Transformation of γ-ketoaldehyde acetals into 3-substituted-2-cyclopentenones via cyanophosphates under mild conditions

Article abstract of DOI:10.1016/j.tet.2020.131914

The reaction of cyanophosphates, which are readily derived from γ-ketoaldehyde acetals, with TMSN₃ (3 eq)/Bu₂SnO (0.3 eq) in refluxing toluene directly furnished 3-substituted-2-cyclopentenones in modest to good yield under mild conditions. The present method was further applied toward the synthesis of dechlorotrichodenone C isolated from Trichoderma asperellum.

Full text of DOI:10.1016/j.tet.2020.131914

Tetrahedron 82 (2021) 131914
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Transformation of
g
-ketoaldehyde acetals into 3-substituted-2-
cyclopentenones via cyanophosphates under mild conditions
Hiroki Yoneyama, Kumi Takatsuji, Aiko Ito, Yoshihide Usami, Shinya Harusawa*
Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka, 569-1094, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
The reaction of cyanophosphates, which are readily derived from g-ketoaldehyde acetals, with TMSN3 (3
Received 19 November 2020
Received in revised form
18 December 2020
Accepted 28 December 2020
Available online 30 December 2020
eq)/Bu2SnO (0.3 eq) in refluxing toluene directly furnished 3-substituted-2-cyclopentenones in modest
to good yield under mild conditions. The present method was further applied toward the synthesis of
dechlorotrichodenone C isolated from Trichoderma asperellum.
© 2021 Elsevier Ltd. All rights reserved.
Keywords:
3-Substituted-2-cyclopentenones
g
-Ketoaldehyde acetals
Cyanophosphates
Alkylidene carbene
Dechlorotrichodenone C
Diethyl trimethylsilylphosphate
1. Introduction
6 via fragmentation of putative tetrazolylphosphate intermediate 3
with the elimination of diethyl trimethylsilylphosphate (TMS-
Cyanophosphates (2, CPs) [1] were initially developed by our
group in 1983 as a novel intermediate for one-carbon homologa-
tion [2]. Since then, CPs have been extensively utilized as useful
synthetic intermediates in organic synthesis [1]. That is based on
the facile preparation of CPs from carbonyl compounds 1 using
diethyl phosphorocyanidate [(EtO)2P(O)CN, DEPC] [1] in the pres-
ence of a catalytic amount of lithium cyanide [2b]. On the other
phosphate, 4) and 2 mol of dinitrogen [6,7].
The intramolecular [1,5]-C_H bond insertion reaction of alkyli-
dene carbenes is a useful method for the construction of cyclo-
pentene skeletons [5]. In 2000, Shioiri and co-workers revealed
that the reaction of g-ketoaldehyde acetals 9 with lithium trime-
thylsilyldiazomethane [TMSC(Li)N2] [8], which was prepared upon
the reaction of trimethylsilyldiazomethane (TMSCHN2) [9] with n-
BuLi, efficiently affords ketal-protected 2-cyclopentenones 12 via a
[1,5]-C_H insertion reaction of their alkylidene carbenes 11 into
acetals bearing a stereogenic center; and the ketal protecting group
in 12 was removed using 1 N aqueous HCl to furnish 3-substituted
2-cyclopentenones 13, as shown at the bottom of Scheme 2 [10].
This inspired our group to study the transformation of CPs 10
hand,
a-hydroxy-tetrazoles [3] and a-cyano-mesylates [4] have
been reported to generate alkylidene carbenes [5] via the decom-
position of their tetrazole-intermediates, but they have some
drawbacks such as the need for a strong base, substrate depen-
dence, and high cost of reagents [5]. We recently clarified the po-
tential of CPs as latent alkylidene carbenes, as illustrated in Scheme
1, in which the two-step transformation of carbonyl compounds 1
into homologous alkynes 7 [6a,d] as well as five-membered un-
saturated cyclic compounds 8 [6b,c] have been conducted effi-
ciently under nearly neutral conditions [1b,7]. The reactions of CPs
2 with trimethylsilyl azide (TMSN3) in the presence of a catalytic
amount of dibutyltin oxide (Bu2SnO) generates alkylidene carbenes
bearing
a 1,3-dioxane functionality into cyclopentenones 13
(Scheme 2, the top). Herein we report the transformation of
g-
ketoaldehyde acetals 9 into 3-substituted-2-cyclopentenones 13
via CPs 10 under mild conditions. Interestingly, the deprotection of
ketal intermediate 12 was spontaneously caused by the secondary
action of TMS-phosphate 4 formed in situ. In addition, the present
method has been applied to the synthesis of dechlorotrichodenone
C (21) isolated from Trichoderma asperellum.
* Corresponding author.
E-mail addresses: harusawa@gly.oups.ac.jp, shinya.harusawa@ompu.ac.jp
(S. Harusawa).
https://doi.org/10.1016/j.tet.2020.131914
0040-4020/© 2021 Elsevier Ltd. All rights reserved.

H. Yoneyama, K. Takatsuji, A. Ito et al.
Tetrahedron 82 (2021) 131914
Subsequently, the reaction conditions used in the CP method
were further investigated, as shown in Table 1. Increasing the
amount of Bu2SnO (0.1e0.3 eq) was effective and provided an
improved yield of 13a (80%) (entry 4), accompanied by a small
amount of the [1,2]-rearrangement product 7a (7%). On the other
hand, we recently revealed a modified reagent system used for the
synthesis of tetrazoles, in which the treatment of various nitriles
with TMSN3 and Bu2Sn(OAc)2 at 30 ꢀC yielded their corresponding
5-substituted 1H-tetrazoles in excellent yield [11]. Application of
this reagent system [TMSN3 (3 eq) and Bu2Sn(OAc)2 (0.3 eq)] to CP
10a in refluxing toluene for 2 h yielded cyclopentenone 13a in 78%
yield (entry 6). Accordingly, Bu2Sn(OAc)2 may be used as a Sn-based
catalyst for the formation of cyclopentenones 13, while the reaction
at 30 ꢀC proceeded sluggishly (60 h) to give a ketal-protected in-
termediate 12a in 21% yield along with a large amount of recovered
CP 10a (65%) (entry 8).
Scheme 1. Synthesis of homologous alkynes 7 and five-membered cyclic compounds 8
from carbonyl compounds 1 using CPs 2.
Furthermore, we investigated the effect of the acetal moiety on
the formation of cyclopentene product. Among the acetal func-
tionalities studied, such as 1,3-dioxane, 1,3-dioxolane, dimethyl
acetal, and 1,3-dithiane derivatives 10a, 14, 15, and 16, respectively
(Table 2), 1,3-dioxane-protected CP 10a was preferable to the other
acetal-containing CPs as the acetal functionality in the starting g-
ketoaldehyde 9, as indicated by Shioiri [8]. In addition,1,3-dithiane-
protected CP 16 gave only 1,3-dithiane protected 2-cyclopentenone
in low yield (11%)(entry 4).
To study the scope and limitations of this transformation, the
formation of cyclopentenones 13 from
g-ketoaldehyde acetals 9
was carried out upon the reaction of CP 10 with TMSN3/Bu2SnO, as
shown in Table 3, using the synthetic procedure described above
(Table 1, entry 4) [12]. First, phenethyl ketone CPs 10b_e, which
contain para-substituent on the phenyl ring (R2 ¼ Me, Cl, CH3O, or
CF3), appear to afford their corresponding cyclopentenones 13b_e
in modest to high yield (48_85%), accompanied by a small amount
of the [1,2]-rearrangement product 7b_e (4_8%). (Table 3, entries
2_5). However, the reaction was dependent on the type of substrate
used. The transformations of furan-2-yl-ethyl, thiophen-2-yl-ethyl,
and indol-2-yl-ethyl ketone CPs 10f, 10g, and 10h resulted in low
yields of cyclopentenones 13f (21%), 13g (31%), and 13h (11%),
Scheme 2. A comparison of the present and Shioiri methods used for the trans-
formation of g-ketoaldehyde acetals 9 into cyclopentenones 13.
2. Results and discussion
When we first performed the reaction of CP 10a, which was
readily prepared via conventional cyanophosphorylation [2b,6a] of
-ketoaldehyde acetal 9a, with TMSN3 [1 equivalent (eq)] in the
Table 1
Investigation of the reaction conditions used for the transformation of CP 10a into
cyclopentenone 13a.
g
presence of a catalytic amount of Bu2SnO (0.1 eq) in refluxing
toluene for 2 h, 3-phenethyl-2-cyclopentenone 13a was obtained in
54% yield, accompanied by homologous alkyne 7a (3%) and
recovered CP 10a (29%), as shown in Scheme 3. In contrast to the
TMSC(Li)N2 method, the transformation using CP 10a indicates that
it can directly provide cyclopentenone 13a without the need of an
acid-treatment step for ketal-protected intermediate 12a.
TMSN3
(eq.)
Sn catalyst
(eq.)
Time
(h)
Yield (%)
Entry
12a
13a
7a
10a
Bu2SnO
0.1
0.1
0.2
0.3
1
2
3
4
1
1
2
3
2
6
2
2
0
0
0
0
54
56
72
80
3
5
6
7
29
13
trace
trace
Bu2Sn(OAc)2
5
6
2
3
3
3
0.2
0.3
0.3
0.3
2
2
6
0
0
0
71
78
57
0
5
7
9
0
19
12
trace
65
7
8a
60
21
a
Reaction temperature: 30 ꢀC.
Scheme 3. Reaction of CP 10a with TMSN3/Bu2SnO.
