Spiro γ-lactones via aluminum enolate-spiroepoxide openings

Article abstract of DOI:10.1055/s-1998-2108

The opening of several spiroepoxides by aluminum ester enolates is described. The isolated γ-hydroxy esters are cyclized to the corresponding spirolactones with high efficiency. Alternatively, the crude product from epoxide opening may be directly converted to the spirolactone without purification of the intermediate hydroxy ester. This methodology provides another complementary route to 1-oxaspiro[4.n]-2-one systems that are of structural and biological interest.

Full text of DOI:10.1055/s-1998-2108

SYNTHESIS
July 1998
1009
Spiro γ-Lactones via Aluminum EnolateÐSpiroepoxide Openings
Stephen K. Taylor,* Nikolas H. Chmiel, Emily E. Mann, Michael E. Silver, James R. Vyvyan
Department of Chemistry, Hope College, Holland, Michigan 49422-9000, USA
Received 24 January 1997; revised 4 September 1997
Abstract: The opening of several spiroepoxides by aluminum
We have previously explored the opening of monosubsti-
tuted epoxides with aluminum ester enolates. This chem-
istry provides γ-hydroxy esters in good yields and
reasonable diastereoselectivity.8 These hydroxy esters are
readily converted to the corresponding γ-lactones by treat-
ment with acid.9 The utility of the aluminum enolate route
to lactones was demonstrated by featuring it as the key
step in a short synthesis of (±)-rubrynolide.10
ester enolates is described. The isolated γ -hydroxy esters are
cyclized to the corresponding spirolactones with high efficiency.
Alternatively, the crude product from epoxide opening may be
directly converted to the spirolactone without purification of the
intermediate hydroxy ester. This methodology provides another
complementary route to 1-oxaspiro[4.n]-2-one systems that are of
structural and biological interest.
Key words: spiroepoxides, epoxide ring opening, γ-hydroxy
esters, 1-oxaspiro[4.n]-2-one spirolactone systems, aluminum
ester enolates
In the present work, we have extended the aluminum eno-
late methodology to spiroepoxides 8 which provides tertia-
ry hydroxy esters 10 that yield spiro γ-lactones 11 upon
treatment with acid (Scheme). The spiroepoxides 8 are
readily obtained from their respective olefins via epoxida-
tion or from treatment of the appropriate ketone with a sul-
fur ylide. (Scheme). This convenient and versatile approach
to starting materials makes the aluminum ester enolate
strategy very attractive. This approach also allows for prep-
aration of varied ring sizes in just a few simple steps. A rou-
tine literature search revealed just one other approach to
spirolactones from spiroepoxides – an isolated study of
opening an epoxide with carboxylic acid lithiodianions.11
Spiro γ-lactones have been shown to be an important class
of molecules owing to their interesting structures and bio-
logical activity. Some natural products that possess this
structural element include the antitumor–antibiotic plu-
mericin (1),1 the antitumor agent allamandin (2),2 the nor-
sesquiterpenoids napalilactone (3)3 and pathylactone A
(4),4 and the zedoary extract curcumanolide A (5) and its
derivatives.5 Synthetic spiro γ-lactones like 6 and 7 have
been employed as templates for the construction of con-
formationally constrained diacylglycerol mimics for bind-
ing protein kinase C (PKC).6 Many spiro[4.5]decane
lactones and ethers have interesting olfactory properties.
Over many years, various methods for preparing spiro δ-
and γ-lactones have appeared in the literature, but recent
reports7 regarding the synthesis of spirolactones demon-
strate that this is still a very active research area and have
prompted us to disclose our own efforts in this area.
