Electroreductive coupling of aromatic ketones, aldehydes, and aldimines with α,β-unsaturated esters: Synthesis of 5-aryl substituted γ-butyrolactones and lactams

Article abstract of DOI:10.1016/j.tet.2017.01.013

The electroreductive intermolecular coupling of aromatic ketones and aldehydes with α,β-unsaturated esters in the presence of TMSCl gave the adducts as γ-trimethylsiloxy esters. The detrimethylsilylation of the adducts with TBAF afforded 5-aryl substituted γ-butyrolactones. The electroreductive coupling of N-(4-methoxyphenyl)-1-arylmethaneimines with methyl acrylate in the presence of TMSCl gave the adducts as methyl 4-aryl-4-((4-methoxyphenyl)amino)butanoates. The adducts were transformed to 5-aryl-γ-butyrolactams by cyclization with NaH and subsequent oxidation with CAN. (±)-Norcotinine was prepared from nicotinaldehyde by this method. The electroreductive coupling of aromatic ketones and aldimines with acrylonitrile in the presence of TMSCl gave 4-aryl-4-(trimethylsiloxy)butanenitriles and 4-aryl-4-((4-methoxyphenyl)amino)butanenitriles, respectively.

Full text of DOI:10.1016/j.tet.2017.01.013

Accepted Manuscript
Electroreductive coupling of aromatic ketones, aldehydes, and aldimines with α,β-
unsaturated esters: Synthesis of 5-aryl substituted γ-butyrolactones and lactams
Naoki Kise, Yusuke Hamada, Toshihiko Sakurai
PII:
S0040-4020(17)30026-1
10.1016/j.tet.2017.01.013
TET 28383
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 28 September 2016
Revised Date: 4 January 2017
Accepted Date: 6 January 2017
Please cite this article as: Kise N, Hamada Y, Sakurai T, Electroreductive coupling of aromatic ketones,
aldehydes, and aldimines with α,β-unsaturated esters: Synthesis of 5-aryl substituted γ-butyrolactones
and lactams, Tetrahedron (2017), doi: 10.1016/j.tet.2017.01.013.
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ACCEPTED MANUSCRIPT
Graphical abstract
Electroreductive coupling of aromatic ketones, aldehydes, and aldimines
with
-unsaturated esters: synthesis of 5-aryl- -butyrolactones and lactams
Naoki Kise*, Yusuke Hamada, and Toshihiko Sakurai
Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University,
4-101, Koyama-cho Minami, Tottori 680-8552, Japan
R1 R2
1) +2e
R2
Ar
R
TMSCl
R1
+
Ar
CO2Me
CO2Me
O
O
O
2) TBAF
O
R
R = Ar, alkyl, H
1) +2e
TMSCl
Ar
+
Ar
N
H
N
2) NaH
3) CAN
An

ACCEPTED MANUSCRIPT
Electroreductive coupling of aromatic ketones, aldehydes, and aldimines with
α,β-unsaturated esters: synthesis of 5-aryl substituted γ-butyrolactones and
lactams
Naoki Kise,* Yusuke Hamada, and Toshihiko Sakurai
Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University,
4-101, Koyama-cho Minami, Tottori 680-8552, Japan
*Corresponding author. E-mail address: kise@bio.tottori-u.ac.jp (N. Kise)
ABSTRACT
The electroreductive intermolecular coupling of aromatic ketones and aldehydes with
α,β-unsaturated esters in the presence of TMSCl gave the adducts as γ-trimethylsiloxy esters. The
detrimethylsilylation of the adducts with TBAF afforded 5-aryl substituted γ-butyrolactones. The
electroreductive coupling of N-(4-methoxyphenyl)-1-arylmethaneimines with methyl acrylate in the
presence of TMSCl gave the adducts as methyl 4-aryl-4-((4-methoxyphenyl)amino)butanoates.
The adducts were transformed to 5-aryl-γ-butyrolactams by cyclization with NaH and subsequent
oxidation with CAN. (±)-Norcotinine was prepared from nicotinaldehyde by this method. The
electroreductive coupling of aromatic ketones and aldimines with acrylonitrile in the presence of
TMSCl
gave
4-aryl-4-(trimethylsiloxy)butanenitriles
and
4-aryl-4-((4-methoxyphenyl)amino)butanenitriles, respectively.
Keywords: Reductive coupling; Electroreduction; Aromatic ketones; Aromatic aldimines;
γ-Butyrolactones; γ-Butyrolactams
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1. Introduction
In 1980, Shono and co-workers reported that the electroreductive cross-coupling of carbonyl
compounds with α,β-unsaturated esters is a useful method for the synthesis of γ-butyrolactones.1
After that, this type of reaction has also been realized with Zn2 and SmI23,4 as a reducing agent. In
the first electroreductive intermolecular coupling1 and the intramolecular coupling subsequently
reported by Little and co-workers,5 the employed carbonyl compounds were unfortunately limited
to aliphatic ketones and aldehydes. Therefore, we attempted the inter- and intramolecular
electroreductive coupling of aromatic carbonyl compounds with α,β-unsaturated esters to extend
the scope of the electroreductive coupling. Meanwhile, we have already reported the preliminary
results of the electroreductive coupling of aromatic aldimines with α,β-unsaturated esters.6
Thereafter, the Ni-catalyzed reductive coupling of aldimines with activated alkenes was reported.7
This paper prompted us to further investigate the scope of the electroreductive coupling of aromatic
aldimines with α,β-unsaturated esters. We report in this paper the electroreductive coupling of
aromatic ketones, aldehydes, and aldimines with α,β-unsaturated esters (Scheme 1). From the
resultant γ-trimethylsiloxy and γ-amino esters (Y = CO2Me), the corresponding 5-aryl substituted
γ-butyrolactones and lactams were readily provided, respectively.8 (±)-Norcotinine could be
synthesized from nicotinaldehyde by this method. In addition, we report that the electroreductive
coupling of aromatic ketones and aldimines with acrylonitrile (Y = CN) produced
4-aryl-4-(trimethylsiloxy)butanenitriles
(Scheme 1).
and
4-aryl-4-((4-methoxyphenyl)amino)butanenitriles
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R1
+2e
TMSCl
R2
R
Ar
R
Ar
Y
R1
+
Y
O
TMSO
R2
R = aryl, alkyl, H R1 = H, Me, Ph
R2 = H, Me
Y = CO2Me, CN
R1
R2
O
R1
TBAF
THF
R
Ar
CO2Me
R
O
TMSO
R2
Ar
+2e
TMSCl
Ar
Ar
Y
+
Y
N
An
NHAn
An = 4-MeOC6H4
Y = CO2Me, CN
1) NaH
/THF
Ar
CO2Me
O
Ar
N
H
2) CAN
NHAn
Ar = 3-pyridyl: (±)-Norcotinine
Scheme 1. Electroreductive coupling of aromatic ketones, aldehydes and aldimines with
α,β-unsaturated esters and acrylonitrile.
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ACCEPTED MANUSCRIPT
2. Results and discussion
2.1. Electroreductive coupling of aromatic ketones and aldehydes with α,β-unsaturated esters
and nitriles.
In the previous report,1 the electroreduction was carried out in Et4NOTs/DMF in the presence
of TMSCl. Under these conditions, aromatic ketones and aldehydes did not give any coupled
product with α,β-unsaturated esters. On the other hand, we have already reported that the
electroreductive coupling of aromatic ketones with N-acylimidazoles,9a aliphatic aldehydes and
ketones,9b 3-methoxycarbonylindoles,9c 1-E-crotonyl- and 1-cinnnamoylimidazolidine-2-ones,9d and
1,3-dimethyluracils9e,f were effected in Bu4NClO4/THF or Bu4NPF6/THF in the presence of TMSCl.
We therefore applied these conditions to the electroreduction of benzophenone (1a) with methyl
acrylate (2a), and found that methyl 4,4-diphenyl-4-((trimethylsilyl)oxy)butanoate (3a) was
obtained in almost the same yield (93-95%) under the both conditions. In addition, Pt, Au, Ag, Zn,
and Pb gave almost the same results as a cathode material. Hence, we carried out the
electroreduction of benzophenones 1a-g with α,β-unsaturated esters 2a-d (5 or 2 equiv) in
Bu4NClO4/THF using a Pt cathode, and the results are summarized in Table 1. The adducts were
obtained as TMS ethers 3a-g by the reductive coupling of 1a-g with 2a, and subsequent
detrimethylsilylation of 3a-g with TBAF gave 5,5-diaryl-γ-butyrolactones 4a-g (runs 1-7).
Although the adducts 3h-v obtained by the reactions with 2b-d could not be purified, the
corresponding γ-butyrolactones 4h-v could be isolated after detrimethylsilylation of the crude 3h-v
(runs 8-22).
Similarly to our already reported reactions,9 the presence of TMSCl is essential for the present
electroreductive couplings. When the electroreduction of 1a with 2a was carried out in the
absence of TMSCl, 1,1,2,2,-tetraphenylethane-1,2-diol was obtained as an only product by pinacol
coupling of 1a. This catholyte system (Bu4NClO4/THF) was employed to the electroreduction of
hexanal with 2a to compare with the previously reported catholyte system (Et4NOTs/DMF).1 As
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ACCEPTED MANUSCRIPT
shown in Scheme 2, the corresponding γ-butyrolactone i was obtained in 33% yield, and dimethyl
adipate (ii) was formed as the major product (60% yield) by hydrodimerization of 2a. Since it has
been reported that the same γ-butyrolactone i was obtained in 86% yield,1 these results show that
Et4NOTs/DMF is superior to Bu4NClO4/THF as the catholyte for the electroreductive coupling of
aliphatic aldehydes with 2a.
+2e
TMSCl
1M HCl
CHO
2a
+
Bu4NClO4/THF
(Et4NOTs/DMF)
(1 mmol)
(5 mmol)
CO2Me
CO2Me
+
O
O
i 33%
ii 60%
(86% in ref. 1)
Scheme 2. Electroreduction of hexanal with 2a.
