Synthesis of spiranes by thiol-mediated acyl radical cyclization

Article abstract of DOI:10.1002/ejoc.201501305

A general and efficient method for the preparation of spiro compounds is described. Various enone-aldehydes were exposed to t-dodecanethiol and AIBN at 75 °C in toluene to afford spirocyclic 1,4-diketones in moderate to good yields. Intramolecular acyl radical cyclization of a series of enone-aldehydes in the presence of AIBN and a thiol was studied. Various ring size of the all-carbon spirocyclic 1,4-diketones were obtained in moderate to good yields.

Full text of DOI:10.1002/ejoc.201501305

DOI: 10.1002/ejoc.201501305
Full Paper
Radical Cyclization
Synthesis of Spiranes by Thiol-Mediated Acyl Radical Cyclization
[a]
[a]
[a]
Day-Shin Hsu,* Chih-Hao Chen, and Chi-Wei Hsu
Abstract: A general and efficient method for the preparation were exposed to t-dodecanethiol and AIBN at 75 °C in toluene
of spiro compounds is described. Various enone-aldehydes to afford spirocyclic 1,4-diketones in moderate to good yields.
Introduction
Moreover, samarium diiodide is an air-sensitive and relatively
expensive reagent. These factors prompted us to develop an-
other method for construction of spiro compounds.
Spiro compounds, bicyclic structures fused at single central
carbon atoms, are of recent interest due to their interesting
conformational features and structural implications in biological
In 2005, Tomioka et al. reported thiol-catalyzed acyl radical
cyclization of alkenals to give five- and six-membered cyclic
[
1]
systems. The asymmetry usually present in such molecules as
a result of the presence of the chiral spiro carbon is one of
the important criteria for showing biological activity. Spiro core
systems are found in a variety of natural products with a wide
[
7]
ketones. In this strategy, the acyl radical was produced
through reaction between an aldehyde and a thiyl radical. Thiyl
radicals have found widespread use in organic synthesis for sev-
eral decades and have proved to be valuable intermediates for
[
1,2]
range of biological activities.
Owing to the importance of
[
8]
the synthesis of natural products. In our ongoing efforts to
develop a general and efficient method for the preparation of
spiro compounds, here we report another synthesis of spiro-
cyclic 1,4-diketones based on thiol-mediated acyl radical cycli-
zation (Scheme 1).
spiro cores in nature, the development of new and efficient
strategies for their construction has become a major focal point
for synthetic chemistry. For this reason, there has been great
interest in the development of a multitude of methods for their
[
3]
synthesis. Among these, Tu et al. reported enantioselective
preparation of spirocyclic 1,4-diketones from various cyclic
hydroxy-enones, each containing a substituted cyclobutanol
Results and Discussion
[
4]
motif, through a semipinacol-type rearrangement. Recently,
we developed an intramolecular reductive cyclization of enone- (a) Preparation of Enone-Aldehydes
aldehydes by treatment with samarium diiodide to prepare spi-
The spirane precursors, enone-aldehydes 6–9, were prepared
from 3-alkoxyenones 1–4, which were in turn obtained either
commercially or from the corresponding cyclic 1,3-diones by a
[
5]
rocyclic γ-hydroxy ketones (Scheme 1). This strategy has since
been successfully applied to the total synthesis of (±)-majuscu-
[
6]
lone. However, most of these intramolecular reductive cycliza-
tions of enone-aldehydes resulted in mixtures of diastereomers.
[9]
method reported in the literature. 1,2-Addition of Grignard
[10]
reagents 5a–c to 3-alkoxyenones 1–4 and subsequent treat-
ment of the resulting addition products with an acidic aqueous
solution gave enone-aldehydes 6–8 in moderate to good yields,
with the exception of 9b (Table 1).
Because of the low yield of 9b, we designed an alternative
synthetic route to compounds 9, as outlined in Scheme 2. Simi-
larly, treatment of cyclohept-2-en-1-one (10) with Grignard rea-
gents 5a–c resulted in 1,2-addition, generating the tertiary all-
ylic alcohols 11. Oxidative rearrangement of compounds 11 to
enones 12 was performed with pyridinium chlorochromate
[
11]
(
PCC).
under acidic conditions to give the desired enone-aldehydes
b and 9c in good overall yields. However, cyclohept-2-en-1-
Without purification, compounds 12 were hydrolyzed
9
Scheme 1. Strategies for constructing spiro skeletons.
one 12a, with a three-carbon side chain, gave a complex mix-
ture under these conditions. Gratifyingly, though, this problem
[
a] Department of Chemistry and Biochemistry,
National Chung Cheng University,
[
12]
could be solved by using a mild Lewis acid, PdCl (CH CN) ,
2
3
2
Minhsiung, Taiwan 621
E-mail: chedsh@ccu.edu.tw
http://deptche.ccu.edu.tw/faculty/dsh.html
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/ejoc.201501305.
to hydrolyze the acetal, affording the desired enone-aldehyde
9a in 63 % overall yield.
To examine their reactivity, gem-dimethylcyclohexenone de-
rivatives 16 and 19 were also prepared (Scheme 3). Compounds
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Table 1. Preparation of enone-aldehydes 6–9 from 3-alkoxyenones 1–4.
Scheme 2. Preparation of enone-aldehydes 9 from cyclohept-2-en-1-one (10).
Addition of Grignard reagents 5a–c to 13 was performed in the
presence of copper(I) cyanide, and the resulting enolates were
trapped with TMSCl to form silyl enol ethers 17. These crude
[
13]
products were then subjected to Saegusa oxidation
to give
cyclohexenones 18a–c. Acidic conditions were again used to
hydrolyze the acetals, affording the desired products 19a–c in
excellent yields.
1
6a–c were prepared from 4,4-dimethylcyclohex-2-en-1-one
In order to extend the scope of the acyl radical cyclization,
(
13) by a synthetic pathway similar to that in Scheme 2. 1,2- indenone-aldehydes 23 were also prepared (Scheme 4). Treat-
[
14]
Addition of Grignard reagents 5a–c to 13 and subsequent ment of indenone (20)
with Grignard reagents 5b–c in the
oxidation with pyridinium chlorochromate resulted in enones presence of copper(I) cyanide, followed by oxidation with o-
1
5. Acetal hydrolysis under acidic conditions gave 6,6-dimethyl- iodoxybenzoic acid (IBX),[15] afforded enones 22. Hydrolysis of
cyclohexenones 16a–c. By an alternative route, 4,4-dimethyl- the acetal moiety with 1
cyclohexenone derivatives 19 were also prepared from 13. 1,4- hydes 23 in good yields.
M HCl in THF afforded indenone-alde-
Scheme 3. Preparation of gem-dimethylcyclohexenones from 4,4-dimethylcyclohex-2-en-1-one (13).
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Table 2. Conditions for attempted intramolecular acyl radical cyclization.
Scheme 4. Preparation of indenone-aldehydes 23 from indenone (20).
(
b) Intramolecular Acyl Radical Cyclization
Having obtained the enone-aldehydes, we first used 6b to ex-
plore the reaction conditions. Acyl radical generation from an
aldehyde can be accelerated by thiols, especially tertiary thiols,
[
7]
which give the best yields. Therefore, we first carried out this
reaction with 1 equiv. of azoisobutyronitrile (AIBN) in the pres-
ence of 0.3 equiv. of t-dodecanethiol in toluene at 75 °C. The
reaction mixture was stirred at this temperature for 19 h, after
which the reaction was still incomplete. An additional 1 equiv.
of AIBN was added, and the mixture was stirred at 75 °C for a
further 12 h. The desired product 24b was obtained in 38 %
yield. In order to improve the yield further, we increased the
amount of t-dodecanethiol, finding that 5 equiv. gave the best
yield of 71 % (Table 2, Entries 1–7). In the absence of t-dodec-
anethiol, the reaction was found to be sluggish and low-yield-
ing (Entry 8). When the reaction was attempted at higher or
lower concentrations, the yields also dropped (Entries 9–10).
The best yield was achieved when the reaction was carried out
in toluene at reflux, although a large amount of AIBN was re-
quired under these conditions (Entry 11). We reasoned that the
quantity of AIBN needed to drive the reaction to completion
was due to its poor thermal stability at higher temperatures
andsotriedtoimprovetheyieldbyreplacingAIBNwith1,1′-azobis-
[
1
a] An additional 1 equiv. of AIBN was added to the reaction mixture after
9 h and this addition was repeated every 12 h until enone-aldehyde was
completely consumed. [b] Based on recovery of starting material. [c] Recovery
of starting material. [d] A solution of AIBN in toluene was added to the reac-
tion mixture over 7 h by syringe pump.
Table 3. Intramolecular acyl radical cyclization in the presence of various thi-
ols.
(
cyclohexanecarbonitrile) (V-40), which is more stable at higher
temperatures, but at 75 °C and reflux the reactions were unsuc-
cessful (Entries 12–13). Alternatively, use of a syringe pump to
add 1 equiv. of AIBN to the reaction mixture over 7 h, with
various amount of t-dodecanethiol, either at 75 °C or at reflux,
also did not improve yields (Entries 14–23). Although the best
yield was observed with 5 equiv. of t-dodecanethiol and
[a] An additional 1 equiv. of AIBN was added to the reaction mixture after
19 h and this addition was repeated every 12 h until enone-aldehyde was
completely consumed.
7
equiv. of AIBN in toluene at reflux (Entry 11), the amount of
AIBN used was considerable. Thus, in subsequent syntheses of
other enone-aldehyde substrates, we used 5 equiv. of t-do- of four-membered rings in these substrates was difficult: the
decanethiol and 2 equiv. of AIBN at 75 °C in toluene (Entry 6).
desired spiro[3.5]nonane and spiro[3.4]octane skeletons could
Other thiols were also tested under the optimized condi- not be obtained, with only complex mixtures being produced
tions, but the yields were lower (Table 3, Entries 2–5). Tertiary (Entries 1, 4, 7, 10, and 13). However, in the case of the seven-
thiols afforded the best yields in the reaction, probably due to membered-ring enone with a three-carbon side chain, the de-
their ability to prevent hemithioacetal formation from alde- sired spiro[3.6]decane was obtained in 36 % yield (Entry 16).