Scheme
Spiroepoxides 8 of varying ring sizes and substituents
were added to a solution of the diethyl aluminum enolate
of tert-butyl acetate 9 to give the tertiary γ-hydroxy esters
10 (Table 1). The first set of substrates (entries 1–4) were
simple unsubstituted 4- to 7-membered ring systems. The
epoxide opening by 9 proceeded smoothly in fair to good
yield. These yields are comparable to the yields we have
obtained from the aluminum enolate opening of monosub-
stituted epoxides such as propylene oxide and 1,2-ep-
oxybutane (66% and 71%, respectively).8
Temperature and reaction time were found to be important
variables in this reaction. Maintaining a reaction tempera-

SYNTHESIS
Papers
1010
ture between –50 and –35°C for 4 to 6 hours provided the Often it was more convenient to submit the crude product
highest yields of γ-hydroxy ester product. Higher reaction mixture from epoxide opening to the lactonization condi-
temperatures and/or overnight reaction times tended to in- tions directly, rather than purifying the hydroxy ester
crease side product formation from Claisen condensation (yields in parentheses Table 1). This protocol not only
of the ester and Lewis acid promoted rearrangements. eliminates a purification step, but the spirolactones are
Warming the reaction mixture slowly overnight to room more easily separated (chromatography on silica gel)
temperature resulted in varying amounts of spontaneous from the side products formed in the epoxide opening step
lactonization of the alkoxide ester intermediate.
than are the hydroxy esters.
The isolated hydroxy esters were then lactonized (catalyt- Entries 5,6 in Table 1 describe the results for 6-substituted
ic TsOH in CHCl3) in good to excellent yield (Table 1). 1-oxaspiro[2.5]octanes. Epoxide 8e, prepared by treat-
Table 1. Hydroxy Ester and Lactone Products
Entry
1
Epoxide
8
Hydroxy Ester
10
Yield of
Lactone 11
Yield of
Overall
10 (%)a
11 (%)b
Yield (%)c
64
76
62
91
81
86
58
2
3
62 (63)
54 (58)
d
4
5
–
99
99
(68)
60
61
45
6
99
45
a
Yield of pure hydroxy ester 10 isolated from the epoxide opening.
Yield of pure lactone 11 starting from purified hydroxy ester 10.
Overall yield of lactone 11 from epoxide 8 for the two discrete steps. Yields in parentheses refer to direct lactonizations of crude 10 as
described in the text.
b
c
d
This hydroxy ester was isolated in pure form for characterization purposes only.

SYNTHESIS
July 1998
1011
ment of 4-tert-butylcyclohexanone with dimethyloxo-
sulfonium methylide,12 was opened with aluminum
enolate 9 to provide hydroxy ester 10e in 61% yield. One
preparation of 8e surprisingly resulted in a mixture of 8e
and 8f, which when reacted with 9 yielded the diastereo-
meric hydroxy esters 10e and 10f. The diastereomers
were separated by chromatography in 73% and 17%
yields, respectively, taking into account the starting ratio
of 8e/8f. The relative configuration of 10e was con-
firmed by single crystal X-ray diffraction (Figure 1 and
Table 2).13 These hydroxy esters were lactonized sepa-
rately to provide 11e and 11f as crystalline solids that
were subjected to X-ray diffraction to unambiguously
determine their diastereomeric relationship (Figure 2
and Table 3).13 This was especially important to estab-
lish since the methyl-substituted epoxide 8g gave a 1:1
mixture of diastereomers which remained unresolved
throughout the synthetic sequence (as was the case in
other work7a).
Figure 2. ORTEP drawing of spirolactones 11e (top) and 11f (bot-
tom). Nonhydrogen atoms are represented by ellipsoids correspon-
ding to 50% probability. Hydrogen atoms are represented by spheres
of arbitrary size.
Table 3. Selected Bond Lengths (Å) and Angles (°) for Lactones 11e
and 11f.
