Copper-catalyzed asymmetric silylative cyclization of cyclohexadienone-containing 1,6-enynes

Article abstract of DOI:10.1016/j.tet.2018.12.002

The first copper-catalyzed asymmetric silylative cyclization of cyclohexadienone-containing 1,6-enynes has been accomplished through a tandem process: regioselective silylcupration of terminal unactivated alkynes and subsequently enantioselective conjugate addition to cyclohexadienones. This reaction proceeded smoothly to afford the cis-hydrobenzofuran and cis-hydroindole frameworks bearing two consecutive chiral carbon centers in high to excellent yields and moderate enantioselectivities. Additionally, the cyclization products could be readily subjected to several transformations for elaborating synthetic utilities.

Full text of DOI:10.1016/j.tet.2018.12.002

Tetrahedron xxx (xxxx) xxx
Contents lists available at ScienceDirect
Tetrahedron
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Copper-catalyzed asymmetric silylative cyclization of
cyclohexadienone-containing 1,6-enynes
,
,
,
b
,
, b, **
Cheng-Yu He a 1, Li-Bo Xie a 1, Rui Ding b, Ping Tian a *, Guo-Qiang Lin a
a CAS Key Laboratory of Synthetic Chemistry of Natural Substances, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry,
University of Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032, China
b Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, 201203,
China
a r t i c l e i n f o
a b s t r a c t
Article history:
The first copper-catalyzed asymmetric silylative cyclization of cyclohexadienone-containing 1,6-enynes
has been accomplished through a tandem process: regioselective silylcupration of terminal unac-
tivated alkynes and subsequently enantioselective conjugate addition to cyclohexadienones. This reac-
tion proceeded smoothly to afford the cis-hydrobenzofuran and cis-hydroindole frameworks bearing two
consecutive chiral carbon centers in high to excellent yields and moderate enantioselectivities. Addi-
tionally, the cyclization products could be readily subjected to several transformations for elaborating
synthetic utilities.
Received 13 October 2018
Received in revised form
29 November 2018
Accepted 2 December 2018
Available online xxx
Keywords:
Copper catalysis
1,6-Enynes
© 2018 Elsevier Ltd. All rights reserved.
Silylative cyclization
cis-Hydrobenzofuran
1. Introduction
Ojima and coworkers in 1992 [3]. Subsequently, several research
groups have made contributions in this field [4]. However, the
Alkenylsilanes have found widespread applications in modern
organic synthesis community as versatile building blocks, which
could be efficiently utilized in Fleming-Tamao oxidation,
palladium-catalyzed cross-coupling reactions, etc [1]. In recent
years, transition-metal-catalyzed tandem silylation of alkynes by
trapping the alkenylsilyl-metal intermediates with various elec-
trophiles has been extensively studied, affording a variety of
functionalized alkenylsilanes [2]. Among these works, the silylative
cyclization of 1,6-enynes has spurred substantial interests of
chemists for its applications in the construction of five-membered
carbocyclic and heterocyclic frameworks since its first report by
asymmetric variants still remain extremely rare [5,6]until 2003
Widenhoefer and co-workers disclosed the first example of the
asymmetric silylative cyclization of 1,6-enynes catalyzed by a
cationic rhodium bis(phosphine) complex to offer silylated alkyli-
denecyclopentanes in good to excellent enantioselectivities
(Scheme 1a) [5]. Soon afterwards, Zhou and coworkers achieved
the excellent enantioselectivities in the same reaction using a
powerful catalyst, namely the rhodium complex of spiro diphos-
phine SDP (Scheme 1a) [6]. Although these elegant reports have
exerted a significant impact in this field [7], the non-noble metal
catalysis, including Cu-catalyzed asymmetric silylative cyclization
of cyclohexadienone-containing 1,6-enynes is under developed,
which generates more than one stereocenters to gain access to
more complicated bicyclic scaffolds.
Recently, we have devoted to the subject of transition-metal-
catalyzed desymmetrization of cyclohexadienone-containing 1,6-
enynes and 1,6-enallenes [8]. Encouraged by these advances, we
decide to investigate the Cu-catalyzed asymmetric silylative cycli-
zation of cyclohexadienone-containing 1,6-enynes (Scheme 1b). In
the presence of a silylboronate reagent (PhMe2Si-Bpin) introduced
by Suginome and Ito [9], the direct conjugate silylation of enone
need to be minimized in order to obtain the cyclization products,
and such pathway is supposed to be suppressed by the neighboring
* Corresponding author. CAS Key Laboratory of Synthetic Chemistry of Natural
Substances, Center for Excellence in Molecular Synthesis, Shanghai Institute of
Organic Chemistry, University of Chinese Academy of Sciences, 345 Lingling Road,
Shanghai, 200032, China.
** Corresponding author. CAS Key Laboratory of Synthetic Chemistry of Natural
Substances, Center for Excellence in Molecular Synthesis, Shanghai Institute of
Organic Chemistry, University of Chinese Academy of Sciences, 345 Lingling Road,
Shanghai, 200032, China.
E-mail addresses: tianping@shutcm.edu.cn, tianping@sioc.ac.cn (P. Tian), lingq@
sioc.ac.cn (G.-Q. Lin).
1
These authors contributed equally.
https://doi.org/10.1016/j.tet.2018.12.002
0040-4020/© 2018 Elsevier Ltd. All rights reserved.
Please cite this article as: C.-Y. He et al., Copper-catalyzed asymmetric silylative cyclization of cyclohexadienone-containing 1,6-enynes,
Tetrahedron, https://doi.org/10.1016/j.tet.2018.12.002

2
C.-Y. He et al. / Tetrahedron xxx (xxxx) xxx
Table 1
Selected optimization studies.a
Entry
L
Solvent
Yield [%]b
eec
1
2
3
4
5
6
7
8
PPh3
L1
L2
L3
L4
L5
L6
L6
L6
L6
THF
THF
THF
THF
THF
THF
THF
Toluene
Et2O
THF
98
35
<10
77
0
0
e
Scheme 1. Strategic design of Cu-catalyzed asymmetric silylative cyclization of
cyclohexadienone-containing 1,6-enynes.
16
e
<10
80
5
99d
99d
95d
96d
68
53
50
71
steric hindrance [10]. The regioselective
a-silylcupration over b-
9
10e
silylcupration process has been found in the Cu-catalyzed hydro-
silylation of terminal unactivated alkynes [11]. However, the
regioselective b-silylcupration of terminal alkynes is supposed to
take place due to the O-coordination between copper and the
propargyl ether unit in our case (Scheme 1, T1). Then, the resulting
silylated alkenyl-copper intermediates (T2) undergo enantiose-
lective conjugate addition to the cyclohexadienone moieties in a
syn-fashion to generate the desired silylative cyclization products.
Nevertheless, the enantioselective control remains quite chal-
lenging during the cyclization process.
a
Reactions were performed under an Ar atmosphere.
b
c
Determined by 1H NMR (400 MHz) analysis of crude mixtures.
Determined by HPLC analysis.
d
e
Yield of isolated product 3a.
t-BuOH and KF were used instead of MeOH and t-BuONa, respectively.
With the optimal reaction condition identified, various sub-
strates were investigated and the results are summarized in Table 2.