[
7a]
hydes and conjugate addition to the α,β-unsaturated ketone.
Spiro[3.5]nonane and spiro[3.4]octane skeletons were not ob-
With optimized conditions in hand, other enone-aldehydes served, presumably because of ring strain. Substrates with
were subjected to them. In most cases the desired products geminal dimethyl systems at the γ-position gave slightly lower
were obtained in moderate to good yields (Table 4). Formation yields (Entries 11 and 12). This was probably due to steric hin-
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Table 4. Intramolecular acyl radical cyclization.
[
a] Complex mixtures of products.
drance between the geminal dimethyl system and the acyl radi-
cal side chain in the cyclization. In contrast to simple aliphatic
enone-aldehydes, indenone-aldehydes gave poor yields under
the same conditions (Entries 19 and 20).
The structures of 24–30 were characterized by IR, H and 13C
NMR, and low- and high-resolution mass spectrometry. For
spiro compounds containing cyclopentanone rings, carbonyl
absorptions were observed around 1740 cm–1 in the IR spectra.
For 29a, carbonyl absorption in the four-membered ring was
1
–1
observed at 1780 cm .
(
c) Reaction Mechanism
A plausible mechanism for the formation of a spirocyclic 1,4-
[
16]
diketone from an enone-aldehyde is depicted in Scheme 5.
Firstly, a thiyl radical could be generated by the reaction be-
tween the thiol and AIBN. The thiyl radical could then react
Scheme 5. A plausible reaction mechanism.
592 © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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with 6b to form acyl radical A, with subsequent cyclization to H), 2.40 (t, J = 7.3 Hz, 2 H), 2.26–2.12 (m, 6 H), 1.90–1.85 (m, 2 H),
1
1
2
1
.75–1.68 (m, 2 H) ppm. 13C NMR (100 MHz, CDCl ): δ = 201.4, 199.6,
form intermediate B. Hydrogen abstraction from thiol could
then give the desired product 24b. Large quantities of reagents
are used in this reaction, probably due to the steric hindrance
between the β-disubstituted double bond and the acyl radical
in cyclization. The generation of the spiro atom by 1,4-addition
of the acyl radical to the β-disubstituted enone is slow. Conse-
quently, use of excess reagents helped the reaction to proceed
to completion.
3
65.1, 125.6, 42.7, 37.0, 36.8, 29.2, 22.3, 18.9 ppm. IR (neat): ν˜ =
–
1
+
941, 2871, 1721, 1665, 1624 cm . MS (EI): m/z (%) = 166 (4) [M] ,
38 (21), 123 (22), 110 (70), 95 (12), 82 (100). HRMS (EI) calcd. for
C H O 166.0994; found 166.0999.
10 14 2
5
(
-(3-Oxocyclohex-1-enyl)pentanal (6c): Yellowish oil. 1H NMR
400 MHz, CDCl ): δ = 9.75 (m, 1 H), 5.84 (br. s, 1 H), 2.46 (t, J =
3
7.2 Hz, 2 H), 2.36–2.21 (m, 6 H), 2.00–1.94 (m, 2 H), 1.65–1.59 (m, 2
13
H), 1.56–1.48 (m, 2 H) ppm. C NMR (100 MHz, CDCl ): δ = 202.1,
3
2
00.0, 165.8, 126.0, 43.7, 37.9, 37.5, 29.8, 26.5, 22.9, 21.7 ppm. IR
–
1
(
(
neat): ν˜ = 2943, 2868, 2726, 1721, 1659, 1414 cm . MS (EI): m/z
Conclusions
+
%) = 180 (2) [M] , 152 (21), 123 (75), 110 (53), 95 (56), 82 (100).
HRMS (EI) calcd. for C H O 180.1150; found 180.1152.
11 16 2
In summary, we have developed a general method for the prep-
aration of various all-carbon spirocyclic 1,4-diketones through 3-(5,5-Dimethyl-3-oxocyclohex-1-enyl)propanal (7a):
[
19]
Yellow-
1
ish oil. H NMR (400 MHz, CDCl ): δ = 9.78 (br. s, 1 H), 5.81 (s, 1 H),
an acyl radical cyclization. Although intramolecular acyl radical
cyclization is well-known, use of this methodology to generate
a quaternary carbon center is rare. The ring sizes of the spiro
compounds are easily controlled either by using different cyclic
enones or by altering the length of the side chain. The applica-
tion of this efficient method to the preparation of heteroatomic
spirocyclic 1,4-diketones and natural product synthesis is cur-
rently under investigation.
3
2
(
.67 (t, J = 7.3 Hz, 2 H), 2.48 (t, J = 7.3 Hz, 2 H), 2.19 (s, 2 H), 2.17
s, 2 H), 1.01 (s, 6 H) ppm. 13C NMR (100 MHz, CDCl ): δ = 200.1,
3
199.6, 161.3, 124.5, 50.9, 44.1, 40.6, 33.5, 29.6, 28.1 ppm. IR (neat):
ν˜ = 2958, 2869, 2818, 2721, 1723, 1665, 1360, 1299, 1280, 1248,
–1
+
1
196, 1138, 902 cm . MS (EI): m/z (%) = 180 (2) [M] , 101 (12), 83
(13), 73 (12), 59 (47), 58 (100), 57 (12). HRMS (EI) calcd. for C H O
1
1 16 2
180.1150; found 180.1153.
4
-(5,5-Dimethyl-3-oxocyclohex-1-enyl)butanal (7b): Yellowish oil.
1
H NMR (400 MHz, CDCl ): δ = 9.78 (br. s, 1 H), 5.86 (br. s, 1 H), 2.49
3
(
1
t, J = 7.2 Hz, 2 H), 2.22–2.17 (m, 2 H), 2.21 (s, 2 H), 2.16 (s, 2 H),
.86–1.79 (m, 2 H), 1.02 (s, 6 H) ppm. C NMR (100 MHz, CDCl3):
Experimental Section
13
δ = 201.3, 199.8, 162.4, 125.0, 51.0, 43.8, 43.0, 37.0, 33.6, 28.2,
General Information: Unless stated otherwise, reagents were ob-
tained from commercial sources and used without further purifica-
tion. All reactions were performed under nitrogen in anhydrous sol-
vents, which were dried prior to use by standard procedures. Reac-
tions were monitored by thin-layer chromatography with 0.25 mm
E. Merck silica gel plates (60F-254) and ethanolic phosphomolybdic
acid (7 %) as developing agent. Merck silica gel 60 (particle size
1
1
9.1 ppm. IR (neat): ν˜ = 2956, 2870, 2723, 1723, 1666, 1628, 1596,
–1 +
369, 1247, 903 cm . MS (EI): m/z (%) = 194 (5) [M] , 177 (22), 151
(33), 138 (21), 125 (21), 112 (56), 97 (28), 83 (100). HRMS (EI) calcd.
for C H O 194.1307; found 194.1311.
12 18
2
5-(5,5-Dimethyl-3-oxocyclohex-1-enyl)pentanal (7c): Yellowish
1
oil. H NMR (400 MHz, CDCl ): δ = 9.76 (t, J = 1.4 Hz, 1 H), 5.86 (br.
3
0
.04–0.063 mm) was employed for flash chromatography. Melting s, 1 H), 2.47 (dt, J = 7.2, 1.4 Hz, 2 H), 2.22–2.17 (m, 2 H), 2.20 (s, 2
points are uncorrected. IR spectra were recorded as films on KBr
H), 2.16 (s, 2 H), 1.66–1.62 (m, 2 H), 1.54–1.50 (m, 2 H), 1.02 (s, 6
plates. 1H NMR spectra were obtained in CDCl unless otherwise
13
3
H) ppm. C NMR (100 MHz, CDCl ): δ = 201.9, 200.0, 163.1, 124.8,
3
13
noted, at 400 MHz. C NMR spectra were obtained at 100 MHz.
Chemical shifts are reported in δ (ppm) with the solvent resonance
as the internal reference.
51.0, 43.8, 43.5, 37.7, 33.6, 28.2, 26.2, 21.6 ppm. IR (neat): ν = 2941,
˜
–
1
+
2869, 2729, 1723, 1664, 1194 cm . MS (EI): m/z (%) = 208 (3) [M] ,
191 (20), 165 (19), 151 (100), 138 (18), 121 (17), 109 (19), 95 (28), 82
(
74). HRMS (EI) calcd. for C H O 208.1463; found 208.1462.
13 20 2
General Procedure for Preparation of Enone-Aldehydes: The ap-
propriate 3-alkoxyenone (2.1 mmol) was added at room tempera- 3-(3-Oxocyclopent-1-enyl)propanal (8a): Yellowish oil. 1H NMR
ture to a stirred solution of the appropriate Grignard reagent
2.5 mmol) in THF (5 mL). The mixture was stirred at room tempera-
ture for another 5 h and then quenched with HCl (1 , 5 mL) at
°C and stirred at room temperature for 5 h. The aqueous layer
was extracted with EtOAc. The combined extracts were washed
(400 MHz, CDCl ): δ = 9.79 (br. s, 1 H), 5.87 (s, 1 H), 2.77 (t, J =
3
(
6.9 Hz, 2 H), 2.68 (t, J = 6.9 Hz, 2 H), 2.57 (t, J = 3.7 Hz, 2 H), 2.38–
2.35 (m, 2 H) ppm. 13C NMR (100 MHz, CDCl ): δ = 209.5, 199.9,
M
3
0
180.3, 129.4, 40.8, 35.1, 31.6, 25.4 ppm. IR (neat): ν = 2923, 2842,
˜
–
1
2726, 1705, 1675, 1612, 1439, 1280, 1191, 1112, 1051 cm . MS (EI):
+
with brine, dried with MgSO , filtered, and concentrated. The crude m/z (%) = 138 (3) [M] , 110 (100), 109 (21), 81 (46), 67 (30), 53 (27).