11e
11f
11e
11f
C1–C2 1.523(5) 1.536(6) C1–C2–C3 112.4(3) 111.4(3)
C2–C3 1.517(5) 1.530(5) C2–C3–C4 113.2(3) 112.0(3)
C3–C4 1.500(5) 1.519(5) C3–C4–C5 110.2(3) 110.7(3)
C4–C5 1.517(6) 1.512(6) C3–C4–O7 107.5(3) 106.9(3)
C4–O7 1.470(4) 1.481(4) C3–C4–C10 114.0(4) 113.4(4)
C4–C10 1.525(5) 1.536(5) C4–O7–C8 111.0(3) 111.95(23)
O7–C8 1.339(5) 1.346(4) O7–C8–O11 120.8(4) 121.62(28)
C8–O11 1.193(4) 1.202(4) O7–C8–C9 110.2(4) 110.22(27)
C8–C9 1.495(6) 1.495(5) O11–C8–C9 129.0(4) 128.2(4)
C9–C10 1.495(7) 1.529(6) C8–C9–C10 104.0(4) 104.4(3)
C10–C4–O7 103.4(3) 103.4(3)
Figure 1. ORTEP drawing of hydroxy ester 10e. Nonhydrogen atoms
are represented by ellipsoids corresponding to 50% probability. Hy-
drogen atoms are represented by spheres of arbitrary size.
In summary, we have demonstrated the utility of the alu-
minum enolate epoxide opening reaction as a route to the
preparation of spiro γ-lactones of various ring sizes. The
epoxide openings proceed in moderate to good yield and
the hydroxy ester products are efficiently lactonized with
acid. The efficiency of the lactone production can be im-
proved by directly treating the crude product mixture from
epoxide opening with TsOH.
Table 2. Selected Bond Lengths (Å) and Angles (°) for Hydroxy Ester
10e.
C1–C2
1.530(4)
1.524(4)
1.526(4)
1.435(3)
1.530(4)
1.519(4)
1.491(4)
1.209(3)
1.336(3)
1.477(3)
C1–C2–C3
111.77(25)
113.65(26)
109.27(24)
110.35(24)
109.69(24)
114.69(27)
113.7(3)
C2–C3
C2–C3–C4
C3–C4
C3–C4–C5
C4–O7
C3–C4–O7
C4–C8
C3–C4–C8
THF was distilled from sodium/benzophenone under N2 or argon im-
mediately before use. i-Pr2NH was distilled from KOH and stored
over 4Å molecular sieves until use. Mps (Mel-Temp) are uncorrected.
Spiroepoxide 8a was prepared by MCPBA epoxidation of methy-
lenecyclobutane.14 Spiroepoxides 8b–g were prepared from the
corresponding ketones by reaction with dimethyloxosulfonium
methylide.12
C8–C9
C4–C8–C9
C9–C10
C10–O11
C10–O12
O12–C13
C8–C9–C10
C9–C10–O11
C9–C10–O12
O11–C10–O12
C10–O12–C13
124.8(3)
110.63(28)
124.61(27)
122.50(23)

SYNTHESIS
Papers
1012
tert-Butyl 3-(1-Hydroxycyclobutyl)propanoate (10a); Typical
Procedure for Epoxide Openings:
13C NMR (75 MHz, CDCl3): δ = 174.2, 80.3, 74.9, 41.1, 37.5, 29.9,
28.0 (2C), 22.5.
To a cooled (–78°C) solution of LDA (15.7 mmol) in THF (40 mL)
was added tert-butyl acetate (2.0 mL, 15.0 mmol). After 30 min,
1.0 M Et2AlCl in hexanes (15.0 mL) was added, and the resulting
mixture was stirred for an additional 15 min before adding 8a (1.00 g,
11.9 mmol). The mixture was kept below –35°C for 6 h. The reaction
was quenched by the addition of sat. NH4Cl, diluted with water and
warmed to r.t. The resulting gel was dispersed by stirring with 10%
HCl (50 mL) until a clear biphasic mixture formed. The layers were
separated, and the aqueous layer was extracted with Et2O. The com-
bined organic layers were washed (sat. NH4Cl, sat. NaHCO3, and
brine), dried (MgSO4), and concentrated. Flash chromatography (sil-
ica gel, hexanes/EtOAc 6:1) provided hydroxy ester 10a (1.53 g,
64%) as a colorless oil; TLC: Rf 0.25 (hexanes/EtOAc 6:1).