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Table 1. Electroreductive coupling of 1a-g with 2a-d and transformation to 4a-va
run
1
Ar2C=O
R1 R2
% yieldb
95
% yieldb
90
1
2
3
4
Ar = Ph
2ac
2ac
2ac
2ac
H
H
H
H
H
H
H
H
H
H
H
H
H
H
1a
1b
1c
1d
1e
1f
3a
3b
3c
3d
3e
3f
4a
4b
4c
4d
4e
4f
2
Ar = 4-MeOC6H4
Ar = 4-FC6H4
dibenzosuberone
90
85
3
86
80
4
87
69
5
dibenzosuberenone 2ac
84
71
6
9-fluorenone
xanthone
2ac
2ac
37
32
7
65
57
1g
1a
1b
1c
1d
1e
1g
1a
1d
1g
1a
1b
1c
1d
1e
1g
3g
4g
4h
4i
8
Ar = Ph
2bc Me H
2bc Me H
2bc Me H
2bc Me H
58
9
Ar = 4-MeOC6H4
Ar = 4-FC6H4
dibenzosuberone
65
10
11
12
13
14
15
16
17
18
19
20
21
22
54
4j
37
4k
4l
dibenzosuberenone 2bc Me H
38
xanthone
2bc Me H
30
4m
4n
4o
4p
4q
4r
4s
4t
Ar = Ph
2cc
2cc
2cc
H
H
H
Me
Me
Me
H
63
dibenzosuberone
xanthone
46
51
Ar = Ph
2dd Ph
2dd Ph
2dd Ph
2dd Ph
53
Ar = 4-MeOC6H4
Ar = 4-FC6H4
dibenzosuberone
dibenzosuberenone 2dd Ph
xanthone
2dd Ph
H
25
H
48
H
47
H
58
4u
4v
H
36
aThe electroreduction of 1 (1 mmol) and 2 (5 or 2 mmol) in Bu4NClO4/THF using a Pt cathode at a
constant current of 200 mA (200 C). bIsolated yields based on 1. c5 mmol. d2 mmol.
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The electroreduction of 1a with methyl cinnamates 2d-h was carried out with the molar ratio
of 1a/2d-h as 2/1, since 2d-h are more expensive than 1a (Table 2). After desilylation of the crude
adduct 3q, the yield of 4q was improved to 75% (run 1) in comparison to 53% yield of run 17 in
Table 1. As shown in Table 3, aryl alkyl ketones 1h-n (runs 1-9) and aromatic aldehydes 1o-s
(runs 10-14) were employed in place of benzophenones 1a-g. The reaction of acetophenone (1h)
with 2a gave the product 5a in 78% yield, and subsequent desilylation of 5a afforded
5-phenyl-5methyl-γ-butyrolactone (6a) in 96% yield (run 1). Although the adducts 5b,c obtained
by the reactions of 1h with 2b,c could not be purified, the corresponding γ-butyrolactones 6b (63%)
and 6c (69%) could be isolated as mixtures of two diastereomers (50:50 dr) after treatment of the
crude 2b,c with TBAF (runs 2 and 3). Other acetophenones 1i-k (runs 4-6) and phenyl alkyl
ketones 1l-n (runs 7-9) also applicable to the electroreductive coupling with 2a, and the
corresponding 5-aryl-5-methyl-γ-butyrolactones 6d-f and 5-phenyl-5-alkyl-γ-butyrolactones 6g-i
were obtained by desilylation of the adducts 5d-f and 5g-i, respectively. Although the yields were
lowered (35-56%), aromatic aldehydes 1o-s were reacted with 2a to give 5j-n (runs 10-14).
Desilylation of 5j-n produced 5-aryl-γ-butyrolactones 6j-n in high yields.
Table 2. Electroreductive coupling of 1a with 2d-h and transformation to 4q,w-z
run
1
R1
% yielda
75
2
4
Ph
2d
2e
2f
2g
2h
4q
4w
4x
4y
4z
2
4-MeOC6H4
71
3
4-FC6H4
73
4
3,4-methylenedioxyphenyl
2-naphthyl
73
5
63
aIsolated yields based on 2.
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ACCEPTED MANUSCRIPT
Table 3. Electroreductive coupling of 1h-p with 2a-c and transformation to 6a-k
run
1
Ar
R
% yielda
78
% yieldb (dr)c
1
2
5
6
Ph
Me
Me
Me
Me
Me
Me
Et
96
1h
1h
1h
1i
2a
2b
2c
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
5a
6a
6b
6c
6d
6e
6f
2
Ph
63a (50:50)
69a (50:50)
3
Ph
4
4-MeOC6H4
4-FC6H4
2-naphthyl
Ph
63
85
82
87
89
93
49
56
35
50
45
90
92
96
93
91
92
92
91
89
94
95
5d
5e
5f
5
1j
6
1k
1l
7
5g
5h
5i
6g
6h
6i
8
Ph
n-Pr
i-Pr
H
1m
1n
1o
1p
1q
1r
1s
9
Ph
10
11
12
13
14
Ph
5j
6j
4-MeOC6H4
4-FC6H4
H
5k
5l
6k
6l
H
3,4-methylenedioxyphenyl H
2-naphthyl
5m
5n
6m
6n
H
aIsolated yields based on 1. bIsolated yields based on 5. cDiastereomeric ratio.
In the previous report,1 it is presumed that the electroreductive coupling is initiated by the
electron transfer to methyl acrylate (2a), since 2a is more reducible than aliphatic carbonyl
compounds. We measured the cyclic voltammetry (CV) of 1a, 1h, 1l, and 2a (3 mM) in 0.03 M
Bu4NClO4/DMF on a platinum cathode. The first reduction peaks of their CV data showed that 1a
(−1.85 V vs SCE), 1h (−2.10 V vs SCE), and 1l (−1.94 V vs SCE) were more reducible than 2a,
since the CV data of 2a gave no reduction peak from 0 to −2.20 V vs SCE. These results suggest
that the electroreductive coupling of aromatic carbonyl compounds 1a, 1h, and 1l with 2a is
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ACCEPTED MANUSCRIPT
initiated by the electron transfer to 1a, 1h, and 1ly. Hence, the presumed reaction mechanism of
the electroreductive coupling of 1a with 2a can be illustrated as Scheme 3. As previously
reported,9 carbanion A is formed by the two-electron transfer to 1a and O-silylation with TMSCl.
The successive nucleophilic 1,4-addition of A to 2a and O-silylation of the resultant enolate anion B
produce silyl ketene acetal C. Finally, the labile C is readily desilylated to 3a during workup.
CO2Me
+2e
TMSCl
O
2a
Ph
Ph
Ph
OTMS
A
Ph
1a
OMe
OTMS
B
+H+
-TMS+
OTMS
OMe
Ph
Ph
TMSCl
Ph
CO2Me
Ph
OTMS
OTMS
C
3a
Scheme 3. Presumed reaction mechanism of electroreductive coupling of 1a with 2a.
Next, to expand the scope of the electroreductive coupling of aromatic ketones with
α,β-unsaturated carbonyl compounds, acrylonitrile (7) was employed in place of methyl acrylate 2a.
The electroreduction of 1a,h with 7 under the same conditions as described above also gave the
adducts as 4-trimethylsiloxybutanenitriles 8a,h, although the yields of 8a,h were moderate (Scheme
4). The desilylation of 8a,h by treatment with TBAF afforded 4-hydroxybutanenitriles 9a,h.
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ACCEPTED MANUSCRIPT
Scheme 4. Electroreductive coupling of 1a,h with 7 and desilylation of 8a,h.
The electroreductive intramolecular coupling of ω-keto-α,β-unsaturated esters 10a-c (n =
0~2) were also effected under the same conditions, although the four-, five-, and six-membered
cyclized products 11a-c were obtained as diastereomeric mixtures (Scheme 5). The desilylation of
11a-c with TBAF gave cis-γ-butyrolactones 12a-c and trans-γ-hydroxy esters 13a-c.
Scheme 5. Electroreductive intramolecular coupling of 10a-c and desilylation of 11a-c.
Unfortunately, the electroreduction of 10d (n = 3) and subsequent desilylation with TBAF
gave complex mixture. From the mixture, simply reduced alcohol iii and 4-(trimethylsilyl)phenyl
analog of 10d (iv) were isolated, although intramolecularly coupled products 12d and 13d could not
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ACCEPTED MANUSCRIPT
be detected (Scheme 6).
Scheme 6. Electroreduction of 10d.
2.2. Electroreductive coupling of aromatic aldimines with methyl acrylate and acetonitrile.
In
the
preliminary
report,6
we
disclosed
that
the
electroreduction
(14a)
of
N-(4-methoxyphenyl)-1-phenylmethanimine
and
1-(4-chlorophenyl)-N-(4-methoxyphenyl)methanimine (14b) with 2a in Et4NOTs/DMF in the
presence of TMSCl gave the adduct 15a and 15b in 63% and 65% yields, respectively (Table 4,
runs 1 and 2). We have also revealed that the electroreductive coupling of 14a with
N-acetylimidazole gave the adduct in slightly higher yields under the conditions in Bu4NClO4/THF
and Bu4NPF6/THF than those in Et4NOTs/DMF.10 Although the electroreduction of 14a with 2a
was carried out in Bu4NClO4/THF and Bu4NPF6/THF, the yield of 15a decreased to some extent
(58% and 55%, respectively). Therefore, the electroreduction of the other aromatic aldimines
14c-j with 2a was performed in Et4NOTs/DMF and the adducts 15c-j were obtained in moderate to
good yields (Table 4, runs 3-10). The cyclization of 15a-j by treatment with NaH in THF gave
5-aryl-N-(4-methoxyphenyl)-γ-butyrolactams 16a-j and then the N-4-methoxyphenyl group (An) in
16a-j was removed by treatment with CAN in aqueous acetonitrile to give 5-aryl-γ-butyrolactams
17a-j. From 14j (Ar = 3-pyridyl) derived from nicotinaldehyde, (±)-norcotinine (17j) was
synthesized in three steps (run 10). The An group in the adducts 15a-h could be removed by
treatment with CAN, and subsequent N-protection of the resultant methyl 4-aryl-4-aminobutyrates
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ACCEPTED MANUSCRIPT
with (Boc)2O gave methyl 4-aryl-4-((t-butoxycarbonyl)amino)butyrates 18a-h (Table 5). These
procedures provide a convenient method for the synthesis of γ-aryl substituted γ-amino acid
(GABA) derivatives.