4
product was purified by silica gel chromatography with EtOAc/hex-
HRMS (EI) calcd. for C H O 138.0681; found 138.0681.
8 10 2
anes as the eluent to furnish the enone-aldehydes 6–8 and 9b.
4
-(3-Oxocyclopent-1-enyl)butanal (8b): Yellowish oil. 1H NMR
-(3-Oxocyclohex-1-enyl)propanal (6a):[17] Yellowish oil. H NMR
1
3
(400 MHz, CDCl ): δ = 9.79 (br. s, 1 H), 5.95 (t, J = 1.3 Hz, 1 H), 2.58–
3
(
7
400 MHz, CDCl ): δ = 9.81 (br. s, 1 H), 5.82 (br. s, 1 H), 2.69 (t, J =
2.54 (m, 2 H), 2.53 (t, J = 7.2 Hz, 2 H), 2.45–2.39 (m, 4 H), 1.95–1.89
3
(m, 2 H) ppm. 13C NMR (100 MHz, CDCl ): δ = 209.7, 201.2, 181.2,
.4 Hz, 2 H), 2.53 (t, J = 7.4 Hz, 2 H), 2.36 (t, J = 6.0 Hz, 2 H), 2.30 (t,
3
1
3
J = 6.0 Hz, 2 H), 2.03–1.98 (m, 2 H) ppm. C NMR (100 MHz, CDCl3):
δ = 200.1, 199.4, 163.7, 125.6, 40.7, 37.2, 29.9, 29.6, 22.5 ppm. IR
129.8, 43.1, 35.2, 32.6, 31.4, 19.3 ppm. IR (neat): ν = 2925, 2729,
˜
–
1
+
1704, 1673, 1613, 1186, 842 cm . MS (EI): m/z (%) = 152 (5) [M] ,
(
8
neat): ν˜ = 2949, 2825, 2730, 1723, 1665, 1625, 1254, 1193, 150 (12), 138 (48), 124 (34), 109 (100), 96 (92), 81 (60), 67 (54), 55
–1
+
90 cm . MS (EI): m/z (%) = 152 (45) [M] , 124 (58), 110 (41), 96
(91). HRMS (EI) calcd. for C H O 152.0837; found 152.0843.
9
12 2
(
1
56), 82 (100), 67 (50). HRMS (EI) calcd. for C H O 152.0837; found
52.0839.
-(3-Oxocyclohex-1-enyl)butanal (6b):[18] Yellowish oil. 1H NMR
-(3-Oxocyclopent-1-enyl)pentanal (8c): Yellowish oil. 1H NMR
400 MHz, CDCl ): δ = 9.79 (t, J = 1.4 Hz, 1 H), 5.96 (br. s, 1 H), 2.59–
2.57 (m, 2 H), 2.50 (dt, J = 6.3, 1.4 Hz, 2 H), 2.43–2.39 (m, 4 H), 1.69–
9
12 2
5
(
3
4
(
400 MHz, CDCl ): δ = 9.66 (t, J = 1.3 Hz, 1 H), 5.75 (t, J = 1.2 Hz, 1 1.64 (m, 4 H) ppm. 13C NMR (100 MHz, CDCl ): δ = 209.9, 201.8,
3
3
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1
2
1
81.9, 129.6, 43.5, 35.3, 33.2, 31.5, 26.5, 21.7 ppm. IR (neat): ν˜ = 10.0 Hz, 1 H), 5.45 (d, J = 10.0 Hz, 1 H), 4.86 (t, J = 4.7 Hz, 1 H),
–
1
930, 1727, 1657, 1600, 1408, 1281, 1180 cm . MS (EI): m/z (%) = 3.98–3.84 (m, 4 H), 1.68–1.47 (m, 10 H), 1.01 (s, 3 H), 0.94 (s, 3
+
13
66 (0.8) [M] , 148 (3), 138 (23), 122 (11), 109 (100), 96 (62), 81 (28).
H) ppm. C NMR (100 MHz, CDCl ): δ = 139.9, 129.9, 104.4, 69.6,
3
HRMS (EI) calcd. for C H O 166.0994; found 166.0986.
64.7, 41.8, 34.2, 33.5, 32.3, 31.8, 29.8, 27.7, 18.2 ppm. IR (neat): ν˜ =
1
0 14 2
–1
-(3-Oxocyclohept-1-enyl)butanal (9b): Yellowish oil. 1H NMR
400 MHz, CDCl ): δ = 9.78 (br. s, 1 H), 5.90 (br. s, 1 H), 2.58 (t, J =
3450, 2951, 2871, 1204, 1139, 1051, 1027, 938, 905, 793 cm . MS
4
(
+
(
EI): m/z (%) = 240 (2) [M] , 223 (48), 126 (34), 125 (100), 88 (41), 73
3
(
92), 59 (29), 58 (38). HRMS (EI) calcd. for C H O 240.1725; found
1
4 24 3
6
.2 Hz, 2 H), 2.49 (t, J = 7.5 Hz, 2 H), 2.41 (t, J = 5.8 Hz, 2 H), 2.22 (t,
1
3
240.1725.
J = 7.5 Hz, 2 H), 1.85–1.58 (m, 6 H) ppm. C NMR (100 MHz, CDCl3):
δ = 203.9, 201.5, 160.5, 129.8, 43.1, 42.2, 40.1, 32.5, 25.1, 21.2,
1
(
-[4-(1,3-Dioxolan-2-yl)butyl]-4,4-dimethylcyclohex-2-enol
1
1
9.8 ppm. IR (neat): ν˜ = 2936, 2867, 2724, 1722, 1658, 1451,
14c): Yellowish oil. 1H NMR (400 MHz, CDCl ): δ = 5.42 (d, J =
3
–
1
+
267 cm . MS (EI): m/z (%) = 180 (24) [M] , 152 (19), 137 (19), 124
10.0 Hz, 1 H), 5.38 (d, J = 10.0 Hz, 1 H), 4.79 (t, J = 4.7 Hz, 1 H),
(34), 109 (51), 98 (100), 81 (64), 55 (76). HRMS (EI) calcd. for C H O
11 16 2
3.92–3.76 (m, 4 H), 1.80 (br. s, 1 H), 1.71–1.31 (m, 12 H), 0.95 (s, 3
1
80.1150; found 180.1158.
13
H), 0.89 (s, 3 H) ppm. C NMR (100 MHz, CDCl ): δ = 139.7, 130.1,
3
General Procedure for 1,2-Addition of Grignard Reagents: The
104.4, 69.5, 64.7, 41.9, 33.7, 33.5, 32.3, 31.8, 29.8, 27.7, 24.5,
appropriate cyclic enone (1.8 mmol) was added at room tempera- 23.4 ppm. IR (neat): ν˜ = 3458, 2947, 2865, 1464, 1408, 1361, 1228,
–
1
+
ture to a stirred solution of the appropriate Grignard reagent
2.5 mmol) in THF (5 mL). The mixture was stirred at room tempera-
1140, 1032, 945, 906, 853, 772 cm . MS (EI): m/z (%) = 254 (3) [M] ,
(
148 (58), 125 (42), 99 (38), 73 (75), 59 (43), 58 (100). HRMS (EI) calcd.
ture for 4 h and then quenched with water and extracted with
EtOAc. The combined extracts were washed with brine, dried with
for C15
H O 254.1882; found 254.1881.
26 3
3
-(3-Oxocyclohept-1-enyl)propanal (9a): Compound 11a
MgSO , filtered, and concentrated. The crude product was purified
4
(300 mg, 1.41 mmol) was added at room temperature to a stirred
by silica gel chromatography with EtOAc/hexanes as the eluent to
furnish adducts 11 or 14.
mixture of PCC (609 mmg, 2.82 mmol) and celite (1.22 g) in CH Cl
2
2
(10 mL). After having been stirred at room temperature for 2 h, the
1
-[2-(1,3-Dioxolan-2-yl)ethyl]cyclohept-2-enol (11a): Yellowish
reaction mixture was diluted with Et O (20 mL) and filtered through
2
1
oil. H NMR (400 MHz, CDCl ): δ = 5.72–5.66 (m, 1 H), 5.59 (d, J =
3
a pad of celite. The filtrate was concentrated, the crude product
was dissolved in acetone (114 mL), and PdCl (CH CN) (36.6 mg,
1
1.9 Hz, 1 H), 4.89 (t, J = 4.3 Hz, 1 H), 3.99–3.83 (m, 4 H), 2.17–2.02
2
3
2
1
3
(m, 3 H), 1.85–1.58 (m, 10 H) ppm. C NMR (100 MHz, CDCl ): δ =
3
0.14 mmol) was added. The mixture was stirred at room tempera-
ture for 5 h and then filtered through a pad of celite. The filtrate
was concentrated, and the crude product was dissolved in water
and extracted with CH Cl . The combined extracts were washed
1
38.9, 129.8, 104.6, 75.3, 64.8, 38.6, 34.5, 27.9, 27.5, 27.3, 24.1 ppm.
IR (neat): ν˜ = 3453, 2927, 2862, 1450, 1408, 1140, 1103, 1035, 956,
–
1
+
9
9
2
39, 796, 751, 691 cm . MS (EI): m/z (%) = 212 (2) [M] , 111 (46),
2
2
9 (60), 93 (34), 79 (39), 73 (100). HRMS (EI) calcd. for C H O
12.1412; found 212.1414.
12
20
3
with brine, dried with MgSO , filtered, and concentrated. The crude
4
product was purified by silica gel chromatography (EtOAc/hexanes
1
1
:2) to furnish 9a (148 mg, 63 %) as a yellowish oil. H NMR
1
-[3-(1,3-Dioxolan-2-yl)propyl]cyclohept-2-enol (11b): Colorless
1
(400 MHz, CDCl ): δ = 9.80 (br. s, 1 H), 5.87 (s, 1 H), 2.66 (t, J =
oil. H NMR (400 MHz, CDCl ): δ = 5.70 (dt, J = 12.0, 5.8 Hz, 1 H),
3
3
7
.3 Hz, 2 H), 2.57 (t, J = 6.2 Hz, 2 H), 2.53 (t, J = 7.3 Hz, 2 H), 2.43 (t,
5
.59 (d, J = 12.0 Hz, 1 H), 4.86 (t, J = 4.7 Hz, 1 H), 3.94–3.82 (m, 4
13
1
3
J = 6.2 Hz, 2 H), 1.82–1.77 (m, 4 H) ppm. C NMR (100 MHz, CDCl3):
δ = 203.7, 200.4, 159.3, 129.1, 42.0, 41.3, 32.7, 32.4, 24.9, 21.0 ppm.