With the R substituent as alkyl, cycloalkyl, phenyl, benzyl, vinyl,
and allyl group, the reactions proceeded smoothly with excellent
yields (88e98%) and moderate enantioselectivities (up to 71% ee,
Table 2, 3a‒3j). With a heteroatom (Br, I, O, Si, S, and N) as part of R
in the substrates 1, the outcome of the reactions remained prom-
ising, and the absolute configuration of (S,S)-3k was unambigu-
ously determined by X-ray crystallography (Table 2, 3k‒3r) [12,13].
It is a remarkable fact that the bromo- and iodopropyl groups in
substrates 1k and 1m could be tolerated in this reaction, which
implied that the silylated alkenyl-copper intermediates selectively
underwent conjugate addition to enone rather than nucleophilic
substitution in both cases [14]. As for the pharmaceutical com-
pound, estrone-tethered 1,6-enyne 1s, the cyclization occurred
uneventfully with high yield and moderate diastereoselectivity
(80:20 d.r., Table 2, 3s). In consistence with O-linked substrates, the
N-linked 1,6-enyne 1t also afforded the corresponding cis-hydro-
indole product. However, the C-linked 1,6-enyne 1u underwent
direct protonation after silylcupration of alkyne and failed to
generate the cyclization product, presumably due to the absence of
the Thorpe-Ingold effect [15]. As for the cyclohexadienone-tethered
internal alkyne substrate 1v, the silylative cyclization also
happened with 32% yield but low enantioselectivity (31% ee). The
main byproduct is the further conjugate silylation product.
2. Results/discussion
With these considerations in mind, we commenced to investi-
gate the silylative cyclization of the model substrate 1a with PPh3 as
the ligand. To our delight, the desired racemic product 3a was ob-
tained in almost quantitative yield (Table 1, entry 1). In order to gain
the enantioenriched product, chiral monophosphine ligands,
including (Ra)-Monophos (L1) and (Ra)-MOP (L2) were immedi-
ately examined. However, low yields and no enantioselectivities
were observed to our disappointment (Table 1, entries 2 and 3).
Next, a set of privileged nonracemic bisphosphine ligands were
evaluated and selected results were summarized in Table 1 [12]. As
for the commonly used bisphosphine ligand, (R)-BINAP (L3), high
yield and poor enantioselectivity (16% ee) was obtained (Table 1,
entry 4). When electronically biased bisphosphine ligand, (R, R)-
Quinoxp* (L4) was used in this reaction, the desired product was
formed in very low yield (Table 1, entry 5). Electron-rich bisphos-
phine ligand, (R,R,S,S)-Duanphos (L5), promoted the reaction with
good yield, but showed almost invalid in the enantioselective
control (Table 1, entry 6). Eventually, (R,R)-Ph-BPE (L6) was found
to be an optimal choice for the Cu-catalyzed silylative cyclization of
1,6-enyne (Table 1, entry 7). Other solvents, including toluene and
diethyl ether, were used instead of THF, but no further improve-
ment was observed (Table 1, entries 8 and 9). When t-BuOH and KF
were used instead of MeOH and t-BuONa, respectively, a slightly
better enantioselectivity (71% ee) was achieved (Table 1, entry 10).
To demonstrate the utility of the cyclization products, their
further transformations were elaborated in Scheme 2. The alke-
nylsilane 3a was readily converted, through Hiyama cross-coupling
with phenyl iodide, to a known compound (S,S)-4a [16]. When 3m
Please cite this article as: C.-Y. He et al., Copper-catalyzed asymmetric silylative cyclization of cyclohexadienone-containing 1,6-enynes,
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C.-Y. He et al. / Tetrahedron xxx (xxxx) xxx
3
Table 2
Substrate scope.a
Scheme 2. Synthetic transformation.
3. Conclusion
In summary, through tandem regioselective silylcupration of
terminal unactivated alkynes and enantioselective conjugate
addition to cyclohexadienones, copper-catalyzed asymmetric sily-
lative cyclization of cyclohexadienone-containing 1,6-enynes has
been developed with high efficiency, thus providing enantioen-
riched cis-hydrobenzofuran and cis-hydroindole frameworks with
high to excellent yields (up to 98%) and moderate enantiose-
lectivities (up to 71% ee). Meanwhile, this mild transformation is
well compatible with a wide range of functional groups, which
allows further conversion of the cyclization products to the bridged
and tricyclic ring structures. Further studies on the applications of
the cyclohexadienone-containing 1,6-enynes are in progress in our
laboratories and will be reported in due course.
4. Experimental section
4.1. General methods
All solvents were dried before use following the standard pro-
cedures. Unless otherwise indicated, all starting materials were
obtained from commercial suppliers and were used without further
purification. The 1H and 13C NMR spectra were recorded on Bruker
AV-400 MHz in the indicated solvents. Chemical shifts are reported
in
CDCl3 (
d
(ppm) referenced to an internal TMS standard for 1H NMR and
d
¼ 77.0 ppm) for 13C NMR. Coupling constants (J) are quoted
in Hz. Optical rotations were measured on a JASCO P-1030 polar-
imeter. IR spectra were recorded on Nicolet iN 10 MX. ESI mass
spectra were recorded on Agilent1200/G6100A.
was treated with t-BuLi, the resulting alkyllithium underwent an
intramolecular Michael addition to deliver the tricyclic ketone 4m.
Alternatively, a weaker base LiHMDS could promoted an intra-
molecular alkylation reaction to afford the bridged ring product
5m. Additionally, an intramolecular oxa-Michael addition reaction
occurred equally well in situ in a syn fashion to furnish 4o after
removing the t-butyldimethylsilyl protecting group in 3o under
TBAF conditions. All transformations as above proceeded smoothly
with almost no loss of the enantiomeric excesses.
4.2. General procedure for the synthesis of 3a-3v
A dried Schlenk flask was charged with CuCl (1.0 mg, 0.01 mmol,
10 mol%), ligand L6 (6.1 mg, 0.012 mmol, 12 mol%), PhMe2Si-Bpin
(2, 41 mL, 0.15 mmol, 1.5 equiv), KF (2.4 mg, 0.040 mmol, 40 mol%)
and anhydrous THF (1.0 mL) under argon atmosphere. After the
mixture was stirred at room temperature for 10 min, a solution of
Please cite this article as: C.-Y. He et al., Copper-catalyzed asymmetric silylative cyclization of cyclohexadienone-containing 1,6-enynes,
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4
C.-Y. He et al. / Tetrahedron xxx (xxxx) xxx
substrate 1 (0.10 mmol) in anhydrous THF (1.0 mL) was added,
followed by anhydrous t-BuOH (9 L, 0.10 mmol, 1.0 equiv). The
1.0, CHCl3) for 68% ee. 1H NMR (400 MHz, CDCl3)
d (ppm) 7.56e7.54
m
(m, 2H), 7.38e7.37 (m, 3H), 6.56 (d, J ¼ 10.0 Hz, 1H), 6.02 (d,
J ¼ 10.0 Hz, 1H), 5.56 (s, 1H), 4.27 (d, J ¼ 14.0 Hz, 1H), 4.38 (d,
J ¼ 14.0 Hz, 1H), 2.83e2.80 (m, 1H), 2.49e2.43 (m, 1H), 2.26e2.20
(m, 1H), 1.83e0.74 (m, 11H), 0.46 (s, 3H), 0.38 (s, 3H); 13C NMR
resulting mixture was stirred at room temperature for 12 h. Then
the reaction mixture was filtered, washed with EtOAc (5 mL ꢀ 3),
dried over anhydrous Na2SO4, filtered and concentrated in vacuo.
