 13C NMR keto tautomer; δ 12.4 (CH2), 13.1
(CH), 124.2 (CH), 127.1 (CH), 132.8 (C), 133.4 (CH), 135.3
(CH3), 16.2 (CH3), 49.4 (CH2), 52.1 (CH3), 62.3 (CH2), 73.6
(C), 154.8 (C), 170.2 (C), 173.7 (C); LRMS (EI) m/z 260, 242,
(C), 91.6 (C), 124.6 (CH), 127.9 (CH), 132.4 (C), 133.3 (C),
186, 176, 159, 134, 106; HRMS (EI) Calcd for C15H16O4 (M+):
135.7 (CH), 155.2 (C), 168.3 (C), 195.0 (C); enol tautomer: δ
260.1048. Found: 260.1047.
12.4 (CH2), 13.4 (CH3), 16.6 (CH3), 51.3 (CH3), 61.4 (CH2),
Methyl 3-[2-(2-butynyloxy)-3-methylphenyl]-2-diazo-3-
oxopropionate (4b)
74.5 (C), 89.5 (C), 91.5 (CH), 124.2 (CH), 127.1 (CH), 127.8
(C), 132.9 (C), 133.5 (CH), 154.9 (C), 170.2 (C), 173.8 (C);
LRMS (FAB) m/z 275 (M++H); HRMS (FAB) Calcd for
C16H19O4 (M++H): 275.1283. Found: 275.1290.
Following the procedure for the preparation of 4a, starting
from 13b (564 mg, 2.17 mmol), 4b (589 mg, 95%, yellow
needles) was obtained: TLC Rf 0.48 (2:1 hexane/EtOAc); mp
48.5–49.5 °C (Et2O-hexane); IR (CHCl3) ν 2957, 2924, 2255,
Methyl 2-diazo-3-[3-methyl-2-(2-pentynyloxy)phenyl]-3-
oxopropionate (4c)
1
2137, 1732, 1632 cm–1; H NMR δ 1.82 (3H, t, J = 2.4 Hz),
Following the procedure for the preparation of 4a, starting
from 13c (880 mg, 3.21 mmol), 4c (958 mg, 99%, yellow oil)
was obtained: TLC Rf 0.24 (5:1 hexane/EtOAc); IR (film) ν
2978, 2132, 1736, 1632 cm–1; 1H NMR δ 1.10 (3H, t, J = 7.3
Hz), 2.20 (2H, qt, J = 7.3, 2.3 Hz), 2.33 (3H, s), 3.75 (3H, s),
4.50 (2H, t, J = 2.3 Hz), 7.10 (1H, t, J = 7.3 Hz), 7.19–7.22
(1H, m), 7.30–7.32 (1H, m); 13C NMR δ 12.5 (CH2), 13.4
(CH3), 16.2 (CH3), 52.2 (CH3), 62.8 (CH2), 74.1 (C), 90.2 (C),
124.4 (CH), 126.3 (CH), 131.9 (C), 132.8 (C), 134.1 (CH),
154.0 (C), 161.4 (C), 185.8 (C); LRMS (FAB) m/z 301
(M++H); HRMS (FAB) Calcd for C16H17N2O4 (M++H):
301.1188. Found: 301.1199.
2.33 (3H, s), 3.75 (3H, s), 4.48 (2H, q, J = 2.4 Hz), 7.10 (1H, t,
J = 7.3 Hz), 7.19–7.23 (1H, m), 7.30–7.33 (1H, m); 13C NMR δ
3.7 (CH3), 16.1 (CH3), 52.2 (CH3), 62.7 (CH2), 74.0 (C), 84.5
(C), 124.4 (CH), 126.3 (CH), 131.8 (C), 132.8 (C), 134.2
(CH), 153.9 (C), 161.4 (C), 185.8 (C); LRMS (FAB) m/z 287
(M++H); HRMS (FAB) Calcd for C15H15N2O4 (M++H):
287.1024. Found: 287.1028. Anal. Calcd for C15H14N2O4: C,
62.93; H, 4.93; N, 9.79. Found: C, 62.78; H, 5.03; N, 10.11.
Methyl 3-methyl-2-(2-pentynyloxy)benzoate (11c)
Following the procedure for the preparation of 11b, start-
ing from 10 (2.0 g, 12.0 mmol), 11c (2.38 g, 85%, colorless
oil) was obtained: TLC Rf 0.66 (2:1 hexane/EtOAc); IR (film)
ν 2978, 2949, 2234, 1728 cm–1; 1H NMR δ 1.11 (3H, t, J = 7.3
Hz), 2.21 (2H, qt, J = 7.3, 2.2 Hz), 2.36 (3H, s), 3.91 (3H, s),
4.62 (2H, t, J = 2.2 Hz), 7.07 (1H, t, J = 7.6 Hz), 7.33–7.36
(1H, m), 7.64–7.67 (1H, m); 13C NMR δ 12.4 (CH2), 13.4
(CH3), 16.4 (CH3), 52.0 (CH3), 62.1 (CH2), 74.6 (C), 89.3 (C),
123.9 (CH), 125.0 (C), 129.1 (CH), 133.4 (C), 135.0 (CH),
156.1 (C), 166.7 (C); LRMS (EI) m/z 232 (M+); HRMS (EI)
Calcd for C14H16O3 (M+): 232.1099. Found: 232.1100.
1-[2-(4-Methoxy-2-butynyloxy)-3-methylphenyl]ethanone
(15d)
Following the procedure for the preparation of 11b, starting
from 1-(2-hydroxy-3-methylphenyl)ethanone (14)20 (1.50 g,
10.0 mmol) and 4-methoxy-2-butyn-1-ol21 (1.50 g, 15.0 mmol),
15d (1.12 g, 48%, colorless oil) was obtained: TLC Rf 0.48
(2:1 hexane/EtOAc); IR (film) ν 2932, 1686 cm–1; 1H NMR δ
2.36 (3H, s), 2.64 (3H, s), 3.31 (3H, s), 4.08 (2H, t, J = 1.9 Hz),
4.62 (2H, t, J = 1.9 Hz), 7.10 (1H, t, J = 7.3 Hz), 7.29–7.35
(1H, m), 7.43–7.46 (1H, m); 13C NMR δ 16.1 (CH3), 30.7
(CH3), 57.5 (CH3), 59.6 (CH2), 61.7 (CH2), 81.0 (C), 84.3 (C),
124.5 (CH), 127.3 (CH), 132.4 (C), 134.4 (C), 134.8 (CH),
154.8 (C), 200.7 (C); LRMS (EI) m/z 232 (M+); HRMS (EI)
Calcd for C14H16O3 (M+): 232.1099. Found: 232.1087.