IR (neat): ν˜ = 2934, 2866, 2728, 1723, 1653, 1452, 1418, 1344, 1267,
H), 2.20–2.01 (m, 2 H), 1.85–1.53 (m, 12 H) ppm. C NMR (100 MHz,
CDCl ): δ = 138.9, 130.2, 104.6, 76.0, 64.8, 41.2, 38.5, 34.3, 27.6, 27.4,
3
2
1
4.0, 18.1 ppm. IR (neat): ν˜ = 3465, 2925, 2878, 1454, 1409, 1141,
–
1
+
–
1
+
1183, 1056, 879 cm . MS (EI): m/z (%) = 166 (10) [M] , 167 (100),
104, 1045, 941 cm . MS (EI): m/z (%) = 226 (0.3) [M] , 164 (4), 136
124 (76), 111 (57), 98 (75), 81 (53), 55 (66). HRMS (EI) calcd. for
(
4), 111 (100), 88 (23), 73 (76). HRMS (EI) calcd. for C H O
13 22 3
C H O 166.0994; found 166.0992.
10 14 2
2
26.1569; found 226.1571.
-[4-(1,3-Dioxolan-2-yl)butyl]cyclohept-2-enol (11c): Colorless
1
General Procedure for PCC Oxidation and Acetal Hydrolysis: The
oil. H NMR (400 MHz, CDCl ): δ = 5.67 (dt, J = 12.0, 5.7 Hz, 1 H), appropriate compound 11 or 14 (2.20 mmol) was added at room
1
3
5
.58 (d, J = 12.0 Hz, 1 H), 4.84 (t, J = 4.8 Hz, 1 H), 3.97–3.82 (m, 4
temperature to a stirred mixture of PCC (4.40 mmol) and celite
H), 2.23–2.03 (m, 2 H), 1.74–1.44 (m, 12 H), 1.43–1.41 (m, 2 H) ppm. (2.0 g) in CH Cl (20 mL). After having been stirred at room temper-
2
2
13
C NMR (100 MHz, CDCl ): δ = 139.0, 130.0, 104.6, 76.0, 64.8, 41.2,
ature for 2 h, the reaction mixture was diluted with Et O (20 mL)
2
3
3
2
8.6, 33.8, 27.6, 27.4, 24.6, 24.1, 23.4 ppm. IR (neat): ν˜ = 3482, 2926, and filtered through a pad of celite. The filtrate was concentrated,
–1
860, 1456, 1407, 1140, 1032, 944 cm . MS (EI): m/z (%) = 240 (2)
the crude product was dissolved in THF (20 mL), and HCl (1 M,
+
[M] , 239 (8), 178 (3), 155 (17), 111 (17), 99 (20), 73 (100). HRMS (EI)
20 mL) was added. The mixture was stirred at room temperature
for 4 h. The aqueous layer was extracted with EtOAc. The combined
calcd. for C H O 240.1725; found 240.1725.
14 24 3
extracts were washed with brine, dried with MgSO , filtered, and
1
-[2-(1,3-Dioxolan-2-yl)ethyl]-4,4-dimethylcyclohex-2-enol
4
1
concentrated. The crude product was purified by silica gel chroma-
tography with EtOAc/hexanes as the eluent to furnish the enone-
aldehydes 9 or 16.
(14a): Yellowish oil. H NMR (400 MHz, CDCl ): δ = 5.46 (d, J =
3
1
0.0 Hz, 1 H), 5.42 (d, J = 10.0 Hz, 1 H), 4.86 (t, J = 4.5 Hz, 1 H),
3
.96–3.81 (m, 4 H), 2.02 (br. s, 1 H), 1.79–1.54 (m, 6 H), 1.43–1.39 (m,
1
3
1
H), 0.98 (s, 3 H), 0.91 (s, 3 H) ppm. C NMR (100 MHz, CDCl ): δ =
1
3
5
-(3-Oxocyclohept-1-enyl)pentanal (9c): Colorless oil. H NMR
1
2
1
40.0, 129.8, 104.6, 69.0, 64.8, 35.7, 33.5, 32.5, 31.9, 29.8, 28.0,
7.7 ppm. IR (neat): ν˜ = 3460, 2951, 2871, 1460, 1405, 1235, 1202,
(
400 MHz, CDCl ): δ = 9.76 (t, J = 1.4 Hz, 1 H), 5.89 (br. s, 1 H), 2.56
3
(t, J = 5.8 Hz, 2 H), 2.46 (dt, J = 7.2, 1.4 Hz, 2 H), 2.39 (t, J = 5.8 Hz,
–1
+
140, 1030 cm . MS (EI): m/z (%) = 226 (1) [M] , 209 (30), 125 (100),
2
1
1
H), 2.20 (t, J = 7.3 Hz, 2 H), 1.79–1.77 (m, 4 H), 1.65–1.59 (m, 2 H),
7
3 (27), 59 (40), 58 (25). HRMS (EI) calcd. for C H O 226.1569;
13
1
3 22 3
.55–1.49 (m, 2 H) ppm. C NMR (100 MHz, CDCl ): δ = 204.0, 202.0,
3
found 226.1570.
61.3, 129.4, 43.5, 42.1, 40.6, 32.5, 27.0, 25.1, 21.6, 21.2 ppm. IR
–
1
1
-[3-(1,3-Dioxolan-2-yl)propyl]-4,4-dimethylcyclohex-2-enol (neat): ν˜ = 2936, 2865, 2722, 1724, 1656, 1458, 1266 cm . MS (EI):
1
+
(14b): Yellowish oil. H NMR (400 MHz, CDCl ): δ = 5.50 (d, J =
m/z (%) = 194 (18) [M] , 166 (12), 150 (16), 137 (41), 124 (38), 109
3
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(
100), 98 (38), 81 (52), 67 (49). HRMS (EI) calcd. for C12H18O2 H), 1.13 (s, 6 H) ppm. 13C NMR (100 MHz, CDCl ): δ = 199.4, 172.1,
3
1
94.1307; found 194.1306.
124.3, 104.0, 64.8, 37.8, 35.5, 34.2, 33.3, 31.6, 26.3, 21.5 ppm. IR
(
neat): ν˜ = 2958, 2926, 2873, 1732, 1667, 1612, 1466, 1415, 1275,
3
-(4,4-Dimethyl-3-oxocyclohex-1-enyl)propanal (16a): Yellowish
–
1
+
1
1
2
242, 1139, 1031, 945, 865 cm . MS (EI): m/z (%) = 238 (6) [M] ,
1
oil. H NMR (400 MHz, CDCl ): δ = 9.82 (br. s, 1 H), 5.74 (t, J = 1.3 Hz,
3
38 (20), 112 (18), 99 (39), 73 (100). HRMS (EI) calcd. for C H O
1
4 22 3
1
5
H), 2.70 (t, J = 7.2 Hz, 2 H), 2.52 (t, J = 7.2 Hz, 2 H), 2.33 (t, J =
38.1569; found 238.1566.
.9 Hz, 2 H), 1.82 (t, J = 5.9 Hz, 2 H), 1.09 (s, 6 H) ppm. 13C NMR
(
2
1
100 MHz, CDCl ): δ = 204.3, 200.3, 161.4, 124.1, 40.8, 40.4, 36.2,
3
3-[4-(1,3-Dioxolan-2-yl)butyl]-4,4-dimethylcyclohex-2-en-1-one
9.2, 27.3, 24.1 ppm. IR (neat): ν˜ = 2964, 2924, 2726, 1722, 1665,
1
(
18c): Yellowish oil. H NMR (400 MHz, CDCl ): δ = 5.78 (s, 1 H), 4.85
3
–
1
460, 1378, 1310, 1217, 1166, 881 cm . MS (EI): m/z (%) = 180 (5)
(t, J = 4.7 Hz, 1 H), 3.96–3.83 (m, 4 H), 2.43 (t, J = 6.7 Hz, 2 H), 2.20
+
[M] , 140 (87), 112 (100), 96 (34), 95 (41), 82 (31). HRMS (EI) calcd.
(
t, J = 7.1 Hz, 2 H), 1.84 (t, J = 6.8 Hz, 2 H), 1.71–1.66 (m, 2 H), 1.62–
for C H O 180.1150; found 180.1147.
13
11
16
2
1.45 (m, 4 H), 1.15 (s, 6 H) ppm. C NMR (100 MHz, CDCl ): δ =
3
1
99.4, 172.4, 124.2, 104.3, 64.8, 37.8, 35.5, 34.2, 33.5, 31.7, 27.3, 26.3,
4
-(4,4-Dimethyl-3-oxocyclohex-1-enyl)butanal (16b): Yellowish
1
23.8 ppm. IR (neat): ν = 2943, 2871, 1731, 1663, 1466, 1418, 1242,
1
oil. H NMR (400 MHz, CDCl ): δ = 9.77 (t, J = 1.3 Hz, 1 H), 5.75 (t,
˜
3
–
1
+
197, 1030, 947 cm . MS (EI): m/z (%) = 252 (2) [M] , 151 (59), 124
J = 1.2 Hz, 1 H), 2.48 (dt, J = 7.5, 1.3 Hz, 2 H), 2.29 (t, J = 5.6 Hz, 2
H), 2.21 (t, J = 7.6 Hz, 2 H), 1.86–1.78 (m, 4 H), 1.08 (s, 6 H) ppm.
(51), 109 (29), 99 (26), 95 (25), 73 (100). HRMS (EI) calcd. for C H O
15 24
3
13
252.1725; found 252.1724.