The residue was purified by flash silica gel (300e400 mesh) chro-
matography to afford the desired products 3.
(100 MHz, CDCl3)
d (ppm) 197.8, 160.9, 147.3, 138.0, 133.7, 130.7,
129.3, 127.9, 118.0, 83.8, 72.0, 44.6, 42.8, 40.3, 31.6, 29.6, 27.5, 26.6,
26.3, ꢁ1.0, ꢁ1.7. HRMS (ESI): [MþH]4 calcd for C23H31O2Si4
4.2.1. (3aS,7aS,E)-3-((Dimethyl(phenyl)silyl)methylene)-7a-
367.2088, found 367.2077. IR (KBr) n
(cmꢁ1) 3079, 3045, 2941, 2855,
methyl-2,3,3a,4-tetrahydrobenzofuran-5(7aH)-one (3a)
1693, 1630, 1392, 1267, 1043, 847, 810, 471.
Colorless oil. 28.5 mg, 96% yield. [
a
]
25.0 -119.2 (c 0.75, CHCl3) for
D
71% ee. 1H NMR (400 MHz, CDCl3)
d
(ppm) 7.55e7.52 (m, 2H),
4.2.6. (3aS,7aS,E)-3-((Dimethyl(phenyl)silyl)methylene)-7a-
7.38e7.35 (m, 3H), 6.55 (d, J ¼ 10.0 Hz, 1H), 5.96 (d, J ¼ 10.0 Hz, 1H),
5.60e5.59 (m, 1H), 4.47e4.35 (m, 2H), 2.70e2.67 (m, 1H),
2.55e2.49 (m, 1H), 2.25e2.16 (m, 1H), 1.33 (s, 3H), 0.46 (s, 3H), 0.37
phenyl-2,3,3a,4-tetrahydrobenzofuran-5(7aH)-one (3f)
White solid. 31.7 mg, 88% yield. mp 60e63 ꢂC [ 25.0 -132.90 (c
a]
D
1.0, CHCl3) for 53% ee. 1H NMR (400 MHz, CDCl3)
d (ppm) 7.39e7.25
(s, 3H); 13C NMR (100 MHz, CDCl3)
d
(ppm) 197.3,159.6,149.6,138.2,
(m, 10H), 6.57e6.55 (d, J ¼ 10.0 Hz, 1H), 6.09e6.06 (d, J ¼ 10.0 Hz,
1H), 5.52 (m, 1H), 4.70e4.66 (m, 1H), 4.51e4.47 (m, 1H), 3.15e3.12
(m, 1H), 2.63e2.57 (m, 1H), 2.37e2.32 (m, 1H), 0.37 (m, 3H), 0.29
133.7, 129.6, 129.3, 128.0, 118.6, 79.3, 72.5, 47.3, 38.8,
24.3, ꢁ0.7, ꢁ1.8. HRMS (ESI): [MþH]4 calcd for C18H23O2Si4
299.1462, found 299.1463. IR (KBr)
n
(cmꢁ1) 3336, 3068, 2964, 2855,
(m, 3H); 13C NMR (100 MHz, CDCl3)
d (ppm) 197.6, 158.5, 147.8,
1686, 1427, 1389, 1276, 1111, 1000, 817, 702, 473.
141.9, 137.9, 133.6, 129.5, 129.2, 128.7, 128.0, 127.9, 125.3, 118.7, 83.2,
73.1, 48.7, 39.0, ꢁ1.1, ꢁ1.6. HRMS (ESI): [MþH]4 calcd for
4.2.2. (3aS,7aS,E)-3-((Dimethyl(phenyl)silyl)methylene)-7a-ethyl-
C n
23H25O2Si4 361.1618, found 361.1617. IR (KBr) (cmꢁ1) 3066, 2952,
2,3,3a,4-tetrahydrobenzofuran-5(7aH)-one (3b)
2852, 1770, 1688, 1489, 1426, 1250, 1052, 833, 700, 470.
25.6
Colorless oil. 28.0 mg, 90% yield. [
a]
D
-95.4 (c 1.15, CHCl3) for
71% ee. 1H NMR (400 MHz, CDCl3)
d
(ppm) 7.55e7.53 (m, 2H),
4.2.7. (3aS,7aS,E)-7a-(4-Bromophenyl)-3-((dimethyl(phenyl)silyl)
7.37e7.34 (m, 3H), 6.57 (d, J ¼ 10.0 Hz, 1H), 6.01 (d, J ¼ 10.0 Hz, 1H),
5.59e5.58 (m, 1H), 4.48e4.31 (m, 2H), 2.77e2.73 (m, 1H),
2.53e2.47 (m, 1H), 2.25e2.20 (m, 1H), 1.62 (q, J ¼ 6.4 Hz, 2H), 0.81
(t, J ¼ 6.4 Hz, 3H), 0.46 (s, 3H), 0.37 (s, 3H); 13C NMR (100 MHz,
methylene)-2,3,3a,4-tetrahydrobenzofuran-5(7aH)-one (3g)
24.9
White soild. 39.4 mg, 90% yield. mp 95e97 ꢂC [
a]
-161.18 (c
D
1.0, CHCl3) for 61% ee. 1H NMR (400 MHz, CDCl3)
d (ppm) 7.46e7.44
(d, J ¼ 7.6 Hz, 2H), 7.38e7.28 (m, 5H), 7.11e7.09 (d, J ¼ 7.6 Hz, 2H),
6.50 (d, J ¼ 10.0 Hz, 1H), 6.07 (d, J ¼ 10.0 Hz, 1H), 5.53 (m, 1H),
4.70e4.66 (m, 1H), 4.47e4.44 (m, 1H), 3.07e3.03 (m, 1H), 2.61e2.55
(m, 1H), 2.35e2.30 (m, 1H), 0.39 (s, 3H), 0.29 (s, 3H); 13C NMR
CDCl3)
d (ppm) 197.6, 160.1, 148.4, 138.2, 133.7, 130.6, 129.3, 128.0,
118.5, 82.0, 72.4, 44.6, 39.3, 30.3, 8.0, ꢁ0.8, ꢁ1.7. HRMS (ESI):
[MþH]4 calcd for C19H25O2Si4 313.1618, found 313.1618. IR (KBr)
n
(cmꢁ1) 2965, 1763, 1685, 1459, 1427, 1250, 1114, 1038, 935, 837, 734,
702.