3-Methyl-2-(2-pentynyloxy)benzoic acid (12c)
Following the procedure for the preparation of 12a, start-
ing from 11c (2.30 g, 9.90 mmol), 12c (2.11 g, 98%, colorless
needles) was obtained: mp 86.0–86.5 °C (Et2O–hexane); IR
(CHCl3) ν 3250, 3027, 1738 cm–1; 1H NMR δ 1.10 (3H, t, J =
7.3 Hz), 2.20 (2H, qt, J = 7.3, 2.2 Hz), 2.38 (3H, s), 4.70 (2H,
t, J = 2.7 Hz), 7.18 (1H, t, J = 7.8 Hz), 7.42–7.44 (1H, m), Methyl 3-[2-(4-methoxy-2-butynyloxy)-3-methylphenyl]-3-
7.93–7.95 (1H, m); 13C NMR δ 12.4 (CH2), 13.2 (CH3), 16.3 oxopropionate (13d)
(CH3), 62.8 (CH2), 72.9 (C), 92.1 (C), 123.5 (C), 125.0 (CH),
To a solution of 1,1,1,3,3,3-hexamethyldisilazane
130.3 (CH), 132.2 (C), 136.6 (CH), 155.6 (C), 167.5 (C); (HMDS) (2.59 mL, 12.3 mmol) in THF (20 ml) at 0 °C was
Tsutsui et al. / Enantioselective [2,3]-Sigmatropic Rearrangement

290
added n-BuLi (1.55 M in hexane, 7.41 mL, 11.5 mmol) and the m/z 333 (M++H); HRMS (FAB) Calcd for C19H29O3Si (M++H):
mixture was stirred at –78 °C for 30 min. To this solution at 333.1886. Found: 333.1875.
–78 °C was added a solution of 15d (890 mg, 3.83 mmol)
Methyl 3-[2-(4-tert-butyldimethylsilyloxy-2-butynyloxy)-3-
in THF (5 mL) and hexamethylphosphoramide (HMPA)
methylphenyl]-3-oxopropionate (13e)
(0.67 mL, 3.8 mmol). After 1 h, methyl cyanoformate
Following the procedure for the preparation of 13d, start-
(0.91 mL, 11.5 mmol) was added and the mixture was stirred
ing from 15e (565 mg, 1.7 mmol), 13e (522 mg, 79%, yellow
at –78 °C for 40 min and at 0 °C for 10 min. The reaction was
oil) was obtained: TLC Rf 0.66 (2:1 hexane/EtOAc); IR (film)
quenched with saturated aqueous NH4Cl (15 mL). The whole
ν 2955, 1750, 1688 cm–1; 1H NMR keto tautomer: δ 0.07 (6H,
was extracted with EtOAc (60 mL), and the organic extract
s), 0.87 (9H, s), 2.34 (3H, s), 3.72 (3H, s), 4.09 (2H, s), 4.28
was successively washed with water and brine, and dried over
(2H, t, J = 1.9 Hz), 4.60 (2H, t, J = 1.9 Hz), 7.11 (1H, t, J = 7.6
anhydrous Na2SO4. Filtration and evaporation in vacuo fur-
Hz), 7.35–7.38 (1H, m), 7.48–7.51 (1H, m); enol tautomer: δ
nished the crude product, which was purified by column chro-
0.08 (6H, s), 0.89 (9H, s), 2.35 (3H, s), 3.79 (3H, s), 4.32 (2H,
matography on silica gel (50 g, 10:1 hexane/EtOAc) to pro-
t, J = 1.9 Hz), 4.56 (2H, t, J = 1.9 Hz), 5.87 (1H, s), 7.08 (1H,
vide 13d (611 mg, 55%) as a colorless oil: TLC Rf 0.42 (2 : 1
t, J = 7.8 Hz), 7.24–7.27 (1H, m), 7.48–7.51 (1H, m), 12.51
hexane/EtOAc); IR (film) ν 2951, 1746, 1684 cm–1; 1H NMR
(1H, s); 13C NMR keto tautomer: δ –5.3 (CH3), 16.3 (CH3),
keto tautomer: δ 2.35 (3H, s), 3.30 (3H, s), 3.73 (3H, s), 4.07
18.2 (C) 25.8 (CH3), 49.2 (CH2), 51.6 (CH3), 51.7 (CH2), 62.0
(2H, t, J = 1.6 Hz), 4.11 (2H, s), 4.64 (2H, t, J = 1.9 Hz), 7.13
(CH2), 79.0 (C), 87.7 (C), 124.7 (CH), 128.0 (CH), 132.5 (C),
(1H, t, J = 7.6 Hz), 7.37–7.39 (1H, m), 7.49–7.52 (1H, m);
133.1 (CH), 135.7 (CH), 155.1 (C), 168.2 (C), 194.9 (C); enol
enol tautomer: δ 2.36 (3H, s), 3.33 (3H, s), 3.79 (3H, s), 4.11
tautomer: δ –5.3 (CH3), 16.6 (CH3), 18.2 (C), 25.8 (CH3), 51.3
(2H, overlapped with CH2 of keto tautomer), 4.59 (2H, t, J =
(CH2), 52.1 (CH3), 61.0 (CH2), 79.9 (C), 86.1 (C), 91.4 (CH),
1.9 Hz), 5.89 (1H, s), 7.09 (1H, t, J = 7.6 Hz), 7.26–7.28 (1H,
124.4 (CH), 127.2 (CH), 127.7 (C), 132.8 (CH), 133.6 (CH),
m), 7.49–7.52 (1H, m), 12.52 (1H, s); 13C NMR keto tautomer:
155.1 (C), 170.3 (C), 173.7 (C); LRMS (FAB) m/z 391
δ 16.2 (CH3), 49.1 (CH2), 52.1 (CH3), 57.6 (CH3), 59.7 (CH2),
(M++H); HRMS (FAB) Calcd for C21H31O5Si (M++H):
61.8 (CH2), 80.7 (C), 85.2 (C), 124.8 (CH), 127.9 (CH), 132.4
391.1941. Found: 391.1969.
(C), 133.2 (CH), 135.7 (CH), 154.9 (C), 168.1 (C), 194.9 (C);
enol tautomer: δ 16.5 (CH3), 51.3 (CH3), 57.5 (CH3), 59.7
(CH2), 60.9 (CH2), 81.6 (C), 83.3 (C), 91.6 (CH), 124.4 (CH),
127.2 (CH), 127.8 (C), 132.8 (CH), 133.5 (CH), 154.6 (C),
170.2 (C), 173.6 (C); LRMS (EI) m/z 290 (M+); HRMS (EI)
Calcd for C16H1O5 (M+): 290.1154. Found: 290.1157.
Methyl 3-[2-(4-tert-butyldimethylsilyloxy-2-butynyloxy)-3-
methylphenyl]-2-diazo-3-oxopropionate (4e)
Following the procedure for the preparation of 4a, starting
from 13e (250 mg, 0.64 mmol), 4e (175 mg, 66%, yellow oil)
was obtained: TLC Rf 0.56 (2:1 hexane/EtOAc); IR (film)
ν 2955, 2133, 1736, 1634 cm–1; 1H NMR δ 0.09 (6H, s), 0.89
(9H, s), 2.34 (3H, s), 3.75 (3H, s), 4.32 (2H, t, J = 2.2 Hz), 4.55
(2H, t, J = 2.2 Hz), 7.10 (1H, t, J = 7.3 Hz), 7.17–7.20 (1H, m),
7.29–7.32 (1H, m); 13C NMR δ –5.3 (CH3), –5.2 (CH3), 16.3
(CH3), 18.3 (C), 25.8 (CH3), 51.7 (CH3), 52.2 (CH2), 62.5
(CH2), 79.5 (C), 86.6 (C), 124.5 (CH), 126.3 (CH), 131.9 (C),
132.7 (C), 134.1 (CH), 153.8 (C), 161.3 (C), 185.9 (C); LRMS
(FAB) m/z 417 (M++H); HRMS (FAB) Calcd for
C21H29N2O5Si (M++H): 417.1846. Found: 417.1834.