2

H. Yoneyama, K. Takatsuji, A. Ito et al.
Tetrahedron 82 (2021) 131914
Table 2
synthetic study starting from optically active cyclopentenones, in
which 22 was prepared via the chlorination of dechloro-
trichodenone C (21) [15]. Shioiri and co-workers have also effi-
ciently synthesized trichodenone C using the TMSC(Li)N2 method
over eight steps from methyl (R)-lactate [8]. In 2018, Ji and co-
workers isolated dechlorotrichodenone C (21) from Trichoderma
asperellum cf44-2 [16]. In this context, our attention was turned to
the application of the present method to 21, as shown in Scheme 4.
Ketone 9q was prepared upon the reaction of commercially avail-
able (R)-2-acetoxypropionic acid chloride (20) with 2-(1,3-dioxan-
2-yl)ethylmagnesium bromide in 89% yield. Treatment of 9q with
DEPC in the presence of LiCN gave CP 10q (quant). The reaction of
10q with TMSN3/Bu2SnO in refluxing toluene for 4 h afforded the
desired 2-cyclopentenone 13q in 46% yield. Then, acid hydrolysis of
Investigation of the acetal functionality for cyclopentenone formation.
13q yielded dechlorotrichodenone C [21, 82%; [
a
]
ꢁ1.6 (c 1.00,
D
CHCl3)] [17] in a 33.6% overall yield in four steps from the starting
acid chloride 20. Synthetic 21 was identical to that of natural
dechhlorotrichodenone C based on a comparison of their 1H NMR,
13C NMR, and HRMS data [15,16]. Thus, chlorination (Cl2, Et3N) [15]
of 21 as previously described may provide 22.
A plausible mechanism for the present reaction is proposed in
Scheme 5. As this procedure does not require an acid treatment
step, we focused on the role of TMS-phosphate 4 [18] which was
excluded through the fragmentation of tetrazolylphosphates 3, as
indicated in Scheme 1. TMS-phosphate 4 can activate the C_O bond
in 1,3 dioxane 12 to form an oxonium-cation intermediate 23.
Subsequent elimination of oxetane from 23 produces 2-
cyclopentenone 13 (eq. 1 in Scheme 5). Indeed, the reaction of
protected 2-cyclopentenone 12a with 4 (1 eq) readily provides
cyclopentenone 13a in 93% yield in refluxing toluene for 1 h (eq. 2),
while that of 12a with TMSN3 did not give 13a (eq. 3). Although
TMS-phosphate 4 has not been greatly documented in the litera-
ture [18], it should be noted that TMS-phosphate may be used as an
activating agent for the cleavage of cyclic acetals [19].
respectively (entries 6_8). The reaction of methyl ketone CP 10i
(R1 ¼ CH3) proceeded successfully, but the isolated yield of 3-
methylcyclopentenone 13i was 63% due to its low boiling point
(150_160 ꢀC) (entry 9). In the cases of CPs 10j (R1 ¼ pentyl) and 10k
(R1 ¼ isopentyl) bearing linear alkyl groups, the competitive acetal
C_H and alkyl C_H insertion reactions of the alkylidene carbene
occurred (entries 10 and 11), which is similar to that observed using
the TMSC(Li)N2 method [8], that is, the reaction of CP 10j shows
selectivity toward acetal C_H insertion to produce cyclopentenone
13j (53%) and cyclopentene 17j (11%), respectively (entry 10), while
that of CP 10k was slightly selective toward tertiary alkyl C_H
insertion, yielding 13k (37%) and 17k (42%) (entry 11) [13]. The
reaction of cyclohexylketone-CP 10l with TMSN3/Bu2SnO in
refluxing toluene for 10 h gave its corresponding cyclopentene
product 13l in 38% yield (entry 12). The presence of the tert-butyl
group in CP 10m was not compatible with these reaction conditions
with recovery of 10m (98%) (entry 13), probably which was
attributed to steric hindrance. The reaction of 10m with the alter-
native reagent system [TMSN3/Bu2Sn(OAc)2] did not occur. In
contrast, the TMSC(Li)N2 method furnished 13l (89%) and 13m
(54%) in good yield from their respective secondary and tertiary
ketones 9l and 9m (entries 12 and 13) [8]. CP 10n derived from
cyclohexanone 9n afforded a two-ring fused 2-cyclopentenone
product 13n in 12% yield along with a dephosphorylated com-
pound 18 (15%) (entry 14). In addition, phenyl ketone CP 10o gave
only the [1,2]-rearrangement-product 7o in 78% yield (entry 15),
which was in accordance with that reported by Shioiri [8]. The
reaction of methoxyethylketone CP 10p with TMSN3/Bu2SnO
afforded only a trace amount of cyclopentenone 13p (entry 16),
along with an unexpected azide derivative 19 (28%) [see Supple-
mentary data (S.D.)].
3. Conclusions
In this study, we have demonstrated that the reaction of CPs 10,
which are readily derived from
g-ketoaldehyde acetals 9, with
TMSN3/Bu2SnO in refluxing toluene directly affords 3-substituted-
2-cyclopentenones 12 under nearly neutral conditions in modest to
good yield, with a reasonable substrate scope. The present method
complements the TMSC(Li)N2 method, which requires strong basic
and acidic conditions. The procedure was further applied to the
synthesis of dechlorotrichodenone C. In addition, the role of TMS-
phosphate 4 as the cleavage agent of 1,3-dioxane ketals was indi-
cated. Furthermore, this study contributes to the diversity of CPs as
key intermediates in a variety of organic synthesis [1].
4. Experimental
4.1. General information
All reactions were carried out under an argon atmosphere. Su-
per dehydration solvents (toluene and THF) were purchased from
the WAKO Chemical Company. Fuji Silysia FL-60D silica gel was
used for flash column chromatography. Thin layer chromatography
was performed using pre-coated plates (WAKO silica gel 70 F254). 1H
NMR spectroscopy was recorded on an Agilent 400-MR-DD2
spectrometer in CDCl3 using tetramethylsilane (TMS) as an internal
standard. Coupling constants (J) were reported in Hertz (Hz). For
multiplicities the following abbreviations were used: s (singlet),
d (doublet), t (triplet), q (quartet), quint (quintet), sext (sextet), sept
(septet), m (multiplet), and br (broad). 13C NMR spectroscopy was
recorded on an Agilent 400-MR-DD2 spectrometer in CDCl3.
(_)-Trichodenone C (22) was first isolated in 1998 in our labo-
ratory from a strain of Trichoderma harzianum (OUPSeN115), which
exhibits cytotoxicity against cultured P388 cells [14]. Furthermore,
we determined the stereochemistry of trichodenones A_C using a
3

Table 3
Synthesis of 2-cyclopentenes 13 from acyclic g-ketoaldehyde acetals 9.
4

H. Yoneyama, K. Takatsuji, A. Ito et al.
Tetrahedron 82 (2021) 131914
mixture was stirred for 0.5 h at room temperature (rt). Then, the
reaction mixture was diluted with AcOEt and washed using satu-
rated NH4Cl and brine. The organic layer was dried over Na2SO4,
filtered and evaporated to give a crude residue, which was purified
by column chromatography (Hexane_AcOEt ¼ 1:1) to give CP 10.
4.2.1. 3-Cyano-1-(1,3-dioxan-2-yl)-5-phenylpentan-3-yl diethyl
phosphate (10a)
Yield: 88% (360 mg); oil. 1H NMR (400 MHz, CDCl3):
d
1.32_1.40
(m, 7H), 1.80_1.95 (m, 2H), 2.00_2.24 (m, 1H), 2.25_2.42 (m, 4H),
2.79_2.94 (m, 2H), 3.72_3.80 (m, 2H), 4.07_4.23 (m, 6H), 4.61 (t,
J ¼ 4.8 Hz, 1H), 7.19_7.33 (m, 5H); 13C NMR (100 MHz, CDCl3):
d 16.0
(15.96), 16.0 (16.03), 16.1, 25.6, 28.6 (28.57), 28.6 (28.62), 29.5, 30.1,
33.0, 33.1, 40.5 (40.48), 40.5 (40.52), 63.6 (63.56), 63.6 (63.61), 64.4,
64.5 (64.48), 64.5 (64.50), 64.5 (64.54), 67.0, 77.7, 77.8, 100.7, 117.7,
117.8, 126.4, 128.3, 128.6, 128.7, 139.7; HRMS (EI): m/z calcd for
C
20H29NO6P [M ꢁ H]þ 410.1734, found 410.1732.
Scheme 4. Synthesis of dechlorotrichodenone (21) using the present method.
4.2.2. 3-Cyano-1-(1,3-dioxan-2-yl)-5-(4-methylphenyl)pentan-3-
yl diethyl phosphate (10b)
Yield: 82% (350 mg); oil. 1H NMR (400 MHz, CDCl3):
d
1.32_1.40
(m, 7H), 1.80_1.94 (m, 2H), 2.00_2.11 (m, 1H), 2.12_2.40 (m, 4H), 2.32
(s, 3H), 2.74_2.90 (m, 2H), 3.72_3.80 (m, 2H), 4.06_4.23 (m, 6H), 4.61
(t, J ¼ 4.8 Hz, 1H), 7.10 (s, 4H); 13C NMR (100 MHz, CDCl3):
d 16.0
(15.97), 16.0 (16.04), 16.1, 21.0, 25.6, 28.6 (28.57), 28.6 (28.62), 29.5,
29.6, 33.0, 33.1, 40.6. 40.7, 63.6, 64.4, 64.5 (64.49), 64.5 (64.54), 66.8,
77.7, 77.8, 100.7, 117.7, 117.8, 128.2, 129.2, 135.9, 136.6; HRMS (EI): m/
z calcd for C21H33NO6P [M ꢁ H]þ 426.2045, found 426.2043.