(100 MHz, CDCl3) d (ppm) 197.2, 157.9, 147.0, 141.2, 137.7, 133.6,
131.8, 129.6, 129.3, 128.0, 127.0, 122.0, 119.3, 83.8, 73.1, 48.6,
39.0, ꢁ1.1, ꢁ1.6. HRMS (ESI): [MþH]4 calcd for C23H24O2BrSi4
4.2.3. (3aS,7aS,E)-3-((Dimethyl(phenyl)silyl)methylene)-7a-
439.0723, found 439.0723. IR (KBr) n
(cmꢁ1) 3446, 3065, 2955,
isopropyl-2,3,3a,4-tetrahydrobenzofuran-5(7aH)-one (3c)
2856, 1767, 1492, 1423, 1245, 1051, 839, 711, 478.
Colorless oil. 30.0 mg, 92% yield. [
a
]
24.6 -97.6 (c 0.50, CHCl3) for
D
68% ee. 1H NMR (400 MHz, CDCl3)
d
(ppm) 7.56e7.53 (m, 2H),
4.2.8. (3aS,7aS,E)-7a-Benzyl-3-((dimethyl(phenyl)silyl)methylene)-
7.38e7.35 (m, 3H), 6.56 (d, J ¼ 10.0 Hz, 1H), 6.07 (d, J ¼ 10.0 Hz, 1H),
5.56 (m, 1H), 4.45e4.26 (m, 2H), 2.83e2.79 (m, 1H), 2.50e2.45 (m,
1H), 2.26e2.20 (m, 1H), 1.89e1.82 (m, 1H), 0.94 (d, J ¼ 7.0 Hz, 3H),
0.72 (d, J ¼ 7.0 Hz, 3H), 0.46 (s, 3H), 0.37 (s, 3H); 13C NMR (100 MHz,
2,3,3a,4-tetrahydrobenzofuran-5(7aH)-one (3h)
25.2
White soild. 35.9 mg, 96% yield. mp 53e55 ꢂC [
a]
-78.40 (c
D
1.0, CHCl3) for 42% ee. 1H NMR (400 MHz, CDCl3)
d (ppm) 7.53e7.51
(m, 2H), 7.41e7.34 (m, 3H), 7.26e7.23 (m, 3H), 7.07e7.05 (m, 2H),
6.51 (d, J ¼ 10.0 Hz, 1H), 5.96 (d, J ¼ 10.0 Hz, 1H), 5.59 (m, 1H), 4.40
(s, 2H), 3.02e2.99 (m, 1H), 2.84e2.80 (m, 2H), 2.44e2.39 (m, 1H),
1.94e1.88 (m, 1H), 0.45 (s, 3H), 0.34 (s, 3H); 13C NMR (100 MHz,
CDCl3)
d (ppm) 197.7, 160.8, 146.6, 138.0, 133.7, 131.2, 129.3, 128.0,
118.1, 84.0, 72.1, 42.8, 34.1, 17.2, 16.6, ꢁ0.9, ꢁ1.8. HRMS (ESI):
[MþH]4 calcd for C20H27O2Si4 327.1775, found 327.1774. IR (KBr)
n
(cmꢁ1), 3068, 2959, 1689, 1635, 1465, 1386, 1250, 1113, 1104, 848,
834, 701, 414.
CDCl3) d (ppm) 197.2, 159.5, 148.3, 138.0, 135.3, 133.7, 130.5, 130.1,
129.2, 128,3, 128.0, 126.9, 118.4, 82.0, 72,5, 45.1, 43.9,
39.1, ꢁ0.7, ꢁ2.0. HRMS (ESI): [MþH]4 calcd for C24H27O2Si4
4.2.4. (3aS,7aS,E)-7a-Dutyl-3-((dimethyl(phenyl)silyl)methylene)-
375.1775, found 375.1775. IR (KBr) n
(cmꢁ1) 3065, 2953, 2915, 2837,
2,3,3a,4-tetrahydrobenzofuran-5(7aH)-one (3d)
1688, 1427, 1384, 1249, 1043, 849, 832, 701, 472.
25.5
Colorless oil. 31.9 mg, 94% yield. [
a]
-97.5 (c 1.30, CHCl3) for
D
69% ee. 1H NMR (400 MHz, CDCl3)
d
(ppm) 7.55e7.53 (m, 2H),
4.2.9. (3aS,7aS,E)-3-((Dimethyl(phenyl)silyl)methylene)-7a-vinyl-
7.37e7.36 (m, 3H), 6.57 (d, J ¼ 10.0 Hz, 1H), 6.00 (d, J ¼ 10.0 Hz, 1H),
5.58 (m, 1H), 4.47e4.30 (m, 2H), 2.76e2.73 (m, 1H), 2.53e2.47 (m,
1H), 2.26e2.20 (m, 1H), 1.57 (m, 2H), 1.32e1.01 (m, 4H), 0.88 (t,
J ¼ 7.0 Hz, 3H), 0.46 (m, 3H), 0.37 (m, 3H); 13C NMR (100 MHz,
2,3,3a,4-tetrahydrobenzofuran-5(7aH)-one (3i)
24.5
Yellow oil. 27.0 mg, 88% yield. [
a]
-95.60 (c 1.25, CHCl3) for
(ppm) 7.54e7.51 (m, 2H).
D
d
64% ee. 1H NMR (400 MHz, CDCl3)
7.37e7.35 (m, 3H), 6.49 (d, J ¼ 10.0 Hz, 1H), 6.05 (d, J ¼ 10.0 Hz, 1H),
5.82e5.75 (m, 1H), 5.58 (m, 1H), 5.27e5.22 (m, 2H), 4.51e4.47 (m,
1H), 4.40e4.37 (m, 1H), 2.83e2.80 (m, 1H), 2.55e2.49 (m, 1H),
2.26e2.21 (m, 1H), 0.45 (s, 3H), 0.36 (s, 3H); 13C NMR (100 MHz,
CDCl3)
d (ppm) 197.6, 160.0, 148.8, 138.2, 133.7, 130.3, 129.3, 128.0,
118.5, 81.7, 72.4, 45.0, 39.2, 37.4, 26.0, 23.1, 13.9, ꢁ0.8, ꢁ1.8. HRMS
(ESI): [MþH]4 calcd for C21H29O2Si4 341.1931, found 341.1932. IR
(KBr)
n
(cmꢁ1) 2956, 2871, 1763, 1689, 1427, 1250, 1114, 837, 701.
CDCl3) d (ppm) 197.3, 158.7, 147.0, 138.2, 138.1, 133.7, 130.6, 129.3,
128.0, 118.4, 116.6, 81.9. 72.9, 46.3, 38.3, ꢁ0.7, ꢁ1.8. HRMS (ESI):
4.2.5(3aS,7aS,E)-7a-Cyclohexyl-3-((dimethyl(phenyl)silyl)
[MþH]4 calcd for C19H23O2Si4 311.1462, found 311.1461. IR (KBr)
n
methylene)-2,3,3a,4-tetrahydrobenzofuran-5(7aH)-one (3e)
(cmꢁ1) 3068, 2954, 1689, 1636, 1427, 1329, 1249, 1112, 1025, 935,
834, 733, 701, 418.