Similarly, the electroreduction of 14a-h with 7 in Et4NOTs/DMF in the presence of TMSCl
afforded 4-aryl-4-((4-methoxyphenyl)amino)butanenitriles 19a-h (Table 6). The adducts 19a-h
were converted to 4-aryl-4-((t-butoxycarbonyl)amino)butanenitriles 20a-h by the same method as
described above.
Table 4. Electroreductive coupling of 14a-j with 2a and transformation to 16a-j and 17a-j
run
1
Ar
% yielda
63
% yieldb
90
% yieldc
78
14
15
16
17
Ph
14a
14b
14c
14d
14e
14f
14g
14h
14i
15a
15b
15c
15d
15e
15f
15g
15h
15i
16a
16b
16c
16d
16e
16f
16g
16h
16i
17a
17b
17c
17d
17e
17f
17g
17h
17i
2
4-ClC6H4
4-MeOC6H4
2-MeOC6H4
4-FC6H4
65
86
79
3
51
81
65
4
65
90
72
5
60
89
70
6
4-NCC6H4
1-naphthyl
2-naphthyl
3,4-(MeO)2C6H3
3-pyridyl
45
80
78
7
80
86
80
8
74
80
72
9
63
84
63
10
53
80
52
14j
15j
16j
17j
aIsolated yields based on 14. bIsolated yields based on 15. cIsolated yields based on 16.
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Table 5. Transformation of 15a-h to 18a-h
run
1
Ar
% yielda
70
15
18
Ph
15a
15b
15c
15d
15e
15f
15g
15h
18a
18b
18c
18d
18e
18f
18g
18h
2
4-ClC6H4
4-MeOC6H4
2-MeOC6H4
4-FC6H4
4-NCC6H4
1-naphthyl
2-naphthyl
71
3
58
4
53
5
67
6
63
7
62
8
65
aIsolated yields based on 15.
Table 6. Electroreductive coupling of 14a-h with 7 and transformation to 20a-h
run
1
Ar
% yielda
68
% yieldb
85
14
19
20
Ph
14a
14b
14c
14d
14e
14f
14g
14h
19a
19b
19c
19d
19e
19f
19g
19h
20a
20b
20c
20d
20e
20f
20g
20h
2
4-ClC6H4
4-MeOC6H4
2-MeOC6H4
4-FC6H4
4-NCC6H4
1-naphthyl
2-naphthyl
63
86
3
51
81
4
65
90
5
60
89
6
45
80
7
80
86
8
74
80
aIsolated yields based on 14. bIsolated yields based on 19.
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3. Conclusion
The electroreductive intermolecular coupling of aromatic ketones 1a-n and aldehydes 1o-s with
α,β-unsaturated esters 2a-h in the presence of TMSCl in Bu4NClO4/THF gave the adducts as 5-aryl
substituted γ-trimethylsiloxy esters 3a-z and 5a-n. The adducts 3a-z and 5a-n were transformed to
the corresponding γ-butyrolactones 4a-z and 6a-n by treatment with TBAF. The electroreductive
coupling of aromatic ketones 1a and 1h with acrylonitrile (7) afforded
4-(trimethylsiloxy)butanenitriles 8a and 8h. The electroreductive intramolecular coupling of
aromatic ketones with α,β-unsaturated esters was also effected and four-, five-, and six-membered
cyclized products 11a-c were produced from ω-keto-α,β-unsaturated esters 10a-c, respectively.
The electroreductive coupling of N-(4-methoxyphenyl)-1-arylmethaneimines 14a-j with methyl
acrylate (2a) in the presence of TMSCl in Et4NOTs/DMF gave methyl
4-aryl-4-((4-methoxyphenyl)amino)butanoates 15a-j. The adducts 15a-j were transformed to
5-aryl-γ-butyrolactams 17a-j by cyclization with NaH and subsequent N-deprotection of the
resultant 5-aryl-N-(4-methoxyphenyl)-γ-butyrolactams 16a-j with CAN. (±)-Norcotinine (17j)
was prepared from nicotinaldehyde by this method. The electroreductive coupling of 14a-h with 7
afforded 4-aryl-4-((4-methoxyphenyl)amino)butanenitriles 19a-h. The adducts 15a-h and 19a-h
were transformed to methyl 4-aryl-4-((t-butoxycarbonyl)amino)butyrates 18a-h and
4-aryl-4-((t-butoxycarbonyl)amino)butanenitriles 20a-h, respectively, by treatment with CAN and
subsequent N-protection with (Boc)2O.
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4. Experimental section
4.1. General
THF was freshly distilled from sodium benzophenone ketyl radical. DMF, TMSCl, and TEA
1
were distilled from CaH2. Column chromatography was performed on silica gel 60. H NMR (500
MHz) and 13C NMR (125 MHz) spectra were measured on a JEOL JNM-ECP500 spectrometer with
tetramethylsilane (TMS) as an internal standard. IR spectra were recorded on a Shimadzu
IRAffinity-1 infrared spectrometer. HRMS were measured on a Thermo Scientic Exactive FTMS
spectrometer. Melting points were uncorrected. Compound 10a-d were prepared according to the
reported method.11
4.2. Typical procedure of electroreductive coupling of 1 with 2
A 0.3 M solution of Bu4NClO4 in THF (15 mL) was placed in the cathodic chamber of a
divided cell (40 mL beaker, 3 cm diameter, 6 cm height) equipped with a platinum cathode (5 X 5
cm2), a platinum anode (2 X 1 cm2), and a ceramic cylindrical diaphragm (1.5 cm diameter). A 0.3
M solution of Et4NOTs in DMF (4 mL) was placed in the anodic chamber (inside the diaphragm).
Benzophenone (1a) (182 mg, 1.0 mmol), methyl acrylate (2a) (0.45 mL, 5.0 mmol), TMSCl (0.64
mL, 5.0 mmol), and TEA (0.70 mL, 5.0 mmol) were added to the cathodic chamber. After 300 C (3
F/mol for 1a) of electricity was passed at a constant current of 200 mA at 25 ºC under nitrogen
atmosphere, the catholyte was evaporated in vacuo. The residue was dissolved in diethyl ether (20
mL) and insoluble solid was filtered off. After removal of the solvent in vacuo, the residue was
purified by column chromatography on silica gel (hexanes-EtOAc) to give 3a (325 mg) in 95%
yield.
4.2.1. Methyl 4,4-diphenyl-4-((trimethylsilyl)oxy)butanoate (3a): Colorless paste; Rf 0.65
(hexanes-ethyl acetate, 10:1); IR (ATR) 1736 cm-1; 1H NMR (CDCl3) δ −0.10 (s, 9H), 2.16-2.20 (m,
2H), 2.64-2.69 (m, 2H), 3.61 (s, 3H), 7.18-7.22 (m, 2H), 7.24-7.28 (m, 4H), 7.30-7.33 (m, 4H); 13C
NMR (CDCl3) δ 1.6 (q), 28.8 (t), 35.9 (t), 51.3 (q), 79.8 (s), 126.7 (d), 127.7 (d), 146.8 (s), 174.1
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(s); HRMS (ESI) calcd for C20H27O3Si (M + H+) 343.1729; found 343.1727.
4.2.2. Methyl 4,4-bis(4-methoxyphenyl)-4-((trimethylsilyl)oxy)butanoate (3b): Colorless paste; Rf
1
0.35 (hexanes-ethyl acetate, 10:1); IR (ATR) 1736 cm-1; H NMR (CDCl3) δ −0.11 (s, 9H),
2.15-2.20 (m, 2H), 2.57-2.62 (m, 2H), 3.61 (s, 3H), 3.79 (s, 6H), 6.77-6.81 (m, 4H), 7.20-7.24 (m,
4H); 13C NMR (CDCl3) δ 1.4 (q), 28.7 (t), 36.1 (t), 51.0 (q), 54.7 (q), 79.1 (s), 112.7 (d), 127.7 (d),
139.0 (s), 158.1 (s), 174.0 (s); HRMS (ESI) calcd for C22H31O5Si (M + H+) 403.1941; found
403.1938.
4.2.3. Methyl 4,4-bis(4-fluorophenyl)-4-((trimethylsilyl)oxy)butanoate (3c): Colorless paste; Rf 0.55
(hexanes-ethyl acetate, 10:1); IR (ATR) 1736 cm-1; 1H NMR (CDCl3) δ −0.09 (s, 9H), 2.14-2.18 (m,
13
2H), 2.59-2.64 (m, 2H), 3.61 (s, 3H), 6.93-6.99 (m, 4H), 7.24-7.29 (m, 4H); C NMR (CDCl3)
δ 1.5 (q), 28.7 (t), 36.0 (t), 51.3 (q), 79.1 (s), 114.6 (d, JCCF=21.3 Hz), 128.4 (d, JCCCF=7.5 Hz),
142.5 (s, JCCCCF=3.6 Hz), 161.6 (s, JCF=246.2 Hz), 173.9 (s); HRMS (ESI) calcd for C20H25F2O3Si
(M + H+) 379.1541; found 379.1538.
4.2.4. Methyl 3-(5-((trimethylsilyl)oxy)-10,11-dihydro-5H-dibenzo[a,d][7]annulen-5-yl)propanoate
(3d): Colorless paste; Rf 0.5 (hexanes-ethyl acetate, 10:1); IR (ATR) 1736 cm-1; 1H NMR (CDCl3) δ
−0.13 (s, 9H), 2.13 (t, 2H, J=8.0 Hz), 2.49 (t, 2H, J=8.0 Hz), 2.98-3.13 (m, 4H), 3.57 (s, 3H),
13
7.04-7.07 (m, 2H), 7.14-7.18 (m, 2H), 7.21-7.25 (m, 2H), 7.77-7.81 (m, 2H); C NMR (CDCl3)
δ 1.8 (q), 29.5 (t), 35.9 (t), 43.6 (t), 51.2 (q), 83.3 (s), 125.7 (d), 127.1 (d), 129.6 (d), 130.3 (d),
140.2 (s), 143.7 (s), 173.9 (s); HRMS (ESI) calcd for C22H29O3Si (M + H+) 369.1886; found
369.1884.