Methyl 2-diazo-3-[2-(4-methoxy-2-butynyloxy)-3-
methylphenyl]-3-oxopropionate (4d)
Following the procedure for the preparation of 4a, starting
from 13d (215 mg, 0.74 mmol), 4d (218 mg, 93%, yellow oil)
was obtained: TLC Rf 0.33 (2:1 hexane/EtOAc); IR (film) ν
1
2953, 2133, 1734, 1632 cm–1; H NMR δ 2.34 (3H, s), 3.34
(3H, s), 3.75 (3H, s), 4.11 (2H, t, J = 2.2 Hz), 4.59 (2H, t, J =
2.2 Hz), 7.11 (1H, t, J = 7.6 Hz), 7.18–7.22 (1H, m), 7.30–7.34
(1H, m); 13C NMR δ 16.2 (CH3), 52.3 (CH3), 57.6 (CH3), 59.9
(CH2), 62.3 (CH2), 81.2 (C), 84.0 (C), 100.5 (C), 124.6 (CH),
126.3 (CH), 131.8 (C), 132.8 (C), 134.2 (CH), 153.7 (C),
161.3 (C), 185.8 (C); LRMS (FAB) m/z 317 (M++H); HRMS
(FAB) Calcd for C16H17N2O5: (M++H) 317.1137. Found:
317.1150.
1-[3-Methyl-2-(3-trimethylsilyl-2-
propynyloxy)phenyl]ethanone (15f)
Following the procedure for the preparation of 11b, start-
ing from 14 (2.18 g, 14.6 mmol) and 3-trimethylsilyl-2-
propyn-1-ol23 (2.8 g, 21.8 mmol), 15f (2.5 g, 66%, pale yellow
oil) was obtained: TLC Rf 0.50 (5:1 hexane/EtOAc); IR (film)
ν 2961, 2180, 1686 cm–1; 1H NMR δ 0.13 (9H, s), 2.35 (3H, s),
2.65 (3H, s), 4.55 (2H, s), 7.09 (1H, t, J = 7.6 Hz), 7.31–7.34
(1H, m), 7.44–7.47 (1H, m); 13C NMR δ –0.6 (CH3), 16.4
(CH3), 30.8 (CH3), 62.4 (CH2), 93.8 (C), 99.8 (C), 124.5 (CH),
127.5 (CH), 132.6 (C), 134.2 (C), 134.9 (CH), 155.3 (C) 200.6
(C); LRMS (EI) m/z 260 (M+); HRMS (EI) Calcd for
C15H20O2Si (M+): 260.1232. Found: 260.1222.
1-[2-(4-tert-Butyldimethylsilyloxy-2-butynyloxy)-3-
methylphenyl]ethanone (15e)
Following the procedure for the preparation of 11b, start-
ing from 14 (854 mg, 5.69 mmol) and 4-tert-butyldi-
methylsilyloxy-2-butyn-1-ol22 (4.0 g, 20.0 mmol), 15e (596 mg,
32%, colorless oil) was obtained: TLC Rf 0.51 (5:1 hexane/
EtOAc); IR (film) ν 2930, 1686, 1588 cm–1; 1H NMR δ 0.08
(6H, s), 0.89 (9H, s), 2.35 (3H, s), 2.64 (3H, s), 4.30 (2H, t, J =
1.9 Hz), 4.58 (2H, t, J = 1.9 Hz), 7.08 (1H, t, J = 7.6 Hz), 7.30– Methyl 3-[3-methyl-2-(3-trimethylsilyl-2-
7.34 (1H, m), 7.42–7.45 (1H, m); 13C NMR δ –5.3 (CH3), 16.3 propynyloxy)phenyl]-3-oxopropionate (13f)
(CH3), 18.2 (C), 25.8 (CH3), 30.8 (CH3), 51.6 (CH2), 62.0
Following the procedure for the preparation of 13d, start-
(CH2), 79.4 (C), 87.0 (C), 124.5 (CH), 127.4 (CH), 132.5 (C), ing from 15f (1.19 g, 4.57 mmol), 13f (704 mg, 48%, yellow
134.4 (C), 134.9 (CH), 155.0 (C), 200.9 (C); LRMS (FAB) oil) was obtained: TLC Rf 0.41 (5:1 hexane/EtOAc); IR (film)
Israel Journal of Chemistry
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2001

291
ν 2957, 2179, 1748, 1686 cm–1; 1H NMR keto tautomer: δ 0.14 tautomer: δ –4.9 (CH3), 16.6 (C), 16.8 (CH3), 25.9 (CH3), 51.3
(9H, s), 2.35 (3H, s), 3.72 (3H, s), 4.12 (2H, s), 4.59 (2H, s), (CH3), 61.3 (CH2), 91.0 (C), 92.8 (CH), 100.9 (C), 124.3 (CH),
7.12 (1H, t, J = 7.6 Hz), 7.35–7.38 (1H, m), 7.51–7.56 (1H, 127.2 (CH), 127.5 (C), 133.0 (C), 133.5 (CH), 154.9 (C),
m); enol tautomer: δ 0.15 (9H, s), 2.36 (3H, s), 3.79 (3H, s), 170.2 (C), 173.8 (C); LRMS (EI) m/z 360 (M+); HRMS (EI)
4.53 (2H, s), 5.92 (1H, s), 7.08 (1H, t, J = 7.8 Hz), 7.24–7.27 Calcd for C20H28O4Si (M+): 360.1757. Found: 360.1744.
(1H, m), 7.51–7.56 (1H, m), 12.52 (1H, s); 13C NMR keto
Methyl 3-[2-(3-tert-butyldimethylsilyl-2-propynyloxy)-3-
tautomer: δ –0.63 (CH3), 16.4 (CH3), 49.4 (CH2), 52.1 (CH3),
methylphenyl]-2-diazo-3-oxopropionate (4g)
62.3 (CH2), 91.6 (C), 99.2 (C), 124.7 (CH), 128.0 (CH), 132.5
Following the procedure for the preparation of 4a, starting
(C), 132.9 (C), 135.8 (CH), 155.3 (C), 168.3 (C), 194.7 (C);
from 13g (720 mg, 2.0 mmol), 4g (472 mg, 61%, yellow oil)
enol tautomer: δ –0.43 (CH3), 16.7 (CH3), 51.3 (CH3), 61.5
was obtained: TLC Rf 0.59 (2:1 hexane/EtOAc); IR (film) ν
(CH2), 92.7 (C), 94.6 (CH), 100.3 (C), 124.4 (CH), 127.2
1
2955, 2133, 1736, 1701, 1636 cm–1; H NMR δ 0.09 (6H, s),
(CH), 127.7 (C), 132.9 (C), 133.5 (CH), 154.8 (C), 170.1 (C),
0.90 (9H, s), 2.35 (3H, s), 3.75 (3H, s), 4.54 (2H, s), 7.09 (1H,
173.7 (C); LRMS (EI) m/z 318 (M+); HRMS (EI) Calcd for
t, J = 7.3 Hz), 7.15–7.19 (1H, m), 7.28–7.31 (1H, m);
C17H22O4Si (M+): 318.1287. Found: 318.1290.