C NMR (100 MHz, CDCl ): δ = 204.4, 201.4, 162.5, 124.4, 42.9 40.3,
3
3
1
6.6, 36.1, 26.8, 24.0, 19.1 ppm. IR (neat): ν˜ = 2958, 2926, 2871, 2722,
General Procedure for Acetal Hydrolysis: HCl (1
M
, 10 mL) was
–
1
723, 1667, 1453, 1381, 1310, 1209, 1166, 1122, 877 cm . MS (EI):
added to a stirred solution of the appropriate acetal (0.6 mmol) in
THF (10 mL). The mixture was stirred at room temperature for 5 h.
The aqueous layer was extracted with EtOAc. The combined ex-
+
m/z (%) = 194 (27) [M] , 110 (38), 97 (59), 95 (35), 82 (100), 69 (35),
6
7 (35). HRMS (EI) calcd. for C H O 194.1307; found 194.1307.
12 18 2
5
-(4,4-Dimethyl-3-oxocyclohex-1-enyl)pentanal (16c): Yellowish
tracts were washed with saturated aqueous NaHCO
3
and brine,
1
oil. H NMR (400 MHz, CDCl ): δ = 9.75 (t, J = 1.4 Hz, 1 H), 5.74 (s,
1
J = 7.4 Hz, 2 H), 1.79 (t, J = 6.1 Hz, 2 H), 1.66–1.48 (m, 4 H), 1.07 (s,
6
dried with MgSO , filtered, and concentrated. The crude product
4
3
H), 2.46 (dt, J = 7.0, 1.4 Hz, 2 H), 2.28 (t, J = 6.0 Hz, 2 H), 2.19 (t,
was purified by silica gel chromatography with EtOAc/hexanes as
the eluent to furnish the enone-aldehydes 19 or 23.
H) ppm. 13C NMR (100 MHz, CDCl ): δ = 204.5, 201.9, 163.2, 124.2,
3
3
-(6,6-Dimethyl-3-oxocyclohex-1-enyl)propanal (19a): Yellowish
4
3.4, 40.3, 37.2, 36.2, 26.9, 26.3, 24.1, 21.5 ppm. IR (neat): ν˜ = 2927,
1
oil. H NMR (400 MHz, CDCl ): δ = 9.76 (br. s, 1 H), 5.61 (s, 1 H), 2.64
3
2
865, 2720, 1721, 1667, 1454, 1423, 1382, 1311, 1212, 1167, 1123,
(
1
t, J = 7.2 Hz, 2 H), 2.49 (t, J = 7.2 Hz, 2 H), 2.37 (t, J = 6.8 Hz, 2 H),
–1
+
7
90 cm . MS (EI): m/z (%) = 208 (3) [M] , 101 (36), 82 (100), 69 (43),
.80 (t, J = 6.8 Hz, 2 H), 1.14 (s, 6 H) ppm. 13C NMR (100 MHz, CDCl3):
6
7 (36), 59 (60), 55 (32). HRMS (EI) calcd. for C H O 208.1463;
1
3 20 2
δ = 200.3, 199.1, 170.2, 123.9, 40.8, 37.6, 35.6, 34.0, 26.2, 23.6 ppm.
found 208.1461.
IR (neat): ν˜ = 2961, 2927, 2873, 2723, 1716, 1665, 1613, 1120, 1164,
–
1
+
General Procedure for 1,4-Addition and Saegusa Oxidation: A
solution of Grignard reagent (4.0 mmol) in THF (8 mL) was added
at –20 °C under Ar to a suspension of copper(I) cyanide (0.8 mmol)
in THF (1 mL). After the mixture had been stirred at –20 °C for
1115, 1056, 991, 787 cm . MS (EI): m/z (%) = 180 (25) [M] , 142
(70), 124 (47), 95 (63), 85 (73), 71 (62), 58 (100). HRMS (EI) calcd. for
C H O 180.1150; found 180.1153.
11 16 2
4
-(6,6-Dimethyl-3-oxocyclohex-1-enyl)butanal (19b): Yellowish
4
0 min, HMPA (4.0 mmol) was added, and the mixture was stirred
1
oil. H NMR (400 MHz, CDCl ): δ = 9.78 (t, J = 1.2 Hz, 1 H), 5.78 (s,
3
for another 10 min. TMSCl (8.0 mmol) and 4,4-dimethylcyclohex-2-
en-1-one (13, 2.0 mmol) were added, the mixture was stirred at
1
H), 2.52 (t, J = 7.0 Hz, 2 H), 2.44 (dt, J = 6.9, 1.2 Hz, 2 H), 2.23 (t,
1
3
J = 7.7 Hz, 2 H), 1.87–1.81 (m, 4 H), 1.16 (s, 6 H) ppm. C NMR
100 MHz, CDCl ): δ = 201.5, 199.4, 171.3, 124.5, 43.2, 37.8, 35.6,
–20 °C for 30 min, Et N (8.0 mmol) was then added, and the mixture
3
(
3
was stirred at –20 °C for 2 h, quenched with saturated aqueous
NaHCO , and extracted with EtOAc. The combined extracts were
washed with brine, dried with MgSO , filtered, and concentrated to
give the crude product. The crude product was then dissolved in
CH CN (14 mL), and Pd(OAc) (2.4 mmol) was added to the solution.
3
1
1
4.2, 31.0, 26.4, 19.7 ppm. IR (neat): ν˜ = 2963, 2873, 2726, 1716,
3
–1
658, 1469, 1413, 1279, 1243, 1200, 1164 cm . MS (EI): m/z (%) =
4
+
94 (14) [M] , 140 (16), 138 (23), 97 (31), 58 (100). HRMS (EI) calcd.
for C H O 194.1307; found 194.1304.
12 18 2
3
2
The mixture was stirred at room temperature for 4 h, filtered
through a pad of celite, and washed with EtOAc. The filtrate was
concentrated to give the residue and purified by silica gel chroma-
tography with EtOAc/hexanes as the eluent to furnish cyclohex-2-
en-1-ones 18.
5
-(6,6-Dimethyl-3-oxocyclohex-1-enyl)pentanal (19c): Yellowish
1
oil. H NMR (400 MHz, CDCl ): δ = 9.74 (t, J = 1.4 Hz, 1 H), 5.73 (s,
1
J = 7.6 Hz, 2 H), 1.81 (t, J = 6.6 Hz, 2 H), 1.67–1.61 (m, 2 H), 1.51–
3
H), 2.45 (dt, J = 7.1, 1.4 Hz, 2 H), 2.40 (t, J = 6.6 Hz, 2 H), 2.19 (t,
13
1
2
.47 (m, 2 H), 1.13 (s, 6 H) ppm. C NMR (100 MHz, CDCl ): δ =
02.0, 199.5, 172.0, 124.2, 43.6, 37.8, 35.6, 34.1, 31.5, 26.8, 26.3,
3
3
-[2-(1,3-Dioxolan-2-yl)ethyl]-4,4-dimethylcyclohex-2-en-1-one
1
21.7 ppm. IR (neat): ν = 2940, 2869, 2722, 1725, 1667, 1612, 1467,
(18a): Yellowish oil. H NMR (400 MHz, CDCl ): δ = 5.70 (s, 1 H), 4.84
˜
3
–1
+
1415, 1243, 1198 cm . MS (EI): m/z (%) = 208 (8) [M] , 109 (31), 69
(
(
(
t, J = 4.6 Hz, 1 H), 3.91–3.77 (m, 4 H), 2.36 (t, J = 6.9 Hz, 2 H), 2.27
t, J = 8.1 Hz, 2 H), 1.80–1.73 (m, 4 H), 1.11 (s, 6 H) ppm. 13C NMR
(34), 67 (33), 58 (100). HRMS (EI) calcd. for C H O 208.1463; found
13 20
2
208.1462.
100 MHz, CDCl ): δ = 199.2, 171.6, 124.0, 103.4, 64.8, 37.7, 35.6,
3
3
1
4.1, 31.4, 26.2, 25.7 ppm. IR (neat): ν˜ = 2958, 2885, 1670, 1613,
1
4
(
(
-(1-Oxo-1H-inden-3-yl)butanal (23b): Yellowish oil. H NMR
–1
473, 1419, 1330, 1277, 1242, 1201, 1141, 1028, 945, 902 cm . MS
400 MHz, CDCl ): δ = 9.82 (br. s, 1 H), 7.40 (d, J = 7.2 Hz, 1 H), 7.36
dd, J = 7.2, 7.2 Hz, 1 H), 7.24 (dd, J = 7.2, 7.2 Hz, 1 H), 7.12 (d, J =
.2 Hz, 1 H), 5.68 (s, 1 H), 2.63–2.57 (m, 4 H), 2.06–2.01 (m, 2 H) ppm.
C NMR (100 MHz, CDCl ): δ = 201.3, 197.5, 165.2, 144.8, 133.1,
+
3
(
(
EI): m/z (%) = 224 (1) [M] , 99 (15), 86 (57), 73 (64), 59 (26), 58
100). HRMS (EI) calcd. for C H O 224.1412; found 224.1412.
1
3 20 3
7
13
3
-[3-(1,3-Dioxolan-2-yl)propyl]-4,4-dimethylcyclohex-2-en-1-
3
1
one (18b): Yellowish oil. H NMR (400 MHz, CDCl ): δ = 5.76 (s, 1 131.3, 129.1, 122.4, 121.8, 119.5, 43.0, 27.4, 19.0 ppm. IR (neat): ν˜ =
3
–1
H), 4.84 (t, J = 4.3 Hz, 1 H), 3.94–3.80 (m, 4 H), 2.39 (t, J = 6.6 Hz, 2
H), 2.21 (t, J = 7.6 Hz, 2 H), 1.81 (t, J = 6.8 Hz, 2 H), 1.68–1.57 (m, 4
2925, 2732, 1706, 1604, 1574, 1454, 1389, 1279, 1191, 1082 cm .