4.2.5. Methyl 3-(5-((trimethylsilyl)oxy)-5H-dibenzo[a,d][7]annulen-5-yl)propanoate (3e): Colorless
1
paste; Rf 0.4 (hexanes-ethyl acetate, 10:1); IR (ATR) 1734 cm-1; H NMR (CDCl3) δ 0.36 (s, 9H),
1.80-1.85 (m, 2H), 2.36-2.42 (m, 2H), 3.53 (s, 3H), 7.03 (s, 2H), 7.21-7.25 (m, 2H), 7.29-7.33 (m,
2H), 7.36-7.42 (m, 2H), 7.80-7.84 (m, 2H); 13C NMR (CDCl3) δ 2.8 (q), 29.5 (t), 30.2 (t), 51.2 (q),
81.5 (s), 124.7 (d), 126.2 (d), 128.3 (d), 128.9 (d), 131.5 (d), 131.9 (s), 142.0 (s), 173.3 (s); HRMS
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(ESI) calcd for C22H27O3Si (M + H+) 367.1729; found 367.1727.
4.2.6. Methyl 3-(9-((trimethylsilyl)oxy)-9H-fluoren-9-yl)propanoate (3f): Colorless paste; Rf 0.5
(hexanes-ethyl acetate, 10:1); IR (ATR) 1736 cm-1; 1H NMR (CDCl3) δ −0.36 (s, 9H), 2.04-2.08 (m,
2H), 2.36-2.40 (m, 2H), 3.54 (s, 3H), 7.26-7.30 (m, 2H), 7.34-7.37 (m, 2H), 7.46-7.48 (m, 2H),
7.60-7.62 (m, 2H); 13C NMR (CDCl3) δ 1.2 (q), 29.1 (t), 37.1 (t), 51.3 (q), 83.1 (s), 119.9 (d), 124.3
(d), 127.6 (d), 128.8 (d), 139.5 (s), 148.1 (s), 173.8 (s); HRMS (ESI) calcd for C20H25O3Si (M + H+)
341.1573; found 341.1572.
4.2.7. Methyl 3-(9-((trimethylsilyl)oxy)-9H-xanthen-9-yl)propanoate (3g): Colorless paste; Rf 0.5
(hexanes-ethyl acetate, 10:1); IR (ATR) 1736 cm-1; 1H NMR (CDCl3) δ −0.29 (s, 9H), 1.80-1.84 (m,
2H), 2.45-2.49 (m, 2H), 3.47 (s, 3H), 7.06-7.09 (m, 2H), 7.12-7.16 (m, 2H), 7.28-7.32 (m, 2H),
7.59-7.62 (m, 2H); 13C NMR (CDCl3) δ 1.3 (q), 29.5 (t), 43.2 (t), 51.2 (q), 70.4 (s), 116.0 (d), 123.1
(d), 124.8 (s), 127.7 (d), 129.0 (d), 149.8 (s), 173.1 (s); HRMS (ESI) calcd for C20H25O4Si (M + H+)
357.1522; found 357.1520.
4.2.8. Methyl 4-phenyl-4-((trimethylsilyl)oxy)pentanoate (5a): Colorless paste; Rf 0.55
1
(hexanes-ethyl acetate, 10:1); IR (ATR) 1738 cm-1; H NMR (CDCl3) δ 0.13 (s, 9H), 1.64 (s, 3H),
1.99-2.11 (m, 3H), 2.27-2.35 (m, 1H), 3.59 (s, 3H), 7.18-7.23 (m, 1H), 7.28-7.33 (m, 2H), 7.34-7.38
(m, 2H); 13C NMR (CDCl3) δ 2.2 (q), 29.2 (t), 29.8 (q), 40.4 (t), 51.3 (q), 76.7 (s), 125.0 (d), 126.4
(d), 127.8 (d), 147.4 (s), 174.2 (s); HRMS (ESI) calcd for C15H25O3Si (M + H+) 281.1573; found
281.1571.
4.2.9. Methyl 4-(4-methoxyphenyl)-4-((trimethylsilyl)oxy)pentanoate (5d): Colorless paste; Rf 0.4
(hexanes-ethyl acetate, 10:1); IR (ATR) 1736 cm-1; 1H NMR (CDCl3) δ −0.06 (s, 9H), 1.45 (s, 3H),
1.84-1.92 (m, 3H), 2.08-2.18 (m, 1H), 3.42 (s, 3H), 3.61 (s, 3H), 6.64-6.69 (m, 2H), 7.08-7.13 (m,
13
2H); C NMR (CDCl3) δ 2.2 (q), 29.2 (t), 29.6 (q), 40.5 (t), 51.2 (q), 55.0 (q), 76.4 (s), 113.1 (d),
126.1 (d), 139.5 (s), 158.1 (s), 174.2 (s); HRMS (ESI) calcd for C16H27O4Si (M + H+) 311.1679;
found 311.1676.
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4.2.10. Methyl 4-(4-fluorophenyl)-4-((trimethylsilyl)oxy)pentanoate (5e): Colorless paste; Rf 0.5
1
(hexanes-ethyl acetate, 10:1); IR (ATR) 1736 cm-1; H NMR (CDCl3) δ 0.12 (s, 9H), 1.63 (s, 3H),
13
1.98-2.09 (m, 3H), 2.24-2.35 (m, 1H), 3.60 (s, 3H), 6.95-7.01 (m, 2H), 7.30-7.34 (m, 2H); C
NMR (CDCl3) δ 2.2 (q), 29.1 (t), 29.8 (q), 40.5 (t), 51.3 (q), 76.5 (s), 114.5 (d, JCCF=20.7 Hz), 126.7
(d, JCCCF=7.5 Hz), 143.2 (s, JCCCCF=3.6 Hz), 161.4 (s, JCF=244.7 Hz), 174.1 (s); HRMS (ESI) calcd
for C15H24FO3Si (M + H+) 299.1479; found 299.1476.
4.2.11. Methyl 4-(naphthalen-2-yl)-4-((trimethylsilyl)oxy)pentanoate (5f): Colorless paste; Rf 0.5
1
(hexanes-ethyl acetate, 10:1); IR (ATR) 1736 cm-1; H NMR (CDCl3) δ 0.15 (s, 9H), 1.74 (s, 3H),
2.01-2.09 (m, 1H), 2.11-2.23 (m, 2H), 2.29-2.39 (m, 1H), 3.55 (s, 3H), 7.42-7.51 (m, 3H), 7.77-7.85
13
(m, 4H); C NMR (CDCl3) δ 2.3 (q), 29.2 (t), 29.6 (q), 40.3 (t), 51.2 (q), 76.9(s), 123.6 (d), 123.8
(d), 125.5 (d), 125.8 (d), 127.3 (d), 127.6 (d), 128.0 (d), 132.2 (s), 133.0 (s), 144.8 (s), 174.1 (s);
HRMS (ESI) calcd for C19H28O3Si (M + H+) 331.1729; found 331.1724.
4.2.12. Methyl 4-phenyl-4-((trimethylsilyl)oxy)hexanoate (5g): Colorless paste; Rf 0.55
(hexanes-ethyl acetate, 10:1); IR (ATR) 1736 cm-1; 1H NMR (CDCl3) δ 0.19 (s, 9H), 0.65 (t, 3H, J
= 7.4 Hz), 1.85-1.96 (m, 3H), 2.10-2.32 (m, 3H), 3.57 (s, 3H), 7.16-7.20 (m, 1H), 7.27-7.32 (m,
13
4H); C NMR (CDCl3) δ 2.2 (q), 8.1 (q), 28.9 (t), 35.6 (t), 37.7 (t), 51.3 (q), 80.4 (s), 125.6 (d),
126.2 (d), 127.8 (d), 144.9 (s), 174.1 (s); HRMS (ESI) calcd for C16H27O3Si (M + H+) 295.1729;
found 295.1726.
4.2.13. Methyl 4-phenyl-4-((trimethylsilyl)oxy)heptanoate (5h): Colorless paste; Rf 0.55
(hexanes-ethyl acetate, 10:1); IR (ATR) 1738 cm-1; 1H NMR (CDCl3) δ 0.19 (s, 9H), 0.79 (t, 3H, J
= 7.3 Hz), 0.84-0.95 (m, 1H), 1.16-1.28 (m, 1H), 1.75-1.95 (m, 3H), 2.09-2.32 (m, 3H), 3.58 (s, 3H),
7.16-7.21 (m, 1H), 7.27-7.33 (m, 4H); 13C NMR (CDCl3) δ 2.2 (q), 14.0 (q), 16.9 (t), 28.8 (t), 37.9
(t), 45.6 (t), 51.3 (q), 80.0 (s), 125.5 (d), 126.1 (d), 127.8 (d), 145.3 (s), 174.1 (s); HRMS (ESI)
calcd for C17H29O3Si (M + H+) 309.1886; found 309.1883.
4.2.14. Methyl 5-methyl-4-phenyl-4-((trimethylsilyl)oxy)hexanoate (5i): Colorless paste; Rf 0.5
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(hexanes-ethyl acetate, 10:1); IR (ATR) 1738 cm-1; 1H NMR (CDCl3) δ 0.22 (s, 9H), 0.75 (d, 3H, J
= 6.9 Hz), 0.82 (d, 3H, J = 6.6 Hz), 1.91-2.04 (m, 2H), 2.13-2.41 (m, 3H), 3.60 (s, 3H), 7.17-7.21
13
(m, 1H), 7.27-7.31 (m, 4H); C NMR (CDCl3) δ 2.5 (q), 17.3 (q), 17.9 (q), 29.4 (t), 34.4 (t), 39.0
(d), 51.3 (q), 83.3 (s), 126.1 (d), 126.3 (d), 127.4 (d), 143.7 (s), 174.2 (s); HRMS (ESI) calcd for
C17H29O3Si (M + H+) 309.1886; found 309.1882.
4.2.15. Methyl 4-phenyl-4-((trimethylsilyl)oxy)butanoate (5j): Colorless paste; Rf 0.55
(hexanes-ethyl acetate, 10:1); IR (ATR) 1738 cm-1; 1H NMR (CDCl3) δ −0.14 (s, 9H), 1.76-1.88 (m,
2H), 2.13-2.27 (m, 2H), 3.49 (s, 3H), 4.54 (dd, 1H, J=5.0, 7.3 Hz), 7.05-7.09 (m, 1H), 7.12-7.15 (m,
13
4H); C NMR (CDCl3) δ −0.1 (q), 30.1 (t), 35.3 (t), 51.4 (q), 73.5 (d), 125.7 (d), 127.1 (d), 128.1
(d), 144.5 (s), 174.0 (s); HRMS (ESI) calcd for C14H23O3Si (M + H+) 267.1416; found 267.1414.