IR (neat, NaCl plates): ν = 3445 (br, OH), 2978, 2934, 1728, 1368,
1291, 1256, 1154, 1109, 953, 847 cm–1.
HRMS (CI, CH4) Calcd for C14H26O3 [M + H] 243.1959, found
243.1948.
tert-Butyl 3-(cis-4-tert-Butyl-1-hydroxycyclohexyl)propanoate
(10e):
LDA (11.5 mmol) in THF (20 mL), tert-butyl acetate (1.95 mL,
13.4 mmol), 1.0 M Et2AlCl in hexanes (11.5 mL), and 8e (5.9 mmol)
provided hydroxy ester 10e (1.03 g, 61%) as a crystalline solid (mp
73–76°C) after workup and chromatography using the typical proce-
dure described for 10a.
IR (neat, deposited from CH2Cl2 on NaCl plates): ν = 3450 (br, OH),
2966, 1724 cm–1.
1H NMR (300 MHz, CDCl3): δ = 2.35 (t, J = 7 Hz, 2H), 1.70 (m, 4H),
1.55 (m, 4H), 1.45 (s, 9H), 1.30 (m, 4H), 0.86 (s, 9H).
13C NMR (75 MHz, CDCl3): δ = 174.7, 80.9, 70.5, 48.5, 39.1, 38.1,
33.0, 30.3, 28.7, 28.2, 23.0.
1H NMR (300 MHz, CDCl3): δ = 2.70 (br s, 1H), 2.31 (t, J = 7.3 Hz,
2H), 1.99 (m, 4H), 1.87 (t, J = 7.3 Hz, 2H), 1.70 (m, 1H), 1.48 (m,
1H), 1.41 (s, 9H).
Anal. Calcd for C17H32O3 C, 71.79; H, 11.33. Found C, 72.23; H,
11.00.
Crystallographic Data: triclinic space group P 1 at r.t., a = 10.244(1)
Å, b = 14.404(2) Å, c = 6.140(1) Å, α = 97.03(1)˚, β = 90.67(1)˚, γ =
103.32(1)˚, Z = 2, ρcalcd = 1.081 g/cm3, µ(Mo Kα) = 0.670 cm–1, R =
0.070, Rw = 0.066.
13C NMR (75 MHz, CDCl3): δ = 174.2, 80.5, 74.6, 35.7, 34.0, 30.2,
28.0, 11.9.
Anal. Calcd for C11H20O3 C, 65.97; H, 10.07. Found C, 65.99; H,
10.13.
tert-Butyl 3-(1-Hydroxycyclopentyl)propanoate (10b):
LDA (20.0 mmol) in THF (50 mL), tert-butyl acetate (2.6 mL,
19.3 mmol), 1.0 M Et2AlCl in hexanes (20.0 mL), and 8b (1.14 g,
11.6 mmol) provided hydroxy ester 10b (1.88 g, 76%) as a colorless
oil after workup and chromatography using the typical procedure de-
scribed for 10a.
tert-Butyl 3-(trans-4-tert-Butyl-1-hydroxycyclohexyl)propanoate
(10f):
Hydroxy ester 10f was isolated from a reaction of 9 with a mixture of
8e and 8f (see text) as a crystalline solid (mp 86–87°C) using the typ-
ical procedure described for 10a.
IR (neat, NaCl plates): ν = 3426 (br, OH), 2963, 1726, 1368,
1153 cm–1.
IR (neat, deposited from CH2Cl2 on NaCl plates): ν = 3450 (br, OH),
1H NMR (300 MHz, CDCl3): δ = 2.39 (t, J = 7.5 Hz, 2H), 1.86 (t, J =
7.5 Hz, 2H), 1.70–1.40 (m, 9H), 1.44 (s, 9H).
2966, 1722 cm–1.