25.0
White solid. 37.2 mg, 98% yield. mp 59e61 ꢂC [
a]
-147.98 (c
D
Please cite this article as: C.-Y. He et al., Copper-catalyzed asymmetric silylative cyclization of cyclohexadienone-containing 1,6-enynes,
Tetrahedron, https://doi.org/10.1016/j.tet.2018.12.002

C.-Y. He et al. / Tetrahedron xxx (xxxx) xxx
5
4.2.10. (3aS,7aS,E)-7a-Allyl-3-((dimethyl(phenyl)silyl)methylene)-
138.3, 133.7, 129.9, 129.3, 128.0, 118.5, 81.1, 72.4, 58.6, 45.8, 40.4,
2,3,3a,4-tetrahydrobenzofuran-5(7aH)-one (3j)
39.0, 25.9, 18.2, ꢁ0.8, ꢁ1.7, ꢁ5.4. HRMS (ESI): [MþH]4 calcd for
24.8
Colorless oil. 28.6 mg, 89% yield. [
a
]
d
-191.33 (c 0.35, CHCl3)
C n
25H39O3Si42 443.2432, found 443.2433. IR (KBr) (cmꢁ1) 3068,
2953, 2855, 1690, 1635, 1471, 1388, 1251, 1111, 1042, 835, 776, 471.
D
for 59% ee. 1H NMR (400 MHz, CDCl3)
(ppm) 7.54e7.52 (m, 2H),
7.37e7.35 (m, 3H), 6.58 (d, J ¼ 10.0 Hz, 1H), 6.01 (d, J ¼ 10.0 Hz, 1H),
5.69e5.60 (m, 2H), 5.11e5.01 (m, 2H), 4.50e4.46 (m,1H), 4.36e4.33
(m, 1H), 2.82e2.79 (m, 1H), 2.51e2.18 (m, 4H), 0.45 (s, 3H), 0.37 (s,
4.2.15. S-(2-((3aS,7aS,E)-3-((Dimethyl(phenyl)silyl)methylene)-5-
oxo-2,3,3a,4,5,7a-hexahydrobenzofuran-7a-yl)ethyl) ethanethioate
(3p)
3H); 13C NMR (100 MHz, CDCl3)
d (ppm) 197.4, 159.4, 148.0, 138.1,
133.7, 131.9, 130.5, 129.3, 128.0, 119.3, 118.7, 81.0, 72,5, 44.9, 42.2,
Colorless oil. 29.3 mg, 76% yield. [
a
]
d
23.1 -30.51 (c 0.60, CHCl3) for
D
39.1, ꢁ0.8, ꢁ1.8. HRMS (ESI): [MþH]4 calcd for C10H25O2Si4
63% ee. 1H NMR (400 MHz, CDCl3)
(ppm) 7.55e7.53 (m, 2H),
325.1618, found 325.1618. IR (KBr)
n
(cmꢁ1) 3069, 2954, 1690, 1638,
7.37e7.35 (m, 3H), 6.64 (d, J ¼ 10.0 Hz, 1H), 6.03 (d, J ¼ 10.0 Hz, 1H),
5.61 (m, 1H), 4.49e4.46 (m, 1H), 4.36e4.34 (m, 1H), 2.84e2.76 (m,
2H), 2.69e2.61 (m, 1H), 2.53e2.46 (m, 1H), 2.32 (s, 3H), 2.26e2.20
(m, 1H), 1.85e1.80 (m, 2H), 0.46 (s, 3H), 0.38 (s, 3H); 13C NMR
1427, 1249, 1112, 1042, 927, 833, 782, 701, 427.
4.2.11. (3aS,7aS,E)-7a-(3-Bromopropyl)-3-((dimethyl(phenyl)silyl)
methylene)-2,3,3a,4-tetrahydrobenzofuran-5(7aH)-one (3k)
(100 MHz, CDCl3) d (ppm) 197.1, 195.3, 159.0, 147.1, 138.0, 133.7,
25.1
Yellow solid. 35.6 mg, 88% yield. mp 82e84 ꢂC [
a]
-52.24 (c
(ppm)
130.8, 129.4, 128.0, 119.2, 80.9, 72.5, 45.1, 39.0, 37.4, 30.5,
D
1.00, CHCl3) for 67% ee. 1H NMR (400 MHz, CDCl3)
d
23.4, ꢁ0.8, ꢁ1.8. HRMS (ESI): [MþH]4 calcd for C21H27O3SSi4
7.55e7.53 (m, 2H), 7.38e7.36 (m, 3H), 6.55 (d, J ¼ 10.0 Hz, 1H), 6.00
(d, J ¼ 10.0 Hz, 1H), 5.61 (m, 1H), 4.49e4.44 (m, 1H), 4.35e4.31 (m,
1H), 3.37e3.34 (m, 2H), 2.72e2.68 (m, 1H), 2.53e2.47 (m, 1H),
387.1445, found 387.1444. IR (KBr) n
(cmꢁ1) 3367, 3068, 2954, 1766,
1690, 1427, 1250, 1113, 836, 734, 625, 471.
2.25e2.17 (m, 1H), 1.85e1.66 (m, 4H), 0.46 (s, 3H), 0.37 (s, 3H); 13
C
4.2.16. Methyl2-((3aS,7aS,E)-3-((dimethyl(phenyl)silyl)methylene)-
NMR (100 MHz, CDCl3)
d
(ppm) 197.2, 159.3, 147.7, 138.0, 133.7,
5-oxo-2,3,3a,4,5,7a-hexahydrobenzofuran-7a-yl)acetate (3q)
130.6, 129.4, 128.0, 119.0, 81.0, 72.4, 45.1, 39.0, 36.0, 33.4,
Colorless oil. 29.6 mg, 83% yield. [
a
]
d
24.0 -97.96 (c 1.00, CHCl3) for
D
27.1, ꢁ0.8, ꢁ1.8. HRMS (ESI): [MþH]4 calcd for C20H26O2BrSi4
67% ee. 1H NMR (400 MHz, CDCl3)
(ppm) 7.54e7.52 (m, 2H),
405.0880, found 405.0880. IR (KBr)
n
(cmꢁ1) 3069, 2950, 2908,
7.38e7.36 (m, 3H), 6.82 (d, J ¼ 10.0 Hz, 1H), 6.03 (d, J ¼ 10.0 Hz, 1H),
5.65 (m, 1H), 4.57e4.53 (m, 1H), 4.38e4.35 (m, 1H), 3.65 (s, 3H),
3.07e3.03 (m, 1H), 2.67e2.55 (m, 2H), 2.50e2.43 (m, 1H),
2.26e2.21 (m, 1H), 0.45 (s, 3H), 0.39 (s, 3H); 13C NMR (100 MHz,
1682, 1444, 1245, 1112, 1080, 835, 704, 474.