4.2.16. Methyl 4-(4-methoxyphenyl)-4-((trimethylsilyl)oxy)butanoate (5k): Colorless paste; Rf 0.45
1
(hexanes-ethyl acetate, 10:1); IR (ATR) 1736 cm-1; H NMR (CDCl3) δ 1.93-1.99 (m, 2H),
2.30-2.41 (m, 2H), 3.65 (s, 3H), 3.80 (s, 3H), 4.65 (t, 1H, J=6.3 Hz), 6.83-6.86 (m, 2H), 7.19-7.23
(m, 2H); 13C NMR (CDCl3) δ −0.1 (q), 30.1 (t), 35.3 (t), 51.3 (q), 55.0 (q), 73.2 (d), 113.4 (d), 126.8
(d), 136.6 (s), 158.6 (s), 173.9 (s); HRMS (ESI) calcd for C15H25O4Si (M + H+) 297.1522; found
297.1520.
4.2.17. Methyl 4-(4-fluorophenyl)-4-((trimethylsilyl)oxy)butanoate (5l): Colorless paste; Rf 0.5
(hexanes-ethyl acetate, 10:1); IR (ATR) 1736 cm-1; 1H NMR (CDCl3) δ −0.15 (s, 9H), 1.74-1.83 (m,
2H), 2.12-2.26 (m, 2H), 3.49 (s, 3H), 4.52 (dd, 1H, J=5.2, 7.3 Hz), 6.80-6.86 (m, 2H), 7.08-7.12 (m,
13
2H); C NMR (CDCl3) δ −0.1 (q), 30.0 (t), 35.4 (t), 51.5 (q), 72.9 (d), 114.9 (d, JCCF=21.3 Hz),
127.3 (d, JCCCF=8.4 Hz), 140.4 (s, JCCCCF=3.3 Hz), 161.9 (s, JCF=245.0 Hz), 173.9 (s); HRMS (ESI)
calcd for C14H22FO3Si (M + H+) 285.1322; found 285.1320.
4.2.18. Methyl 4-(benzo[d][1,3]dioxol-5-yl)-4-((trimethylsilyl)oxy)butanoate (5m): Colorless paste;
1
Rf 0.4 (hexanes-ethyl acetate, 10:1); IR (ATR) 1736, 1693 cm-1; H NMR (CDCl3) δ 0.03 (s, 9H),
1.91-1.96 (m, 2H), 2.29-2.41 (m, 2H), 3.66, (s, 3H), 4.61 (t, 1H, J=6.4 Hz), 5.93-5.95 (m, 2H),
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6.71-6.75 (m, 2H), 6.82-6.84 (m, 1H); 13C NMR (CDCl3) δ −0.1 (s), 30.0 (t), 35.4 (t), 51.3 (q), 73.3
(d), 100.8 (t), 106.2 (d), 107.7 (d), 118.9 (d), 138.7 (s), 146.5 (s), 147.4 (s), 173.9 (s); HRMS (ESI)
calcd for C15H23O5Si (M + H+) 311.1315; found 311.1312.
4.2.19. Methyl 4-(naphthalen-2-yl)-4-((trimethylsilyl)oxy)butanoate (5n): Colorless paste; Rf 0.4
1
(hexanes-ethyl acetate, 10:1); IR (ATR) 1736, 1697 cm-1; H NMR (CDCl3) δ 0.04 (s, 9H),
2.00-2.12 (m, 2H), 2.32-2.48 (m, 2H), 3.65 (s, 3H), 4.86-4.90 (m, 1H), 7.41-7.49 (m, 3H), 7.72-7.74
(m, 1H), 7.79-7.83 (m, 3H); 13C NMR (CDCl3) δ 0.0 (q), 30.1 (t), 35.3 (t), 51.4 (q), 73.7 (d), 124.1
(d), 124.4 (d), 125.6 (d), 126.0 (d), 127.6 (d), 127.9 (d), 128.0 (d), 132.9 (s), 133.2 (s), 142.1 (s),
174.0 (s); HRMS (ESI) calcd for C18H25O3Si (M + H+) 317.1573; found 317.1570.
4.2.20. 4,4-Diphenyl-4-((trimethylsilyl)oxy)butanenitrile (8a): Colorless paste; Rf 0.5 (hexanes-ethyl
acetate, 10:1); IR (ATR) 2249 cm-1; 1H NMR (CDCl3) δ −0.09 (s, 9H), 2.11-2.16 (m, 2H), 2.67-2.72
13
(m, 2H), 7.23-7.33 (m, 10H); C NMR (CDCl3) δ 1.6 (q), 12.0 (t), 37.3 (t), 79.5 (s), 120.1 (s),
126.7 (d), 127.3 (d), 128.0 (d), 145.2 (s); HRMS (ESI) calcd for C19H24NOSi (M + H+) 310.1627;
found 310.1625.
4.2.21. 4-Hydroxy-4,4-diphenylbutanenitrile (8h): Colorless paste; Rf 0.5 (hexanes-ethyl acetate,
1
10:1); IR (ATR) 2247 cm-1; H NMR (CDCl3) δ 0.16 (s, 9H), 1.67 (s, 3H), 1.93-2.00 (m, 1H),
2.05-2.12 (m, 2H), 2.28-2.35 (m, 1H), 7.22-7.28 (m, 1H), 7.32-7.35 (m, 4H); 13C NMR (CDCl3)
δ 2.2 (q), 12.1 (t), 29.6 (q), 41.3 (t), 76.3 (s), 120.2 (s), 124.9 (d), 126.9 (d), 128.2 (d), 146.1 (s);
HRMS (ESI) calcd for C14H22NOSi (M + H+) 248.1471; found 248.1469..
4.2.22. Ethyl 2-(2-Phenyl-2-((trimethylsilyl)oxy)cyclobutyl)acetate (11a): Diastereomeric mixture
1
(80:20); colorless paste; Rf 0.3, 0.25 (hexanes-ethyl acetate, 20:1); H NMR (CDCl3) δ −0.10 (s,
7.2H), −0.01 (s, 1.8H), 1.18 (t, 0.6H, J=7.0 Hz), 1.24 (t, 2.4H, J=7.0 Hz), 1.64-3.16 (m, 7H), 4.02 (q,
0.4H, J=7.0 Hz), 4.11 (q, 1.6H, J=7.0 Hz), 7.21-7.48 (m, 5H); 13C NMR (CDCl3) δ 1.3 (q), 14.1 (q),
19.9 (t), 32.2 (t), 35.3 (t), 45.1 (d), 59.9 (t), 78.6 (s), 125.6 (d), 126.8 (d), 128.0 (d), 146.4 (s), 173.2
(s); HRMS (ESI) calcd for C17H27O3Si (M + H+) 307.1729; found 307.1726.
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4.2.23. Ethyl 2-(2-Phenyl-2-((trimethylsilyl)oxy)cyclopentyl)acetate (11b): Diastereomeric mixture
1
(50:50); colorless paste: Rf 0.3 (hexanes-ethyl acetate, 20:1); H NMR (CDCl3) δ −0.07 (s, 4.5H),
0.09 (s, 4.5H), 1.19 (t, 1.5H, J=7.0 Hz), 1.20 (t, 1.5H, J=7.0 Hz), 1.28-2.65 (m, 9H), 4.00 (q, 1H,
J=7.0 Hz), 4.04 (q, 1H, J=7.0 Hz), 7.20-7.42 (m, 5H); 13C NMR (CDCl3) δ 1.6 (q), 1.7 (q), 14.0 (q),
21.0 (t), 21.5 (t), 28.2 (t), 29.6 (t), 33.3 (t), 35.8 (t), 36.7 (t), 39.3 (t), 48.9 (d), 50.7 (d), 59.7 (t), 59.8
(t), 86.3 (s), 86.7 (s), 125.4 (d), 126.3 (d), 126.7 (d), 126.9 (d), 127.6 (d), 127.7 (d), 144.0 (s), 145.5
(s), 172.8 (s), 173.5 (s); HRMS (ESI) calcd for C18H29O3Si (M + H+) 321.1886; found 321.1883.
4.2.24. Ethyl 2-(2-phenyl-2-((trimethylsilyl)oxy)cyclohexyl)acetate (11c): Diastereomeric mixture
1
(50:50); colorless paste; Rf 0.3 (hexanes-ethyl acetate, 20:1); H NMR (CDCl3) δ −0.15 (s, 4.5H),
0.16 (s, 4.5H), 1.15 (t, 1.5H, J=7.0 Hz), 1.16 (t, 1.5H, J=7.0 Hz), 1.37-2.20 (m, 10.5H), 2.51-2.64
13
(m, 0.5H), 3.92-4.00 (m, 2H), 7.18-7.43 (m, 5H); C NMR (CDCl3) δ 1.8 (q), 2.6 (q), 13.96 (q),
14.00 (q), 19.7 (t), 21.6 (t), 22.1 (t), 25.0 (t), 25.3 (t), 27.7 (t), 30.9 (t), 34.0 (t), 35.5 (t), 38.3 (t),
42.9 (d), 44.8 (d), 59.7 (q), 59.8 (q), 77.1 (s), 80.2 (s), 125.7 (d), 126.1 (d), 126.3 (d), 127.0 (d),
127.6 (d), 127.9 (d), 146.4 (s), 147.0 (s), 172.7 (s), 173.5 (s); HRMS (ESI) calcd for C19H31O3Si (M
+ H+) 335.5390; found 335.5386.
4.3. Typical Procedure of Desilylation of 3a-z with TBAF in THF
To a solution of 3a (86 mg, 0.25 mmol) in THF (5 mL) was added 1 M TBAF in THF (0.25 mL,
0.25 mmol) at 25 ˚C and the mixture was stirred for 15 min. After addition of AcOH (15 mg, 0.25
mmol), the solvent was removed in vacuo. The residue was purified by column chromatography on
silica gel (hexanes-EtOAc) to give 4a (78 mg) in 95% yield. Compounds 4a,3c,8a 4b,12 4c,8a,12 4h,6,8a
4n,6 4q,6 4t,6 6a,3c,8a 6b,13 6c,3c,8a 6d,8a 6e,14 6g,8a 6h,8a 6j,3c,8e 6k,8e 6l,8e 6m,15 6n,8e 9h,3b,8a 12b,16
and 12c17 were known.