4.2.3. 5-(4-Chlorophenyl)-3-cyano-1-(1,3-dioxan-2-yl)pentan-3-yl
diethyl phosphate (10c)
Yield: 88% (390 mg); oil. 1H NMR (400 MHz, CDCl3):
d
1.32_1.40
(m, 7H), 1.79_1.94 (m, 2H), 2.00_2.40 (m, 5H), 2.77_2.92 (m, 2H),
3.72_3.80 (m, 2H), 4.07_4.23 (m, 6H), 4.61 (t, J ¼ 4.8 Hz, 1H), 7.15 (d,
J ¼ 8.4 Hz, 2H), 7.26 (d, J ¼ 8.4 Hz, 2H); 13C NMR (100 MHz, CDCl3):
d
16.0,16.1 (16.06),16.1 (16.14), 25.6, 29.5, 33.0, 33.1, 40.3, 40.4, 64.5,
64.6 (64.57), 64.6 (64.60), 64.6 (64.63), 66.8, 76.8, 77.2, 77.6, 77.7,
100.6, 117.6, 117.7, 128.7, 129.7, 132.2, 138.2; HRMS (EI): m/z calcd for
C
20H2835ClNO6P [M ꢁ H]þ 444.1342, found 444.1344.
4.2.4. 3-Cyano-1-(1,3-dioxan-2-yl)-5-(4-methoxyphenyl)pentan-
3-yl diethyl phosphate (10d)
Yield: 86% (380 mg); oil. 1H NMR (400 MHz, CDCl3):
d
1.32_1.40
(m, 7H), 1.80_1.94 (m, 2H), 2.00_2.38 (m, 5H), 2.73_2.88 (m, 2H),
3.72_3.80 (m, 2H), 3.79 (s, 3H), 4.07_4.23 (m, 6H), 4.61 (t, J ¼ 4.8 Hz,
1H), 6.84 (d, J ¼ 8.8 Hz, 2H), 7.13 (d, J ¼ 8.8 Hz, 2H); 13C NMR
(100 MHz, CDCl3):
d 16.0 (15.97), 16.0 (16.04), 16.1, 25.6, 29.2, 33.0,
Scheme 5. A plausible mechanism for the formation of cyclopentenones 13 from
ketal-protected intermediate 12.
33.1, 40.7, 40.8, 55.2, 64.5 (64.47), 64.5 (64.54), 66.8, 77.7, 77.8,
400.7, 114.0, 117.7, 117.8, 129.3, 131.7, 158.1; HRMS (EI): m/z calcd for
C
21H32NO7P [M]þ 441.1916, found 441.1914.
Chemical shifts (d) were given relative to CDCl3 (77.0 ppm). High-
4.2.5. 3-Cyano-1-(1,3-dioxan-2-yl)-5-(4-trifluoromethylphenyl)
pentan-3-yl diethyl phosphate (10e)
resolution mass spectra were obtained using a JMS-700(2) dou-
ble-focusing magnetic sector mass spectrometer (JOEL Ltd., Tokyo,
Japan) operated in positive-ion mode, with 3-nitrobenzyl alcohol
(NBA)-NaCl. Infrared spectroscopy was recorded on an IR Affinity-
1S Fourier transformation-infrared spectrometer (Shimadzu,
Kyoto, Japan). Specific rotations were measured using a JASCO P-
2300 spectrometer (JASCO Co., Tokyo, Japan).
Yield: 86% (410 mg); oil; 1H NMR (400 MHz, CDCl3):
d
1.32_1.40
(m, 7H), 1.80_1.95 (m, 2H), 2.00_2.44 (m, 5H), 2.87_3.01 (m, 2H),
3.73_3.80 (m, 2H), 4.07_4.24 (m, 6H), 4.62 (t, J ¼ 4.8 Hz, 1H), 7.35 (d,
J ¼ 8.0 Hz, 2H), 7.56 (d, J ¼ 8.0 Hz, 2H); 13C NMR (100 MHz, CDCl3):
d
15.9 (15.86), 15.9 (15.93), 16.0 (15.95), 16.0 (16.02), 16.1, 16.2, 25.5,
28.5 (28.47), 28.5 (28.51), 29.4, 29.9, 32.9, 33.0, 40.0, 40.1, 63.5
(63.47), 63.5 (63.52), 64.3, 64.4, 64.5 (64.46), 64.5 (64.51), 64.6,
66.7, 77.4, 77.5, 100.5, 117.5 (117.47), 117.5 (117.52), 124.1 (q,
J ¼ 271 Hz), 125.4 (q, J ¼ 3.8 Hz), 128.7, 128.7 (q, J ¼ 31.9 Hz), 143.8;
HRMS (EI): m/z calcd for C21H28F3NO6P [M ꢁ H]þ 478.1606, found
478.1603.
4.2. General procedure for the synthesis of CPs 10 [2b,6a]
DEPC (0.18 mL, 1.2 mmol) and LiCN (20 mg, 0.6 mmol) were
added to a solution of ketone 9 (1 mmol) in THF (5 mL). The reaction
5

H. Yoneyama, K. Takatsuji, A. Ito et al.
Tetrahedron 82 (2021) 131914
4.2.6. 3-Cyano-1-(1,3-dioxan-2-yl)-5-(furan-2-yl)pentan-3-yl
32.9, 33.0, 36.6 (36.61), 36.6 (36.64), 64.4 (64.38), 64.4 (64.43), 66.8,
diethyl phosphate (10f)
71.2, 71.3, 78.2, 78.3, 100.8, 117.9, 118.0; HRMS (EI): m/z calcd for
C
Yield: 99% (398 mg); oil. 1H NMR (400 MHz, CDCl3):
d
1.31_1.38
17H31NO6P [M ꢁ H]þ 376.1889, found 376.1889.
(m, 7H), 1.79_1.93 (m, 2H), 2.00_2.46 (m, 5H), 2.83_2.98 (m, 2H),
3.72_3.80 (m, 2H), 4.06_4.22 (m, 6H), 4.60 (t, J ¼ 4.8 Hz, 1H), 6.05
(dd, J ¼ 3.2, 0.8 Hz,1H), 6.28 (dd, J ¼ 3.2, 1.6 Hz,1H), 7.31 (dd, J ¼ 3.2,
4.2.12. 3-Cyano-3-cyclohexyl-1-(1,3-dioxan-2-yl)propyl diethyl
0.8 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d 15.9, 16.0, 16.1 (16.05),
phosphate (10l)
Yield: 84% (325 mg); oil. 1H NMR (400 MHz, CDCl3):
d
1.12_1.40
16.1 (16.12), 22.7, 25.6, 29.4, 33.0 (33.00), 33.0 (33.04), 37.0 (36.97),
37.0 (37.01), 64.5, 64.6, 66.8, 100.6, 105.6, 110.2, 117.4, 117.5, 141.3,
153.1; HRMS (EI): m/z calcd for C18H27NO7P [M ꢁ H]þ 400.1525,
found 400.1523.
(m, 12H), 1.66_2.22 (m, 11H), 3.75 (td, J ¼ 12.0, 2.4 Hz, 2H), 4.06_4.23
(m, 6H), 4.58 (t, J ¼ 4.8 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d 16.0
(15.97), 16.0 (16.03), 16.1, 21.1, 25.6, 25.7, 25.8, 26.8, 29.0, 30.0, 30.1,
44.2, 44.3, 63.6, 63.7, 64.4, 64.5 (64.45), 64.5 (64.51), 66.8, 81.5, 81.6,
101.0, 117.5 (117.45), 117.5 (117.49); HRMS (EI): m/z calcd for
4.2.7. 3-Cyano-1-(1,3-dioxan-2-yl)-5-(thiophen-2-yl)pentan-3-yl
C
18H31NO6P [M ꢁ H]þ 388.1889, found 388.1891.
diethyl phosphate (10g)
Yield: 98% (406 mg); oil. 1H NMR (400 MHz, CDCl3):
d
1.32_1.40
(m, 7H), 1.80_1.94 (m, 2H), 2.00_2.49 (m, 5H), 3.02_3.18 (m, 2H),
3.72_3.80 (m, 2H), 4.06_4.24 (m, 6H), 4.61 (t, J ¼ 4.8 Hz, 1H), 6.84
(dd, J ¼ 3.6, 1.2 Hz, 1H), 6.92 (dd, J ¼ 4.8, 3.6 Hz, 1H), 7.15 (dd, J ¼ 4.8,
4.2.13. 3-Cyano-1-(1,3-dioxan-2-yl)-4,4-dimethylpentan-3-yl
diethyl phosphate (10m)
Yield: 98% (355 mg); oil. 1H NMR (400 MHz, CDCl3):
d 1.15 (s,
1.2 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d 15.9, 16.0, 16.1, 24.3, 25.6,
9H), 1.34_1.38 (m, 6H), 1.92_2.16 (m, 4H), 3.72_3.80 (m, 2H),
28.5, 29.5, 33.0, 33.1, 40.5, 40.6, 63.5, 63.6, 64.4, 64.5, 64.6, 66.8,
77.3, 100.6, 117.4, 117.5, 123.6, 124.7, 126.9, 142.0; HRMS (EI): m/z
calcd for C18H27NO6PS [M ꢁ H]þ 416.1297, found 416.1291.
4.06_4.23 (m, 6H), 4.62 (t, J ¼ 4.4 Hz, 1H); 13C NMR (100 MHz,
CDCl3): d 16.0 (15.96), 16.0 (15.97), 16.0 (16.02), 16.1, 25.3, 25.7, 29.4
(29.35), 29.4 (29.37), 30.7, 40.2 (40.15), 40.2 (40.19), 64.5 (64.47),
64.5 (64.54), 66.8 (66.79), 66.8 (66.80), 84.5, 84.7, 101.1, 116.7, 116.8;
HRMS (EI): m/z calcd for C16H29NO6P [M ꢁ H]þ 362.1733, found
362.1732.