4.2.12. (3aS,7aS,E)-3-((Dimethyl(phenyl)silyl)methylene)-7a-(3-
iodopropyl)-2,3,3a,4-tetrahydrobenzofuran-5(7aH)-one (3m)
CDCl3) d (ppm) 197.0, 169.6, 158.2, 146.1, 138.0, 133.7, 130.5, 129.4,
25.1
White solid. 40.2 mg, 89% yield. mp 66e68 ꢂC [
a]
-21.15 (c
(ppm)
128.0, 119.8, 79.3, 72.6, 51,9, 45.8, 42.5, 38.9, ꢁ1.1, ꢁ1.8. HRMS (ESI):
D
1.00, CHCl3) for 69% ee. 1H NMR (400 MHz, CDCl3)
d
[MþH]4 calcd for C20H24O4Si4 357.1517, found 357.1517. IR (KBr)
n
7.55e7.53 (m, 2H), 7.39e7.36 (m, 3H), 6.56e6.53 (d, J ¼ 10.0 Hz,1H),
6.01e6.98 (d, J ¼ 10.0 Hz, 1H), 5.61 (m, 1H), 4.48e4.44 (m, 1H),
4.35e4.31 (m, 1H), 3.13e3.10 (m, 2H), 2.71e2.67 (m, 1H), 2.52e2.46
(m, 1H), 2.25e2.20 (m, 1H), 1.81e1.60 (m, 4H), 0.46 (s, 3H), 0.37 (s,
(cmꢁ1) 3048, 2952, 1737, 1690, 1435, 1250, 1141, 1112, 1028, 848,
835, 734, 698.
4.2.17. 2-((3aS,7aS,E)-3-((Dimethyl(phenyl)silyl)methylene)-5-oxo-
3H); 13C NMR (100 MHz, CDCl3)
d
(ppm) 197.2, 159.3, 147.7, 138.0,
2,3,3a,4,5,7a-hexahydrobenzofuran-7a-yl)acetonitrile (3r)
24.0
133.7, 130.6, 129.4, 128.0, 119.0, 80.9, 72.4, 45.1, 39.0, 38.3, 27.8,
Yellow oil. 31.7 mg, 98% yield. [
a]
-20.10 (c 1.00, CHCl3) for
(ppm) 7.55e7.52 (m, 2H),
D
6.2, ꢁ0.8, ꢁ1.8. HRMS (ESI): [MþH]4 calcd for C20H26O2ISi4
65% ee. 1H NMR (400 MHz, CDCl3)
d
453.0741, found 453.0741. IR (KBr)
n
(cmꢁ1) 2953, 2853, 1689, 1427,
7.39e7.36 (m, 3H), 6.65 (d, J ¼ 10.0 Hz, 1H), 6.10 (d, J ¼ 10.0 Hz, 1H),
5.71 (m, 1H), 4.61e4.57 (m, 1H), 4.42e4.38 (m, 1H), 2.87e2.84 (m,
1H), 2.65e2.44 (m, 3H), 2.27e2.21 (m, 1H), 0.47 (m, 3H), 0.40 (m,
1249, 1112, 1040, 849, 833, 733, 701.
4.2.13. 2-((3aS,7aS,E)-3-((Dimethyl(phenyl)silyl)methylene)-5-oxo-
3H); 13C NMR (100 MHz, CDCl3)
d (ppm) 195.8, 156.5, 143.8, 137.5,
2,3,3a,4,5,7a-hexahydrobenzofuran-7a-yl)ethyl acetate (3n)
133.6, 131.9, 129.6, 128.2, 121.4, 115.4, 78.5, 72.9, 45.6, 38.6, 29.6,
Colorless oil. 32.6 mg, 87% yield. [
a
]
d
24.2 -28.08 (c 1.25, CHCl3) for
29.6, 27.1, ꢁ1.1, ꢁ1.9. HRMS (ESI): [MþH]4 calcd for C19H22O2NSi4
D
64% ee. 1H NMR (400 MHz, CDCl3)
(ppm) 7.55e7.52 (m, 2H),
324.1414, found 324.1412. IR (KBr) n
(cmꢁ1) 3445, 3068, 2958, 2251,
7.37e7.35 (m, 3H), 6.60 (d, J ¼ 10.0 Hz, 1H), 6.00 (d, J ¼ 10.0 Hz, 1H),
5.61e5.60 (m, 1H), 4.45e4.41 (m, 1H), 4.35e4.31 (m, 1H), 4.17e4.03
(m, 2H), 2.80e2.77 (m, 1H), 2.55e2.49 (m, 1H), 2.27e2.21 (m, 1H),
1.99 (s, 3H), 1.97e1.93 (m, 2H), 0.46 (s, 3H), 0.37 (s, 3H); 13C NMR
1772, 1694, 1427, 1250, 1160, 1114, 999, 836,702, 471.
4.2.18. (3aS,7aS,Z)-3-((Dimethyl(phenyl)silyl)methylene)-7a-(3-
(((8R,9S,13S,14S)-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-
decahydro-6H-cyclopenta[a]phenanthren-3-yl)oxy)propyl)-
(100 MHz, CDCl3)
d (ppm) 197.0, 170.7, 159.0, 147.6, 138.0, 133.7,
130.4, 129.4, 128.0, 119.0, 80.4, 72,4, 59.8, 45.6, 38.8, 36.0,
2,3,3a,7a-tetrahydrobenzofuran-5(4H)-one (3s)
27.9
20.9, ꢁ0.7, ꢁ1.9. HRMS (ESI): [MþH]4 calcd for C21H27O4Si4
Viscous oil. 95.0 mg, 80% yield. [
a
]
41.63 (c 1.00, CHCl3) for
D
371.1673, found 371.1673. IR (KBr)
n
(cmꢁ1) 3067, 2955, 2849, 1740,
61% de. 1H NMR (400 MHz, CDCl3)
d
(ppm) 7.54 (dd, J ¼ 6.4, 3.0 Hz,
1689, 1437, 1247, 849, 834, 701, 542, 472.
2H), 7.38e7.33 (m, 3H), 7.20 (d, J ¼ 8.6 Hz, 1H), 6.69 (dd, J ¼ 8.6,
2.6 Hz, 1H), 6.60 (d, J ¼ 10.2 Hz, 2H), 6.02 (d, J ¼ 10.3 Hz,1H), 5.61 (d,
J ¼ 1.7 Hz, 1H), 4.47 (d, J ¼ 13.7 Hz, 1H), 4.34 (dd, J ¼ 13.8, 1.4 Hz, 1H),
3.89 (t, J ¼ 5.1 Hz, 2H), 2.89 (dd, J ¼ 10.8, 4.6 Hz, 2H), 2.77 (t,
J ¼ 6.8 Hz,1H), 2.56e2.47 (m, 2H), 2.42e2.38 (m,1H), 2.28e2.22 (m,
2H), 2.19e1.08 (m, 1H), 2.06e1.94 (m, 3H), 1.78e1.71 (m, 3H),
1.66e1.60 (m, 3H), 1.54 (m, 1H), 1.51e1.48 (m, 2H), 1.26 (m, 1H), 0.91
4.2.14. (3aS,7aS,E)-7a-(2-((Tert-butyldimethylsilyl)oxy)ethyl)-3-
((dimethyl(phenyl)silyl)methylene)-2,3,3a,4-tetrahydrobenzofuran-
5(7aH)-one (3o)
Colorless oil. 37.8 mg, 85% yield. [
a
]
d
25.2 -25.34 (c 1.10, CHCl3) for
(ppm) 7.54e7.51 (m, 2H),
D
68% ee. 1H NMR (400 MHz, CDCl3)
7.37e7.35 (m, 3H), 6.66 (d, J ¼ 10.0 Hz, 1H), 5.98 (d, J ¼ 10.0 Hz 1H),
5.58 (m, 1H), 4.43e4.39 (m, 1H), 4.32e4.29 (m, 1H), 3.72e3.60 (m,
2H), 2.90e2.87 (m, 1H), 2.57e2.41 (m, 1H), 2.38e2.33 (m, 1H), 1.86
(t, J ¼ 6.4 Hz, 2H), 0.85 (s, 9H), 0.45 (s, 3H), 0.37 (s, 3H), 0.01 (s, 3H),
(s, 3H), 0.46 (s, 3H), 0.37 (s, 3H); 13C NMR (100 MHz, CDCl3)
d (ppm)
221.1,197.5, 159.8,157.0, 148.4,138.3,137.9, 133.9, 132.3,130.7, 129.5,
128.2, 126.5, 118.9, 114.7, 112.2, 81.5, 72.6, 67.7, 50.5, 48.1, 45.3, 44.1,
39.3, 38.5, 36.0, 34.2, 31.7, 29.8, 26.7, 26.1, 24.1, 21.7, 14.0, ꢁ0.6, ꢁ1.7.