4.3.1. 3',4',10,11-Tetrahydro-5'H-spiro[dibenzo[a,d][7]annulene-5,2'-furan]-5'-one (4d): White
solid; Rf 0.4 (hexanes-ethyl acetate, 5:1); mp 148-149 °C; IR (ATR) 1761 cm-1; 1H NMR (CDCl3) δ
2.57 (t, 2H, J=8.2 Hz), 2.92 (t, 2H, J=8.2 Hz), 2.99-3.08 (m, 2H), 3.47-3.55 (m, 2H), 7.15-7.24 (m,
6H), 7.59-7.63 (m, 2H); 13C NMR (CDCl3) δ 27.7 (t), 32.4 (t), 38.6 (t), 88.5 (s), 123.6 (d), 126.1 (d),
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127.8 (d), 130.8 (d), 136.6 (s), 141.1 (s), 176.1 (s). Anal. Calcd for C18H16O2: C, 81.79; H, 6.10.
Found: C, 81.75; H, 6.12.
4.3.2. 3',4'-Dihydro-5'H-spiro[dibenzo[a,d][7]annulene-5,2'-furan]-5'-one (4e): White solid; Rf
0.45 (hexanes-ethyl acetate, 5:1); mp 134-136 °C; IR (ATR) 1765 cm-1; 1H NMR (CDCl3) δ 2.34 (t,
2H, J=8.0 Hz), 2.49 (t, 2H, J=8.0 Hz), 7.06 (s, 2H), 7.29-7.34 (m, 2H), 7.37-7.43 (m, 4H),
13
7.75-7.80 (m, 2H); C NMR (CDCl3) δ 27.5 (t), 32.2 (t), 87.3 (s), 122.5 (d), 127.1 (d), 128.6 (d),
129.3 (d), 131.3 (d), 131.5 (s), 139.8 (s), 175.9 (s). Anal. Calcd for C18H14O2: C, 82.42; H, 5.38.
Found: C, 82.39; H, 5.39.
4.3.3. 3',4'-Dihydro-5'H-spiro[fluorene-9,2'-furan]-5'-one (4f): Colorless paste; Rf 0.3
1
(hexanes-ethyl acetate, 5:1); IR (ATR) 1767 cm-1; H NMR (CDCl3) δ 2.69 (t, 2H, J=8.5 Hz), 3.07
(t, 2H, J=8.5 Hz), 7.31-7.35 (m, 2H), 7.40-7.44 (m, 2H), 7.45-7.48 (m, 2H), 7.63-7.66 (m, 2H); 13C
NMR (CDCl3) δ 29.5 (t), 33.0 (t), 90.5 (s), 120.2 (d), 123.3 (d), 128.3 (d), 130.0 (d), 139.5 (s),
145.1 (s), 177.0 (s); HRMS (ESI) calcd for C16H13O2 (M + H+) 237.0916; found 237.0915.
4.3.4. 3,4-Dihydro-5H-spiro[furan-2,9'-xanthen]-5-one (4g): White solid; Rf 0.3 (hexanes-ethyl
acetate, 5:1); mp 110-112 °C; IR (ATR) 1757 cm-1; 1H NMR (CDCl3) δ 2.58 (t, 2H, J=8.3 Hz), 2.95
13
(t, 2H, J=8.3 Hz), 7.18-7.26 (m, 4H), 7.36-7.43 (m, 2H), 7.43-7.49 (m, 2H); C NMR (CDCl3)
δ 28.8 (t), 40.8 (t), 79.8 (s), 116.8 (d), 123.8 (d), 125.0 (d), 129.6 (d), 149.6 (s), 176.4 (s). Anal.
Calcd for C16H12O3: C, 76.18; H, 4.79. Found: C, 76.13; H, 4.82.
4.3.5. 5,5-Bis(4-methoxyphenyl)-4-methyldihydrofuran-2(3H)-one (4i): White solid; Rf 0.2
1
(hexanes-ethyl acetate, 5:1); mp 109-111 ºC; IR (ATR) 1771, 1753 cm-1; H NMR (CDCl3) δ 0.90
(d, 3H, J=7.0 Hz), 2.31 (dd, 1H, J=5.6, 17.2 Hz), 2.71 (dd, 1H, J=7.5, 17.2 Hz), 3.31-3.39 (m, 1H),
3.78 (s, 3H), 3.80 (s, 3H), 6.80-6.85 (m, 2H), 6.86-6.90 (m, 2H), 7.10-7.14 (m, 2H), 7.37-7.42 (m,
2H); 13C NMR (CDCl3) δ 16.9 (q), 37.3 (t), 37.9 (d), 54.9 (q), 55.0 (q), 91.9 (s), 113.2 (d), 113.6 (d),
126.8 (d), 127.3 (d), 132.8 (s), 134.9 (s), 158.5 (s), 159.0 (s), 175.7 (s). Anal. Calcd for C19H20O4: C,
73.06; H, 6.45. Found: C, 73.01; H, 6.47.
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4.3.6 5,5-Bis(4-fluorophenyl)-4-methyldihydrofuran-2(3H)-one (4j): Colorless paste; Rf 0.25
(hexanes-ethyl acetate, 5:1); IR (ATR) 1782 cm-1; 1H NMR (CDCl3) δ 0.90 (d, 3H, J=6.9 Hz), 2.33
(dd, 1H, J=4.6, 17.2 Hz), 2.72 (dd, 1H, J=7.5, 17.2 Hz), 3.33-3.41 (m, 1H), 6.98-7.09 (m, 4H),
13
7.17-7.22 (m, 2H), 7.44-7.49 (m, 2H); C NMR (CDCl3) δ 17.0 (q), 37.3 (t), 38.0 (d), 91.3 (s),
115.1 (d, JCCF=21.3 Hz), 115.5 (d, JCCF=21.6 Hz), 127.3 (d, JCCCF=7.8 Hz), 128.0 (d, JCCCF=8.4 Hz),
136.1 (s, JCCCCF=3.6 Hz), 138.4 (s, JCCCCF=3.6 Hz), 161.9 (s, JCF=247.1 Hz), 162.3 (s, JCF=248.0
Hz), 175.2 (s); HRMS (ESI) calcd for C17H15F2O2 (M + H+) 289.1040; found 289.1037.
4.3.7. 3'-Methyl-3',4',10,11-tetrahydro-5'H-spiro[dibenzo[a,d][7]annulene-5,2'-furan]-5'-one (4k):
1
White solid; Rf 0.35 (hexanes-ethyl acetate, 5:1); mp 163-165 ºC; IR (ATR) 1761 cm-1; H NMR
(CDCl3) δ 0.87 (d, 3H, J=7.3 Hz), 2.22 (d, 1H, J=17.2 Hz), 2.74 (dd, 1H, J=7.6, 17.2 Hz), 2.90-2.98
(m, 1H), 3.06-3.14 (m, 1H), 3.26-3.34 (m, 1H), 3.41-3.54 (m, 2H), 7.09-7.23 (m, 6H), 7.45-7.49 (m,
13
1H), 7.71-7.75 (m, 1H); C NMR (CDCl3) δ 17.6 (q), 32.2 (t), 32.4 (t), 36.4 (t), 40.6 (d), 91.7 (s),
123.6 (d), 125.2 (d), 126.0 (d), 126.3 (d), 127.9 (d), 130.1 (d), 131.6 (d), 136.2 (s), 136.5 (s), 138.5
(s), 140.4 (s), 176.2 (s). Anal. Calcd for C19H18O2: C, 81.99; H, 6.52. Found: C, 81.92; H, 6.50.
4.3.8. 3'-Methyl-3',4'-dihydro-5'H-spiro[dibenzo[a,d][7]annulene-5,2'-furan]-5'-one (4l): White
1
solid; Rf 0.5 (hexanes-ethyl acetate, 5:1); mp 137-138 °C; IR (ATR) 1780, 1763, 1684 cm-1; H
NMR (CDCl3) δ 0.54 (d, 3H, J=7.4 Hz), 2.06 (d, 2H, J=17.2 Hz), 2.43 (dd, 1H, J=8.0, 17.2 Hz),
2.99-3.07 (m, 1H), 7.04 (d, 1H, J=12.0 Hz), 7.07 (d, 1H, J=12.0 Hz), 7.28-7.44 (m, 6H), 7.65-7.70
13
(m, 1H), 7.83-7.88 (m, 1H); C NMR (CDCl3) δ 17.6 (q), 34.8 (d), 36.1 (t), 90.5 (s), 122.9 (d),
123.9 (d), 127.1 (d), 127.2 (d), 128.5 (d), 128.7 (d), 128.8 (d), 129.3 (d), 131.2 (d), 131.3 (d), 131.8
(s), 131.9 (s), 136.6 (s), 139.7 (s), 176.0 (s). Anal. Calcd for C19H18O2: C, 82.58; H, 5.84. Found: C,
82.54; H, 5.87
4.3.9. 3-Methyl-3,4-dihydro-5H-spiro[furan-2,9'-xanthen]-5-one (4m): Colorless paste; Rf 0.3
1
(hexanes-ethyl acetate, 5:1); IR (ATR) 1775, 1751, 1655 cm-1; H NMR (CDCl3) δ 0.63 (d, 3H,
J=6.9 Hz), 2.54 (dd, 1H, J=11.6, 17.0 Hz), 2.62-2.71 (m, 1H), 2.80 (dd, 1H, J=8.0, 17.0 Hz),
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13
7.16-7.29 (m, 5H), 7.34-7.43 (m, 2H), 7.55-7.59 (m, 1H); C NMR (CDCl3) δ 13.8 (q), 35.8 (t),
47.1 (d), 83.2 (s), 116.4 (d), 116.9 (d), 120.0 (s), 123.5 (d), 124.0 (s), 124.1 (d), 125.1 (d), 125.2 (d),
129.4 (d), 129.7 (d), 150.2 (s), 150.8 (s), 176.4 (s); HRMS (ESI) calcd for C17H15O3 (M + H+)
267.1021; found 267.1019.