1H NMR (300 MHz, CDCl3): δ = 2.30 (t, J = 7 Hz, 2H), 1.90 (br s,
1H), 1.85–1.65 (m, 8H), 1.45 (s, 9H), 1.35 (m, 3H), 0.85 (s, 9H).
13C NMR (75 MHz, CDCl3): δ = 174.9, 81.0, 72.1, 48.2, 39.3, 32.9,
31.7, 30.2, 28.7, 28.3, 25.0.
13C NMR (75 MHz, CDCl3): δ = 174.8, 83.2, 81.1, 40.3, 36.0, 31.8,
28.2, 23.8.
HRMS (CI, CH4) Calcd for C12H22O3 [M + H – HOC(CH3)3]
141.0918, found 141.0951.
Anal. Calcd for C17H32O3 C, 71.79; H, 11.33. Found C, 71.48; H,
11.24.
tert-Butyl 3-(1-Hydroxycyclohexyl)propanoate (10c):
LDA (20.0 mmol) in THF (50 mL), tert-butyl acetate (2.6 mL,
19.3 mmol), 1.0 M Et2AlCl in hexanes (20.0 mL), and 8c (1.46 g,
13.0 mmol) provided hydroxy ester 10c (1.85 g, 62%) as a colorless
oil after workup and chromatography using the typical procedure de-
scribed for 10a.
tert-Butyl 3-(1-Hydroxy-4-methylcyclohexyl)propanoate (10g):
LDA (5.5 mmol) in THF (15 mL), tert-butyl acetate (5.5 mmol),
1.0 M Et2AlCl in hexanes (7.8 mL), and 8g (3.5 mmol) provided hy-
droxy ester 10g (0.381 g, 45%) as a crystalline solid (mp 43–45°C)
after workup and chromatography using the typical procedure de-
scribed for 10a.
IR (neat, NaCl plates): ν = 3410 (br, OH), 2935, 2863, 1730,
1135 cm–1.
IR (neat, NaCl plates): ν = 3455 (br, OH), 2947, 1730 cm–1.
1H NMR (300 MHz, CDCl3): δ = 2.40 (t, J = 7.5 Hz, 2H), 1.70 (t, J =
7.5 Hz, 2H), 1.60–1.40 (m, 5H), 1.44 (s, 9H), 1.3–1.2 (m, 5H), 0.90
(d, J = 5 Hz, 3H).
1H NMR (300 MHz, CDCl3): δ = 2.35 (t, J = 7.5 Hz, 2H), 2.10 (br s,
1H), 1.75 (t, J = 7.5 Hz, 2H), 1.65–1.20 (m, 10H), 1.44 (s, 9H).
13C NMR (75 MHz, CDCl3): δ = 174.1, 80.1, 70.5, 37.3, 36.5, 29.6,
27.9, 26.7, 22.1.
13C NMR (75 MHz, CDCl3): δ = 174.8, 80.9, 70.5, 39.1, 37.5, 32.9,
30.8, 30.3, 28.7, 22.9.
tert-Butyl 3-(1-Hydroxycycloheptyl)propanoate (10d):
LHMDS (10.0 mmol) in THF (10 mL), tert-butyl acetate (1.3 mL,
9.65 mmol), 1.0 M Et2AlCl in hexanes (10.0 mL), and 8d
(5.46 mmol) provided hydroxy ester 10d and lactone 11d as a 1.0:1.3
mixture (1H NMR) (0.74 g, 30% for 10d and 38% for 11d) as a color-
less oil after workup and chromatography using the typical procedure
described for 10a. Treatment of this mixture with TsOH in CHCl3 re-
sulted in essentially quantitative conversion to pure 11d. A smaller scale
reaction was run to provide pure 10d for characterization purposes
IR (neat, NaCl plates): ν = 3450 (br, OH), 2978, 2926, 2857, 1724,
1154 cm–1.