HRMS (ESI): [M þ NH4]4 calcd for C38H50NO4Si4 612.3504, found
0.00 (s, 3H); 13C NMR (100 MHz, CDCl3)
d (ppm) 197.4, 160.0, 149.0,
Please cite this article as: C.-Y. He et al., Copper-catalyzed asymmetric silylative cyclization of cyclohexadienone-containing 1,6-enynes,
Tetrahedron, https://doi.org/10.1016/j.tet.2018.12.002

6
C.-Y. He et al. / Tetrahedron xxx (xxxx) xxx
24.4
612.3502. IR (thin film)
n
(cmꢁ1) 2929, 1738, 1690, 1499, 1280, 1248,
10.4 mg, 48% yield. [
a]
-124.70 (c 0.20, CHCl3) for 66% ee. 1H
D
1112, 1055, 848, 834, 701.
NMR (400 MHz, CDCl3)
d (ppm) 7.54e7.51 (m, 2H), 7.36e7.34 (m,
3H), 5.56 (s, 1H), 4.53e4.50 (m, 1H), 4.28e4.24 (m, 1H), 2.45e1.10
4.2.19. Tert-butyl(3aS,7aS,E)-7a-butyl-3-((dimethyl(phenyl)silyl)
methylene)-5-oxo-2,3,3a,4,5,7a-hexahydro-1H-indole-1-
(m, 12H), 0.40 (s, 3H), 0.37 (s, 3H); 13C NMR (100 MHz, CDCl3)
d
(ppm) 211.4, 160.3, 138.5, 133.7, 129.3, 128.0, 118.0, 92.5, 70.8, 45.7,
carboxylate (3t)
43.2, 42.1, 42.0, 36.2, 31.5, 22.8, ꢁ1.2, ꢁ1.4. HRMS (ESI): [MþH]4
25.4
Colorless oil. 39.0 mg, 89% yield. [
a
]
-4.13 (c 0.4, CHCl3) for
calcd for C20H27O2Si4 327.1775, found 327.1775. IR (KBr) (cmꢁ1
n )
D
53% ee. 1H NMR (400 MHz, CDCl3)
d
(ppm) 7.53e7.50 (m, 2H),
2953, 2924, 1718, 1461, 1376, 1248, 1199, 1113, 1037, 833, 732, 469.
7.37e7.35 (m, 3H), 6.94 (d, J ¼ 10.0 Hz, 1H), 5.92 (d, J ¼ 10.0 Hz, 1H),
5.65 (m, 1H), 4.39e4.30 (m, 1H), 4.00e3.90 (m, 1H), 2.92e2.87 (m,
1H), 2.42e2.35 (m, 1H), 2.19e2.14 (m, 1H), 1.40 (s, 9H), 1.37e0.73
(m, 9H), 0.42 (s, 3H), 0.38 (s, 3H); 13C NMR (100 MHz, CDCl3)
4.5. (3aS,4R,7aS,E)-3-((Dimethyl(phenyl)silyl)methylene)-2,3,3a,4-
tetrahydro-5H-4,7a-propanobenzofuran-5-one (5m)
d
(ppm) 197.9, 154.9, 153.8, 150.1, 138.2, 133.6, 129.5, 128.1, 128.1,
To a solution of 3m (30.0 mg, 0.066 mmol) in dry THF (2 mL) was
added a solution of LiHMDS (1 M THF solution, 0.66 mL, 10.0 equiv)
at 0 ꢂC. The resulting mixture was stirred at 0 ꢂC for 1 h and at room
temperature for 15 h. The reaction mixture was quenched by
aqueous saturated NH4Cl (10 mL) and extracted with EtOAc
(10 mL ꢀ 3). The combined organic phases were dried over anhy-
drous Na2SO4, filtered and concentrated in vacuo. The residue was
purified by flash column chromatography to afford 5m as a color-
122.1, 80.0, 63.2, 53.7, 46.9, 39.5, 36.2, 28.5, 26.9, 23.0,
13.9, ꢁ1.1, ꢁ1.3. HRMS (ESI): [MþH]4 calcd for C26H38O3NSi4
440.2615, found 440.2615. IR (KBr) n
(cmꢁ1) 2957, 2871, 1700, 1457,
1368, 1307, 1252, 1164, 1113, 839, 733, 701.
4.2.20. (3aS,7aS,E)-3-(1-(dimethyl(phenyl)silyl)ethylidene)-7a-
methyl-2,3,3a,7a-tetrahydrobenzofuran-5(4H)-one(3v)
Colorless oil. 20.0 mg, 32% yield. [
a]
25.0 -44.34 (c 1.0, CHCl3) for
less oil. 18.6 mg, 86% yield. [
a]
25.8 -54.61 (c 0.90, CHCl3) for 66% ee.
D
D
31% ee. 1H NMR (400 MHz, CDCl3)
d
(ppm) 7.52e7.50 (m, 2H),
1H NMR (400 MHz, CDCl3)
d
(ppm) 7.54e7.52 (m, 2H), 7.36e7.35 (m,
7.37e7.33 (m, 3H), 6.59 (d, J ¼ 10.1 Hz, 1H), 5.93 (d, J ¼ 10.1 Hz, 1H),
4.59e4.49 (m, 2H), 2.70 (dd, J ¼ 10.6, 5.6 Hz, 1H), 2.42 (dd, J ¼ 16.0,
10.7 Hz, 1H), 2.12 (dd, J ¼ 16.1, 5.6 Hz, 1H), 1.66 (d, J ¼ 0.7 Hz, 3H),
1.22 (s, 3H), 0.45 (s, 3H), 0.40 (s, 3H); 13C NMR (100 MHz, CDCl3)
3H), 6.55 (d, J ¼ 10.0 Hz, 1H), 6.11 (d, J ¼ 10.0 Hz, 1H), 5.57e5.55 (m,
1H), 4.47e4.43 (d, J ¼ 13.8 Hz, 1H), 4.27e4.24 (d, J ¼ 13.8 Hz, 1H),
2.70 (s, 1H), 2.21 (s, 1H), 1.87e1.41 (m, 5H), 1.03e0.94 (m, 1H), 0.41
(s, 3H), 0.26 (s, 3H); 13C NMR (100 MHz, CDCl3)
d (ppm) 198.8, 157.2,
d
(ppm) 198.4, 152.4, 148.6, 138.4, 133.9, 129.6, 129.5, 128.1, 126.3,
152.1, 138.5, 133.7, 133.0, 129.0, 128.0, 116.8, 81.8, 73.4, 54.4, 47.0,
78.4, 70.0, 47.3, 40.2, 24.7, 19.0, ꢁ1.4, ꢁ1.6. HRMS (ESI): [MþH]4
31.0, 28.4 19.3, 0.2, ꢁ2.3. HRMS (EI): [M]4 calcd for C20H24O2Si4
calcd for C19H25O2Si4 313.1618, found 313.1615. IR (KBr)
n
(cmꢁ1
)
324.1546, found 324.1553. IR (KBr) n
(cmꢁ1) 3356, 3185, 2919, 2849,
3068, 2964, 2926, 1686, 1427, 1373, 1251, 1111, 1073, 999, 818, 776,
702.