4.3.10. 4'-Methyl-3',4',10,11-tetrahydro-5'H-spiro[dibenzo[a,d][7]annulene-5,2'-furan]-5'-one (4o):
White solid; Rf 0.5 (hexanes-ethyl acetate, 5:1); mp 155 °C; IR (ATR) 1769 cm-1; 1H NMR (CDCl3)
δ 1.24 (d, 3H, J=7.5 Hz), 2.39 (t, 1H, J=12.0 Hz), 2.63-2.73 (m, 1H), 2.92-3.01 (m, 1H), 3.05-3.14
(m, 1H), 3.35 (dd, 1H, J=9.2, 12.0 Hz), 3.45-3.59 (m, 2H), 7.12-7.24 (m, 1H), 7.49-7.53 (m, 1H),
7.69-7.73 (m, 1H); 13C NMR (CDCl3) δ 14.8 (q), 32.4 (t), 32.7 (t), 34.2 (d), 47.1 (t), 86.4 (s), 123.7
(d), 124.0 (d), 126.2 (d), 126.6 (d), 127.9 (d), 128.1 (d), 130.5 (d), 131.4 (d), 136.6 (s), 136.8 (s),
140.3 (s), 142.6 (s), 178.9 (s). Anal. Calcd for C19H18O2: C, 81.99; H, 6.52. Found: C, 81.96; H,
6.54.
4.3.11. 4-Methyl-3,4-dihydro-5H-spiro[furan-2,9'-xanthen]-5-one (4p): Colorless paste; Rf 0.4
(hexanes-ethyl acetate, 5:1); IR (ATR) 1765, 1722 cm-1; 1H NMR (CDCl3) δ 1.40 (d, 3H, J=7.3 Hz),
2.18 (dd, 1H, J=9.5, 13.3 Hz), 2.74 (dd, 1H, J=9.5, 13.3 Hz), 3.11-3.20 (m, 1H), 7.16-7.24 (m, 4H),
13
7.34-7.40 (m, 3H), 7.49-7.51 (m, 1H); C NMR (CDCl3) δ 15.7 (q), 34.7 (d), 49.4 (t), 77.6 (s),
116.5 (d), 117.0 (d), 123.7 (d), 123.8 (s), 124.0 (d), 124.5 (d), 124.7 (s), 125.2 (d), 129.4 (d), 129.5
(d), 149.7 (s), 150.0 (s), 179.2 (s); HRMS (ESI) calcd for C17H15O3 (M + H+) 267.1021; found
267.1019.
4.3.12. 5,5-Bis(4-methoxyphenyl)-4-phenyldihydrofuran-2(3H)-one (4r): Colorless paste; Rf 0.2
1
(hexanes-ethyl acetate, 5:1); IR (ATR) 1771, 1730 cm-1; H NMR (CDCl3) δ 2.81 (dd, 1H, J=5.7,
17.2 Hz), 2.96 (dd, 1H, J=8.0, 17.2 Hz), 3.68 (s, 3H), 3.80 (s, 3H), 4.43 (dd, 1H, J=5.7, 8.0 Hz),
13
6.57-6.62 (m, 2H), 6.85-6.93 (m, 6H), 7.11-7.15 (m, 3H), 7.49-7.53 (m, 2H); C NMR (CDCl3)
δ 37.1 (t), 51.0 (d), 55.1 (q), 55.3 (q), 92.8 (s), 112.9 (d), 113.8 (d), 127.3 (d), 127.6 (d), 127.7 (d),
128.3 (d), 128.6 (d), 132.1 (s), 135.2 (s), 138.1 (s), 158.5 (s), 159.2 (s), 175.9 (s); HRMS (ESI)
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calcd for C24H23O4 (M + H+) 375.1596; found 375.1594.
4.3.13. 5,5-Bis(4-fluorophenyl)-4-phenyldihydrofuran-2(3H)-one (4s): White solid; Rf 0.4
1
(hexanes-ethyl acetate, 5:1); mp 124-125 ºC; IR (ATR) 1769, 1738 cm-1; H NMR (CDCl3) δ 2.82
(dd, 1H, J=4.8, 17.2 Hz), 2.99 (dd, 1H, J=8.0, 17.2 Hz), 4.43 (dd, 1H, J=4.8, 8.0 Hz), 6.73-6.80 (m,
13
2H), 6.88-6.99 (m, 4H), 7.06-7.17 (m, 5H), 7.56-7.62 (m, 2H); C NMR (CDCl3) δ 37.0 (t), 50.8
(d), 92.0 (s), 114.6 (d, JCCF=21.6 Hz), 115.6 (d, JCCF=21.6 Hz), 127.5 (d), 127.97 (d, JCCCF=8.4 Hz),
127.98 (d, JCCCF=8.4 Hz), 128.36 (d), 128.43 (d), 135.6 (d, JCCCCF=2.4 Hz), 137.9 (s), 138.6 (s,
J
CCCCF=3.6 Hz), 161.6 (s, JCF=247.1 Hz), 162.3 (s, JCF=248.3 Hz), 175.2 (s). Anal. Calcd for
C22H16F2O2: C, 75.42; H, 4.60. Found: C, 75.36; H, 4.65.
4.3.14. 3'-Phenyl-3',4'-dihydro-5'H-spiro[dibenzo[a,d][7]annulene-5,2'-furan]-5'-one
(4u):
Colorless paste; Rf 0.45 (hexanes-ethyl acetate, 5:1); IR (ATR) 1775 cm-1; 1H NMR (CDCl3) δ 2.46
(d, 1H, J=17.8 Hz), 2.79 (dd, 1H, J=8.6, 17.8 Hz), 4.07 (d, 1H, J=8.6 Hz), 6.90 (d, 1H, J=12.0 Hz),
6.92-7.05 (m, 7H), 7.14 (d, 1H, J=12.0 Hz), 7.19-7.24 (m, 1H), 7.33-7.37 (m, 1H), 7.42-7.47 (m,
2H), 7.74-7.79 (m, 2H); 13C NMR (CDCl3) δ 36.4 (t), 46.9 (d), 91.5 (s), 122.9 (d), 123.9 (d), 126.6
(d), 126.8 (d), 127.2 (d), 127.4 (d), 127.8 (d), 128.3 (d), 128.5 (d), 128.9 (d), 129.5 (d), 130.3 (d),
131.6 (s), 131.8 (s), 133.0 (s), 136.5 (s), 140.0 (s), 140.4 (s), 176.3 (s); HRMS (ESI) calcd for
C24H19O2 (M + H+) 339.1385; found 339.1383.
4.3.15. 3-Phenyl-3,4-dihydro-5H-spiro[furan-2,9'-xanthen]-5-one (4v): White solid; Rf 0.45
(hexanes-ethyl acetate, 5:1); mp 166-167 ºC; IR (ATR) 1798, 1771, 1734 cm-1; 1H NMR (CDCl3) δ
2.99 (dd, 1H, J=8.2, 17.7 Hz), 3.24 (dd, 1H, J=12.3, 17.7 Hz), 3.79 (dd, 1H, J=8.2, 12.3 Hz),
6.40-6.46 (m, 2H), 6.81-6.86 (m, 1H), 6.95-7.02 (m, 2H), 7.05-7.16 (m, 3H), 7.20-7.41 (m, 4H),
13
7.67-7.72 (m, 1H); C NMR (CDCl3) δ 33.4 (t), 58.0 (d), 83.6 (s), 116.2 (d), 116.5 (d), 119.9 (s),
123.1 (d), 123.5 (s), 124.1 (d), 124.5 (d), 124.7 (d), 127.5 (d), 127.8 (d), 127.9 (d), 129.5 (d), 129.6
(d), 133.5 (s), 150.3 (s), 150.7 (s), 175.7 (s). Anal. Calcd for C22H16O3: C, 80.47; H, 4.91. Found: C,
80.46; H, 4.94.
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4.3.16. 4-(4-Methoxyphenyl)-5,5-diphenyldihydrofuran-2(3H)-one (4w): White solid; Rf 0.3
1
(hexanes-ethyl acetate, 5:1); mp 131-132 ºC; IR (ATR) 1786, 1769 cm-1; H NMR (CDCl3) δ 2.76
(dd, 1H, J=5.4, 17.3 Hz), 2.96 (dd, 1H, J=8.0, 17.3 Hz), 3.72 (s, 3H), 4.44 (dd, 1H, J=5.4, 8.0 Hz),
6.64-6.68 (m, 2H), 6.81-6.85 (m, 2H), 7.02-7.13 (m, 5H), 7.30-7.34 (m, 1H), 7.36-7.41 (m, 2H),
13
7.61-7.65 (m, 2H); C NMR (CDCl3) δ 37.4 (t), 50.2 (d), 55.0 (q), 92.8 (s), 113.6 (d), 126.0 (d),
126.2 (d), 127.1 (d), 127.6 (d), 128.0 (d), 128.5 (d), 129.5 (d), 130.1 (s), 139.8 (s), 143.1 (s), 158.5
(s), 175.8 (s). Anal. Calcd for C23H20O3: C, 80.21; H, 5.85. Found: C, 80.26; H, 5.82.
4.3.17. 4-(4-Fluorophenyl)-5,5-diphenyldihydrofuran-2(3H)-one (4x): White solid; Rf 0.35
(hexanes-ethyl acetate, 5:1); mp 154-156 ºC; IR (ATR) 1771 cm-1; 1H NMR (CDCl3) δ 2.75 (dd, 1H,
J=4.5, 17.5 Hz), 2.99 (dd, 1H, J=8.0, 17.5 Hz), 4.48 (dd, 1H, J=4.5, 8.0 Hz), 6.77-6.84 (m, 2H),
6.87-6.93 (m, 2H), 7.01-7.12 (m, 5H), 7.30-7.35 (m, 1H), 7.37-7.42 (m, 2H), 7.60-7.65 (m, 2H); 13C
NMR (CDCl3) δ 37.5 (t), 50.1 (d), 92.8 (s), 115.2 (d, JCCF=21.6 Hz), 126.0 (d), 126.1 (d), 127.3 (d),
127.8 (d), 128.2 (d), 128.7 (d), 130.0 (d, JCCCF=8.4 Hz), 134.3 (s, JCCCCF=3.6 Hz), 139.8 (s), 142.8
(s), 161.8 (s, JCF=247.1 Hz), 175.5 (s). Anal. Calcd for C22H17FO2: C, 79.50; H, 5.16. Found: C,
79.55; H, 5.17.