4.2.8. 3-Cyano-1-(1,3-dioxan-2-yl)-5-(1H-indol-3-yl)pentan-3-yl
diethyl phosphate (10h)
Yield: 99% (444 mg); oil. 1H NMR (400 MHz, CDCl3):
d
1.30_140
(m, 7H), 1.82_1.94 (m, 2H), 2.00_2.14 (m, 2H), 1.98_2.53 (m, 3H),
2.94_3.10 (m, 2H), 3.72_3.80 (m, 2H), 4.07_4.30 (m, 6H), 4.61 (t,
J ¼ 4.8 Hz, 1H), 7.01 (brs, 1H), 7.12 (td, J ¼ 7.6, 1.2 Hz, 1H), 7.19 (td,
J ¼ 7.6,1.2 Hz,1H), 7.37 (dt, J ¼ 7.6,1.2 Hz,1H), 7.61 (d, J ¼ 7.6 Hz,1H),
4.2.14. 2-[(1,3-Dioxan-2-yl)methyl]-1-cyanocyclohexyl diethyl
phosphate (10n)
Yield: quant (360 mg); oil. 1H NMR (400 MHz, CDCl3):
8.25 (brs, 1H); 13C NMR (100 MHz, CDCl3):
d 15.9, 16.0 (15.96), 16.0
d
1.32_1.42 (m, 7H), 1.54_1.74 (m, 3H), 1.79_1.89 (m, 2H), 1.98_2.20
(15.99), 16.1, 19.8, 25.6, 29.5, 33.0, 33.1, 39.2, 39.3, 64.5, 64.6, 65.2,
66.8, 77.9, 78.0, 100.7, 111.2, 113.9, 117.9, 118.5, 119.3, 121.4, 122.0,
127.0, 136.3; HRMS (EI): m/z calcd for C22H31N2O6P [M]þ 450.1920,
found 450.1917.
(m, 4H), 2.68_2.74 (m, 1H), 3.70_3.82 (m, 2H), 4.06_4.25 (m, 6H),
4.62_4.68 (m, 1H); 13C NMR (100 MHz, CDCl3):
d
15.9 (15.91), 15.9
(15.92), 16.0 (15.98), 16.0 (16.00), 16.1, 20.1, 23.2, 24.1, 25.6, 26.4,
28.5, 28.6, 29.3, 35.6, 35.8, 36.1, 36.8, 41.0, 41.1, 42.3 (42.26), 42.3
(42.33), 63.5, 63.6, 64.2, 64.3, 64.4 (64.35), 64. 4 (64.41), 66.8, 76.8,
80.0, 80.1, 100.3 (100.26), 100.3 (100.34), 116.6, 116.7; HRMS (EI): m/
z calcd for C16H27NO6P [M ꢁ H]þ 360.1576, found 360.1577.
4.2.9. 3-Cyano-1-(1,3-dioxan-2-yl)butan-3-yl diethyl phosphate
(10i)
Yield: 83% (265 mg); oil. 1H NMR (400 MHz, CDCl3):
d
1.32_1.40
(m, 7H), 1.79_1.94 (m, 1H), 1.85 (s, 3H), 2.00_2.19 (m, 3H), 3.72_3.82
(m, 2H), 4.07_4.23 (m, 6H), 4.61 (t, J ¼ 4.8 Hz, 1H); 13C NMR
4.2.15. 3-Cyano-1-(1,3-dioxan-2-yl)-3-phenylpropyl diethyl
(100 MHz, CDCl3):
d 15.9, 16.0 (15.99), 16.0 (16.04), 16.1, 25.6, 26.3
phosphate (10o)
Yield: 98% (375 mg); oil. 1H NMR (400 MHz, CDCl3):
d
1.20_1.34
(26.30), 26.3 (26.33), 29.6, 35.8 (35.76), 35.8 (35.82), 63.5, 63.6,
64.3, 64.4, 64.5, 66.8, 74.2, 74.3, 100.6, 118.5 (118.47), 118.5 (118.51);
HRMS (EI): m/z calcd for C13H23NO6P [M ꢁ H]þ 320.1263, found
320.1262.
(m, 7H), 1.65 (ddt, J ¼ 13.6, 12.4, 4.8 Hz, 1H), 1.82 (ddt, J ¼ 13.2, 12.4,
4.8 Hz, 1H), 2.02 (qt, J ¼ 12.4, 4.8 Hz, 1H), 2.32 (dddd, J ¼ 14.0, 12.0,
4.8, 2.0 Hz, 1H), 2.48 (ddd, J ¼ 14.0, 12.4, 4.8 Hz, 1H), 3.67_3.74 (m,
2H), 3.89_420 (m, 6H), 4.53 (t, J ¼ 5.2 Hz, 1H), 7.39_7.45 (m, 3H),
7.58_7.62 (m, 2H); 13C NMR (100 MHz, CDCl3):
d 15.8, 15.9 (15.86),
4.2.10. 3-Cyano-1-(1,3-dioxan-2-yl)octan-3-yl diethyl phosphate
(10j)
15.9 (15.92), 25.6, 29.9, 37.8 (37.76), 37.8 (37.83), 64.3, 64.4, 66.8,
79.3, 79.4, 100.6, 117.2 (117.21), 117.2 (117.24), 125.6, 128.7, 129.6,
136.4 (136.39), 136.4 (136.41); HRMS (EI): m/z calcd for C18H26NO6P
[M]þ 383.1497, found 383.1496.
Yield: quant (380 mg); oil. 1H NMR (400 MHz, CDCl3):
d 0.90 (t,
J ¼ 6.8 Hz, 3H), 1.30_1.41 (m, 10H), 1.44_1.60 (m, 2H), 1.80_2.16 (m,
8H), 3.72_3.81 (m, 2H), 4.06_4.22 (m, 6H), 4.60 (t, J ¼ 4.8 Hz,1H); 13
C
NMR (100 MHz, CDCl3):
d 13.8, 15.9, 16.0 (15.95), 16.0 (16.01), 16.1,
22.3, 23.4, 25.6, 28.5, 28.6, 29.4, 31.2, 32.9 (32.89), 32.9 (32.94), 38.5
(38.47), 38.5 (38.51), 63.5, 63.6, 64.3, 64.4, 66.8, 71.2, 71.3, 78.1, 78.2,
100.8, 117.9, 118.0, 119.4 (119.35), 119.4 (119.39); HRMS (EI): m/z
calcd for C17H31NO6P [M ꢁ H]þ 376.1889, found 376.1888.
4.2.16. 3-Cyano-1-(1,3-dioxan-2-yl)-5-methoxypentan-3-yl diethyl
phosphate (10p)
Yield: 93% (365 mg); oil. 1H NMR (400 MHz, CDCl3):
d
1.32_1.39
(m, 6H), 1.83_1.90 (m, 2H), 1.93_2.13 (m, 2H), 2.14_2.20 (m, 2H), 2.28
(dt, J ¼ 14.4, 6.4 Hz, 1H), 2.41 (dt, J ¼ 14.4, 6.4 Hz, 1H), 3.45 (s, 3H),
3.62 (t, J ¼ 6.4 Hz, 2H), 3.72_3.81 (m, 2H), 4.07_4.22 (m, 6H), 4.59 (t,
4.2.11. 3-Cyano-1-(1,3-dioxan-2-yl)-6-methylheptan-3-yl diethyl
phosphate (10k)
Yield: quant (380 mg); oil. 1H NMR (400 MHz, CDCl3):
d
0.92 (d,
J ¼ 5.2 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d 15.9, 16.0, 16.1 (16.05),
J ¼ 5.6 Hz, 6H), 1.32_1.50 (m, 8H), 1.59 (quint, J ¼ 5.6 Hz, 1H),
16.1 (16.12), 25.6, 25.7, 29.5, 33.8 (33.79), 33.8 (33.83), 35.8, 35.9,
38.2 (38.20), 38.2 (38.23), 58.8, 63.1, 63.2, 63.6, 63.7, 64.4, 64.5, 64.6,
66.8, 67.4, 76.5, 76.6, 98.9, 100.8, 117.5, 117.6; HRMS (EI): m/z calcd
for C15H27NO7P [M ꢁ H]þ 364.1525, found 364.1522.
1.80_2.16 (m, 8H), 3.72_3.80 (m, 2H), 4.06_4.22 (m, 6H), 4.60 (t,
J ¼ 4.8 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d 15.9, 16.0 (16.00), 16.0
(16.04), 22.3, 22.4, 25.6, 27.8, 28.6 (28.56), 28.6 (28.60), 29.4, 32.5,
6

H. Yoneyama, K. Takatsuji, A. Ito et al.
Tetrahedron 82 (2021) 131914
4.3. General procedure for the reaction of CPs (10) with TMSN3/
Bu2SnO
4.3.7. 2-[6-(4-Methoxyphenyl)hex-3-yn-1-yl]-1,3-dioxane (7d)
Yield: 4% (11 mg); oil. 1H NMR (400 MHz, CDCl3):
d 1.33 (dsept,
J ¼ 13.2, 1.2 Hz, 1H), 1.74 (td, J ¼ 7.2, 5.6 Hz, 2H), 2.06 (qt, J ¼ 13.2,
4.8 Hz, 1H), 2.24 (tt, J ¼ 7.2, 2.4 Hz, 2H), 2.40 (tt, J ¼ 7.6, 2.4 Hz, 2H),
2.74 (t, J ¼ 7.2 Hz, 2H), 3.70_3.80 (m, 2H), 3.79 (s, 3H), 4.09 (qt,
J ¼ 5.2, 1.2 Hz, 2H), 4.57 (t, J ¼ 5.2 Hz, 1H), 6.84 (d, J ¼ 8.4 Hz, 2H),
TMSN3 (0.39 mL, 3 mmol) and Bu2SnO (75 mg, 0.3 mmol) were
added to a solution of CP 10 (1 mmol) in toluene (10 mL). The re-
action mixture was refluxed for 2 h. The solvent was evaporated to
give a crude residue, which was purified by column chromatog-
raphy (Hexane_AcOEt ¼ 9:1 to 7:3) to give cyclopentenone 13
together with alkyne 7.