1-Oxaspiro[4,3]octan-2-one (11a); Typical Procedure for Lacton-
ization:
TsOH•H2O (16 mg, 0.08 mmol) was added to a solution of 10a (435
mg, 2.17 mmol) in CHCl3 (15 mL) and the solution was stirred at r.t.
for 24 h. Alternatively, the solution may be refluxed for 30 min to 2 h.
to effect the lactonization. The mixture was passed through a plug of
silica gel topped with NaHCO3. After solvent removal, flash chroma-
tography (hexanes/EtOAc 3:1) provided 11a (251 mg, 91%) as a light
yellow oil. In some cases passing the crude product through a simple
silica gel plug was sufficient to provide analytically pure material.
The lactones that follow were prepared by this method in the yields
indicated in Table 1. TLC: Rf = 0.5 (hexanes/EtOAc 1:1).
1H NMR (300 MHz, CDCl3): δ = 2.35 (t, J = 7.5 Hz, 2H), 1.76 (t, J =
7.5 Hz, 2H), 1.70–1.35 (m, 13H), 1.44 (s, 9H).

SYNTHESIS
July 1998
1013
IR (neat, NaCl plates): ν = 2986, 2942, 2880, 1775, 1422, 1292, 1182,
1146, 1107, 955, 909 cm–1.
8.5 Hz, 2H), 1.90 (d, J = 11 Hz, 2H), 1.7–1.3 (m, 7H), 0.92 (d, J =
5.5 Hz, 3H).
1H NMR (300 MHz, CDCl3): δ = 2.52 (t, J = 7.8 Hz, 2H), 2.50 (m,
2H), 2.27 (t, J = 7.8 Hz, 2H), 2.12 (m, 2H), 1.85 (m, 1H), 1.63 (m,
1H).
13C NMR (75 MHz, CDCl3): δ = 176.9, 85.5, 36.8, 34.0, 31.4, 28.6,
21.8.
13C NMR (75 MHz, CDCl3): δ = 176.3, 85.0, 34.5, 33.3, 28.5, 11.9.
Anal. Calcd for C7H10O2 C, 66.65; H, 7.99. Found C, 66.79; H, 7.75.
This work was supported by the Camille and Henry Dreyfus Scholar/
Fellow Program for Undergraduate Institutions, the NSF-REU pro-
gram (CHE-8804803), and by grant GM 44318-01 from the National
Institutes of Health. The authors gratefully acknowledge Dr. John
C. Huffman of Indiana University for collecting a low temperature
X-ray diffraction data set for lactone 11f.
1-Oxaspiro[4.4]nonan-2-one (11b):15
IR (neat, NaCl plates): ν = 2959, 2874, 1771, 1344, 1283, 1163, 1005
cm–1.
1H NMR (300 MHz, CDCl3): δ = 2.60 (t, J = 8 Hz, 2H), 2.21 (t, J =
8 Hz, 2H), 2.00 (m, 2H), 1.85 (m, 2H), 1.70 (m, 4H).
13C NMR (75 MHz, CDCl3): δ = 176.7, 94.9, 38.3, 32.2, 29.7, 23.7.
(1) Trost, B. M.; Balkovec, J. M.; Mao, M. K.-T. J. Am. Chem. Soc.
1983, 105, 6755.
1-Oxaspiro[4.5]decan-2-one (11c):7, 16, 17
Little, J. E.; Johnstone, D. B. Arch. Biochem. 1951, 30, 445.
Albers-Schonberg, G.; Schmid, G. Helv. Chim. Acta 1961, 44,
1447.
IR (neat, NaCl plates): ν = 2935, 1774 cm–1.
1H NMR (300 MHz, CDCl3): δ = 2.60 (t, J = 8.5 Hz, 2H), 2.00 (t, J =
8.5 Hz, 2H), 1.90–1.70 (m, 4H), 1.70–1.50 (m, 6H).
13C NMR (75 MHz, CDCl3): δ = 177.5, 87.1, 37.6, 33.5, 29.3, 25.6,
23.2.
(2) Kupchan, S. M.; Dessertine, A. L.; Blaylock, B. T.; Bryan, R. F.
J. Org. Chem. 1974, 39, 2477.
(3) Carney, J. R.; Pham, A. T.; Yoshida, W. Y.; Scheuer, P. J.
Tetrahedron Lett. 1992, 33, 7115.
(4) Su, J.-Y.; Zhong, Y.-L.; Zeng, L.-M. J. Nat. Prod. 1993, 56,
288.
(5) Hirukawa, T.; Oguchi, M.; Yoshikawa, N.; Kato, T. Chem. Lett.
1992, 2343.
1-Oxaspiro[4.6]undecan-2-one (11d):16, 17
IR (neat, NaCl plates): ν = 2930, 2859, 1769, 1244, 1161 cm–1.
1H NMR (300 MHz, CDCl3): δ = 2.57 (t, J = 8.3 Hz, 2H), 2.02 (t, J =
8.3 Hz, 2H), 2.00–1.80 (m, 2H), 1.75–1.4 (m, 10H).
13C NMR (75 MHz, CDCl3): δ = 176.8, 90.2, 39.8, 34.1, 29.0, 28.6,
22.1.
Honda, T.; Ishige, H. J. Chem. Soc., Perkin Trans. 1 1994, 3567.
Shiobara, Y.; Asakawa, M.; Kodama, M.; Yasuda, K.; Take-
shita, T. Phytochemistry 1985, 24, 2629.
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1987, 107, 237049p.
(6) Lee, J.; Marquez, V. E.; Lewin, N. E.; Blumberg, P. M. Synlett
1994, 206.
cis-8-tert-Butyl-1-oxaspiro[4.5]decan-2-one (11e):15, 16
mp 69–70°C.
Lee, J.; Wang, S.; Milne, G. W. A.; Sharma, R.; Lewin, N. E.;
Blumberg, P. M.; Marquez, V. E. J. Med. Chem. 1996, 39, 29.
(7) (a) Alonso, D.; Font, J.; Ortuño, R. M. J. Org. Chem. 1991, 56,
5567.
IR (neat, deposited on NaCl plates from CH2Cl2): ν = 2943, 2868,
1761 cm–1.
1H NMR (300 MHz, CDCl3): δ = 2.52 (t, J = 8.3 Hz, 2H), 1.97 (t, J =
8.3 Hz, 2H), 1.95 (m, 1H), 1.7–1.3 (m, 8H), 0.87 (s, 9H).
13C NMR (75 MHz, CDCl3): δ = 177.0, 85.6, 47.3, 37.6, 34.2, 32.4,
28.6, 27.5, 23.1.
(b) Das, J.; Choudhury, P. K.; Chandrasekaran, S. Tetrahedron
1995, 51, 3389.
(c) Xiong, H.; Rieke, R. D. J. Org. Chem. 1992, 57, 7007.
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34, 6007.
(e) Rieke, R. D.; Sell, M. S.; Xiong, H. J. Org. Chem. 1995, 60,
5143.
Anal. Calcd for C13H22O2 C, 74.24; H, 10.53. Found C, 74.43; H,
10.52.
Crystallographic Data: monoclinic space group P21/α at r.t., a =
10.240(5) Å, b = 6.109(4) Å, c = 20.876(10) Å, β = 101.17(3)˚, Z = 4,
ρcalcd = 1.090 g/cm3, µ(Mo Kα) = 0.666 cm–1, R = 0.082, Rw = 0.079.
(f) Das, J.; Choudjury, P. K.; Chandrasekaran, S. Tetrahedron
1995, 51, 3389.
(8) Strurm, T.-J.; Marolewski, A. E.; Rezenka, D. S.; Taylor, S. K.
J. Org. Chem. 1989, 54, 2039.
trans-8-tert-Butyl-1-oxaspiro[4.5]decan-2-one (11f):15, 16
mp 97–98°C.
Taylor, S.K.; Fried, J. A.; Grassl, Y. N.; Marolewski, A. E. Pel-
ton, E. A.; Poel, T.-J. Rezenka, D. S.; Whittaker, M. R. J. Org.
Chem. 1993, 58, 7304.
Our earlier work was prompted by a pioneering report by:
Danishefsky, S.; Kitahara, T.; Tsai, M.; Dynak, J. J. Org, Chem.
1976, 41, 1669.
IR (neat, deposited on NaCl plates from CH2Cl2): ν = 2950, 2864,
1774 cm–1.
1H NMR (300 MHz, CDCl3): δ = 2.59 (t, J = 8.3 Hz, 2H), 2.07 (t, J =
8.3 Hz, 2H), 1.9–1.6 (m, 6H), 1.08 (m, 3H), 0.87 (s, 9H).
13C NMR (75 MHz, CDCl3): δ = 176.5, 87.1, 46.7, 36.8, 32.1, 30.2,
28.5, 27.5, 23.0.
(9) White, J. D.; Somers, T. C.; Reddy, G. N. J. Am. Chem. Soc.
1986, 108, 5352.
Anal. Calcd for C13H22O2 C, 74.24; H, 10.53. Found C, 73.62; H,
10.54.
Nakamura, E.; Kuwajima, I. J. Am. Chem. Soc. 1985, 107, 2138.
(10) Taylor, S. K.; Hopkins, J. A.; Spangenberg, K. A.; McMillen,
D. W.; Grutzner, J. B. J. Org. Chem. 1991, 56, 5951.
(11) Creger, P. L. J. Org. Chem. 1972, 37, 1907.
(12) Corey, E. J.; Chaykovsky, M. J. Am. Chem. Soc. 1965, 87, 1353.
(13) Data were collected using a standard moving crystal, moving
detector technique with fixed background counts at the extreme
of each scan. Data were collected for Lorentz and polarization
terms and equivalent data were averaged. The structure was
Crystallographic Data: monoclinic space group P21 at –165°C, a =
9.788(3) Å, b = 6.248(2) Å, c = 20.158(6) Å, β = 101.72(1)˚, Z = 4,
ρcalcd = 1.157 g/cm3, µ(Mo Kα) = 0.707 cm–1, R = 0.047, Rw
=
0.038.
8-Methyl-1-oxaspiro[4.5]undecan-2-one (11g):7
IR (neat, NaCl plates): ν = 2949, 2858, 1769 cm–1.
1H NMR (300 MHz, CDCl3): δ = 2.60 (t, J = 8.5 Hz, 2H), 2.00 (t, J =

SYNTHESIS
Papers
1014
solved by direct methods (SHELXS-86) and Fourier tech-
niques. For more information contact the authors. The authors
have deposited atomic coordinates for this structure with the
Cambridge Crystallographic Centre. The coordinates can be ob-
tained, on request, from the director, Cambridge Crystallogra-
phic Centre, 12 Union Road, Cambridge, CB2 1EZ, UK.
Trost, B. M.; Bogdanowicz, M. J. J. Am. Chem. Soc. 1973, 95,
5311.
(16) Eaton, P. E.; Cooper, G. F.; Johnson, R. C.; Mueller, R. H.
J. Org. Chem. 1972, 37, 1947.
Trost, B. M.; Bogdanowicz, M. J. J. Am. Chem. Soc. 1973, 95,
5321.
(14) Lambert, J. B.; Magyar, E. S. Org. Magn. Reson. 1973, 5, 403.
(15) Caine, D.; Frobese, A. S. Tetrahedron Lett. 1978, 883.
Bogdanowicz, M. J.; Trost, B. M. Tetrahedron Lett. 1972, 887.
Trost, B. M.; Bogdanowicz, M. J. J. Am. Chem. Soc. 1973, 95,
289.
Bogdanowicz, M. J.; Ambelang, T.; Trost, B. M. Tetrahedron
Lett. 1973, 923.
(17) Schlect, M. F.; Kim, H.-J. Tetrahedron Lett. 1985, 26, 127.