13C NMR δ –4.9 (CH3), 16.4 (C), 16.5 (CH3), 26.0 (CH3), 52.3
(CH3), 63.1 (CH2), 91.2 (C), 100.6 (C), 124.4 (CH), 126.2
(CH), 132.0 (C), 132.4 (C), 134.0 (CH), 154.0 (C), 161.2 (C),
185.9 (C); LRMS (EI) m/z 387 (M++H), 386 (M+); HRMS (EI)
Calcd for C20H27N2O4Si (M++H): 387.1740. Found: 387.1768.
Methyl 2-diazo-3-[3-methyl-2-(3-trimethylsilyl-2-
propynyloxy)phenyl]-3-oxopropionate (4f)
Following the procedure for the preparation of 4a, starting
from 13f (638 mg, 2.00 mmol), 4f (592 mg, 86%, yellow oil)
was obtained: TLC Rf 0.34 (5:1 hexane/EtOAc); IR (film)
ν 2959, 2133, 1736, 1701, 1634 cm–1; 1H NMR δ 0.16 (9H, s),
2.34 (3H, s), 3.75 (3H, s), 4.52 (2H, s), 7.09 (1H, t, J = 7.6 Hz),
7.16–7.20 (1H, m), 7.28–7.32 (1H, m); 13C NMR δ –0.4 (CH3),
16.4 (CH3), 52.3 (CH3), 63.0 (CH2), 92.9 (C), 100.0 (C), 124.5
(CH), 126.2 (CH), 131.9 (C), 132.6 (C), 134.0 (CH), 154.0
(C), 161.3 (C), 185.9 (C); LRMS (FAB) m/z 345 (M++H);
HRMS (FAB) Calcd for C17H21N2O4Si (M++H): 345.1271.
Found: 345.1267.
Methyl 3-oxo-5-(2-propynyloxy)pentanoate (19a)
A solution of tert-butyl 3-(2-propynyloxy)propionate
(17a)25 (530 mg, 2.88 mmol) and trifluoroacetic acid (TFA)
(984 mg, 8.63 mmol) in CH2Cl2 (10 mL) was heated at reflux
for 50 min. The solvent was removed in vacuo to give the
crude acid 18a, which was used without further purification
for the next reaction.
Following the procedure for the preparation of 13a, start-
ing from 18a obtained above, 19a (321 mg, 62%, pale yellow
oil) was obtained: TLC Rf 0.38 (2:1 hexane/EtOAc); IR (film)
ν 3279, 2955, 2116, 1746, 1719 cm–1; 1H NMR keto tautomer:
δ 2.46 (1H, t, J = 2.4 Hz), 2.83 (2H, t, J = 6.2 Hz), 3.74 (3H, s),
3.80 (2H, t, J = 6.2 Hz), 4.15 (2H, d, J = 2.4 Hz); enol
tautomer: δ 4.16 (2H, d, J = 2.4 Hz), 5.09 (1H, s), 12.04 (1H,
s). The other signals are overlapped with the signals of keto
tautomer; 13C NMR keto tautomer: δ 42.8 (CH2), 49.3 (CH3),
52.3 (CH2), 58.3 (CH2), 64.5 (CH2), 74.6 (CH), 79.3 (C), 167.3
(C), 200.8 (C); enol tautomer: δ 44.6 (CH2), 51.1 (CH3), 58.1
(CH2), 65.9 (CH2), 74.6 (CH), 79.3 (C), 90.0 (CH), 157.2 (C),
175.2 (C); LRMS (EI) m/z 185 (M++H); HRMS (EI) Calcd for
C9H13O4 (M++H): 185.0814. Found: 185.0816.
1-[2-(3-tert-butyldimethylsilyl-2-propynyloxy)-3-
methylphenyl]ethanone (15g)
Following the procedure for the preparation of 11b, start-
ing from 14 (2.17 g, 14.47 mmol) and 3-tert-butyldimethyl-
silyl-2-propyn-1-ol24 (3.70 g, 21.7 mmol), 15g (1.21 g, 28%,
pale yellow oil) was obtained: TLC Rf 0.52 (5:1 hexane/
1
EtOAc); IR (film) ν 2930, 2180, 1688 cm–1; H NMR δ 0.07
(6H, s), 0.87 (9H, s), 2.36 (3H, s), 2.65 (3H, s), 4.59 (2H, s),
7.08 (1H, t, J = 7.8 Hz), 7.31–7.34 (1H, m), 7.44–7.48 (1H,
m); 13C NMR δ –5.0 (CH3), 16.3 (C), 16.5 (CH3), 25.9 (CH3),
30.7 (CH3), 62.3 (CH2), 91.9 (C), 100.4 (C), 124.3 (CH), 127.5
(CH), 132.6 (C), 133.9 (C), 134.8 (CH), 155.3 (C), 200.5 (C);
LRMS (EI) m/z 302 (M+); HRMS (EI) Calcd for C18H26O2Si
(M+): 302.1702. Found: 302.1685.
Methyl 2-diazo-3-oxo-5-(2-propynyloxy)pentanoate (8a)
Following the procedure for the preparation of 4a, starting
from 19a (240 mg, 1.30 mmol), 8a (225 mg, 82%, yellow oil)
was obtained: TLC Rf 0.42 (2:1 hexane/EtOAc); IR (film) ν
3277, 2957, 2141, 1723, 1653 cm–1; 1H NMR δ 2.44 (1H, t, J =
2.7 Hz), 3.16 (2H, t, J = 5.9 Hz), 3.84 (3H, s), 3.87 (2H, t, J =
5.9 Hz), 4.17 (2H, d, J = 2.7 Hz); 13C NMR δ 39.6 (CH2), 51.9
(CH3), 57.9 (CH2), 64.3 (CH2), 74.3 (CH), 75.9 (C), 79.2 (C),
161.2 (C), 189.7 (C); LRMS (FAB) m/z 211 (M++H); HRMS
(FAB) Calcd for C9H11N2O4 (M++H): 211.0719. Found:
211.0713.