4.3.18. 4-(Benzo[d][1,3]dioxol-5-yl)-5,5-diphenyldihydrofuran-2(3H)-one (4y): White solid; Rf
1
0.25 (hexanes-ethyl acetate, 5:1); mp 198-200 ºC; IR (ATR) 1763 cm-1; H NMR (CDCl3) δ 2.72
(dd, 1H, J=5.0, 17.5 Hz), 2.95 (dd, 1H, J=8.0, 17.5 Hz), 4.41 (dd, 1H, J=5.0, 8.0 Hz), 5.85-5.87 (m,
2H), 6.34 (d, 1H, J=1.7 Hz), 6.48 (dd, 1H, J=1.7, 8.0 Hz), 6.59 (d, 1H, J=8.0 Hz), 7.07-7.15 (m,
5H), 7.29-7.34 (m, 1H), 7.36-7.41 (m, 2H), 7.60-7.63 (m, 2H); 13C NMR (CDCl3) δ 37.5 (t), 50.7
(d), 92.8 (d), 101.0 (t), 107.9 (d), 108.6 (d), 122.0 (d), 125.9 (d), 126.2 (d), 127.2 (d), 127.7 (d),
128.1 (d), 128.6 (d), 132.1 (s), 139.8 (s), 143.1 (s), 146.6 (s), 147.5 (s), 175.6 (s). Anal. Calcd for
C23H18O4: C, 77.08; H, 5.06. Found: C, 77.02; H, 5.06.
4.3.19. 4-(Naphthalen-2-yl)-5,5-diphenyldihydrofuran-2(3H)-one (4z): White solid; Rf 0.35
(hexanes-ethyl acetate, 5:1); mp 213-215 ºC; IR (ATR) 1767 cm-1; 1H NMR (CDCl3) δ 2.88 (dd, 1H,
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J=5.2, 17.6 Hz), 3.06 (dd, 1H, J=8.2, 17.6 Hz), 4.66 (dd, 1H, J=5.2, 8.2 Hz), 6.92-6.96 (m, 1H),
7.00-7.05 (m, 3H), 7.07-7.12 (m, 2H), 7.31-7.36 (m, 1H), 7.38-7.46 (m, 4H), 7.49 (brs, 1H), 7.56 (d,
13
1H, J=8.6 Hz), 7.67-7.73 (m, 4H); C NMR (CDCl3) δ 37.5 (t), 51.2 (d), 92.8 (s), 125.97 (d),
126.01 (d), 126.1 (d), 126.16 (d), 126.21 (d), 127.2 (d), 127.4 (d), 127.6 (d), 127.9 (d), 128.1 (d),
128.6 (d), 132.3 (s), 132.9 (s), 135.9 (s), 139.8 (s), 143.2 (s), 175.5 (s). Anal. Calcd for C26H20O2: C,
85.69; H, 5.53. Found: C, 85.73; H, 5.57.
4.3.20. 5-Methyl-5-(naphthalen-2-yl)dihydrofuran-2(3H)-one (6f): Colorless paste; Rf 0.25
1
(hexanes-ethyl acetate, 5:1); IR (ATR) 1761 cm-1; H NMR (CDCl3) δ 1.81 (s, 3H), 2.44-2.71 (m,
4H), 7.41-7.53 (m, 3H), 7.81-7.88 (m, 4H); 13C NMR (CDCl3) δ 28.6 (t), 28.9 (q), 35.6 (t), 86.7 (s),
122.2 (d), 122.3 (d), 126.0 (d), 126.3 (d), 127.3 (d), 127.9 (d), 128.3 (d), 132.3 (s), 132.6 (s), 141.2
(s), 176.3 (S); HRMS (ESI) calcd for C15H15O2 (M + H+) 227.1072; found 227.1069.
4.3.21. 5-Isopropyl-5-phenyldihydrofuran-2(3H)-one (6i): Colorless paste; Rf 0.2 (hexanes-ethyl
1
acetate, 10:1); IR (ATR) 1765 cm-1; H NMR (CDCl3) δ 0.86 (d, 3H J=6.9 Hz), 0.92 (d, 3H J=6.9
Hz), 2.11-2.19 (m, 1H), 2.36-2.44 (m, 1H), 2.48-2.58 (m, 3H), 7.27-7.38 (m, 5H); 13C NMR
(CDCl3) δ 16.7 (q), 17.1 (q), 28.7 (t), 31.8 (t), 37.9 (d), 91.8 (s), 125.4 (d), 127.2 (d), 127.8 (d),
141.3 (s), 176.4 (S); HRMS (ESI) calcd for C13H17O2 (M + H+) 205.2729; found 205.2727.
4.3.22. 4-Hydroxy-4,4-diphenylbutanenitrile (9a): Colorless paste; Rf 0.3 (hexanes-ethyl acetate,
5:1); IR (ATR) 3447, 2249 cm-1; 1H NMR (CDCl3) δ 2.12 (s, 1H), 2.29-2.34 (m, 2H), 2.65-2.71 (m,
2H), 7.26-7.31 (m, 2H), 7.32-7.39 (m, 8H); 13C NMR (CDCl3) δ 12.1 (t), 37.6 (t), 77.4 (s), 120.4 (s),
125.9 (d), 127.5 (d), 128.5 (d), 145.2 (s); HRMS (ESI) calcd for C16H16NO (M + H+) 238.1232;
found 238.1230.
4.3.23. (1R*,5R*)-1-Phenyl-2-oxabicyclo[3.2.0]heptan-3-one (12a): Colorless paste; Rf 0.3
(hexanes-ethyl acetate, 5:1); IR (ATR) 1771 cm-1; 1H NMR (CDCl3) δ 1.86-1.96 (m, 1H), 2.35-2.44
(m, 1H), 2.56-2.65 (m, 2H), 2.67-2.75 (m, 1H), 2.81 (dd, 1H, J=8.6, 18.3 Hz), 3.25-3.31 (m, 1H),
13
7.30-7.42 (m, 5H); C NMR (CDCl3) δ 21.8 (t), 33.4 (t), 36.2 (t), 40.2 (d), 90.4 (s), 124.5 (d),
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128.0 (d), 128.5 (d), 140.6 (s), 177.3 (s); HRMS (ESI) calcd for C12H13O2 (M + H+) 189.0916;
found 189.0915.
4.3.24. Ethyl 2-((1R*,2S*)-2-hydroxy-2-phenylcyclobutyl)acetate (13a): Colorless paste; Rf 0.2
1
(hexanes-ethyl acetate, 5:1); IR (ATR) 3426, 1730, 1713 cm-1; H NMR (CDCl3) δ 1.16 (t, 3H,
J=7.2 Hz), 1.44-1.53 (m, 1H), 1.88-2.01 (m, 2H), 2.08-2.18 (m, 1H), 2.31-2.41 (m, 1H), 2.63-2.71
13
(m, 1H), 2.94-3.06 (m, 2H), 3.97-4.07 (m, 2H), 7.25-7.47 (m, 5H); C NMR (CDCl3) δ 14.1 (q),
19.2 (t), 34.4 (t), 36.0 (t), 45.0 (d), 60.3 (t), 78.1 (s), 125.6 (d), 127.2 (d), 128.2 (d), 142.3 (s), 173.1
(s); HRMS (ESI) calcd for C14H19O3 (M + H+) 235.1334 found 235.1332.
4.3.25. Ethyl 2-((1R*,2S*)-2-hydroxy-2-phenylcyclopentyl)acetate (13b): Colorless paste; Rf 0.25
1
(hexanes-ethyl acetate, 5:1); IR (ATR) 3460, 1730, 1713 cm-1; H NMR (CDCl3) δ 1.16 (t, 3H,
J=7.3 Hz), 1.44-1.54 (m, 1H), 1.82-2.15 (m, 6H), 2.28-2.37 (m, 1H), 2.56-2.66 (m, 1H), 3.12 (brs,
13
1H), 4.00 (q, 2H, J=7.3 Hz), 7.22-7.27 (m, 1H), 7.30-7.40 (m, 4H); C NMR (CDCl3) δ 14.0 (q),
21.9 (t), 30.9 (t), 36.6 (t), 39.8 (t), 48.2 (d), 60.4 (t), 84.1 (s), 126.0 (d), 126.8 (d), 127.9 (d), 144.8
(s), 173.7 (s); HRMS (ESI) calcd for C15H21O3 (M + H+) 249.1491; found 249.1489.
4.3.26. Ethyl 2-((1R*,2S*)-2-hydroxy-2-phenylcyclohexyl)acetate (13c): Colorless paste; Rf 0.3
1
(hexanes-ethyl acetate, 5:1); IR (ATR) 3495, 1730, 1717 cm-1; H NMR (CDCl3) δ 1.15 (t, 3H,
J=7.3 Hz), 1.42-1.59 (m, 3H), 1.66-1.91 (m, 5H), 2.04-2.19 (m, 2H), 2.23 (dd, 1H, J=10.5, 15.5 Hz),
2.46-2.53 (m, 1H), 3.92-3.99 (m, 2H), 7.23-7.28 (m, 1H), 7.30-7.37 (m, 2H), 7.45-7.51 (m, 2H); 13C
NMR (CDCl3) δ 14.1 (q), 20.1 (t), 21.4 (t), 25.7 (t), 32.5 (t), 34.8 (t), 41.7 (d), 60.2 (t), 74.5 (s),
125.7 (d), 127.2 (d), 128.2 (d), 146.8 (s), 172.9 (s); HRMS (ESI) calcd for C16H23O3 (M + H+)
263.1647; found 263.1646.
4.3.27. Ethyl (E)-9-hydroxy-9-phenylnon-2-enoate (iii): Colorless paste; Rf 0.25 (hexanes-ethyl
acetate, 5:1); IR (ATR) 1717, 1699, 1651 cm-1; 1H NMR (CDCl3) δ 1.24-1.49 (m, 6H), 1.28 (t, 3H,
J=7.2 Hz), 1.66-1.74 (m, 1H), 1.76-1.85 (m, 1H), 2.14-2.20 (m, 2H), 4.18 (q, 2H, J=7.2Hz), 4.66
(dd, 1H, J=5.8, 7.5 Hz), 5.77-5.81 (m, 1H), 6.94 (dt, 1H, J=6.9, 15.5 Hz), 7.25-7.30 (m, 1H),
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