7.14 (d, J ¼ 8.4 Hz, 2H); 13C NMR (100 MHz, CDCl3):
d 13.6, 21.2, 25.8,
34.3, 34.5, 55.2, 66.8, 79.7, 79.9, 100.6, 113.7, 129.4, 133.1, 157.9;
HRMS (EI): m/z calcd for C17H22O3 [M]þ 274.1569, found 274.1568.
4.3.8. 3-(4-Methoxyphenethyl)cyclopent-2-en-1-one (13d)
4.3.1. 2-(6-Phenylhex-3-yn-1-yl)-1,3-dioxane (7a)
Yield: 76% (164 mg); oil. 1H NMR (400 MHz, CDCl3):
d
2.38_2.42
Yield: 7% (17 mg); oil. 1H NMR (400 MHz, CDCl3):
d 1.33 (dsept,
(m, 2H), 2.56_2.60 (m, 2H), 2.70 (t, J ¼ 7.6 Hz, 2H), 2.86 (t, J ¼ 7.6 Hz,
2H), 3.79 (s, 3H),5.97 (quint, J ¼ 1.6 Hz, 1H), 6.84 (d, J ¼ 8.4 Hz, 2H),
J ¼ 13.2, 2.0 Hz, 1H), 1.74 (td, J ¼ 7.2, 5.2 Hz, 2H), 2.06 (qt, J ¼ 13.2,
5.2 Hz, 1H), 2.24 (tt, J ¼ 7.6, 2.4 Hz, 2H), 2.44 (tt, J ¼ 7.6, 2.4 Hz, 2H),
2.80 (t, J ¼ 7.2 Hz, 2H), 3.75 (tdd, J ¼ 11.2, 2.4, 1.6 Hz, 2H), 4.08 (ddt,
7.11 (d, J ¼ 8.4 Hz, 2H); 13C NMR (100 MHz, CDCl3):
d 31.7, 32.4, 35.2,
J ¼ 11.2, 4.8, 1.6 Hz, 2H), 4.57 (t, J ¼ 5.2 Hz,1H), 7.16_7.32 (m, 5H); 13
C
35.3, 55.2, 113.9, 129.0, 129.8, 132.5, 158.0, 181.9; HRMS (EI): m/z
calcd for C14H16O2 [M]þ 216.1150, found 216.1149.
NMR (100 MHz, CDCl3): d 13.6, 20.9, 25.8, 34.3, 34.8, 35.4, 66.8, 69.6,
80.0, 100.9, 125.8, 126.1, 128.3 (128.27), 128.3 (128.31), 128.4, 140.9,
141.5; HRMS (EI): m/z calcd for C16H20O2 [M]þ 244.1463, found
244.1460.
4.3.9. 2-[6-(4-Trifluoromethylphenyl)hex-3-yn-1-yl]-1,3-dioxane
(7e)
Yield: 8% (20 mg); oil. 1H NMR (400 MHz, CDCl3): 1.30_1.36 (m,
d
1H), 1.70_1.76 (m, 2H), 2.02_2.13 (m, 1H), 2.23 (t, J ¼ 7.2 Hz, 2H), 2.47
(t, J ¼ 7.2 Hz, 2H), 2.85 (t, J ¼ 7.2 Hz, 2H), 3.66_3.74 (m, 2H), 4.05_4.12
(m, 2H), 4.53 (t, J ¼ 5.2 Hz, 1H), 7.34 (d, J ¼ 8.0 Hz, 2H), 7.55 (d,
4.3.2. 3-Phenethylcyclopent-2-en-1-one (13a)
Yield: 80% (149 mg); wax. 1H NMR (400 MHz, CDCl3):
d
¼ 2.39_2.42 (m, 2H), 2.57_2.65 (m, 2H), 2.74 (t, J ¼ 8.0 Hz, 2H), 2.92
J ¼ 8.0 Hz, 2H); 13C NMR (100 MHz, CDCl3):
d 13.5, 20.5, 25.8, 34.3,
(t, J ¼ 8.0Hz, 2H), 5.99 (quint, J ¼ 1.6 Hz, 1H), 7.18_7.35 (m, 5H); 13
C
35.1, 66.8, 78.8, 80.6, 100.8, 124.3 (q, J ¼ 270.2 Hz), 125.2 (q,
J ¼ 3.8 Hz), 128.5 (q, J ¼ 34.9 Hz), 128.7, 128.8, 141.9; HRMS (EI): m/z
calcd for C17H19F3O2 [M]þ 258.1620, found 258.1621.
NMR (100 MHz, CDCl3):
d
¼ 31.7, 33.2, 35.0, 35.2, 126.3, 128.1, 128.5,
129.8, 140.4, 181.8, 210.0; HRMS (EI): m/z calcd for C13H14O [M]þ
186.1045, found 186.1041.
4.3.10. 3-(4-Trifluoromethylphenethyl)cyclopent-2-en-1-one (13e)
4.3.3. 2-[6-(p-Tolyl)hex-3-yn-1-yl]-1,3-dioxane (7b)
Yield: 58% (147 mg); oil. 1H NMR (400 MHz, CDCl3):
d
2.40_2.44
Yield: 5% (13 mg); oil. 1H NMR (400 MHz, CDCl3):
d 1.34 (dsept,
(m, 2H), 2.59_2.63 (m, 2H), 2.76 (t, J ¼ 8.0 Hz, 2H), 2.99 (t, J ¼ 8.0Hz,
2H), 5.99 (quint, J ¼ 1.6 Hz, 1H), 7.32 (d, J ¼ 8.0 Hz, 2H), 7.56 (d,
J ¼ 12.8, 2.4 Hz, 1H), 1.74 (td, J ¼ 7.2, 5.6 Hz, 2H), 2.06 (qt, J ¼ 12.8,
4.8 Hz, 1H), 2.24 (tt, J ¼ 7.2, 2.4 Hz, 2H), 2.32 (s, 3H), 2.42 (tt, J ¼ 7.6,
2.4 Hz, 2H), 2.76 (t, J ¼ 7.6 Hz, 2H), 3.70_3.78 (m, 2H), 4.09 (qt,
J ¼ 5.2, 1.2 Hz, 2H), 4.57 (t, J ¼ 5.2 Hz, 1H), 7.11 (s, 4H); 13C NMR
J ¼ 8.0 Hz, 2H); 13C NMR (100 MHz, CDCl3):
d 31.6, 32.9, 34.5, 35.2,
124.1 (q, J ¼ 270.2 Hz), 125.5 (q, J ¼ 3.8 Hz), 128.5, 128.7 (q,
J ¼ 32.6 Hz), 129.9, 144.5, 180.8, 209.7; HRMS (EI): m/z calcd for
(100 MHz, CDCl3): d 13.6, 21.0, 25.8, 34.3, 35.0, 66.8, 66.9, 79.7, 79.8,
C
14H13F3O [M]þ 254.0918, found 254.0916.
100.9, 128.2, 128.3, 129.0, 135.6, 137.9; HRMS (EI): m/z calcd for
C
17H20O2 [M]þ 258.1620, found 258.1621.
4.3.11. 2-[6-(Furan-2-yl)hex-3-yn-1-yl]-1,3-dioxane (7f)
Yield: 3% (7 mg); oil. 1H NMR (400 MHz, CDCl3):
d
1.32_1.38 (m,
1H), 1.74 (td, J ¼ 7.2, 5.2 Hz, 2H), 2.02_2.12 (m, 1H), 2.24 (tt, J ¼ 7.2,
2.4 Hz, 2H), 2.48 (tt, J ¼ 7.2, 2.4 Hz, 2H), 2.82 (t, J ¼ 7.6 Hz, 2H),
3.72_3.81 (m, 2H), 4.07_4.14 (m, 2H), 4.60 (t, J ¼ 5.2 Hz, 1H), 6.07
(dd, J ¼ 3.2, 0.8 Hz, 1H), 6.29 (dd, J ¼ 3.2, 1.6 Hz, 1H), 7.31 (dd, J ¼ 1.6,
4.3.4. 3-(4-Methylphenethyl)cyclopent-2-en-1-one (13b)
Yield: 48% (96 mg); oil. 1H NMR (400 MHz, CDCl3):
d 2.32 (s, 3H),
2.38_2.42 (m, 2H), 2.57_2.60 (m, 2H), 2.72 (t, J ¼ 8.0 Hz, 2H), 2.87 (t,
J ¼ 8.0Hz, 2H), 5.98 (quint, J ¼ 1.6 Hz, 1H), 7.08 (d, J ¼ 8.0 Hz, 2H),
7.11 (d, J ¼ 8.0 Hz, 2H); 13C NMR (100 MHz, CDCl3):
d 21.0, 31.7, 32.8,
0.8 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d 13.6, 18.0, 25.8, 27.9, 34.3,
35.1, 35.2, 128.0, 129.2, 129.8, 135.8, 137.4, 182.0, 210.1; HRMS (EI):
66.9, 79.1, 80.0, 100.9, 105.4, 110.1, 141.0, 154.6; HRMS (EI): m/z calcd
m/z calcd for C14H16O [M]þ 200.1201, found 200.1203.
for C14H18O3 [M]þ 234.1256, found 234.1255.