MS (EI): m/z (%) = 200 (34) [M] , 145 (31), 144 (100), 128 (55), 116
+
Eur. J. Org. Chem. 2016, 589–598
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© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
+
(
2
35), 115 (61). HRMS (EI) calcd. for C13H12O2 200.0837; found 244 (9) [M] , 180 (88), 109 (50), 97 (83), 82 (42), 81 (100). HRMS (EI)
00.0837. calcd. for C H O 244.1099; found 244.1101.
1
5 16 3
1
5
(
-(1-Oxo-1H-inden-3-yl)pentanal (23c): Yellowish oil. H NMR
3-[4-(1,3-Dioxolan-2-yl)butyl]-1H-inden-1-one (22c): Bright yel-
1
400 MHz, CDCl ): δ = 9.79 (br. s, 1 H), 7.41 (d, J = 7.2 Hz, 1 H), 7.37
low oil. H NMR (400 MHz, CDCl
3
): δ = 7.37 (d, J = 7.2 Hz, 1 H), 7.33
3
(
dd, J = 7.2, 7.2 Hz, 1 H), 7.25 (dd, J = 7.2, 7.2 Hz, 1 H), 7.10 (d, J = (dd, J = 7.2, 7.2 Hz, 1 H), 7.21 (dd, J = 7.2, 7.2 Hz, 1 H), 7.07 (d, J =
7
2
1
2
1
.2 Hz, 1 H), 5.68 (s, 1 H), 2.58 (t, J = 6.6 Hz, 2 H), 2.53 (t, J = 6.5 Hz,
7.2 Hz, 1 H), 5.65 (s, 1 H), 4.84 (t, J = 4.7 Hz, 1 H), 3.96–3.80 (m, 4
H), 2.54 (t, J = 6.7 Hz, 2 H), 1.74–1.68 (m, 4 H), 1.58–1.52 (m, 2
1
3
H), 1.80–1.65 (m, 4 H) ppm. C NMR (100 MHz, CDCl ): δ = 201.9,
3
H) ppm. 13C NMR (100 MHz, CDCl
): δ = 197.7, 166.3, 145.2, 133.0,
97.7, 165.8, 145.1, 133.1, 131.5, 129.2, 122.4, 121.9, 119.4, 43.5, 28.1,
3
6.2, 21.8 ppm. IR (neat): ν˜ = 2937, 2869, 2723, 1707, 1606, 1573, 131.5, 129.0, 122.3, 121.7, 119.4, 104.2, 64.8, 33.4, 28.2, 26.6,
–
1
454, 1385, 1275, 1188, 1179, 834 cm . MS (EI): m/z (%) = 214 (19) 23.7 ppm. IR (neat): ν˜ = 2945, 2869, 1708, 1605, 1575, 1454, 1412,
+
–1
[
M] , 170 (89), 157 (50), 144 (100), 115 (67), 58 (74). HRMS (EI) calcd. 1282, 1137, 1034, 945, 766, 695 cm . MS (EI): m/z (%) = 258 (7)
+
for C H O 214.0994; found 214.0995.
[M] , 180 (50), 111 (79), 99 (53), 128 (49), 81 (61), 73 (100). HRMS
14 14 2
(
EI) calcd. for C H O 258.1256; found 258.1258.
1
6 18 3
General Procedure for 1,4-Addition to Indenone: A solution of
Grignard reagent (5.7 mmol) in THF (8 mL) was added at –20 °C
under Ar to a suspension of copper(I) cyanide (1.5 mmol) in THF
General Procedure for the Intramolecular Acyl Radical Cycliza-
tion: A solution of the appropriate enol-aldehyde (0.9 mmol) and
t-dodecanethiol (4.5 mmol) in toluene (5 mL) was added at room
temperature to a stirred solution of AIBN (0.9 mmol) in toluene
(55 mL). The mixture was stirred at 75 °C for 19 h and then addi-
tional AIBN (0.9 mmol) was added to the reaction mixture. The stir-
(3 mL). After the mixture had been stirred at –20 °C for 40 min,
indenone (20, 3.8 mmol) was added, and the mixture was stirred
for another 3 h. The mixture was quenched with water and ex-
tracted with Et O. The combined extracts were washed with brine,
2
dried with MgSO , filtered, and concentrated. The crude product ring was continued at 75 °C for a further 12 h. The solvent was
4
was purified by silica gel chromatography with EtOAc/hexanes as
the eluent to furnish the enone-aldehydes 21.
removed under reduced pressure, and the residue was purified by
silica gel chromatography with EtOAc/hexanes as the eluent to fur-
nish the spiro compounds 24–30.
Spiro[4.5]decane-1,7-dione (24b):[4] Colorless oil. 1H NMR
3
-[3-(1,3-Dioxolan-2-yl)propyl]-2,3-dihydro-1H-inden-1-one
1
(21b): Colorless oil. H NMR (400 MHz, CDCl ): δ = 7.70 (d, J = 7.4 Hz,
3
(
2
400 MHz, CDCl ): δ = 2.46 (d, J = 14.3 Hz, 1 H), 2.43–2.22 (m, 4 H),
1
H), 7.58 (dd, J = 7.4, 7.4 Hz, 1 H), 7.49 (d, J = 7.4 Hz, 1 H), 7.35
3
1
3
.11–2.03 (m, 2 H), 1.96–1.78 (m, 6 H), 1.59–1.55 (m, 1 H) ppm.
C
(dd, J = 7.4, 7.4 Hz, 1 H), 4.84 (t, J = 4.7 Hz, 1 H), 3.96–3.81 (m, 4 H),
NMR (100 MHz, CDCl ): δ = 219.8, 209.8, 52.7, 47.1, 40.9, 36.8, 34.2,
3
3
.40–3.30 (m, 1 H), 2.84 (dd, J = 19.0, 7.4 Hz, 1 H), 2.35 (dd, J = 19.0,
3
.4 Hz, 1 H), 1.99–1.92 (m, 1 H), 1.72–1.51 (m, 5 H) ppm. 13C NMR
30.9, 22.7, 18.6 ppm. IR (neat): ν = 2952, 2872, 1735, 1715, 1448,
˜
–
1
+
1
406, 1228, 1187, 1161 cm . MS (EI): m/z (%) = 166 (66) [M] , 138
(
100 MHz, CDCl ): δ = 206.3, 158.6, 136.6, 134.6, 127.4, 125.5, 123.5,
3
(34), 123 (35), 110 (100), 97 (41), 82 (61), 67 (93), 55 (80). HRMS (EI)
1
2
04.2, 64.8, 64.7, 42.9, 38.2, 35.9, 33.7, 22.0 ppm. IR (neat): ν˜ = 2923,
–1
calcd. for C H O 166.0994; found 166.0985.
880, 1713, 1604, 1462, 1406, 1281, 1137, 1045, 761 cm . MS (EI):
10 14 2
+
m/z (%) = 246 (8) [M] , 185 (8), 184 (39), 131 (12), 73 (100). HRMS
Spiro[5.5]undecane-1,8-dione (24c): White solid, m.p. 72–73 °C
(
EI) calcd. for C H O 246.1256; found 246.1257.
1
15
18
3
(Et O/hexanes). H NMR (400 MHz, CDCl ): δ = 2.64 (d, J = 14.7 Hz,
2
3
1
H), 2.55–2.33 (m, 3 H), 2.25–2.17 (m, 2 H), 2.02–1.98 (m, 2 H), 1.87–
3
-[4-(1,3-Dioxolan-2-yl)butyl]-2,3-dihydro-1H-inden-1-one
13
1
1.59 (m, 8 H) ppm. C NMR (100 MHz, CDCl ): δ = 213.5, 209.4,
(21c): Yellowish oil. H NMR (400 MHz, CDCl ): δ = 7.70 (d, J = 7.6 Hz,
3
3
5
2
1
2.9, 49.1, 40.3, 38.3, 37.9, 31.7, 27.0, 21.0, 20.7 ppm. IR (neat): ν˜ =
1
H), 7.58 (dd, J = 7.6, 7.6 Hz, 1 H), 7.48 (d, J = 7.6 Hz, 1 H), 7.33
–
1
+
937, 2871, 1706, 1559, 1457 cm . MS (EI): m/z (%) = 180 (82) [M] ,
(dd, J = 7.6, 7.6 Hz, 1 H), 4.82 (t, J = 4.7 Hz, 1 H), 3.96–3.80 (m, 4 H),
52 (28), 137 (46), 123 (65), 109 (83), 95 (43), 81 (56), 67 (68), 55
3
.40–3.30 (m, 1 H), 2.83 (dd, J = 19.0, 7.5 Hz, 1 H), 2.33 (dd, J = 19.0,
(100). HRMS (EI) calcd. for C H O 180.1150; found 180.1152.
3
.2 Hz, 1 H), 1.85–1.95 (m, 1 H), 1.70–1.60 (m, 2 H), 1.49–1.30 (m, 5
11 16 2
13
1
H) ppm. C NMR (100 MHz, CDCl ): δ = 206.4, 158.8, 136.7, 134.6, 8,8-Dimethylspiro[4.5]decane-1,7-dione (25b): Colorless oil. H
3
1
27.4, 125.5, 123.5, 104.3, 64.8, 43.0, 38.1, 35.9, 33.6, 27.4, 24.0 ppm.
NMR (400 MHz, CDCl ): δ = 2.63 (d, J = 14.2 Hz, 1 H), 2.32–2.20 (m,
3
IR (neat): ν˜ = 2929, 2861, 1712, 1605, 1463, 1408, 1333, 1283, 1241, 2 H), 2.02 (dd, J = 14.2, 2.0 Hz, 1 H), 2.04–1.70 (m, 6 H), 1.67–1.58
–
1
+
13
1
139, 1041, 943, 760 cm . MS (EI): m/z (%) = 260 (6) [M] , 198 (18),
(m, 1 H), 1.48–1.42 (m, 1 H), 1.19 (s, 3 H), 1.05 (s, 3 H) ppm. C NMR
1
32 (13), 131 (17), 73 (100). HRMS (EI) calcd. for C H O 260.1412; (100 MHz, CDCl ): δ = 219.9, 214.1, 53.4, 44.6, 43.6, 36.8, 36.8, 34.1,
1
6
20
3
3
found 260.1409.