Methyl 3-[2-(3-tert-butyldimethylsilyl-2-propynyloxy)-3-
methylphenyl]-3-oxopropionate (13g)
Following the procedure for the preparation of 13d, start-
ing from 15g (1.0 g, 3.31 mmol), 13g (742 mg, 62%, pale
yellow oil) was obtained: TLC Rf 0.46 (5:1 hexane/EtOAc); IR
(film) ν 2953, 2180, 1750, 1686 cm–1; 1H NMR keto tautomer:
δ 0.60 (6H, s), 0.86 (9H, s), 2.36 (3H, s), 3.73 (3H, s), 4.11
(2H, s), 4.63 (2H, s), 7.11 (1H, t, J = 7.6 Hz), 7.34–7.38 (1H,
m), 7.53–7.56 (1H, m); enol tautomer: δ 0.70 (6H, s), 0.88
(9H, s), 2.36 (3H, s), 3.79 (3H, s), 4.56 (2H, s), 5.93 (1H, s), tert-Butyl 3-(2-butynyloxy)propionate (17b)
7.08 (1H, t, J = 7.6 Hz), 7.24–7.26 (1H, m), 7.51–7.55 (1H,
The title compound was prepared according to Rousseau’s
m), 12.52 (1H, s); 13C NMR keto tautomer: δ –5.1 (CH3), 16.3 procedure.26 Triton B (40% in MeOH, 326 mg, 0.78 mmol)
(C), 16.6 (CH3), 25.9 (CH3), 49.3 (CH2), 52.1 (CH3), 62.2 was placed in a dried flask and the solvent was removed in
(CH2), 91.5 (C), 99.9 (C), 124.6 (CH), 128.1 (CH), 132.5 (C), vacuo. 2-Butyn-1-ol (1.2 g, 17.2 mmol) was added at room
132.6 (C), 135.8 (CH), 155.5 (C), 168.3 (C), 194.6 (C); enol temperature and the mixture was stirred for 15 min. tert-Butyl
Tsutsui et al. / Enantioselective [2,3]-Sigmatropic Rearrangement

292
acrylate (2.0 g, 15.6 mmol) was added to the mixture and the (C), 170.5 (C), 193.9 (C), 207.5 (C); LRMS (EI) m/z 244 (M+);
whole was heated at 50 °C for 15 min. After cooling to room HRMS (EI) Calcd for C14H12O4 (M+): 244.0735. Found:
25
temperature, the resulting crude product was purified by col- 244.0731; CD (c 4.54 × 10–5, MeOH) [θ] –11,000 (256),
max
umn chromatography on silica gel (50 g, 15:1 hexane/ EtOAc) –1,500 (280), –13,300 (322). The enantiomeric excess was
to provide 17b (2.67 g, 86%) as a colorless oil: TLC Rf 0.47 determined to be 78% by HPLC; tR major enantiomer, 10.5
(5:1 hexane/EtOAc); IR (film) ν 2978, 1730 cm–1; 1H NMR δ min; tR minor enantiomer, 12.2 min (Daicel Chiralcel OD-H,
1.46 (9H, s), 1.85 (3H, t, J = 2.4 Hz), 2.52 (2H, t, J = 6.5 Hz), 100:1 hexane/2-propanol, 254 nm).
3.73 (2H, t, J = 6.5 Hz), 4.11 (2H, q, J = 2.4 Hz); 13C NMR δ
Methyl 2-(buta-1,2-dien-3-yl)-7-methyl-3-oxo-2,3-
3.5 (CH3), 28.0 (CH3), 36.0 (CH2), 58.6 (CH2), 65.3 (CH2),
dihydrobenzofuran-2-carboxylate (5b)
74.9 (C), 80.4 (C), 82.3 (C), 170.6 (C); LRMS (EI) m/z 197
Following the representative procedure for [2,3]-sigma-
(M+–H), 141(M+–t-Bu); HRMS (EI) Calcd for C11H17O3 (M+–
tropic rearrangement, starting from 4b (95 mg, 0.33 mmol), 5b
H): 197.1178. Found: 197.1166.
(70.6 mg, 82%, white solid) was obtained: TLC Rf 0.44 (5:1
Methyl 5-(2-butynyloxy)-3-oxopentanoate (19b)
hexane/EtOAc); mp 52.0–53.0 °C; [α]2D1 –139 (c 1.19, CHCl3)
Following the procedure for the preparation of 19a, start- [76% ee]; IR (CHCl3) ν 3029, 1958, 1753, 1722 cm–1;
ing from 17b (1.9 g, 13.4 mmol), 19b (2.11 g, 79%, pale 1H NMR δ 1.84 (3H, t, J = 3.0 Hz), 2.38 (3H, s), 3.81 (3H, s),
yellow oil) was obtained: TLC Rf 0.37(5:1 hexane/EtOAc); IR 4.88 (1H, dq, J = 11.3, 3.5 Hz), 4.94 (1H, dq, J = 11.3, 3.5 Hz),
(film) ν 2955, 2216, 1748, 1718 cm–1; 1H NMR keto tautomer: 7.02 (1H, t, J = 7.3 Hz), 7.46 (1H, d, J = 7.3 Hz), 7.50 (1H, d,
δ 1.85 (3H, t, J = 2.7 Hz), 2.82 (2H, t, J = 6.8 Hz), 3.52 (2H, s), J = 7.3 Hz); 13C NMR δ 14.3 (CH3), 14.5 (CH3), 53.4 (CH3),
3.74 (3H, s), 3.77 (2H, t, J = 6.8 Hz), 4.08 (2H, q, J = 2.7 Hz); 78.6 (CH2), 90.7 (C), 95.5 (C), 118.9 (C), 122.3 (CH), 122.6
enol tautomer: δ 2.50 (2H, t, J = 6.8 Hz), 5.09 (1H, s), 12.04 (CH), 123.8 (C), 139.0 (CH), 165.4 (C), 170.4 (C), 193.6 (C),
(1H, s). The other signals are overlapped with the signals of 207.5 (C); LRMS (EI) m/z 258 (M+); HRMS (EI) Calcd for
keto tautomer; 13C NMR keto tautomer: δ 3.3 (CH3), 42.7 C15H14O4 (M+): 258.0892. Found: 258.0890; CD (c 4.14 × 10–5,
25
max
(CH2), 49.1 (CH2), 52.0 (CH3), 58.6 (CH2), 64.1 (CH2), 74.6 MeOH) [θ]
(nm) –10,600 (257), +1,400 (285), –7,700
(C), 82.5 (C), 167.3 (C), 200.9 (C); enol tautomer: δ 3.3 (CH3), (329). The enantiomeric excess was determined to be 76% by
35.2 (CH2), 50.9 (CH3), 58.5 (CH2), 65.6 (CH2), 74.6 (C), 82.5 HPLC; tR minor enantiomer, 6.5 min; tR major enantiomer,
(C), 89.8 (CH), 172.7 (C), 175.3 (C); LRMS (EI) m/z 199 7.2 min (Daicel Chiralpak AD-H, 19:1 hexane/2-propanol,
(M++H); HRMS (EI) Calcd for C10H15O4 (M++H): 199.0970. 254 nm).
Found: 199.0979.
Methyl 7-methyl-3-oxo-2-(penta-1,2-dien-3-yl)-2,3-
Methyl 5-(2-butynyloxy)-2-diazo-3-oxopentanoate (8b)
Following the procedure for the preparation of 4a, starting
dihydrobenzofuran-2-carboxylate (5c)
Following the representative procedure for [2,3]-sigma-
from 19b (292 mg, 1.47 mmol), 8b (310 mg, 94%, yellow oil) tropic rearrangement, starting from 4c (90.1 mg, 0.30 mmol),
was obtained: TLC Rf 0.41 (2:1 hexane/EtOAc); IR (film) ν 5c (65.0 mg, 80%, colorless plate) was obtained: TLC Rf 0.68
2957, 2139, 1723, 1655 cm–1; 1H NMR δ 1.85 (3H, t, J = 2.4 (2:1 hexane/EtOAc); mp 76.0–76.5 °C; [α]2D1 –138 (c 1.15,
Hz), 3.16 (2H, t, J = 6.2 Hz), 3.84 (3H, s), 3.84 (2H, t, J = 6.2 CHCl3) [76% ee]; IR (CHCl3) ν 3021, 1956, 1753, 1725 cm–1;
Hz), 4.12 (2H, q, J = 2.4 Hz); 13C NMR δ 3.5 (CH3), 40.0 1H NMR δ 1.04 (3H, t, J = 7.6 Hz), 2.04–2.16 (2H, m), 2.38
(CH2), 52.1 (CH3), 58.7 (CH2), 64.4 (CH2), 74.9 (C), 76.3 (C), (3H, s), 3.81 (3H, s), 5.00 (1H, dt, J = 11.3, 4.1 Hz), 5.10 (1H,
82.4 (C), 161.5 (C), 190.2 (C); HRMS (EI) Calcd for dt, J = 11.3, 4.1 Hz), 7.02 (1H, t, J = 7.6 Hz), 7.44–7.52 (2H,
C10H13N2O4 (M++H): 225.0876. Found: 225.0870.