1683, 1634, 1470, 1427, 1377, 1247, 1149, 1005, 834, 732, 420.
4.6. (3aS,9aR,E)-3-((Dimethyl(phenyl)silyl)methylene)-2,3,3a,4,8,9-
4.3. (3aS,7aS)-3-((E)-Benzylidene)-7a-methyl-2,3,3a,7a-
hexahydro-5H-benzo[1,2-b:6,1-b']difuran-5-one (4o)
tetrahydrobenzofuran-5(4H)-one (4a)
To a well-stirred solution of 3o (44.2 mg, 0.1 mmol) in dry THF
(5 mL) was added 0.3 mL TBAF (1 M in THF, 1.2 equiv) at 0 ꢂC. The
resulting mixture was stirred at 0 ꢂC for 0.5 h, then warmed to room
temperature, stirred for 9 h. The reaction mixture was quenched by
aqueous saturated NH4Cl (10 mL) and extracted with EtOAc
(10 mL ꢀ 3). The combined organic phases were dried over anhy-
drous Na2SO4, filtered and concentrated in vacuo. The residue was
To the well-stirred solution of 3a (60 mg, 0.2 mmol) and
Pd(dba)2 (6 mg, 0.01 mmol, 5% equiv) in THF (2.0 mL) was added
TBAF (1 M in THF, 0.4 mL, 0.4 mmol, 2.0 equiv) and Iodobenzene (27
mL, 0.24 mmol, 1.2 equiv) under argon atmosphere. The resulting
mixture continued to react for 16 h at room temperature. It was
quenched by aqueous saturated NaHCO3 (10 mL), extracted with
DCM (10 mL ꢀ 3), washed with brine (30 mL), dried over anhydrous
Na2SO4 and concentrated under reduced pressure. The residue was
purified by flash silica gel (300e400 mesh) chromatography to
purified by flash column chromatography to afford 4o as a colorless
21.1
oil. 66.1 mg, 84% yield. [
NMR (400 MHz, CDCl3)
a
]
-141.71 (c 0.50, CHCl3) for 68% ee.1H
D
d
(ppm) 7.54e7.51 (m, 2H), 7.37e7.32 (m,
afford the desired products 4a as a colorless oil. 19.0 mg, 40% yield.
3H), 5.63 (s, 1H), 4.57 (d, J ¼ 14.0 Hz, 1H), 4.32 (d, J ¼ 14.0 Hz, 1H).
4.11e4.07 (m, 1H), 3.86e3.82 (m, 2H), 2.69e2.63 (m, 1H). 2.54e2.50
(m, 1H), 2.16e2.01 (m, 4H), 1.57e1.49 (m, 1H). 0.41 (s, 3H), 0.38 (s,
27.9
[
a]
-11.78 (c 0.50, CHCl3) for 48% ee. 1H NMR (400 MHz, CDCl3)
D
d
(ppm) 7.35e7.32 (m, 2H), 7.25e7.19 (m, 3H), 6.57 (d, J ¼ 10.2 Hz,
1H), 6.42 (s, 1H), 5.99 (d, J ¼ 10.2 Hz, 1H), 4.49 (dd, J ¼ 36.3, 13.3 Hz,
3H); 13C NMR (100 MHz, CDCl3)
d (ppm) 208.3, 158.4, 138.1, 133.7,
2H), 3.42 (s, 1H), 2.65e2.59 (m, 1H), 2.49e2.43 (m, 1H), 1.51 (s, 3H);
129.5, 128.0, 119.2, 90.9, 79.6, 71.1, 66.7, 45.0, 43.6, 41.7,
13C NMR (100 MHz, CDCl3)
d
(ppm) 197.3, 150.1, 142.2, 136.1, 129.8,
36.4, ꢁ1.2, ꢁ1.5. HRMS (ESI): [M þ NH4]4 calcd for C19H28NO3Si4
128.6, 128.2, 127.1, 122.4, 80.4, 71.4, 46.2, 36.4, 24.2. HRMS (ESI):
346.1833, found 346.1829. IR (KBr) n
(cmꢁ1) 3065, 2953, 2871, 1717,
[M þ NH4]4 calcd for C16H20NO42 258.1489, found 258.1491. IR (thin
1639, 1425, 1251, 1197, 1112, 1082, 1037, 836, 731, 702, 467.
film)
n
(cmꢁ1) 2920, 1690, 1382, 1280, 1227, 1162, 1114, 1044, 877,
726, 697, 562.
Acknowledgments
4.4. (3aS,6aR,9aS,E)-3-((Dimethyl(phenyl)silyl)methylene)
octahydroindeno[3a,4-b]furan-5(6H)-one (4m)
Financial support was generously provided by the NSFC (Nos.
21572251, 21572253, and 21871184), the 973 Program (No.
2015CB856600), the STCSM (No. 18401933500), the CAS (Nos. XDB
20020100 and QYZDY-SSW-SLH026), and the Collaborative Inno-
vation Center of Chemical Science and Engineering (Tianjin). We
thank Jie Sun (SIOC) for X-ray crystallographic analysis.
To a solution of 3m (30 mg, 0.066 mmol) in dry THF (2 mL) was
added t-BuLi (1.3 M in pentane, 0.2 mL, 4.0 equiv) in 10 min
at ꢁ78 ꢂC. The resulting mixture was stirred for 0.5 h. The reaction
mixture was quenched by MeOH (0.2 mL) and water (10 mL),
extracted with EtOAc (10 mL ꢀ 3), dried over anhydrous Na2SO4,
filtered and concentrated in vacuo. The residue was purified by
flash column chromatography to afford 4m as a colorless oil.
Appendix A. Supplementary data
Supplementary data to this article can be found online at
Please cite this article as: C.-Y. He et al., Copper-catalyzed asymmetric silylative cyclization of cyclohexadienone-containing 1,6-enynes,
Tetrahedron, https://doi.org/10.1016/j.tet.2018.12.002

C.-Y. He et al. / Tetrahedron xxx (xxxx) xxx
7
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17756;
https://doi.org/10.1016/j.tet.2018.12.002.
(j) S. Wakayanagi, T. Shimamoto, M. Chimori, K. Yamamoto, Chem. Lett. 34
(2005) 160;
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Tetrahedron, https://doi.org/10.1016/j.tet.2018.12.002