27.8, 25.2, 24.8, 18.6 ppm. IR (neat): ν = 2956, 2873, 1736, 1707,
˜
–
1
+
1460, 1192, 1107, 1017 cm . MS (EI): m/z (%) = 194 (100) [M] , 135
General Procedure for IBX Oxidation: A mixture of the appropri-
ate compound 21 (1.4 mmol) and IBX (7.0 mmol) in DMSO (28 mL)
was stirred at 55 °C for 12 h. The reaction mixture was quenched
(87), 110 (88), 97 (78), 95 (72), 82 (91), 67 (53). HRMS (EI) calcd. for
C H O 194.1307; found 194.1310.
12 18 2
with water and filtered through a pad of celite. The filtrate was 9,9-Dimethylspiro[5.5]undecane-1,8-dione (25c): Colorless oil. 1H
extracted with Et O, and the combined extracts were washed suc-
NMR (400 MHz, CDCl ): δ = 2.66 (dd, J = 14.7, 1.4 Hz, 1 H), 2.48–
2
3
cessively with water and brine, dried with MgSO , filtered, and con-
2.40 (m, 1 H), 2.35–2.29 (m, 1 H), 2.16–2.10 (m, 1 H), 2.08 (d, J =
4
centrated. The crude product was purified by silica gel chromatog-
raphy with EtOAc/hexanes as the eluent to furnish indenones 22.
14.7 Hz, 1 H), 2.00–1.92 (m, 1 H), 1.84–1.44 (m, 8 H), 1.08 (s, 3 H),
1.06 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl ): δ = 213.9, 213.6, 53.5,
3
4
5.6, 44.0, 38.2, 37.7, 35.4, 28.6, 27.0, 25.6, 25.1, 20.6 ppm. IR
3
-[3-(1,3-Dioxolan-2-yl)propyl]-1H-inden-1-one (22b): Bright yel-
1
(neat): ν˜ = 2933, 2865, 1708, 1707, 1453, 1384, 1362, 1307, 1218,
low oil. H NMR (400 MHz, CDCl ): δ = 7.41 (d, J = 7.2 Hz, 1 H), 7.36
3
–
1
+
1
1
115 cm . MS (EI): m/z (%) = 208 (54) [M] , 149 (47), 138 (100),
(dd, J = 7.2, 7.2 Hz, 1 H), 7.24 (dd, J = 7.2, 7.2 Hz, 1 H), 7.11 (d, J =
09 (58), 81 (42). HRMS (EI) calcd. for C H O 208.1463; found
13 20 2
7
.2 Hz, 1 H), 5.70 (s, 1 H), 4.91 (t, J = 4.1 Hz, 1 H), 4.00–3.84 (m, 4
1
3
208.1465.
H), 2.61 (t, J = 6.4 Hz, 2 H), 1.90–1.78 (m, 4 H) ppm. C NMR
100 MHz, CDCl ): δ = 197.8, 166.1, 145.2, 133.1, 131.6, 129.1, 122.4,
(
1
2
9,9-Dimethylspiro[4.5]decane-1,7-dione (26b): White solid, m.p.
3
1
21.9, 119.5, 104.1, 64.9, 33.4, 28.2, 21.1 ppm. IR (neat): ν˜ = 2923, 46–47 °C (Et O/hexanes). H NMR (400 MHz, CDCl ): δ = 2.37–1.72
2
3
–1
880, 1707, 1604, 1191, 1135, 1082, 946 cm . MS (EI): m/z (%) = (m, 11 H), 1.35 (d, J = 14.2 Hz, 1 H), 1.09 (s, 3 H), 0.99 (s, 3 H) ppm.
596 © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2016, 589–598
www.eurjoc.org

Full Paper
13
C NMR (100 MHz, CDCl ): δ = 220.6, 210.1, 54.4, 52.6, 45.9, 44.8,
212.1, 49.2, 48.7, 43.7, 36.4, 36.2, 33.1, 25.0, 23.5, 18.4 ppm. IR (neat):
3
3
1
1
7.0, 36.6, 36.1, 33.0, 27.6, 19.0 ppm. IR (neat): ν˜ = 2958, 2871, 1737, ν˜ = 2930, 2862, 1736, 1698, 1452, 1406, 1334, 1248, 1141, 1000,
–1 + –1 +
709, 1277, 1151 cm . MS (EI): m/z (%) = 194 (49) [M] , 179 (74), 813 cm . MS (EI): m/z (%) = 180 (80) [M] , 123 (36), 109 (43), 97
66 (39), 151 (42), 138 (79), 110 (55), 95 (32), 83 (100). HRMS (EI) (65), 81 (100), 67 (40). HRMS (EI) calcd. for C H O 180.1150; found
11 16 2
calcd. for C H O 194.1307; found 194.1310.
180.1148.
1
2 18 2
1
0,10-Dimethylspiro[5.5]undecane-1,8-dione (26c): White solid,
Spiro[5.6]dodecane-1,8-dione (29c): Colorless oil. 1H NMR
1
m.p. 85–86 °C (Et O/hexanes). H NMR (400 MHz, CDCl ): δ = 2.81
(400 MHz, CDCl ): δ = 2.92 (d, J = 14.0 Hz, 1 H), 2.52–2.33 (m, 5 H),
2
3
3
1
3
(
(
d, J = 14.4 Hz, 1 H), 2.66 (ddd, J = 14.4, 6.4, 6.4 Hz, 1 H), 2.38–2.29
m, 2 H), 2.18–2.04 (m, 3 H), 1.92–1.87 (m, 2 H), 1.83 (d, J = 14.4 Hz,
2.28–2.19 (m, 1 H), 2.01–1.90 (m, 1 H), 1.79–1.50 (m, 10 H) ppm.
C
NMR (100 MHz, CDCl ): δ = 214.0, 212.8, 51.4, 50.6, 43.7, 39.1, 38.6,
3
1
H), 1.71–1.55 (m, 4 H), 1.05 (s, 3 H), 0.99 (s, 3 H) ppm. 13C NMR 37.6, 27.4, 24.9, 23.9, 20.7 ppm. IR (neat): ν˜ = 2933, 2861, 1701, 1453,
–
1
+
(100 MHz, CDCl ): δ = 214.9, 209.4, 54.0, 52.9, 47.8, 46.0, 43.3, 38.8,
1127 cm . MS (EI): m/z (%) = 194 (65) [M] , 166 (9), 150 (38), 137
3
3
1
1
5.1, 32.6, 28.5, 27.5, 21.0 ppm. IR (neat): ν˜ = 2945, 2870, 1712, 1445, (51), 111 (100), 95 (39), 81 (67), 67 (73). HRMS (EI) calcd. for C H O
1
2 18 2
–
1
+
280, 1236, 1129 cm . MS (EI): m/z (%) = 208 (46) [M] , 193 (18), 194.1307; found 194.1299.
80 (45), 175 (48), 165 (53), 151 (69), 138 (46), 124 (39), 109 (57), 91
Spiro[cyclopentane-1,1′-indene]-2,3′(2′H)-dione (30b): Yellowish
(44), 83 (100), 55 (90). HRMS (EI) calcd. for C H O 208.1463; found
1
1
3 20 2
oil. H NMR (400 MHz, CDCl ): δ = 7.77 (d, J = 7.6 Hz, 1 H), 7.65–
3
2
08.1462.
7.61 (dd, J = 7.6, 7.6 Hz, 1 H), 7.44 (dd, J = 7.6, 7.6 Hz, 1 H), 7.25 (d,
1
0,10-Dimethylspiro[4.5]decane-1,7-dione (27b): Colorless oil.
J = 7.6 Hz, 1 H), 2.87 (d, J = 18.3 Hz, 1 H), 2.58–2.42 (m, 3 H), 2.52
1
13
H NMR (400 MHz, CDCl ): δ = 2.47–2.40 (m, 1 H), 2.36–2.12 (m, 4
(d, J = 18.3 Hz, 1 H), 2.33–2.26 (m, 2 H), 2.12–2.03 (m, 1 H) ppm.
C
3
H), 2.02 (d, J = 14.7 Hz, 1 H), 1.97–1.62 (m, 6 H), 1.06 (s, 3 H), 0.87
NMR (100 MHz, CDCl ): δ = 218.6, 203.5, 156.3, 136.9, 135.3, 128.6,
3
(
s, 3 H) ppm. 13C NMR (100 MHz, CDCl ): δ = 220.7, 210.0, 58.5, 42.2, 124.4, 124.0, 65.9, 47.9, 38.4, 37.6, 20.1 ppm. IR (neat): ν˜ = 2957,
3
–
1
4
2
1.2, 40.1, 33.6, 33.5, 26.6, 24.8, 23.0, 20.5 ppm. IR (neat): ν˜ = 2954, 1714, 1599, 1462, 1399, 1283, 1241, 1160, 1041, 763 cm . MS (EI):
–1
+
876, 1733, 1708, 1466, 1412, 1317, 1236, 1119, 1048, 945 cm . MS m/z (%) = 200 (63) [M] , 145 (28), 144 (100), 116 (28), 115 (37).
+
(EI): m/z (%) = 194 (100) [M] , 179 (41), 138 (54), 110 (43), 95 (36). HRMS (EI) calcd. for C H O 200.0837; found 200.0839.
13 12 2
HRMS (EI) calcd. for C H O 194.1307; found 194.1305.