m); 13C NMR δ 11.9 (CH3), 14.3 (CH3), 20.3 (CH2), 53.4
(CH3), 81.0 (CH2), 91.2 (C), 102.4 (C), 118.9 (C), 122.3 (CH),
122.5 (CH), 123.8 (C), 139.0 (CH), 165.5 (C), 170.4 (C),
193.7 (C), 206.9 (C); LRMS (EI) m/z 272 (M+); HRMS (EI)
Calcd for C16H16O4 (M+): 272.1048. Found: 272.1044. Anal.
Calcd for C16H16O4: C, 70.57; H, 5.92. Found: C, 70.39; H,
6.10. The enantiomeric excess was determined to be 76% by
HPLC; tR major enantiomer, 10.5 min; tR minor enantiomer,
12.7 min (Daicel Chiralcel OJ-H, 40:1 hexane/2-propanol,
254 nm).
Representative Procedure for [2,3]-Sigmatropic Rearrange-
ment: Preparation of Methyl 7-methyl-3-oxo-2-(propa-1,2-
dienyl)-2,3-dihydrobenzofuran-2-carboxylate (5a) (Table 1,
entry 1)
To a stirred solution of 4a (81.7 mg, 0.30 mmol) in toluene
(3.0 mL) was added bis(ethyl acetate) adduct of Rh2(S-PTTL)4
(8.5 mg, 2 mol%) in one portion at 0 °C under argon atmo-
sphere. The mixture was stirred for 1 h at this temperature and
the solvent was removed in vacuo. The greenish residue was
purified by column chromatography on silica gel (10 g, 15:1 Methyl 2-(1-methoxybuta-2,3-dien-2-yl)-7-methyl-3-oxo-2,3-
hexane/EtOAc) to afford 5a (51.2 mg, 70%) as a colorless oil: dihydrobenzofuran-2-carboxylate (5d)
TLC Rf 0.55 (2:1 hexane/EtOAc); [α]2D1 –96.0 (c 1.09, CHCl3)
Following the representative procedure for [2,3]-
[78% ee]; IR (film) ν 2957, 1958, 1757, 1728, 1601, 1252 cm–1; sigmatropic rearrangement, starting from 4d (94.9 mg, 0.30
1H NMR δ 2.37 (3H, s), 3.81 (3H, s), 4.98 (1H, dd, J = 11.9, mmol), 5d (63.4 mg, 73%, colorless oil) was obtained: TLC Rf
6.8 Hz), 5.03 (1H, dd, J = 11.9, 6.8 Hz), 5.77 (1H, t, J = 7.3 0.48 (10:1 CHCl3/EtOAc); [α]2D2 –112 (c 1.12, CHCl3) [76%
Hz), 7.04 (1H, t, J = 7.8 Hz), 7.45–7.52 (2H, m); 13C NMR δ ee]; IR (CHCl3) ν 2928, 1956, 1755, 1728 cm–1; H NMR δ
1
14.1 (CH3), 53.4 (CH3), 80.0 (CH2), 86.8 (C), 87.6 (CH), 117.7 2.39 (3H, s), 3.25 (3H, s), 3.80 (3H, s), 4.12–4.22 (2H, m),
(C), 122.2 (CH), 122.5 (CH), 123.6 (C), 138.9 (CH), 165.3 5.05 (1H, dt, J = 11.9, 2.2 Hz), 5.16 (1H, dt, J = 11.9, 2.2 Hz),
Israel Journal of Chemistry
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293
7.02 (1H, t, J = 7.6 Hz), 7.44–7.52 (2H, m); 13C NMR δ 14.2 5%, pale yellow solid) were obtained: 5g: TLC Rf 0.41 (5:1
(CH3), 53.4 (CH3), 57.6 (CH3), 70.2 (CH2), 79.9 (CH2), 88.9 hexane/EtOAc); [α]2D0 –50.0 (c 1.05, CHCl3) [79% ee]; IR
(C), 97.5 (C), 118.8 (C), 122.2 (CH), 122.5 (CH), 123.6 (C), (film) ν 2955, 1929, 1757, 1730 cm–1; 1H NMR δ 0.10 (3H, s),
138.9 (CH), 165.3 (C), 170.1 (C), 193.0 (C), 207.9 (C); LRMS 0.14 (3H, s), 0.90 (9H, s), 2.36 (3H, s), 3.76 (3H, s), 4.65 (1H,
(EI) m/z 288 (M+); HRMS (EI) Calcd for C16H16O5 (M+): d, J = 12.4 Hz), 4.85 (1H, d, J = 12.4 Hz), 7.02 (1H, t, J = 7.3
288.0997. Found: 288.1013. The enantiomeric excess was Hz), 7.43–7.46 (1H, m), 7.49–7.52 (1H, m); 13C NMR δ –5.0
determined to be 76% by HPLC; tR major enantiomer, 18.0 (CH3), –4.8 (CH3), 14.4 (CH3), 18.5 (C), 26.8 (CH3), 53.3
min; tR minor enantiomer, 19.6 min (Daicel Chiralpak AD-H, (CH3), 73.9 (CH2), 90.4 (C), 90.5 (C), 118.7 (C), 122.4 (CH),
19:1 hexane/2-propanol, 254 nm).
122.5 (CH), 123.5 (C), 138.9 (CH), 166.5 (C), 169.9 (C),
193.7 (C), 212.1 (C); LRMS (EI) m/z 358 (M+); HRMS (EI)
Methyl 2-(1-tert-butyldimethylsilyloxybuta-2,3-dien-2-yl)-7-
methyl-3-oxo-2,3-dihydrobenzofuran-2-carboxylate (5e)
Following the representative procedure for [2,3]-sigma-
tropic rearrangement, starting from 4e (76.5 mg, 0.18 mmol),
5e (49.2 mg, 69%, white solid) was obtained: TLC Rf 0.58 (2:1
hexane/EtOAc); mp 82.5–83.0 °C; [α]2D2 –81.8 (c 1.27,
CHCl3) [77% ee]; IR (CHCl3) ν 2957, 2932, 1956, 1753, 1726,
1603, 1254 cm–1; 1H NMR δ –0.04 (3H, s), –0.02 (3H, s), 0.81
(9H, s), 2.38 (3H, s), 3.78 (3H, s), 4.38 (2H, t, J = 2.7 Hz), 5.01
(1H, dt, J = 11.9, 2.4 Hz), 5.13 (1H, dt, J = 11.9, 2.4 Hz), 7.00
(1H, t, J = 7.8 Hz), 7.43 (1H, d, J = 7.8 Hz), 7.48 (1H, d, J = 7.8
Hz); 13C NMR δ –5.7 (CH3), –5.6 (CH3), 14.3 (CH3), 18.3 (C),
25.8 (CH3), 53.3 (CH3), 61.4 (CH2), 80.4 (CH2), 89.3 (C),
100.6 (C), 118.9 (C), 122.3 (CH), 122.4 (CH), 123.7 (C),
138.7 (CH), 165.4 (C), 170.4 (C), 193.3 (C), 206.8 (C); LRMS
(EI) m/z 388 (M+); HRMS (EI) Calcd for C21H28O5Si (M+):
388.1706. Found: 388.1709; CD (c 2.88 × 10–5, MeOH) [q]5
(nm) –11,400 (257), +700 (280), –13,100 (317). The enantio-
meric excess was determined to be 77% by HPLC; tR major
enantiomer, 6.7 min; tR minor enantiomer, 8.8 min (Daicel
Chiralpak AD-H, 40:1 hexane/2-propanol, 254 nm).
Calcd for C20H26O4Si (M+): 358.1600. Found: 358.1617; CD
25
(c 2.83 × 10–5, MeOH) [θ] (nm) –15,900 (256), –2,500
max
(293), –10,300 (322). The enantiomeric excess was deter-
mined to be 79% by HPLC; tR major enantiomer, 8.4 min; tR
minor enantiomer, 12.2 min (Daicel Chiralpak AD, 99:1 hex-
ane/2-propanol, 254 nm). 6g: TLC Rf 0.46 (5:1 hexane/
EtOAc); mp 73.0–75.0 °C; [α]2D0 –52.6 (c 0.26, CHCl3)
[66% ee]; IR (CHCl3) ν 3027, 2957, 2184, 1753, 1723, 1603
cm–1; 1H NMR δ –0.18 (3H, s), –0.16 (3H, s), 0.66 (9H, s), 2.37
(3H, s), 3.20 (2H, s), 3.75 (3H, s), 7.02 (1H, t, J = 7.6 Hz),
7.44–7.50 (2H, m); 13C NMR δ –5.1 (CH3), –5.0 (CH3), 14.2
(CH3), 16.1 (C), 25.6 (CH2), 25.7 (CH3), 53.5 (CH3), 86.6 (C),
88.6 (C), 98.8 (C), 119.3 (C), 122.1 (CH), 122.6 (CH), 123.7
(C), 139.1 (CH), 165.7 (C), 171.8 (C), 195.7 (C); LRMS
(FAB) m/z 359 (M++H); HRMS (FAB) Calcd for C20H27O4Si
(M+): 359.1679. Found: 359.1671. The enantiomeric excess
was determined to be 66% by HPLC; tR major enantiomer, 8.1
min; tR minor enantiomer, 9.6 min (Daicel Chiralpak AD (2 ×
250 mm), 100:1 hexane/2-propanol, 254 nm).
Methyl 3-oxo-2-(propa-1,2-dien-1-yl)tetrahydrofuran-2-
carboxylate (9a)
Methyl 7-methyl-3-oxo-2-(1-trimethylsilylpropa-1,2-dien-1-
yl)-2,3-dihydrobenzofuran-2-carboxylate (5f)
Following the representative procedure for [2,3]-sigma-
tropic rearrangement, starting from 8a (60 mg, 0.28 mmol), 9a
(41.5 mg, 80%, colorless oil) was obtained: TLC Rf 0.33 (2:1
hexane/EtOAc); [α]2D4 +22.2 (c 1.80, CHCl3) [9% ee]; IR (film)
ν 2957, 1958, 1769, 1746 cm–1; 1H NMR δ 2.64 (2H, t, J = 7.6
Hz), 3.79 (3H, s), 4.32 (1H, dt, J = 9.2, 7.6 Hz), 4.40 (1H, dt, J
= 9.2, 7.6 Hz), 5.02 (2H, d, J = 6.8 Hz), 5.51 (1H, t, J = 6.8
Hz); 13C NMR δ 35.3 (CH2), 53.2 (CH3), 64.3 (CH2), 79.9
(CH2), 82.7 (C), 88.8 (CH), 167.3 (C), 206.9 (C), 207.7 (C);
LRMS (EI) m/z 182 (M+); HRMS (EI) Calcd for C9H10O4 (M+):
182.0579. Found: 182.0588. The enantiomeric excess was
determined to be 9% by HPLC; tR major enantiomer, 10.2 min;
tR minor enantiomer, 12.6 min (Daicel Chiralpak AS, 9:1
hexane/2-propanol, 225 nm).
Following the representative procedure for [2,3]-sigma-
tropic rearrangement, starting from 4f (86.0 mg, 0.25 mmol),
5f (55.1 mg, 70%, colorless oil) was obtained: TLC Rf 0.61
(2:1 hexane/EtOAc); [α]1D6 +12.6 (c 1.08, CHCl3) [79% ee]; IR
(film) ν 2957, 1931, 1757, 1730, 1603 cm–1; 1H NMR δ 0.13
(9H, s), 2.37 (3H, s), 2.77 (3H, s), 4.68 (1H, d, J = 12.2 Hz),
4.82 (1H, d, J = 12.2 Hz), 7.02 (1H, t, J = 7.6 Hz), 7.44–7.52
(2H, m); 13C NMR δ –0.6 (CH3), 14.2 (CH3), 53.3 (CH3), 73.5
(CH2), 90.2 (C), 92.7 (C), 118.6 (C), 122.4 (CH), 122.6 (CH),
123.5 (C), 138.8 (CH), 166.1 (C), 169.9 (C), 193.8 (C), 210.7
(C); LRMS (EI) m/z 316 (M+); HRMS (EI) Calcd for
C17H20O4Si (M+): 316.1131. Found: 316.1126; CD (c 3.35 ×
25
10–5, MeOH) [θ] (nm) –10,500 (256), –1,400 (285), –4,300
max
(322). The enantiomeric excess was determined to be 79% by
HPLC; tR major enantiomer, 8.3 min; tR minor enantiomer,
11.4 min (Daicel Chiralpak AD-H, 100:1 hexane/2-propanol,
254 nm).
Methyl 2-(buta-1,2-dien-3-yl)-3-oxotetrahydrofuran-2-
carboxylate (9b)
Following the representative procedure for [2,3]-sigma-
tropic rearrangement, starting from 8b (60 mg, 0.27 mmol), 9b
(41.4 mg, 79%, colorless oil) was obtained: TLC Rf 0.35 (2 : 1
hexane/EtOAc); [α]2D4 –33.5 (c 1.90, CHCl3) [26% ee]; IR
(film) ν 2957, 1960, 1769, 1746 cm–1; 1H NMR δ 1.75 (3H, t, J
= 3.2 Hz), 2.50–2.71 (2H, m), 3.81 (3H, s), 4.19–4.38 (2H, m),
Methyl 2-(1-tert-butyldimethylsilylpropa-1,2-dien1-1-yl)-7-
methyl-3-oxo-2,3-dihydrobenzofuran-2-carboxylate (5g) and
methyl 2-(3-tert-butyldimethylsilyl-2-propynyl)-7-methyl-3-
oxo-2,3-dihydrobenzofuran-2-carboxylate (6g)
Following the representative procedure for intramolecular 4.82–4.97 (2H, m); 13C NMR δ 14.2 (CH3), 35.8 (CH2), 53.1
[2,3]-sigmatropic rearrangement, starting from 4g (100 mg, (CH3), 63.6 (CH2), 78.2 (CH2), 86.2 (C), 95.2 (C), 167.1 (C),
0.26 mmol), 5g (58.5 mg, 63%, colorless oil) and 6g (4.4 mg, 206.0 (C), 206.9 (C); LRMS (EI) m/z 196 (M+); HRMS (EI)
Tsutsui et al. / Enantioselective [2,3]-Sigmatropic Rearrangement

294
Calcd for C10H12O4 (M+): 196.0735. Found: 196.0721. The
enantiomeric excess was determined to be 26% by HPLC; tR
major enantiomer, 29.5 min; tR minor enantiomer, 35.1 min
(Daicel Chiralcel OD, 99:1 hexane/2-propanol, 225 nm).
arrangement via oxonium ylides generated by catalytic
diazo decomposition, see: (a) McCarthy, N.;
McKervey, M.A.; Ye, T.; McCann, M.; Murphy, E.;
Doyle, M.P. Tetrahedron Lett. 1992, 33, 5983–5986.
(b) Ferris, L.; Haigh, D.; Moody, C.J. Tetrahedron Lett.
1996, 37, 107–110. (c) Pierson, N.; Fernández-García,
C.; McKervey, M.A. Tetrahedron Lett. 1997, 38, 4705–
4708. (d) Clark, J.S.; Fretwell, M.; Whitlock, G.A.;
Burns, C.J.; Fox, D.N.A. Tetrahedron Lett. 1998, 39,
97–100. (e) Calter, M.A.; Sugathapala, P.M. Tetrahe-
dron Lett. 1998, 39, 8813–8816. (f) Doyle, M.P.;
Forbes, D.C.; Vasbinder, M. M.; Peterson C.S. J. Am.
Chem. Soc. 1998, 120, 7653–7654. (g) Hodgson, D.M.;
Petroliagi, M. Tetrahedron: Asymmetry 2001, 12, 877–
881.
Determination of Absolute Configuration. Chemical
Correlation of 5a with (S)-(-)-Methyl 7-methyl-2-propyl-2,3-
dihydrobenzofuran-2-carboxylate (7)
A solution of 5a {82 mg, 0.336 mmol, [77% ee, [α]2D2 –97.0
(c 1.08, CHCl3)]} and c. H2SO4 (15 mg, 0.145 mmol) in AcOH
(3 mL) was stirred with 10% Pd-C (60 mg) under 30 atm of H2
for 3 h. The catalyst was removed by filtration, and the filtrate
was concentrated in vacuo. The residue was dissolved in
EtOAc (20 mL), and the whole was washed with saturated
aqueous NaHCO3 (3 × 10 mL) and brine, and dried over
Na2SO4. Filtration and evaporation in vacuo furnished the
crude product, which was purified by column chromatography
on silica gel (10 g, 15:1 hexane/EtOAc) to give 7 (78 mg,
99%) as a colorless oil: TLC Rf 0.73 (2:1 hexane/EtOAc);
[α]2D1 –25.2 (c 1.12, CHCl3) (77% ee); [α]2D1 –32.5 (c 1.07,
CHCl3) for optically pure (S)-7;15 IR (film) ν 2961, 1736,
1467 cm–1; 1H NMR δ 0.95 (3H, t, J = 7.3 Hz), 1.31–1.59 (2H,
m), 1.86–2.06 (2H, m), 2.25 (3H, s), 3.17 (1H, d, J = 16.2 Hz),
3.56 (1H, d, J = 16.2 Hz), 3.76 (3H, s), 6.76 (1H, t, J = 7.0 Hz),
6.97–7.00 (2H, m); 13C NMR δ 14.1 (CH3), 15.3 (CH2), 17.2
(CH3), 39.6 (CH2), 40.6 (CH2), 52.5 (CH3), 89.4 (C), 119.9
(C), 120.7 (CH), 121.9 (CH), 124.4 (C), 129.4 (CH), 157.3
(C), 173.9 (C); LRMS (EI) m/z 234 (M+); HRMS (EI) Calcd
for C14H18O3 (M+): 234.1256. Found: 234.1267. The enantio-
meric excess was determined to be 77% by HPLC; tR minor
enantiomer, 4.2 min; tR major enantiomer, 5.0 min (Daicel
Chiralcel OD-H, 9:1 hexane/2-propanol, 254 nm).
(7) For examples of enantioselective [1,2]-Stevens rear-
rangement via oxonium ylides generated by catalytic
diazo decomposition, see: (a) Doyle, M.P.; Ene, D.G.;
Forbes, D.C.; Tedrow, J.S. Tetrahedron Lett. 1997, 38,
4367–4370. (b) Ito, K.; Yoshitake, M.; Katsuki, T. Het-
erocycles 1996, 42, 305–317. (c) Lo, M. M-C.; Fu, G.C.
Tetrahedron 2001, 57, 2621–2634.
(8) Kitagaki, S.; Yanamoto, Y.; Tsutsui, H.; Anada, M.;
Nakajima, M.; Hashimoto, S. Tetrahedron Lett. 2001,
42, 6361–6364.
(9) Clark, J.S. Tetrahedron Lett. 1992, 33, 6193–6196.
(10) For the total synthesis of (+)-griseofulvin via
diastereoselective [2,3]-sigmatropic rearrangement of
an oxonium ylide, see: Pirrung, M.C.; Brown, W.L.;
Rege, S.; Laughton, P. J. Am. Chem. Soc. 1991, 113,
8561–8562.
(11) For other examples of the [2,3]-sigmatropic rearrange-
ment of propargylic oxonium ylides, see: (a) Doyle,
M.P.; Bagheri, V.; Claxton, E.E. J. Chem. Soc., Chem.
Commun. 1990, 46–48. (b) Doyle, M. P.; Hu, W. Tetra-
hedron Lett. 2000, 41, 6265–6269.
(12) For reviews, see: (a) Schuster, H.F.; Coppola, G.M.
Allenes in Organic Synthesis; John Wiley and Sons:
New York, 1984. (b) Bruneau, C.; Dixneuf, P.H. In
Comprehensive Organic Functional Group Transfor-
mations; Katritzky, A.R.; Meth-Cohn, O.; Rees, C.W.,
Eds.; Pergamon: Oxford, 1995; Vol. 1, Chapter 20.
(13) (a) Kitagaki, S.; Anada, M.; Kataoka, O.; Matsuno, K.;
Umeda, C.; Watanabe, N.; Hashimoto, S. J. Am. Chem.
Soc. 1999, 121, 1417–1418. (b) Anada, M.; Mita, O.;
Watanabe, H.; Kitagaki, S.; Hashimoto, S. Synlett
1999, 1775–1777.
Acknowledgments. This research was supported in part by a
Grant-in-Aid (No.11470465) from the Ministry of Education,
Culture, Sports, Science and Technology, Japan. We thank
Ms. S. Oka of the Center for Instrumental Analysis at
Hokkaido University, for mass measurements.
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