4.3.5. 2-[6-(4-chlorophenyl)hex-3-yn-1-yl]-1,3-dioxane (7c)
4.3.12. 3-[2-(Furan-2-yl)ethyl]cyclopent-2-en-1-one (13f)
Yield: 4% (11 mg); oil. 1H NMR (400 MHz, CDCl3):
d 1.28 (dsept,
Yield: 21% (37 mg); oil. 1H NMR (400 MHz, CDCl3):
d
2.39_2.42
(m, 2H), 2.57_2.61 (m, 2H), 2.77 (t, J ¼ 7.6 Hz, 2H), 2.94 (t, J ¼ 7.6 Hz,
2H), 5.98 (quint, J ¼ 1.6 Hz, 1H), 6.03 (dd, J ¼ 3.2, 0.8 Hz, 1H), 6.28
(dd, J ¼ 3.2, 1.6 Hz, 1H), 7.31 (dd, J ¼ 1.6, 0.8 Hz, 1H); 13C NMR
J ¼ 12.8, 1.2 Hz, 1H), 1.73 (td, J ¼ 7.2, 5.2 Hz, 2H), 2.06 (qt, J ¼ 12.8,
5.2 Hz, 1H), 2.22 (tt, J ¼ 7.2, 2.4 Hz, 2H), 2.42 (tt, J ¼ 7.2, 2.4 Hz, 2H),
2.76 (t, J ¼ 7.2 Hz, 2H), 3.68_3.76 (m, 2H), 4.09 (ddt, J ¼ 10.8, 4.8,
1.2 Hz, 2H), 4.52 (t, J ¼ 5.2 Hz, 1H), 7.15 (d, J ¼ 8.4 Hz, 2H). 7.26 (d,
(100 MHz, CDCl3):
d 25.6, 31.4, 31.7, 35.2, 105.5, 110.2, 129.8, 141.2,
J ¼ 8.4 Hz, 2H); 13C NMR (100 MHz, CDCl3):
d 13.5, 20.7, 25.8, 34.2,
34.6, 66.8, 79.1, 80.4,100.8,128.3,129.9,131.9,139.3; HRMS (EI): m/z
153.9, 181.0, 209.9; HRMS (EI): m/z calcd for C11H12O2 [M]þ
176.0837, found 176.0835.
calcd for C16H1935ClO2 [M]þ 278.1073, found 278.1072.
4.3.13. 2-[6-(Thiophen-2-yl)hex-3-yn-1-yl]-1,3-dioxane (7g)
4.3.6. 3-(4-Chlorophenethyl)cyclopent-2-en-1-one (13c)
Yield: 12% (29 mg); oil. 1H NMR (400 MHz, CDCl3): 1.31_1.38
d
Yield: 85% (188 mg); oil. 1H NMR (400 MHz, CDCl3):
d
2.39_2.45
(m, 1H), 1.76 (td, J ¼ 7.2, 5.2 Hz, 2H), 2.02_2.14 (m, 1H), 2.25 (tt,
J ¼ 7.2, 2.4 Hz, 2H), 2.49 (tt, J ¼ 7.2, 2.4 Hz, 2H), 3.01 (t, J ¼ 7.2 Hz,
2H), 3.72_3.80 (m, 2H), 4.07_4.15 (m, 2H), 4.60 (t, J ¼ 5.2 Hz, 1H),
6.85 (dd, J ¼ 3.2, 1.2 Hz, 1H), 6.93 (dd, J ¼ 5.2, 3.2 Hz, 1H), 7.14 (dd,
(m, 2H), 2.57_2.65 (m, 2H), 2.71 (t, J ¼ 8.0 Hz, 2H), 2.89 (t, J ¼ 8.0 Hz,
2H), 5.97 (quint, J ¼ 1.6 Hz, 1H), 7.13 (d, J ¼ 8.4 Hz, 2H), 7.27 (d,
J ¼ 8.4 Hz, 2H); 13C NMR (100 MHz, CDCl3):
d 31.6, 32.5, 34.8, 35.2,
128.6, 129.5, 129.9, 132.1, 138.9, 181.2, 209.8; HRMS (EI): m/z calcd
J ¼ 5.2, 1.2 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d 13.6, 21.4, 25.8,
for C13H1335ClO [M]þ 220.0655, found 220.0651.
29.7, 34.3, 66.9, 79.1, 80.5, 100.9, 123.4, 124.6, 126.6, 143.5; HRMS
7

H. Yoneyama, K. Takatsuji, A. Ito et al.
Tetrahedron 82 (2021) 131914
(EI): m/z calcd for C14H18O2S [M]þ 250.1027, found 250.1024.
2H), 2.20_2.13 (m, 3H), 2.23_2.28 (m, 1H), 3.71_3.79 (m, 2H), 4.10
(ddt, J ¼ 10.8, 4.8, 1.2 Hz, 2H), 4.51 (t, J ¼ 5.2 Hz, 1H), 5.12 (quint,
4.3.14. 3-[2-(Thiophen-2-yl)ethyl]cyclopent-2-en-1-one (13g)
J ¼ 1.6 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d 25.4, 25.8, 28.6, 33.3,
Yield: 31% (60 mg); oil. 1H NMR (400 MHz, CDCl3):
d
2.40_2.43
34.2, 39.3, 66.9, 102.0, 134.6, 140.8; HRMS (EI): m/z calcd for
(m, 2H), 2.58_2.62 (m, 2H), 2.81 (t, J ¼ 8.0 Hz, 2H), 3.14 (t, J ¼ 8.0 Hz,
2H), 6.00 (quint, J ¼ 1.6 Hz, 1H), 6.82 (dd, J ¼ 3.6, 1.2 Hz, 1H), 6.92
(dd, J ¼ 5.2, 3.6 Hz, 1H), 7.14 (dd, J ¼ 5.2, 1.2 Hz, 1H); 13C NMR
C
13H22O2 [M]þ 210.1620, found 210.1621.
4.3.22. 3-Cyclohexylcyclopent-2-en-1-one (13l)
(100 MHz, CDCl3):
d
27.4, 31.6, 35.2, 35.3, 123.5, 124.6, 126.9, 130.0,
Yield: 38% (62 mg); oil. 1H NMR (400 MHz, CDCl3): 1.20_1.42
d
143.1, 180.8, 209.8; HRMS (EI): m/z calcd for C11H12OS [M]þ
(m, 5H), 1.70_1.76 (m, 1H), 1.78_1.94 (m, 4H), 2.31 (tt, J ¼ 7.2, 3.2 Hz,
192.0609, found 192.0606.
1H), 2.37_2.42 (m, 2H), 2.58_2.63 (m, 2H), 5.92 (q, J ¼ 1.6 z, 1H); 13
C
NMR (100 MHz, CDCl3):
d 25.9, 26.0, 29.5, 31.2, 35.0, 41.9, 127.9,
4.3.15. 3-[6-(1,3-Dioxan-2-yl)hex-3-yn-1-yl]-1H-indole (7h)
187.7, 210.5; HRMS (EI): m/z calcd for C11H16O [M]þ 164.1201, found
Yield: 6% (17 mg); oil. 1H NMR (400 MHz, CDCl3):
d
1.32 (dsept,
164.1202.
J ¼ 13.6, 2.4 Hz, 1H), 1.75 (td, J ¼ 7.2, 5.2 Hz, 2H), 2.05 (qt, J ¼ 13.6,
4.8 Hz, 1H), 2.25 (tt, J ¼ 7.6, 2.4 Hz, 2H), 2.53 (tt, J ¼ 7.6, 2.4 Hz, 2H),
2.97 (t, J ¼ 7.6 Hz, 2H), 3.67_3.75 (m, 2H), 4.05_4.11 (m, 2H), 4.58 (t,
J ¼ 5.2 Hz, 1H), 7.07 (q, J ¼ 3.2 Hz, 1H), 7.11 (td, J ¼ 8.0, 2.4 Hz, 1H),
7.18 (td, J ¼ 8.0, 2.4 Hz,1H), 7.36 (d, J ¼ 8.0 Hz,1H), 7.61 (d, J ¼ 8.0 Hz,
4.3.23. 2-(4-Phenylbut-3-yn-1-yl)-1,3-dioxane (7o)
Yield: 78% (169 mg); oil. 1H NMR (400 MHz, CDCl3):
d 1.35
(dsept, J ¼ 13.6, 1.2 Hz, 1H), 1.89 (td, J ¼ 7.2, 5.2 Hz, 2H), 2.09 (qt,
J ¼ 13.6, 5.2 Hz, 1H), 2.51 (t, J ¼ 7.2 Hz, 2H), 3.75_3.83 (m, 2H), 4.11
(ddt, J ¼ 10.8, 4.8, 1.2 Hz, 2H), 4.71 (t, J ¼ 5.2 Hz, 1H), 7.25e7.30 (m,
1H), 8.19 (brs, 1H); 13C NMR (100 MHz, CDCl3):
d 13.6, 20.0, 25.2,
25.8, 34.3, 66.8, 79.6, 80.4,100.9,111.1,115.3,118.7,119.1,121.5,121.8,
127.3, 136.2; HRMS (EI): m/z calcd for C18H21NO2 [M]þ 283.1572,
found 283.1571.
2H), 7.38e7.41 (m, 2H); 13C NMR (100 MHz, CDCl3):
d 14.2, 25.8,
34.1, 66.9, 80.6, 89.3, 100.8, 123.8, 127.5, 128.1, 131.5; HRMS (EI): m/z
calcd for C14H16O2 [M]þ 216.1151, found 216.1148.
4.3.16. 3-[2-(1-Oxocyclopent-2-en-3-yl)ethyl]-1H-indole (13h)
4.3.24. (Z)-2-[5-Azido-3-(methoxymethylene)pentyl]-1,3-dioxane
Yield: 11% (25 mg); oil. 1H NMR (400 MHz, CDCl3):
d
2.39_2.43
(19)
(m, 2H), 2.60_2.64 (m, 2H), 2.85 (t, J ¼ 7.6 Hz, 2H), 3.07 (t, J ¼ 7.6 Hz,
2H), 6.04 (S, 1H), 6.99 (s, 1H), 7.13 (t, J ¼ 8.0 Hz, 1H), 7.21 (t,
J ¼ 8.0 Hz,1H), 7.37 (d, J ¼ 8.0 Hz,1H), 7.60 (d, J ¼ 8.0 Hz,1H), 8.06 (s,
Yield: 28% (67 mg); oil. 1H NMR (400 MHz, CDCl3):
d 1.34 (dsept,
J ¼ 13.6, 1.2 Hz, 1H), 1.62_1.70 (m, 2H), 1.98_2.18 (m, 3H), 2.34 (t,
J ¼ 7.2 Hz, 2H), 3.29 (t, J ¼ 7.2 Hz, 2H), 3.55 (s, 3H), 3.72e3.80 (m,
2H), 4.10 (ddt, J ¼ 10.8, 5.2, 1.2 Hz, 2H), 4.50 (t, J ¼ 5.2 Hz, 1H), 5.87
1H); 13C NMR (100 MHz, CDCl3):
d 22.9, 31.7, 33.9, 35.3, 111.2, 114.9,
118.5, 119.4, 121.3, 122.2, 127.0, 129.7, 136.3, 182.7, 210.2; HRMS (EI):
(s, 1H); 13C NMR (100 MHz, CDCl3):
d
¼ 25.8, 26.0, 26.8, 34.0, 49.2,
m/z calcd for C15H15NO [M]þ 225.1154, found 225.1157.
59.4, 66.8, 101.6, 112.8, 144.5; HRMS (EI): m/z calcd for C11H18N3O3
[M ꢁ H]þ 240.1348, found 240.1346; FTIR (NaCl, cmꢁ1): 2095(N3),
1675(C]CeO-).
4.3.17. 3-Methylcyclopent-2-en-1-one (13i) [20]
Yield: 63% (60 mg); oil. 1H NMR (400 MHz, CDCl3):
d 2.14 (s, 3H),
2.41_2.44 (m, 2H), 2.56_2.60 (m, 2H), 5.95 (sext, J ¼ 1.6 Hz, 1H); 13
C
4.4. Reaction of CP 10n with TMSN3/Bu2SnO
NMR (100 MHz, CDCl3):
d
¼ 19.4, 33.0, 35.7, 130.7, 179.0, 210.3.
TMSN3 (0.39 mL, 3 mmol) and Bu2SnO (75 mg, 0.3 mmol) were
added to a solution of CP 10n (360 mg, 1 mmol) in toluene (10 mL).
The reaction mixture was heated at reflux for 2 h and then evap-
orated to give a crude residue, which was purified by chromatog-
raphy (Hexane/AcOEt ¼ 9/1) to give a 1:1 mixture (96 mg) of
cyclopentenone 13n [21] and dephosphorylated compound 18, the
latter of which was further purified.
4.3.18. 3-Pentylcyclopent-2-en-1-one (13j)
Yield: 53% (80 mg); oil. 1H NMR (400 MHz, CDCl3):
d
0.91 (t,
J ¼ 7.2 Hz, 3H), 1.29_1.38 (m, 4H), 1.59 (quint, J ¼ 7.2 Hz, 2H),
2.38_2.44 (m, 4H), 2.56_2.60 (m, 2H), 5.95 (quint, J ¼ 1.6 Hz, 1H); 13
C
NMR (100 MHz, CDCl3):
d
¼ 13.9, 22.4, 26.7, 31.4, 31.5, 33.5, 35.3,
129.4, 183.4, 210.3; HRMS (EI): m/z calcd for C10H16O [M]þ 150.1201,
found 150.1203.
4.4.1. 2-[(1,3-Dioxan-2-yl)methyl]cyclohexane-1-carbonitrile (18)
4.3.19. 2-[2-(3-Ethylcyclopent-1-en-1-yl)ethyl]-1,3-dioxane (17j)
1H NMR (400 MHz, CDCl3): 1.22_1.39 (m, 3H), 1.52_1.87 (m,
d
Yield: 11% (23 mg); oil. 1H NMR (400 MHz, CDCl3):
d
0.87 (t,
7H), 1.91_2.14 (m, 3H), 3.00_3.05 (m, 1H), 3.71_3.81 (m, 2H),
J ¼ 7.6 Hz, 3H), 1.20_1.45 (m, 5H), 1.71_1.78 (m, 2H), 1.98_2.25 (m,
5H), 2.48_2.58 (m, 2H), 3.76 (td, J ¼ 12.4, 2.4 Hz, 2H), 4.11 (qt, J ¼ 5.2,
1.2 Hz, 2H), 4.52 (t, J ¼ 5.2 Hz, 1H), 5.30 (q, J ¼ 1.6 Hz, 1H); 13C NMR
4.06_4.13 (m, 2H), 4.62 (t, J ¼ 5.2 Hz, 1H); 13C NMR (100 MHz,
CDCl3): d 22.0, 25.3, 25.7, 28.7, 29.2, 33.0, 34.0, 39.7, 66.8, 66.9,100.1,
120.7; HRMS (EI): m/z calcd for C12H19NO3 [M]þ 209.1416, found
(100 MHz, CDCl3):
d
12.1, 25.5, 25.8, 29.0, 29.9, 33.4, 34.6, 47.2, 66.9,
209.1416; FTIR (NaCl, cmꢁ1): 2234 (CN).
102.0, 127.9, 143.4; HRMS (EI): m/z calcd for C13H22O2 [M]þ
210.1620, found 210.1617.
4.5. Synthesis of dechlorotrichodenone 21
4.3.20. 3-Isopentylcyclopent-2-en-1-one (13k)
4.5.1. (R)-5-(1,3-Dioxan-2-yl)-3-oxopentan-2-yl acetate (9q)
A solution of 2-(2-bromoethyl)-1,3-dioxane (0.54 mL, 4 mmol)
in THF (5 mL) was added to a suspension of magnesium (96 mg,
4 mmol) in THF (5 mL) with stirring and stirred at rt for 0.5 h. After
the magnesium was consumed by the exothermic reaction, the
solution of the generated Grignard reagent was injected dropwise
Yield: 37% (56 mg); oil. 1H NMR (400 MHz, CDCl3):
d 0.93 (d,
J ¼ 6.8 Hz, 6H), 1.44_1.50 (m, 2H), 1.60 (nonet, J ¼ 6.8 Hz, 1H),
2.38_2.44 (m, 4H), 2.57_2.61 (m, 2H), 5.95 (quint, J ¼ 1.6 Hz, 1H); 13
C
NMR (100 MHz, CDCl3):
d
¼ 22.3, 27.8, 31.4, 31.5, 35.3, 129.3, 183.5;
HRMS (EI): m/z calcd for C10H16O [M]þ 152.1201, found 152.1201.
over 15 min via
a
syringe to
a
solution of (R)-(þ)-2-
4.3.21. 2-[2-(3,3-Dimethylcyclopent-1-en-1-yl)ethyl]-1,3-dioxane
acetoxypropionyl chloride 20 (0.64 mL, 5 mmol) in THF (15 mL)
_
(17k)
in another flask at 78 ꢀC. The mixture was allowed to warm to rt
Yield: 42% (88 mg); oil. 1H NMR (400 MHz, CDCl3):
d
1.01 (s, 6H),
and stirred for 3 h at the same temperature. The reaction mixture
was quenched with saturated NH4Cl and extracted with AcOEt. The
1.34 (dsept, J ¼ 13.6,1.2 Hz,1H),1.65 (t, J ¼ 7.2 Hz, 2H),1.70_1076 (m,
8

H. Yoneyama, K. Takatsuji, A. Ito et al.
Tetrahedron 82 (2021) 131914
organic layer was washed with saturated NH4Cl, saturated NaHCO3,
and brine, dried over anhydrous Na2SO4, filtered and then evapo-
rated. The residual oil was purified by column chromatography
(Hexane/AcOEt ¼ 4/1) to give 9q (821 mg 89%) as an oil.
chromatography (Hexane/AcOEt
phenethylcyclopent-2-en-1-one 13a (6.9 mg, 93%) as an oil.
¼
7/3) to afford 3-
Declaration of competing interest
1H NMR (400 MHz, CDCl3):
d
1.34 (dsept, J ¼ 13.6, 1.2 Hz, 1H),
1.40 (d, J ¼ 7.2 Hz, 3H), 1.90 (td, J ¼ 7.2, 5.2 Hz, 2H), 2.05 (qt, J ¼ 13.6,
5.2 Hz, 1H), 2.14 (s, 3H), 2.57 (dt, J ¼ 18.0, 7.2 Hz, 1H), 2.64 (dt,
J ¼ 18.0, 7.2 Hz, 1H, 3.70_3.79 (m, 2H), 4.07 (ddt, J ¼ 12.0, 5.2, 1.2 Hz,
2H), 4.57 (t, J ¼ 5.2 Hz, 1H), 5.10 (q, J ¼ 7.2 Hz, 1H); 13C NMR
The authors declare that they have no known competing
financial interests or personal relationships that could have
appeared to influence the work reported in this paper.
(100 MHz, CDCl3):
d
¼ 16.1, 20.8, 25.7, 28.4, 32.1, 66.8, 74.6, 100.5,
Acknowledgments
170.3, 207.1; HRMS (EI): m/z calcd for C11H17O5 [M ꢁ H]þ 229.1076,
found 229.1080.
We would like to thank Professor Emeritus Takayuki Shioiri at
Nagoya City University for providing encouragement. We thank Ms.
S. Tajima, and Ms. R. Kadowaki at our lab for their technical support.
This work was financially supported by research funds from the
Osaka University of Pharmaceutical Sciences.
4.5.2. (2R)-3-Cyano-3-[(diethoxyphosphoryl)oxy]-5-(1,3-dioxan-2-
yl)pentan-2-yl acetate (10q)
DEPC (1.4 mL, 8.9 mmol) and LiCN (147 mg, 4.4 mmol) were
added to a solution of ketone 9q (1.70 mg, 7.4 mmol) in THF (20 mL)
and the reaction mixture was stirred for 0.5 h at rt. The resulting
mixture was diluted with AcOEt, washed with saturated NH4Cl and
brine. The organic layer was dried over Na2SO4, filtered, and
evaporated to give a crude residue, which was purified by column
chromatography (Hexane/AcOEt ¼ 1/1) to give 10q (3.00 g, quant).
Appendix A. Supplementary data
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.tet.2020.131914.
1H NMR (400 MHz, CDCl3):
d
1.33_1.45 (m, 10H), 1.80_1.92 (m,
References
2H), 2.00_2.30 (m, 3H), 2.11 (s, 1.5H), 2.12 (s, 1.5), 3.71_3.80 (m, 2H),
4.05_4.24 (m, 6H), 4.57_4.62 (m, 1H), 5.21 (q, J ¼ 5.6 Hz, 0.5H), 5.31
[1] For recent reviews on DEPC and CPs, see:. (a) S. Harusawa, T. Shioiri, Tetra-
hedron 72 (2016) 8125_8200;
(q, J ¼ 5.6 Hz, 0.5H); 13C NMR (100 MHz, CDCl3):
d 14.9, 15.0, 15.9,
(b) S. Harusawa, Chem. Pharm. Bull. 68 (2020) 1_33.
16.0, 21.0, 25.6, 28.9, 29.6, 29.7, 64.7, 64.8, 66.8, 70.9, 71.0, 79.0, 79.1,
[2] (a) S. Harusawa, R. Yoneda, T. Kurihara, Y. Hamada, T. Shioiri, Chem. Pharm.
Bull. 31 (1983) 2932e2935;
100.5, 100.6, 115.9, 169.4, 169.5; HRMS (EI): m/z calcd for
C
16H27NO8P [M ꢁ H]þ 392.1475, found: 392.1471.
(b) S. Harusawa, R. Yoneda, T. Kurihara, Y. Hamada, T. Shioiri, Tetrahedron
Lett. 25 (1984) 427e428.
[3] (a) H. Behringer, M. Matner, Tetrahedron Lett. 7 (1966) 1663e1669;
(b) D.J. Wardrop, J.P. Komenda, Org. Lett. 14 (2012) 1548e1551;
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F. Couty, Eur. J. Org Chem. (2019) 342e350;
4.5.3. (R)-1-(3-Oxocyclopent-1-en-1-yl)ethyl acetate (13q)
TMSN3 (0.39 mL, 3 mmol) and Bu2SnO (75 mg, 0.3 mmol) were
added to a solution of CP 10q (393 mg, 1 mmol) in toluene (10 mL).
The reaction mixture was heated at reflux for 4 h. After evaporation
of the solvent, the residue was purified by column chromatography
(Hexane/AcOEt ¼ 3/1) to give 13q (77 mg, 46%).
(d) P.D. Alexakos, D.J. Wardrop, J. Org. Chem. 84 (2019) 12430e12436.
ꢀ
[4] (a) S. Czernecki, J.-M. Valery, J. Carbohydr. Chem. 5 (1986) 235e240;
ꢀ
ꢀ
(b) M.J. Perez-Perez, M.J. Camarasa, Tetrahedron 50 (1994) 7269e7282;
(c) A. Nguyen Van Nhien, R. Cordonnier, M.D. Le Bas, S. Delacroix, E. Soriano,
J. Marco-Contelles, D. Postel, Tetrahedron 65 (2009) 9378e9394;
(d) A. Nguyen Van Nhien, E. Soriano, J. Marco-Contelles, D. Postel, Carbohydr.
Res. 344 (2009) 1605e1611;
[
a
]
D
¼ þ56.5ꢀ (c 1.00, CHCl3); 1H NMR (400 MHz, CDCl3):
d 1.47
(d, J ¼ 6.8 Hz, 3H), 2.12 (s, 3H), 2.46 (t, J ¼ 4.8 Hz, 2H), 2.56_2.72 (m,
2H), 5.64 (q, J ¼ 6.8 Hz, 1H), 6.07 (q, J ¼ 1.6 Hz, 1H); 13C NMR
(e) R. Cordonnier, A. Nguyen Van Nhien, E. Soriano, J. Marco-Contelles,
D. Postel, Tetrahedron 66 (2010) 736e742.
(100 MHz, CDCl3):
d 18.9, 20.9, 27.9, 34.9, 69.3, 128.7, 169.9, 179.4,
[5] For a recent review on alkylidene carbene chemistry, see, R.S. Grainger,
K.R. Munro, Tetrahedron 71 (2015) 7795e7835.
[6] (a) H. Yoneyama, M. Numata, K. Uemura, Y. Usami, S. Harusawa, J. Org. Chem.
82 (2017) 5538e5556;
208.7; HRMS (EI): m/z calcd for C9H12O3 [M]þ 168.0787, found
168.0787.
(b) H. Yoneyama, K. Uemura, Y. Usami, S. Harusawa, Tetrahedron 73 (2017)
6109e6117;
(c) H. Yoneyama, K. Uemura, Y. Usami, S. Harusawa, Tetrahedron 74 (2018)
2143e2150;
(d) H. Yoneyama, F. Hisaka, D. Fujisue, Y. Usami, Z. Zhao, S. Harusawa, Het-
erocycles 96 (2018) 106e126.
4.5.4. Dechlorotrichodenone (21) [14,15]
3 N HCl (2 mL) was added to a solution of 13q in MeOH (10 mL).
The reaction mixture was stirred for 24 h at rt. The solvent was
evaporated to give a crude residue, which was purified by column
chromatography (Hexane/AcOEt
trichodenone 21 (103 mg, 82%).
¼
1/9) to give dechloro-
[7] For
a review on the generation of alkylidene carbenes from CPs, see
H. Yoneyama, S. Harusawa, Heterocycles 96 (2018) 2037e2078.
[8] A. Sakai, T. Aoyama, T. Shioiri, Tetrahedron Lett. 41 (2000) 6859e6863.
[9] For a review on TMSCHN2, see Y. Hari, T. Aoyama, T. Shioiri, in: M. Oestreich
(Ed.), Science of Synthesis Knowledge Updates 2010/4, Thieme, Stuttgart,
2011, pp. 25e68.
[
a
]
¼ _1.6ꢀ (c 1.00, CHCl3); 1H NMR (400 MHz, CDCl3):
d 1.45 (d,
D
J ¼ 6.8 Hz, 3H), 2.44_2.48 (brm, 2H), 2.63_2.68 (brm, 2H), 4.66 (q,
J ¼ 6.8 Hz, 1H), 6.14 (s, 1H); 13C NMR (100 MHz, CDCl3):
d
¼ 21.9,
[10] For
a recent review of the synthetic method used to prepare 2-
21.8, 35.2, 67.6, 127.7, 185.6, 210.3.
cyclopentenones, see D.J. Aitken, H. Eijsberg, A. Frongia, J. Ollivier, P.P. Piras,
Synthesis 46 (2014) 1e24.
4.6. Reaction of ketal-protected cyclopentenone 12a with TMS-
phosphate (4)
[11] H. Yoneyama, N. Oka, Y. Usami, S. Harusawa, Tetrahedron Lett. 61 (2020)
151517.
[12] When the reaction was carried out with addition of water, the yield of 13a
(13%) was remarkably decreased (see S.D.).
Diethyl phosphate (0.18 mL,1.5 mmol) was added to a mixture of
TMSCl (0.39 mL, 3 mmol) and Et3N (0.84 mL, 6 mmol) at 0 ꢀC. The
reaction mixture was warmed to rt, and stirred for 24 h at the same
temperature, and then distilled under reduced pressure (57_59 ꢀC,
[13] Gilbert and co-workers reported that the order of the reactivity for the CeH
insertion of an alkylidene carbene is primary < secondary < tertiary CeH
bond, see J.C. Gilbert, D.H. Giamalva, U. Weerasooriya, J. Org. Chem. 48 (1983)
5251e5256.
[14] T. Amagata, Y. Usami, K. Minoura, T. Ito, A. Numata, J. Antibiot. 51 (1998)
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[15] Y. Usami, T. Ikura, T. Amagata, A. Numata, Tetrahedron: Asymmetry 11 (2000)
3711e3725.
[16] Y.-P. Song, F.-P. Miao, S.-T. Fang, X.-L. Yin, N.-Y. Ji, Mar. Drugs 16 (2018) 266.
[17] The specific rotation of dechlorotrichodenone c was not be determined due to
7 mmHg) to give TMS-phosphate (4). 4 (9
mL, 0.04 mmol) was
added to a solution of ketal 12a (10.0 mg, 0.04 mmol) in toluene
(2 mL). After heating under reflux for 1 h, the reaction mixture was
evaporated to give a crude residue, which was purified by column
9

H. Yoneyama, K. Takatsuji, A. Ito et al.
Tetrahedron 82 (2021) 131914
John Wiley & Sons, Hoboken, 2014, pp. 576e614.
the very low values reported in References 14 and 15.
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130 (1999) 1257e1268.
[19] P.G.M. Wults, in: Greene’s Protective Groups in Organic Synthesis, _fifth ed.,
10