1
2 18 2
Spiro[cyclohexane-1,1′-indene]-2,3′(2′H)-dione (30c): Yellowish
1
1
1,11-Dimethylspiro[5.5]undecane-1,8-dione (27c): Colorless oil.
oil. H NMR (400 MHz, CDCl ): δ = 7.75 (d, J = 7.6 Hz, 1 H), 7.67 (dd,
3
1
H NMR (400 MHz, CDCl ): δ = 2.48 (dd, J = 15.3, 1.4 Hz, 1 H), 2.41–
J = 7.6, 7.6 Hz, 1 H), 7.54 (d, J = 7.6 Hz, 1 H), 7.45 (dd, J = 7.6, 7.6 Hz,
1 H), 2.88 (d, J = 18.6 Hz, 1 H), 2.79 (d, J = 18.6 Hz, 1 H), 2.65–2.59
3
2
.26 (m, 3 H), 2.10 (d, J = 15.3 Hz, 1 H), 2.12–1.95 (m, 3 H), 1.88–
.70 (m, 3 H), 1.57–1.45 (m, 3 H), 1.09 (s, 3 H), 1.04 (s, 3 H) ppm. 13
NMR (100 MHz, CDCl ): δ = 215.8, 209.7, 56.8, 45.5, 39.7, 37.4, 36.9,
13
1
C
(m, 2 H), 2.22–2.14 (m, 2 H), 2.04–1.80 (m, 4 H) ppm. C NMR
3
(100 MHz, CDCl ): δ = 209.8, 203.1, 156.7, 136.1, 134.8, 128.5, 126.6,
3
3
1
5.3, 32.1, 25.2, 23.3, 22.9, 19.1 ppm. IR (neat): ν˜ = 2951, 2873, 1707, 123.8, 56.6, 47.1, 41.0, 40.0, 27.0, 22.9 ppm. IR (neat): ν = 2933, 2862,
˜
–1
–1
453, 1420, 1371, 1324, 1241, 1117, 1021, 736, 700 cm . MS (EI): 1711, 1602, 1463, 1289, 1260, 1127, 1049, 762 cm . MS (EI): m/z
+
+
m/z (%) = 208 (84) [M] , 152 (37), 139 (44), 111 (100), 108 (42), 91 (%) = 214 (75) [M] , 170 (100), 158 (85), 157 (59), 144 (96), 129 (60),
49). HRMS (EI) calcd. for C H O 208.1463; found 208.1463.
115 (60). HRMS (EI) calcd. for C H O 214.0994; found 214.0993.
(
1
3
20
2
14 14 2
Spiro[4.4]nonane-1,7-dione (28b):[20] Colorless oil. 1H NMR Supporting Information (see footnote on the first page of this
1
13
(
400 MHz, CDCl ): δ = 2.45–2.20 (m, 5 H), 2.09–1.77 (m, 7 H) ppm.
article): Copies of H and C NMR for compounds 6–9, 11, 14, 16,
18–19, and 21–30.
3
1
3
C NMR (100 MHz, CDCl ): δ = 220.8, 216.5, 52.7, 46.8, 37.0, 36.7,
3
+
3
5.9, 31.4, 19.2 ppm. MS (EI): m/z (%) = 152 (41) [M] , 124 (100),
1
1
10 (20), 96 (39), 82 (52), 68 (57). IR (neat): ν˜ = 2960, 2884, 1742,
–
1
Acknowledgments
453, 1404, 1264, 1138 cm . HRMS (EI) calcd. for C H O 152.0837;
9 12 2
found 152.0846.
The authors thank the Ministry of Science and Technology
Spiro[4.5]decane-2,6-dione (28c):[20] Colorless oil. 1H NMR (MOST), Republic of China for financial support (grant number
(
2
400 MHz, CDCl ): δ = 2.79 (d, J = 18.0 Hz, 1 H), 2.60–2.25 (m, 5 H), MOST 102-2113-M-194-001-MY3).
3
1
3
.00 (d, J = 18.0 Hz, 1 H), 1.97–1.70 (m, 7 H) ppm. C NMR (100 MHz,
CDCl ): δ = 216.6, 212.5, 53.7, 47.3, 38.6, 38.5, 36.3, 31.4, 27.0,
3
Keywords: Synthetic methods · Cyclization · Radical
reactions · Spiro compounds · Acyl radicals · Acylation
2
1
1.9 ppm. IR (neat): ν˜ = 2928, 2857, 1744, 1704, 1449, 1163,
–
1
+
127 cm . MS (EI): m/z (%) = 166 (12) [M] , 149 (13), 138 (100), 125
(
9), 110 (16), 97 (8), 82 (12). HRMS (EI) calcd. for C H O 166.0994;
10 14 2
found 166.0991.
[
1] a) W. Herz, H. Grisebach, G. W. Kirby, Fortschritte der Chemie Organischer
Naturstoffe, Springer, New York, 1974, vol. 31, p. 283; b) J. D. Martín, J.
Darias, in: Algal Sesquiterpenoids (Ed.: P. J. Scheuer), Marine Natural Pro-
ducts: Chemical and Biological Perspectives, Academic, New York, 1978,
vol. I, p. 125; c) K. L. Erickson, in: Constituents of Laurencia (Ed.: P. J.
Scheuer), Marine Natural Products: Chemical and Biological Perspectives,
Academic, New York, 1983, vol. V, p. 131.
1
Spiro[3.6]decane-1,6-dione (29a): Colorless oil. H NMR (400 MHz,
CDCl ): δ = 2.99 (dd, J = 14.0, 1.1 Hz, 1 H), 2.81 (d, J = 14.0 Hz, 1
3
H), 2.67–2.59 (m, 3 H), 2.52–2.44 (m, 1 H), 2.14–2.04 (m, 3 H), 1.97–
1
3
1
.83 (m, 3 H), 1.79–1.68 (m, 2 H) ppm. C NMR (100 MHz, CDCl3):
δ = 208.9, 175.7, 84.5, 54.2, 43.8, 41.5, 33.9, 28.1, 24.2, 23.4 ppm. IR
(
neat): ν˜ = 2926, 2856, 1772, 1698, 1457, 1304, 1233, 1181, 1022,
[
2] For more recent reports, see the following: a) B. M. Fraga, Nat. Prod. Rep.
2012, 29, 1334; b) J. W. Blunt, B. R. Copp, R. A. Keyzers, M. H. G. Munro,
M. R. Prinsep, Nat. Prod. Rep. 2014, 31, 160.
–1
+
9
9
1
33, 796 cm . MS (EI): m/z (%) = 166 (1) [M] , 124 (88), 111 (83),
8 (100), 55 (84). HRMS (EI) calcd. for C H O 166.0994; found
66.0993.
1
0 14 2
[3] a) A. P. Krapcho, Synthesis 1974, 383; b) A. P. Krapcho, Synthesis 1976,
25; c) M. Sannigrahi, Tetrahedron 1999, 55, 9007; d) R. Pradhan, M. Patra,
4
Spiro[4.6]undecane-1,7-dione (29b): Colorless oil. 1H NMR
400 MHz, CDCl ): δ = 2.87 (d, J = 12.7 Hz, 1 H), 2.63–2.56 (m, 1 H),
A. K. Behera, B. K. Mishra, R. K. Behera, Tetrahedron 2006, 62, 779; e) S.
Kotha, A. C. Deb, K. Lahiri, E. Manivannan, Synthesis 2009, 165; f) R. Rios,
Chem. Soc. Rev. 2012, 41, 1060; g) K. Undheim, Synthesis 2014, 46, 1957;
h) K. Undheim, Synthesis 2015, 47, 2497.
(
3
2
.40–2.27 (m, 3 H), 2.19 (dd, J = 12.7, 1.4 Hz, 1 H), 2.00–1.65 (m, 9
1
3
H), 1.47–1.37 (m, 1 H) ppm. C NMR (100 MHz, CDCl ): δ = 220.7,
3
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Full Paper
[
4] E. Zhang, C.-A. Fan, Y.-Q. Tu, F.-M. Zhang, Y.-L. Song, J. Am. Chem. Soc.
009, 131, 14626.
5] D.-S. Hsu, C.-W. Hsu, Tetrahedron Lett. 2012, 53, 2185.
[13] Y. Ito, T. Hirao, T. Saegusa, J. Org. Chem. 1978, 43, 1011.
[14]
2
Y. V. Suryanara, H. E. Zimmerman, Eur. J. Org. Chem. 2007, 4091.
15] K. C. Nicolaou, T. Montagnon, P. S. Baran, Y. L. Zhong, J. Am. Chem. Soc.
002, 124, 2245.
[
[
[
[
6] D.-S. Hsu, B.-C. Juo, Tetrahedron Lett. 2013, 54, 1751.
2
7] a) K. Yoshikai, T. Hayama, K. Nishimura, K. Yamada, K. Tomioka, J. Org.
Chem. 2005, 70, 681; b) K. Yamada, T. Sato, M. Hosoi, Y. Yamamoto, K.
Tomioka, Chem. Pharm. Bull. 2010, 58, 1151.
[
16] B. P. Roberts, Chem. Soc. Rev. 1999, 28, 25.
[17] K. Takahashi, M. Asakawa, K. Ogura, Chem. Lett. 1988, 1109.
[18] E. J. Enholm, Y. Xie, K. A. Abboud, J. Org. Chem. 1995, 60, 1112.
[19] M. G. Constantino, M. Beltrame Jr., E. F. de Medeiros, G.-V. J. da Silva,
Synth. Commun. 1992, 22, 2859.
[
[
8] F. Dénès, M. Pichowicz, G. Povie, P. Renaud, Chem. Rev. 2014, 114, 2587.
9] a) A. Clerici, N. Pastori, O. Porta, Tetrahedron 2001, 57, 217; b) S. Rajesh,
V. Sidhanath, V. Sheshanath, T. Wang, P. K. Zubaidha, Tetrahedron Lett.
[
20] P. S. Aburel, C. Rømming, K. Undheim, J. Chem. Soc. Perkin Trans. 1 2001,
2004, 45, 7187.
1
024.
[
10] a) E. Keinan, M. Sahai, R. Shvily, Synthesis 1991, 641; b) G. N. Varseev,
M. E. Maier, Org. Lett. 2005, 7, 3881.
[
[
11] W. G. Dauben, D. M. Michno, J. Org. Chem. 1977, 42, 682.
12] D. Pollart, J. Monforte, H. Kotsuki, B. H. Lipshutz, Tetrahedron Lett. 1985,
Received: October 11, 2015
2
6, 705.
Published Online: December 2, 2015
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© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim