N-Heterocyclic carbene-gold(I)-catalyzed carboheterofunctionalization of alkenes with arylboronic acids

Article abstract of DOI:10.1016/j.tet.2013.09.097

A new approach to the synthesis of pyrrolidine, tetrahydrofuran, and imidazolidin-2-one via N-heterocyclic carbene-gold(I)-catalyzed intramolecular amino- or oxyarylation reactions from a wide variety of alkene substrates such as N-allyl amides, alcohols, carboxylic acids, and ureas in the presence of Selectfluor under mild conditions has been developed.

Full text of DOI:10.1016/j.tet.2013.09.097

Tetrahedron 69 (2013) 10375e10383
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
N-Heterocyclic carbeneegold(I)-catalyzed
carboheterofunctionalization of alkenes with arylboronic acids
*
Shifa Zhu , Lijuan Ye, Wanqing Wu, Huanfeng Jiang
School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 26 July 2013
Received in revised form 20 September 2013
Accepted 26 September 2013
Available online 5 October 2013
A new approach to the synthesis of pyrrolidine, tetrahydrofuran, and imidazolidin-2-one via N-hetero-
cyclic carbeneegold(I)-catalyzed intramolecular amino- or oxyarylation reactions from a wide variety of
alkene substrates such as N-allyl amides, alcohols, carboxylic acids, and ureas in the presence of Se-
lectfluor under mild conditions has been developed.
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Gold-catalyzed
Carboheterofunctionalization
1. Introduction
electron-donating properties of NHC ligands makes the NHCeAu
complexes softer and easier to be oxidized, which make the in-
Heterocycles containing nitrogen or oxygen atoms are common
motifs in complex organic compounds and small molecules with
biological activity.1 Numerous well-established methods for pre-
paring heterocycles from alkenes have been deeply studied.2
Among them, Cu- or Pd-catalyzed inter- or intramolecular re-
actions is one of the most powerful and efficient ways to get these
general targets.3e5 In recent decades, gold has been shown as an
exceptional activating-metal to alkene,6 alkyne,7 and allene8 to-
ward nucleophilic attacks. These catalytic reactions, which supply
a most common strategy to construct CeN and CeO bonds, gen-
erally proceed under exceedingly mild reaction conditions with
high efficiency. For instance, Toste9 and Zhang10 have in-
dependently reported the gold-catalyzed amino- and oxyarylation
of terminal olefins with arylboronic acids in the presence of
Selectfluor as the stoichiometric oxidant. The catalysts typically are
those phosphine-supported gold(I) complex. These protocols have
proved to be very efficient for the terminal alkenes.
terconversion of Au(I)/Au(III) more easily.
Recently, we developed a mild and efficient method for the
synthesis of Au(I)eNHC complexes,13a,b which have been success-
fully used as catalysts in the transformation of the enynals/eny-
nones.13c As part of our continuous interest in the NHCeAu
catalyzed chemical transformations, we are highly curious about
the catalytic-efficiency of gold-catalyzed carboheterofunctionali-
zation of the alkenes (Scheme 1).
P-Au
or
P-Au
AH
A
A
P-Au
Ar
Ar
Selecfluor/ArB(OH)2
previous work
AH
NHC-Au
Selecfluor/ArB(OH)2
?
Notably, gold complexes coordinated with N-heterocyclic car-
bene (NHC) ligands11 have recently attracted more and more at-
tentions due to its excellent catalytic performance compared to
phosphine ligands.12 It is well known that the metal complexes
with NHCs are more stable to air and moisture than those with
phosphine ligands. As for gold catalysis, the use of an exogenous
this work
Scheme 1. Au-catalyzed carboheterofunctionalization.
t
oxidant, such as BuOOH, PhI(OAc)2, or Selectfluor is usually re-
Herein, we would like to report an efficient NHCeAuCl catalyzed
intramolecular aminoarylation and aminocarbonylation of alkenes,
which involve an oxidative cross-coupling reaction with arylbor-
onic acid to provide a series of pyrrolidine and tetrahydrofuran
products.
quired to access the Au(I)/Au(III) catalytic cycle. The strong
* Corresponding author. Tel.: þ86 20 8711 2906; fax: þ86 20 8711 3735; e-mail
addresses: zhusf@scut.edu.cn, 3088814@qq.com (S. Zhu).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.09.097

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S. Zhu et al. / Tetrahedron 69 (2013) 10375e10383
2. Results
pyrrolidine 2a (entries 3 and 4). Higher temperature (80 ꢀC) fur-
nished the product 2a in higher yield (77%) (entry 5). The yield was
decreased to 67% when the temperature was increased further to
100 ꢀC (entry 6). MeCN was the solvent of the choice for this
transformation. No desired product was detected when the re-
action was performed in THF, DCE, toluene or 1,4-dioxane (entries
7e10). Thus, the optimal catalytic condition for this gold-catalyzed
carboheterofunctionalization of alkenes was: 1a (1 equiv),
PhB(OH)2 (2 equiv), Selecfluor (1.5 equiv), and SIMeseAuCl
(5 mol %) in MeCN (1 mL) at 80 ꢀC.
With the optimized reaction conditions in hand (Table 1, entry 5),
the substrate scope of the alkene amines was then examined, as
demonstrated in Table 2. Except arylboronic acid, aryl trimethox-
ysilane PhSi(OCH3)3 could be used as the coupling reagent as well,
giving 2aininferior yield(38%) (Table 2, entry 1). The aminopentene1
Our investigations started with the similar conditions reported
by Toste9 and Zhang,10 in which a mono- or bisphosphinogold(I)
species were used instead. In our system, N-tosyl-4-pentenyl amine
(1a) and phenylboronic acid were initially used as the model sub-
strates to tune the reaction conditions (Table 1). When 1a
(1.0 equiv) and phenylboronic acid (2.0 equiv) were treated with
IMeseAuCl (5 mol %) and Selectfluor (1.5 equiv) in anhydrous
CH3CN at 60 ꢀC, the expected product 2a could be obtained in 61%
yield (Table 1, entry 1). With this encouraging results on hand, the
influence of different gold(I) complexes was then examined (en-
tries 1e4). An improvement of the yield (73%) was observed when
SIMeseAuCl was used as the catalyst (entry 2), while the other two
complexes, IPreAuCl and SIPreAuCl, led to a lower yield of
Table 1
Optimization of reaction conditionsa
Entry
Catalyst
Solvent
T (ꢀC)
Yieldb (%)
1
2
3
4
5
6
7
8
9
10
IMeseAuCl
SIMeseAuCl
IPreAuCl
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
THF
DCE
Toluene
1,4-Dioxane
60
60
60
60
80
100
80
80
80
80
61
73
18
31
77
67
nr
nr
nr
nr
SIPreAuCl
SIMeseAuCl
SIMeseAuCl
SIMeseAuCl
SIMeseAuCl
SIMeseAuCl
SIMeseAuCl
N
N
N
N
N
N
N
N
Au
Cl
IMes-AuCl
Au
Cl
SIMes-AuCl
Au
Cl
IPr-AuCl
Au
Cl
SIPr-AuCl
a
Reactions were carried out using 1a (0.25 mmol), PhB(OH)2 (0.5 mmol), and Au catalyst (5 mol %) in solvent (1 mL) overnight.
Isolated yield.
b
Table 2
Substrate scope for the aminoarylation reaction
R1
N
5mol% SIMes-AuCl
1.5 equiv Selectflour
NHR1
ArB(OH)2
Ar
+
R2
CH3CN, 80oC
R2
R3
R3
1
2
Entry
1
Olefin 1
Product 2
Yielda (%)
77 (38)b
Ts
N
NHTs
Ph
1a
2a
Ms
N
NHMs
2
3
67
68
Ph
2b
1b
Ns
N
NHNs
Ph
2c
1c

S. Zhu et al. / Tetrahedron 69 (2013) 10375e10383
10377
Table 2 (continued )
Entry
Olefin 1
Product 2
Yielda (%)
Ts
N
NHTs
Ph
H3C
4
5
6
72
Ph
Ph
Ph
1d
CH3
2d
Ts
N
NHTs
94 (91)c
Ph
Ph
Ph
1e
Ph
2e
Ts
N
NHTs
1g
Ph
20
2g
Ts
Ts
N
NHTs
7
61
1h
Ph
2h
Ts
N
NHTs
Ph
Ph
Ph
Ph
1e
R
2(i-j)
8
9
10
11
12
13
1e
1e
1e
1e
1e
1e
R¼CH3 2i
R¼t-Bu 2j
R¼Br 2k
R¼Cl 2l
41 (83)c
45 (99)c
65 (85)c
80 (86)c
88 (88)c
43
R¼F 2m
R¼CF3 2n
a
The yield was determined by 1H NMR analysis. Ms¼SO2C4H4OCH3, Ns¼SO2C4H4NO2, Tfs¼SO2C4H4CF3.
b
c
Using PhSi(OCH3)3 instead of PhB(OH)2.
When 2.0 equiv of selectfluor was used.
with different protecting groups was investigated as well (entries
To further investigate the scope of the substrates, a range of
different olefinic alcohol, carboxylic acid, and amide derivatives
were then subjected to the standard reaction conditions (Table 3).
When olefinic alcohol 3a was subjected to the reaction conditions,
the tetrahydrofuran derivative 4a was obtained in 94% yield (Table
3, entry 1). Similarly, the olefinic carboxylic acids 3b and 3c could
afford the lactones in excellent yields (entries 2 and 3). This method
provides a straightforward and efficient approach to tetrahydro-
furans and lactones. Substrates 3d and 3e, with four reacting sites in
each molecule, could be used as the starting materials efficient as
well; it furnished the spiro compounds 4d and 4e were isolated in
87% and 98% yields, respectively (entries 4 and 5). However, in
these cases, the products were obtained as the mixture of cis- and
trans-isomers.
Vicinal diamines and their derivatives have received much at-
tention in the field of medicinal and asymmetric synthesis.14 We
envisioned that if an N-allyl urea 5 derivative was designed as the
substrate, the disubstituted urea 6, a vicinal diamine precursor,
could be obtained under the same reaction conditions (Table 4).
When the tosyl urea 5a (R0¼Ts) was used as the substrate, the de-
sired products 6ae6f could be formed, albeit in an unsatisfactory
yield (12e40%). In these cases, a side product TsNH2 was always
isolated as the major product, which came from the CeN bond-
cleavage of the starting material. The formation of TsNH2 could
account for the low yields of 6ae6f. To avoid the CeN bond-
cleavage, different protecting groups on the urea were then in-
vestigated in detail. After screening different protecting groups, it
was found the benzyl group (Bn-) was an idea one. When benzyl-
protected urea 5a0 was used instead as the starting material, the
yields of the products 6a0e6f0 were improved significantly to
79e88%. Both the electron-rich and electron-poor arylboronic acids
1e3). The electronic properties of the sulfonamide groups have little
effect on the yields of the reactions. For example, both Ms- and Ns-
amides 1b and 1c furnished the desired pyrrolidine products 2b and
2c in similar results (entries 2 and 3). The bulky aminopentenes 1d
and 1e can be served as substrates efficiently, which furnished the
products 2d and 2e in 72% and 94%, respectively (entries 4 and 5). In
the case of aniline derivative 1g, the yield of product 2g was only in
20% (entry 6). When butenamide 1h, one carbon atom short sub-
strate, was used as the starting material, 3-phenyl-1-tosylpyrrolidine
(2h) was formed in 61% yield (entry 7). Except phenylboronic acid,
different arylboronic acid derivatives were also tested. Arylboronic
acids substituted with para methyl-, tert-butyl-, halogen- (Br, Cl, F),
and trifluoromethyl- at the phenyl ring were well-tolerated for this
reaction, providing the corresponding products 2ien in modest to
good yields (41e88%) (entries 8e13). It is worthy to note that when
2.0 equiv of Selectfluor were used in some cases, the yields could be
improved significantly (entries 8e10).
When internal pentenamide 1o, which represents a challenging
substrate for the R3PAuCl-catalyzed system,9,10 was used as the
substrate, a 1:1 mixture of isomers 2o and 2o0 was observed in
a combined yield of 40% (Scheme 2).
Ts
N
Ts
N
PhB(OH)2
NHTs
optimized conditions
+
Ph
Ph
Ph
Ph
Ph
Ph
Ph
40%
Ph
2o'
1o
2o
Scheme 2. Aminoarylation of terminal-substituted alkene.

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S. Zhu et al. / Tetrahedron 69 (2013) 10375e10383
Table 3
Scope of the gold-catalyzed homogeneous oxidative carboheterofunctionalization of alkenesa
5 mol % SIMes-AuCl
YH
1.5 equiv Selectfluor
CH3CN, 80 oC, 24 h
Y
PhB(OH)2
+
R
Ph
R
3
4
Entry
1
Substrate 3
Product 4
Yield (cis/trans)a
94% (45:55)
O
Ph
OH
Ph
4a
H3C
Ph
CH3
3a
O
O
O
Ph
H3C
Ph
OH
2
3
92% (43:57)
88% (44:56)
Ph
CH3
4b
3b
O
O
O
O
Ph
HO
HO
OCH3
COOCH3
4c
3c
O
O
O
Ph
O
OH
O
4
87% (30:70)
98% (50:50)
Ph
Ph
O
3d
4d
Ph
TsHN
NHTs
TsN
5
NTs
4e
3e
a
Isolated yield. Cis/trans ratio was determined by 1H NMR analysis.
could be used as coupling reagent (Table 4, lower part). It’s in-
teresting to find that a mixture of five-membered ring product 6h
and six-membered ring product 6h0 were formed in 1:1 ratio when
the ester-substituted boronic acid was used as coupling reagent. It
is worth to note that the yields of 6a and 6a0 were decreased to 35%
and 68%, respectively, when Ph3PeAuCl was used as catalyst; which
indicated that NHCeAueCl was a superior catalyst than Ph3PeAuCl
in this transformation.
When the similar O-allyl carbamate 7a was used under the same
reaction conditions, however, an unexpected oxazolidinone 8a in
25% yield, accompanied with TseNH2 in almost 60% yield. Trying to
improve the yield by switching the tosyl group to benzyl group
failed (Scheme 3).
R
R
5mol% SIMes-AuCl
1.5 equiv Selectflour
R
NTs
NTs
NHTs
R
R
+
R
1.2 equiv H2O
CH3CN, 80oC
OH
9
NHAc
1
10
Entry
Yield (9/10)
80% (2:1)
85% (2:1)
Substrate 1
1a (R=H)
Product
9a/10a
9f/10f
1
2
1f (R=Ph)
Scheme 4. Controlled reaction without arylboronic acid. Isolated yield, the ratio of
9:10 was determined by 1H NMR analysis.
O
O
5 mol % SIMes-AuCl
1.5 equiv Selectfluor
O
NHTs
+
PhB(OH)2
O
O
+
TsNH2
60%
CH3CN, 80 o
C
Ph
8a (25%)
7a
According to previous reports, a bimolecular reductive elimi-
nation mechanism was then proposed (Scheme 5).9b The reaction
was initiated by the activation of alkene 1 with Au(III) complex A,
which was formed from the oxidation of Au(I) by Selectfluor. The
intramolecular nucleophilic attack by the nitrogen atom to the Au-
activated alkene B gave the cyclization intermediate C. Then the
carboneAu(III) moiety of C reacted with arylboronic acid simulta-
neously via a five-centered transition-state D with BeF bond in-
teraction. Finally, a bimolecular reductive elimination of the
intermediate D took place to afford the target product 2. The re-
leased gold(I) was then subsequently oxidized by Selectfluor to
complete the catalytic cycle.
Scheme 3. Aminoarylation of activated ureas carbamate.
In the absence of boronic acid, a mixture of 2-hydroxyl products
9 and 2-acetamido product 10 was detected. In which, the aceto-
nitrile and trace amount water in the system was supposed to serve
as the nucleophiles. Therefore,1.2 equiv of water was then added in
the system, both substrates 1a and 1f furnished the corresponding
2-hydroxyl product 9 and 2-acetamido product 10 in excellent
yields with the ratio of 9 to 10 being 2:1 (Scheme 4).

S. Zhu et al. / Tetrahedron 69 (2013) 10375e10383
10379
Table 4
Aminoarylation of ureasa
O
O
5 mol % SIMes-AuCl
1.5 equiv Selectfluor
CH3CN, 80 oC, 24h
HN
HN
NHR1
HN NR1
+
ArB(OH)2
O
Ar
5
6
O
O
Ts
Ts
Ts
N
HN
HN
N
HN
N
6a (40%)b
6c (31%)
6b (16%)
O
O
O
Ts
Ts
Ts
HN
N
N
HN
N
F
Br
Cl
6d (27%)
6f (12%)
6e (21%)
O
O
O
Bn
Bn
Bn
HN
HN
N
HN
N
HN
HN
N
6a' (88%)c
6c' (81%)
6b' (80%)
O
O
O
Bn
Bn
Bn
N
HN
O
N
N
F
Br
Cl
6d' (79%)
6f' (84%)
6e' (83%)
O
O
Bn
Bn
Bn
HN
N
HN
N
HN
N
+
Ar =
CF3
Ar
6h(34%)d
Ar
6h'(34%)d
CO2Me
6g (68%)
a
b
c
Isolated yield. The yield of 6a was 35% when Ph3P-AuCl was used as catayst.
The yield of 6a’ was 68% when Ph3P-AuCl was used as catayst. d The ratio of 6h and
6h' was determined by 1HNMR.
3. Conclusions
In conclusion, we have developed an NHCeAuCl catalyzed
intramolecular aminoarylation and oxyarylation of unactive al-
kenes, which provide an expedient access to a wide variety of N-
and O-heterocycles. In consideration of the mild reaction condi-
tions, wide substrate scope, it is a good complementary method for
those R3PAuCl-catalyzed systems.
Ts
N
Ts
N
Ar
Cl
Au
2
L
Selectfluor
LAu-Cl
F
Ar
D
B
OH
4. Experimental section
HO
BF
4.1. General experimental procedure for intramolecular
aminoarylation or oxyarylation reaction of alkene catalyzed
by NHCeAuCl
F
AuIII Cl
L
A
Ts
N
NHTs
SIMeseAuCl (0.0125 mmol, 6.7 mg) was added into a solution of
a substrate (0.25 mmol), Selectfluor (1.5 equiv), and an arylboronic
acid (2 equiv) in anhydrous CH3CN under N2. The reaction mixture
was heated at 80 ꢀC and the progress of the reaction was monitored
by TLC. The reaction typically took 8 h. Upon completion, the re-
action mixture was cooled to room temperature and treated with
water. The resulting mixture was extracted with diethyl ether
ArB(OH)2
F
NHTs
Au
Cl
L
Cl
L
Au
F
1
C
B
Scheme 5. Proposed reaction mechanism.

10380
S. Zhu et al. / Tetrahedron 69 (2013) 10375e10383
(3ꢁ15 mL). The combined organic layers were washed with brine
(15 mL), dried with MgSO4, and filtered. The filtrate was concen-
trated under vacuum, and the residue was purified through silica
gel flash column chromatography (eluant: hexanes/ethylacetate).
29.7. 19F NMR (376 MHz, CDCl3)
d
ꢂ63.18; IR (thin film): nmax
(cmꢂ1)¼2926,1602,1452,1402,1324,1133,1061, 842, 745, 704, 621;
HRMS (ESI) mass calcd for C30H26F3NNaO2S ([MþNa]þ): 544.1529.
Found 544.1527.
4.1.1. 2-Benzyl-1-tosylpyrrolidine (2a). Colorless oil, 77% yield. 1H
4.1.7. 2-Benzyl-1-tosylindoline (2g). Yellow oil, 20% yield. 1H NMR
NMR (400 MHz, CDCl3)
d
7.68 (d, J¼8.1 Hz, 2H), 7.23e7.12 (m, 5H),
(400 MHz, CDCl3)
d
7.67 (d, J¼8.1 Hz, 1H), 7.56 (d, J¼8.2 Hz, 2H),
3.79e3.69 (m, 1H), 3.36e3.27 (m, 1H), 3.16 (dd, J¼13.3, 3.4 Hz, 1H),
3.05 (dt, J¼10.1, 7.1 Hz,1H), 2.68 (dd, J¼13.2, 9.6 Hz,1H), 2.34 (s, 3H),
1.54 (dt, J¼6.3, 5.4 Hz, 2H), 1.42e1.29 (m, 2H); 13C NMR (100 MHz,
7.33e7.28 (m, 2H), 7.25e7.19 (m, 4H), 7.15 (d, J¼8.2 Hz, 2H), 7.01 (d,
J¼4.5 Hz, 2H), 4.45 (dq, J¼6.7, 4.7 Hz,1H), 3.35 (dd, J¼13.4, 4.2 Hz,1H),
2.78 (dd, J¼13.4, 10.2 Hz, 1H), 2.59 (d, J¼5.4 Hz, 2H), 2.33 (s, 3H). 13
C
CDCl3)
d
143.4, 138.5, 134.7, 129.7, 129.6, 128.4, 127.5, 126.4, 61.6,
NMR (100 MHz, CDCl3) d 143.8, 141.3, 137.3, 135.3, 131.7, 129.7, 129.6,
49.3, 42.7, 29.9, 23.8, 21.5.
128.5, 127.7, 126.9, 126.6, 125.3, 124.6, 117.4, 63.6, 42.6, 32.8, 21.5.
4.1.2. 2-Benzyl-1-((4-methoxyphenyl)sulfonyl)pyrrolidine
4.1.8. 3-Phenyl-1-tosylpyrrolidine (2h). Yellow oil, 61% yield. 1H
(2b). Brown oil, 67% yield. 1H NMR (400 MHz, CDCl3)
d
7.83 (d,
NMR (400 MHz, CDCl3)
d
7.75 (d, J¼7.8 Hz, 2H), 7.34 (d, J¼7.8 Hz,
J¼8.4 Hz, 2H), 7.36e7.29 (m, 2H), 7.27 (d, J¼6.7 Hz, 3H), 7.01 (d,
J¼8.4 Hz, 2H), 3.89 (s, 3H), 3.83 (s, 1H), 3.40 (d, J¼9.8 Hz, 1H), 3.27
(d, J¼13.2 Hz, 1H), 3.15 (dd, J¼16.2, 7.3 Hz, 1H), 2.77 (dd, J¼12.7,
10.0 Hz, 1H), 1.67 (s, 2H), 1.47 (d, J¼4.0 Hz, 2H); 13C NMR (100 MHz,
2H), 7.29 (s, 1H), 7.20 (dd, J¼16.1, 9.1 Hz, 2H), 7.10 (d, J¼7.5 Hz, 2H),
3.72 (q, J¼6.7 Hz, 1H), 3.53 (t, J¼9.1 Hz, 1H), 3.36 (dd, J¼17.5, 8.6 Hz,
1H), 3.21 (dt, J¼16.6, 8.4 Hz, 2H), 2.45 (s, 3H), 2.24e2.16 (m, 1H),
1.92e1.80 (m, 1H); 13C NMR (100 MHz, CDCl3)
d 143.5, 140.7, 134.0,
CDCl3)
d
162.9, 138.6, 129.6, 129.6, 129.5, 128.4, 126.4, 114.2, 61.6,
129.7, 128.6, 127.5, 126.9, 126.9, 54.1, 47.8, 43.8, 32.9, 21.5.
55.6, 49.3, 42.7, 29.9, 23.8.
4.1.9. 2-(4-Methylbenzyl)-4,4-diphenyl-1-tosylpyrrolidine
4.1.3. 2-Benzyl-1-((4-nitrophenyl)sulfonyl)pyrrolidine (2c). Yellow
(2i). Yellow solid, 83% yield, mp 169e171 ꢀC. 1H NMR (400 MHz,
oil, 68% yield. 1H NMR (400 MHz, CDCl3)
d
8.39 (d, J¼8.6 Hz, 2H),
CDCl3)
d
7.67 (d, J¼8.0 Hz, 2H), 7.34e7.26 (m, 5H), 7.21 (d, J¼8.0 Hz,
8.06 (d, J¼8.6 Hz, 2H), 7.37e7.30 (m, 2H), 7.30e7.22 (m, 3H),
3.98e3.84 (m, 1H), 3.53e3.41 (m, 1H), 3.28e3.14 (m, 2H), 2.80 (dd,
J¼13.3, 9.4 Hz, 1H), 1.80e1.66 (m, 2H), 1.63e1.45 (m, 2H); 13C NMR
3H), 7.10 (dd, J¼16.0, 7.7 Hz, 4H), 7.03 (d, J¼7.8 Hz, 2H), 6.91 (d,
J¼7.6 Hz, 2H), 4.38 (d, J¼10.2 Hz, 1H), 3.87 (dd, J¼11.3, 7.2 Hz, 1H),
3.67 (d, J¼10.2 Hz, 1H), 3.36 (dd, J¼13.2, 3.3 Hz, 1H), 2.43 (d,
J¼12.6 Hz, 1H), 2.39 (s, 3H), 2.35 (d, J¼4.8 Hz, 1H), 2.32 (s, 3H),
(100 MHz, CDCl3)
d 150.1, 143.7, 137.9, 129.6, 128.6, 128.6, 126.7,
124.4, 62.0, 49.2, 42.5, 29.9, 23.8.
2.18e2.10 (m, 1H). 13C NMR (100 MHz, CDCl3)
d 145.4, 144.9, 143.2,
135.8, 135.4, 134.5, 129.6, 129.2, 129.2, 128.5, 128.5, 127.4, 126.9,
126.5, 126.4, 126.3, 61.4, 58.3, 52.3, 41.8, 41.4, 21.5, 21.0; IR (thin
film): nmax (cmꢂ1)¼2924, 1597, 1452, 1343,1160, 1027, 701, 665, 595,
4.1.4. 2-Benzyl-4-methyl-4-phenyl-1-tosylpyrrolidine (2d). Yellow
oil, 72% yield. Cis/trans: 1H NMR (400 MHz, CDCl3)
d 7.85 (d,
J¼8.1 Hz, 2H), 7.63 (d, J¼8.1 Hz, 2H), 7.39e7.30 (m, 5H), 7.30e7.25
(m, 6H), 7.24e7.14 (m, 7H), 7.14e7.06 (m, 4H), 6.98 (d, J¼7.0 Hz, 2H),
3.99 (td, J¼9.9, 3.6 Hz, 1H), 3.72e3.65 (m, 2H), 2.91 (dd, J¼12.9,
10.3 Hz, 1H), 2.43 (s, 3H), 2.13e1.95 (m, 2H), 1.61 (dd, J¼12.7, 7.5 Hz,
549; HRMS (ESI) mass calcd for
504.1968. Found 504.1966.
C
31H31NNaO2S ([MþNa]þ):
4.1.10. 2-(4-(tert-Butyl)benzyl)-4,4-diphenyl-1-tosylpyrrolidine
1H), 1.42 (s, 3H). Trans-isomer:
d
3.79e3.72 (m, 1H), 3.54 (dd,
(2j). Yellow solid, 45% yield, mp 111 ꢀC. 1H NMR (400 MHz, CDCl3)
J¼13.1, 3.4 Hz, 1H), 3.46 (d, J¼9.6 Hz, 1H), 2.63 (dd, J¼13.0, 10.0 Hz,
d
7.68 (d, J¼7.9 Hz, 2H), 7.28 (d, J¼5.0 Hz, 6H), 7.23e7.15 (m, 4H), 7.11
1H), 2.43 (s, 3H), 1.91 (dd, J¼12.1, 6.5 Hz, 2H), 1.26 (dd, J¼12.7,
(dd, J¼15.2, 7.8 Hz, 3H), 7.04 (d, J¼7.5 Hz, 2H), 6.96 (d, J¼7.8 Hz, 2H),
4.41 (d, J¼10.2 Hz, 1H), 3.88 (d, J¼3.8 Hz, 1H), 3.65 (d, J¼10.2 Hz, 1H),
3.36 (d, J¼10.9 Hz, 1H), 2.43 (d, J¼12.9 Hz, 1H), 2.37 (s, 3H), 2.14 (t,
J¼12.1 Hz, 1H), 1.303 (s, 9H), 1.34e1.26 (m, 1H). 13C NMR (100 MHz,
7.5 Hz, 1H), 0.78 (s, 3H); 13C NMR (101 MHz, CDCl3)
d 146.6, 146.4,
143.5, 143.3, 138.7, 138.3, 135.8, 133.8, 129.7, 129.6, 129.5, 129.5,
128.6, 128.5, 128.5, 127.6, 127.4, 126.4, 126.1, 125.5, 125.3, 61.2, 61.2,
59.8, 44.6, 44.3, 43.1, 42.5, 42.5, 29.7, 27.5, 21.5, 21.5; IR (thin film):
nmax (cmꢂ1)¼3026, 2875, 1598, 1450, 1344, 1156, 1034, 813, 664,
591; HRMS (ESI) mass calcd for C25H27NNaO2S ([MþNa]þ):
428.1655. Found 428.1649.
CDCl3)
d 149.2, 145.4, 145.1, 143.3, 135.48, 134.5, 129.7, 129.1, 128.6,
128.5,127.5, 127.0, 126.6, 126.5, 126.4, 125.4, 61.4, 58.4, 52.4, 41.8, 41.4,
34.4, 31.4, 21.5; IR (thin film): nmax (cmꢂ1)¼3057, 2960, 1597, 1493,
1343,1160, 1092, 1025, 811, 738, 701, 665, 597, 552; HRMS (ESI) mass
calcd for C34H37NNaO2S ([MþNa]þ): 546.2443. Found 546.2439.
4.1.5. 5-Benzyl-2,2-diphenyl-1-tosylpyrrolidine (2e). Yellow oil, 94%
yield. 1H NMR (400 MHz, CDCl3)
d
7.68 (d, J¼7.9 Hz, 2H), 7.28 (dd,
4.1.11. 2-(4-Bromobenzyl)-4,4-diphenyl-1-tosylpyrrolidine
J¼17.4, 8.5 Hz, 6H), 7.21 (d, J¼7.7 Hz, 4H), 7.14e7.07 (m, 3H), 7.02 (d,
J¼7.3 Hz, 4H), 4.40 (d, J¼10.2 Hz, 1H), 3.89 (qd, J¼8.4, 4.2 Hz, 1H),
3.67 (d, J¼10.2 Hz, 1H), 3.41 (dd, J¼13.1, 3.3 Hz, 1H), 2.46e2.40 (m,
1H), 2.38 (s, 3H), 2.33 (dd, J¼12.9, 4.7 Hz, 1H), 2.22e2.14 (m, 1H);
(2k). White solid, 65% yield, mp 172 ꢀC. 1H NMR (400 MHz, CDCl3)
d
7.66 (d, J¼8.1 Hz, 2H), 7.38 (d, J¼8.1 Hz, 2H), 7.33e7.27 (m, 2H),
7.21 (d, J¼8.2 Hz, 4H), 7.11 (t, J¼7.0 Hz, 4H), 7.02 (d, J¼6.6 Hz, 2H),
6.89 (d, J¼8.1 Hz, 2H), 4.37 (d, J¼10.2 Hz, 1H), 3.90e3.78 (m, 1H),
3.65 (d, J¼10.2 Hz, 1H), 3.32 (dd, J¼13.2, 3.4 Hz, 1H), 2.46e2.41 (m,
1H), 2.40 (s, 3H), 2.27 (dd, J¼12.8, 4.7 Hz, 1H), 2.22e2.14 (m, 1H);
13C NMR (100 MHz, CDCl3)
d 171.2, 145.4, 144.9, 143.3, 138.6, 134.5,
129.7,129.4,128.6,128.5,127.4,126.9,126.6,126.4,126.4,126.4, 61.3,
60.4, 58.4, 52.3, 41.9, 41.7, 21.5, 21.1, 14.2.
13C NMR (100 MHz, CDCl3)
d 144.7, 144.7, 143.4, 141.2, 137.5, 134.1,
131.6, 131.1, 130.5, 129.7, 128.6, 127.4, 126.9, 126.7, 126.4, 120.3, 61.0,
58.3, 52.3, 41.6, 41.2, 21.5; IR (thin film): nmax (cmꢂ1)¼2956, 1736,
1489, 1341, 1160, 1015, 700, 665, 510; HRMS (ESI) mass calcd for
4.1.6. 2-Benzyl-4,4-diphenyl-1-((4-(trifluoromethyl)-phenyl)sulfo-
nyl)pyrrolidine (2f). Pale yellow solid, 33% yield, mp 169e171 ꢀC. 1H
NMR (400 MHz, CDCl3)
d
7.80 (d, J¼7.9 Hz, 2H), 7.59 (d, J¼8.0 Hz,
C
30H28BrNNaO2S ([MþNa]þ): 568.0916. Found 568.0920.
2H), 7.34e7.27 (m, 3H), 7.24 (s, 2H), 7.18 (d, J¼7.6 Hz, 1H), 7.13 (d,
J¼7.5 Hz, 4H), 7.04 (s, 3H), 6.98 (s, 2H), 4.30 (d, J¼10.6 Hz, 1H), 3.97
(d, J¼10.4 Hz, 2H), 3.49 (d, J¼13.2 Hz, 1H), 2.63 (dd, J¼12.8, 7.4 Hz,
1H), 2.49 (t, J¼11.7 Hz, 1H), 2.29 (dd, J¼13.1, 6.9 Hz, 1H). 13C NMR
4.1.12. 2-(4-Chlorobenzyl)-4,4-diphenyl-1-tosylpyrrolidine
(2l). White solid, 80% yield, mp 153 ꢀC. 1H NMR (400 MHz, CDCl3)
d
7.69 (d, J¼8.0 Hz, 2H), 7.36e7.29 (m, 3H), 7.27 (s, 2H), 7.25 (s, 2H),
(100 MHz, CDCl3)
d
145.2, 144.0, 137.8, 129.4, 128.6, 128.6, 127.5,
7.23 (s, 2H), 7.15 (d, J¼7.4 Hz, 3H), 7.05 (d, J¼6.7 Hz, 2H), 6.98 (d,
J¼8.1 Hz, 2H), 4.40 (d, J¼10.2 Hz, 1H), 3.87 (dd, J¼15.1, 7.6 Hz, 1H),
126.7, 126.7, 126.6, 126.6, 126.4, 126.0, 61.4, 59.2, 52.6, 42.2, 42.1,

S. Zhu et al. / Tetrahedron 69 (2013) 10375e10383
10381
3.69 (d, J¼10.2 Hz, 1H), 3.37 (dd, J¼13.3, 3.1 Hz, 1H), 2.50e2.44 (m,
1H), 2.42 (s, 3H), 2.30 (dd, J¼12.9, 4.4 Hz, 1H), 2.22 (d, J¼12.7 Hz,
1H), 7.29 (d, J¼1.4 Hz, 2H), 7.24 (s, 2H), 7.22 (s, 2H), 7.20 (s, 2H), 7.18
(s, 1H), 4.22 (dt, J¼14.3, 7.0 Hz, 1H), 4.02 (t, J¼8.3 Hz, 2H), 3.10e2.90
(m, 2H), 2.32 (dd, J¼12.5, 7.4 Hz, 1H), 1.79 (dd, J¼12.5, 8.1 Hz, 1H),
1H); 13C NMR (100 MHz, CDCl3)
d 145.3, 144.7, 143.4, 136.9, 134.3,
132.2, 130.7, 129.7, 128.6, 128.6, 128.5, 127.4, 126.8, 126.6, 126.4,
126.4, 61.1, 58.3, 52.3, 41.6, 41.2, 21.5; IR (thin film): nmax (cmꢂ1)¼
3058, 2924, 1597, 1491, 1343, 1160, 1091, 702, 550; HRMS (ESI) mass
calcd for C30H28ClNNaO2S ([MþNa]þ): 524.1421. Found 524.1429.
1.42 (s, 3H). Trans-isomer: 1H NMR (400 MHz, CDCl3)
d 7.30 (s, 1H),
7.29 (d, J¼1.4 Hz, 2H), 7.24 (s, 2H), 7.22 (s, 2H), 7.20 (s, 2H), 7.18 (s,
1H), 4.45 (dq, J¼9.4, 6.3 Hz, 1H), 3.92 (dd, J¼17.2, 8.3 Hz, 2H), 2.81
(ddd, J¼29.8, 13.5, 6.5 Hz, 2H), 2.14 (dd, J¼12.1, 5.9 Hz, 1H), 1.96 (dd,
J¼11.9, 9.7 Hz, 1H), 1.39 (s, 3H); 13C NMR (100 MHz, CDCl3)
d 147.6,
4.1.13. 2-(4-Fluorobenzyl)-4,4-diphenyl-1-tosylpyrrolidine
147.5,138.6,129.3,128.4,128.4,126.3,126.2,126.1,126.0,125.9, 80.2,
79.9, 79.0, 78.6, 47.6, 47.4, 45.9, 45.4, 42.7, 42.5, 28.7, 28.1; IR (thin
film): nmax (cmꢂ1)¼3059, 2964, 2928, 1601, 1494, 1449, 1375, 1053,
(2m). Pale yellow solid, 88% yield, mp 140e142 ꢀC. 1H NMR
(400 MHz, CDCl3)
d
7.69 (d, J¼7.9Hz, 2H), 7.37e7.29 (m, 3H), 7.27e7.19
(m, 4H), 7.15 (d, J¼7.3 Hz, 3H), 7.05 (d, J¼6.6 Hz, 2H), 6.99 (d, J¼8.6 Hz,
4H), 4.40 (d, J¼10.2 Hz, 1H), 3.88 (s, 1H), 3.69 (d, J¼10.2 Hz, 1H), 3.36
(d, J¼13.3 Hz,1H), 2.46 (d, J¼12.8 Hz,1H), 2.42(s, 3H), 2.32(dd, J¼12.9,
758, 700, 543, 503; HRMS (ESI) mass calcd for C18H20NaO
([MþNa]þ): 275.1406. Found 275.1427.
4.4 Hz, 1H), 2.27e2.18 (m, 1H); 13C NMR (100 MHz, CDCl3)
d
160.4,
4.1.18. Methyl 3-allyl-5-benzyl-2-oxotetrahydrofuran-3-carboxylate
145.3, 144.8, 143.4, 134.4, 134.2, 130.8, 130.7, 129.7, 128.6, 128.5, 127.4,
126.9,126.6,126.4,115.4,115.2, 61.2, 58.3, 52.3, 41.6, 40.9, 21.5; IR (thin
film): nmax (cmꢂ1)¼3058, 2924, 1599, 1506, 1451, 1342, 1222, 1160,
1093, 813, 701, 665, 596; HRMS (ESI) mass calcd for C30H28FNNaO2S
([MþNa]þ): 508.1717. Found 508.1720.
(4c). Yellow oil, 88% yield. Cis-isomer: 1H NMR (400 MHz, CDCl3)
d
7.27e7.21 (m, 2H), 7.21e7.12 (m, 3H), 5.68e5.57 (m, 1H),
5.13e5.07 (m, 2H), 4.61e4.54 (p, J¼7.0 Hz, 1H), 3.70 (s, 3H),
3.11e3.01 (m, 1H), 2.97 (dd, J¼14.1, 6.4 Hz, 1H), 2.69e2.59 (m, 1H),
2.58e2.41 (m, 2H), 2.23 (dd, J¼13.5, 7.4 Hz, 1H). Trans-isomer: 1H
NMR (400 MHz, CDCl3)
d 7.27e7.21 (m, 2H), 7.21e7.12 (m, 3H),
4.1.14. 4,4-Diphenyl-1-tosyl-2-(4-(trifluoromethyl)benzyl)pyrrolidine
(2n). Yellow solid, 43% yield, mp 160 ꢀC. 1H NMR (400 MHz, CDCl3)
5.56e5.42 (m, 1H), 5.07e5.00 (m, 2H), 4.71 (td, J¼12.1, 6.1 Hz, 1H),
3.67 (s, 3H), 2.91e2.79 (m, 2H), 2.69e2.59 (m, 1H), 2.58e2.41 (m,
2H), 1.89 (dd, J¼13.3, 10.0 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d
7.67 (d, J¼7.9 Hz, 2H), 7.52 (d, J¼7.8 Hz, 2H), 7.35e7.27 (m, 4H),
7.25e7.18 (m, 3H), 7.13 (d, J¼5.8 Hz, 4H), 7.02 (d, J¼7.4 Hz, 2H), 4.40
(d, J¼10.2 Hz, 1H), 3.95e3.84 (m, 1H), 3.63 (d, J¼10.2 Hz, 1H),
3.50e3.34 (m, 1H), 2.43 (d, J¼13.1 Hz, 1H), 2.40 (s, 3H), 2.32e2.22
d 174.1, 173.5, 170.3, 169.8, 135.8, 135.6, 131.7, 131.6, 129.5, 129.4,
128.7, 128.6, 127.0, 127.0, 120.6, 120.2, 78.8, 78.5, 55.6, 55.0, 53.2,
53.2, 41.5, 41.0, 38.6, 38.3, 36.3, 35.4; IR (thin film): nmax (cmꢂ1)¼
3029, 1774, 1439, 1013, 928, 753, 703, 501; HRMS (ESI) mass calcd
for C16H18NaO4 ([MþNa]þ): 297.1097. Found 297.1103.
(m, 2H); 13C NMR (100 MHz, CDCl3)
d 145.2, 144.7, 143.5, 134.2,
129.7,129.7,128.6,128.6,127.4,126.8,126.7,126.4,126.3,125.4, 60.9,
58.2, 52.3, 41.7, 41.6, 29.7, 21.5. 19F NMR (376 MHz, CDCl3)
d
ꢂ62.4;
IR (thin film): nmax (cmꢂ1)¼2925, 1737, 1599, 1327, 1162, 1021, 813,
701, 666, 595, 551; HRMS (ESI) mass calcd for C31H28F3NNaO2S
([MþNa]þ): 558.1685. Found 558.1683.
4.1.19. 3,8-Dibenzyl-2,7-dioxaspiro[4.4]nonane-1,6-dione (4d). Pale
yellow oil, 87% yield. Cis-isomer: 1H NMR (400 MHz, CDCl3)
d
7.25e7.20 (m, 4H), 7.17e7.12 (m, 4H), 7.10 (d, J¼7.0 Hz, 2H),
4.64e4.54 (m, 2H), 2.39 (dd, J¼13.2, 6.4 Hz, 2H), 1.96 (dd, J¼13.6,
6.8 Hz, 2H), 1.87 (dd, J¼13.0, 9.7 Hz, 2H), 1.76 (dd, J¼13.2, 8.9 Hz,
4.1.15. 4,4-Diphenyl-2-(2-phenylpropan-2-yl)-1-tosylpyrrolidine
(2o) and 2,2-dimethyl-3,5,5-triphenyl-1-tosylpiperidine
(2o0). Yellow solid, 40% yield, mp 130e135 ꢀC. Compound 2o: 1H
2H). Trans-isomer: 1H NMR (400 MHz, CDCl3)
d 7.25e7.20 (m, 4H),
7.17e7.12 (m, 4H), 7.10 (d, J¼7.0 Hz, 2H), 5.08e4.94 (m, 2H), 3.11
(ddd, J¼53.6, 13.9, 6.4 Hz, 2H), 2.91 (dtd, J¼20.5, 14.2, 6.2 Hz, 4H),
2.55 (ddd, J¼21.5, 13.3, 6.8 Hz, 2H); 13C NMR (100 MHz, CDCl3)
NMR (400 MHz, CDCl3)
d
7.68 (t, J¼8.6 Hz, 5H), 7.48 (d, J¼7.6 Hz,
3H), 7.41e7.27 (m, 8H), 7.26 (s, 5H), 7.21 (d, J¼7.3 Hz, 5H), 7.19e7.05
(m, 5H), 6.99 (d, J¼7.8 Hz, 3H), 6.88 (d, J¼7.9 Hz, 2H), 6.78 (t,
J¼8.1 Hz, 2H), 4.69 (dd, J¼48.1, 7.3 Hz, 1H), 4.10 (t, J¼11.1 Hz, 2H),
3.31 (dd, J¼24.0, 12.3 Hz, 2H), 2.43 (s, 3H), 1.38 (s, 6H). Compound
d
173.4, 173.3, 135.6, 134.9, 129.5, 129.5, 129.3, 128.8, 128.7, 127.3,
127.2, 127.1, 79.7, 79.0, 78.4, 53.0, 52.9, 41.4, 40.9, 40.7, 39.0, 37.5,
37.3; IR (thin film): nmax (cmꢂ1)¼3030, 2929, 2862, 1754, 1495,
1449, 1356, 1196, 1016, 958, 883, 751, 703, 499; HRMS (ESI) mass
calcd for C21H20NaO4 ([MþNa]þ): 359.1254. Found 359.1252.
2o0:
d
4.33 (dd, J¼49.5, 11.8 Hz, 1H), 3.74 (dt, J¼17.0, 11.5 Hz, 2H),
2.78e2.60 (m, 2H), 2.43 (s, 3H), 1.29 (s, 3H), 1.26 (s, 3H); 13C NMR
(100 MHz, CDCl3) 147.9, 147.7, 143.7, 136.8, 136.4, 133.9, 129.8,
d
128.8, 128.5, 128.2, 127.9, 127.3, 127.1, 127.0, 126.6, 126.4, 117.0, 53.0,
51.9, 49.3, 46.8, 44.7, 36.9, 31.9, 29.0, 25.5, 24.9, 21.5, 18.8; IR (thin
film): nmax (cmꢂ1)¼3285, 2964, 1598, 1449, 1332, 1160, 1088, 1024,
762, 738, 701, 553.
4.1.20. 2,7-Dibenzyl-1,6-ditosyl-1,6-diazaspiro[4.4]nonane
(4e). Yellow oil, 98% yield. 1H NMR (400 MHz, CDCl3)
d 7.77 (d,
J¼8.2 Hz, 2H), 7.62 (d, J¼8.1 Hz, 2H), 7.52 (d, J¼8.1 Hz, 2H), 7.40 (dd,
J¼16.2, 8.0 Hz, 4H), 7.32e7.26 (m, 5H), 7.25e7.22 (m, 3H), 7.20 (t,
J¼6.0 Hz, 4H), 7.14 (t, J¼8.1 Hz, 4H), 7.08 (d, J¼6.8 Hz, 2H), 3.69e3.60
(m, 1H), 3.55 (qd, J¼8.9, 4.1 Hz, 2H), 3.40 (dd, J¼13.3, 3.4 Hz, 1H),
3.34e3.23 (m, 3H), 3.11 (d, J¼11.5 Hz, 1H), 2.74 (dt, J¼13.3, 9.3 Hz,
2H), 2.67e2.55 (m, 2H), 2.51 (s, 2H), 2.49 (s, 3H), 2.45e2.40 (m, 1H),
2.39e2.31 (m, 5H), 2.27 (t, J¼11.1 Hz, 2H), 1.63 (t, J¼6.0 Hz, 2H),
1.61e1.50 (m, 2H), 1.38 (dt, J¼13.0, 6.4 Hz, 2H), 1.26 (s, 1H), 1.17 (dd,
J¼13.1, 8.8 Hz, 1H), 1.03 (dd, J¼13.0, 7.2 Hz, 1H); 13C NMR (100 MHz,
4.1.16. 5-Benzyl-3-methyl-3-phenyldihydrofuran-2(3H)-one
(4a). Yellow oil, 92% yield. Cis-isomer: 1H NMR (400 MHz, CDCl3)
d
8.09e6.46 (m, 10H), 4.80e4.73 (m, 1H), 3.11 (dt, J¼13.5, 6.7 Hz,
1H), 2.86 (ddd, J¼25.5, 13.9, 6.4 Hz, 1H), 2.67 (dd, J¼12.9, 4.9 Hz,
1H), 2.40 (d, J¼7.4 Hz, 1H), 1.56 (s, 3H). Trans-isomer: 1H NMR
(400 MHz, CDCl3) d 8.09e6.46 (m, 10H), 4.45e4.38 (m, 1H), 3.11 (dt,
J¼13.5, 6.7 Hz, 1H), 2.86 (ddd, J¼25.5, 13.9, 6.4 Hz, 1H), 2.40 (d,
CDCl3) d 144.5, 144.0, 143.7, 137.7, 137.6, 137.5, 134.3, 134.2, 133.8,
J¼7.4 Hz, 1H), 2.11e2.02 (m, 1H), 1.61 (s, 3H); 13C NMR (100 MHz,
130.0, 129.8, 129.6, 129.6, 129.6, 129.5, 129.3, 128.6, 128.5, 128.4,
127.6, 127.4, 127.3, 126.7, 126.5, 60.9, 60.8, 60.7, 57.4, 57.2, 57.2, 46.4,
46.3, 42.6, 42.4, 42.3, 40.6, 40.2, 39.8, 21.6, 21.6; IR (thin film): nmax
(cmꢂ1)¼2926, 2874, 2308, 1730, 1449, 923.6, 814, 737, 662, 589;
HRMS (ESI) mass calcd for C35H38N2NaO4S2 ([MþNa]þ): 637.2165.
Found 637.2156.
CDCl3)
d 179.3, 142.6, 140.8, 136.0, 135.9, 129.4, 129.4, 128.9, 128.6,
128.6, 127.4, 127.2, 127.0, 126.9, 126.1, 125.7, 49.9, 48.2, 43.8, 43.6,
41.3, 41.1, 26.4, 25.1; IR (thin film): nmax (cmꢂ1)¼3029, 2929, 1770,
1496, 1450, 1190, 1086, 1021, 755, 702; HRMS (ESI) mass calcd for
C
18H18NaO2 ([MþNa]þ): 289.1199. Found 289.1205.
4.1.17. 2-Benzyl-4-methyl-4-phenyltetrahydrofuran (4b). Pale yel-
low oil, 94% yield. Cis-isomer: 1H NMR (400 MHz, CDCl3)
7.30 (s,
4.1.21. 5-Benzyl-1-tosylimidazolidin-2-one (6a). Yellow solid, 40%
d
yield, mp 137 ꢀC. 1H NMR (400 MHz, CDCl3)
d
7.79 (d, J¼8.2 Hz, 2H),

10382
S. Zhu et al. / Tetrahedron 69 (2013) 10375e10383
7.66 (s,1H), 7.28 (d, J¼16.6 Hz, 3H), 7.21e7.12 (m, 2H), 5.06e4.88 (m,
1H), 3.78 (t, J¼9.0 Hz, 1H), 3.58e3.45 (m, 1H), 3.13 (dd, J¼14.2,
6.2 Hz, 1H), 2.98 (dd, J¼14.2, 6.5 Hz, 1H), 2.42 (s, 3H); 13C NMR
2H), 3.85 (t, J¼9.3 Hz,1H), 3.54 (dd, J¼9.4, 7.8 Hz,1H), 3.09e2.87 (m,
2H); 13C NMR (100 MHz, CDCl3)
161.4, 135.3, 133.8, 129.3, 128.9,
128.9, 128.3, 127.6, 127.6, 85.3, 47.4, 46.4, 39.5; IR (thin film): nmax
(cmꢂ1)¼3326, 3032, 2923, 1704, 1550, 1452, 1291, 1067, 750, 703;
HRMS (ESI) mass calcd for C17H19N2O ([MþH]þ): 267.1492. Found
267.1492.
d
(100 MHz, CDCl3)
d 161.4, 142.8, 139.4, 134.3, 129.3, 129.3, 128.8,
127.4, 126.4, 79.4, 46.7, 39.8, 21.5; IR (thin film): nmax (cmꢂ1)¼2922,
1623, 1275, 1152, 1068, 818, 671, 554; HRMS (ESI) mass calcd for
C
17H18N2NaO3S ([MþNa]þ): 353.0930. Found 353.0925.
4.1.28. 1-Benzyl-5-(4-methylbenzyl)imidazolidin-2-one
4.1.22. 5-(4-Methylbenzyl)-1-tosylimidazolidin-2-one
(6b). Pale
7.71
(6b0). Yellow solid, 80% yield, mp 113 ꢀC. 1H NMR (400 MHz, CDCl3)
yellow solid, 16% yield, mp 144 ꢀC. 1H NMR (400 MHz, CDCl3)
d
d
7.32e7.20 (m, 3H), 7.17 (d, J¼9.6 Hz, 2H), 7.01 (d, J¼7.7 Hz, 2H),
(d, J¼8.1 Hz, 2H), 7.45 (s, 1H), 7.17 (s, 1H), 7.00 (q, J¼8.0 Hz, 4H),
4.95e4.75 (m, 1H), 3.66 (t, J¼8.9 Hz, 1H), 3.49e3.34 (m, 1H), 3.01
(dd, J¼14.2, 5.9 Hz, 1H), 2.86 (dd, J¼14.2, 6.8 Hz, 1H), 2.33 (s, 3H),
6.89 (d, J¼7.8 Hz, 2H), 5.16e5.01 (m, 1H), 4.31 (s, 2H), 3.80 (t,
J¼9.3 Hz,1H), 3.55e3.41 (m,1H), 3.11e2.70 (m, 2H), 2.25 (s, 3H); 13
C
NMR (100 MHz, CDCl3) d 161.5,137.2,135.7,130.8,129.6,129.1,128.9,
2.24 (s, 3H); 13C NMR (100 MHz, CDCl3)
d
161.5, 142.8, 139.4, 137.1,
128.2, 127.6, 84.8, 46.4, 39.3, 21.0. IR (thin film): nmax (cmꢂ1)¼3321,
131.1, 129.5, 129.3, 129.2, 126.4, 79.3, 46.6, 39.4, 21.5, 21.0; IR (thin
2923, 1703, 1550, 1453, 1286, 1067, 807, 740, 702, 489; HRMS (ESI)
film): nmax (cmꢂ1)¼2921, 1638, 1455, 1284, 1157, 1007, 880, 811, 708,
mass calcd for C1 21N2O ([MþH]þ): 281.1648. Found 281.1652.
8H
580; HRMS (ESI) mass calcd for
367.1087. Found 367.1085.
C
18H20N2NaO3S ([MþNa]þ):
4.1.29. 1-Benzyl-5-(4-(tert-butyl)benzyl)imidazolidin-2-one
(6c0). Yellow solid, 81% yield, mp 193 ꢀC. 1H NMR (400 MHz, CDCl3)
4.1.23. 5-(4-(tert-Butyl)benzyl)-1-tosylimidazolidin-2-one
d
7.30e7.20 (m, 5H), 7.17 (dd, J¼11.8, 4.4 Hz, 3H), 6.95 (d, J¼8.1 Hz,
(6c). White solid, 31% yield, mp 190e195 ꢀC. 1H NMR (400 MHz,
2H), 5.17 (dt, J¼14.3, 7.0 Hz, 1H), 4.33 (s, 2H), 3.83 (t, J¼9.2 Hz, 1H),
CDCl3)
d
7.82 (d, J¼8.0 Hz, 2H), 7.55 (s, 1H), 7.34 (d, J¼8.0 Hz, 2H),
3.56e3.49 (m, 1H), 2.97 (qd, J¼14.4, 6.4 Hz, 2H), 1.23 (s, 9H); 13C
7.27 (s, 1H), 7.13 (d, J¼8.0 Hz, 2H), 5.13e4.80 (m, 1H), 3.78 (t,
J¼8.9 Hz, 1H), 3.53 (t, J¼8.3 Hz, 1H), 3.14 (dd, J¼14.1, 6.0 Hz, 1H),
2.96 (dd, J¼14.1, 6.9 Hz, 1H), 2.42 (s, 3H), 1.32 (s, 9H); 13C NMR
NMR (100 MHz, CDCl3) d 161.3, 150.4, 136.1, 131.3, 128.9, 128.8,
128.5, 128.1, 127.6, 127.1, 125.8, 84.0, 46.6, 39.4, 34.5, 31.3; IR (thin
film): nmax (cmꢂ1)¼3321, 2923, 1703, 1550, 1453, 1286, 1067, 807,
740, 702, 489; HRMS (ESI) mass calcd for C21H27N2O ([MþH]þ):
323.2118. Found 323.2108.
(100 MHz, CDCl3)
d 161.5, 150.4, 142.8, 139.4, 131.2, 129.3, 129.0,
126.4, 125.8, 79.4, 46.8, 39.3, 34.5, 31.3, 29.7, 21.5; IR (thin film):
nmax (cmꢂ1)¼2923,1647,1456,1155, 1079, 881, 855, 708, 578; HRMS
(ESI) mass calcd for C21H26N2NaO3S ([MþNa]þ): 409.1556. Found
409.1557.
4.1.30. 1-Benzyl-5-(4-fluorobenzyl)imidazolidin-2-one (6d0). Yellow
solid, 79% yield, mp 115 ꢀC. 1H NMR (400 MHz, CDCl3)
d 7.43e7.29
(m, 3H), 7.25 (d, J¼6.5 Hz, 2H), 7.11e7.01 (m, 2H), 6.97 (t, J¼8.5 Hz,
2H), 5.24 (d, J¼6.8 Hz, 1H), 4.41 (s, 2H), 3.95 (t, J¼9.1 Hz, 1H),
3.67e3.54 (m, 1H), 3.06 (d, J¼6.0 Hz, 2H); 13C NMR (100 MHz,
4.1.24. 5-(4-Fluorobenzyl)-1-tosylimidazolidin-2-one
(6d). White
7.68 (d,
solid, 27% yield, mp 168 ꢀC. 1H NMR (400 MHz, CDCl3)
d
J¼8.1 Hz, 2H), 7.54 (s, 1H), 7.17 (s, 1H), 7.12e6.95 (m, 2H), 6.87 (t,
J¼8.5 Hz, 2H), 5.01e4.70 (m, 1H), 3.72 (t, J¼9.0 Hz, 1H), 3.50e3.30
(m, 1H), 2.93 (qd, J¼14.4, 6.0 Hz, 2H), 2.34 (s, 3H); 13C NMR
CDCl3) d 163.4, 161.4, 135.3, 130.9, 130.8, 129.7, 128.9, 128.3, 127.5,
115.9, 115.7, 85.2, 47.4, 46.4, 38.7. 19F NMR (376 MHz, CDCl3)
d
ꢂ150.0; IR (thin film): nmax (cmꢂ1)¼2357, 1697, 1509, 1223, 1073,
(100 MHz, CDCl3)
d
163.3, 161.4, 160.9, 142.9, 139.3, 131.0, 130.9,
822, 701, 532; HRMS (ESI) mass calcd for C17H18FN2O ([MþH]þ):
130.0, 130.0, 129.3, 126.4, 115.8, 115.6, 79.1, 46.6, 39.0, 21.5. 19F NMR
285.1398. Found 285.1395.
(376 MHz, CDCl3)
d
ꢂ114.9; IR (thin film): nmax (cmꢂ1)¼2922, 163,
1454, 1281, 1155, 879, 708, 580, 548; HRMS (ESI) mass calcd for
4.1.31. 1-Benzyl-5-(4-chlorobenzyl)imidazolidin-2-one (6e0). Yellow
C
17H17FN2NaO3S ([MþNa]þ): 371.0836. Found 371.0825.
oil, 83% yield.1H NMR (400 MHz, CDCl3)
d
7.26 (t, J¼7.5Hz, 3H), 7.16 (d,
J¼8.5 Hz, 4H), 6.92 (d, J¼8.1 Hz, 2H), 5.17 (dt, J¼14.4, 7.1 Hz, 1H), 4.33
(s, 2H), 3.88 (t, J¼9.3 Hz, 1H), 3.54 (dd, J¼9.5, 7.7 Hz, 1H), 2.98 (d,
4.1.25. 5-(4-Chlorobenzyl)-1-tosylimidazolidin-2-one (6e). Pale yel-
low solid, 21% yield, mp 177e180 ꢀC. 1H NMR (400 MHz, CDCl3)
J¼6.0 Hz, 2H); 13C NMR (100 MHz, CDCl3)
d 161.4, 135.1, 133.6, 132.3,
d
7.68 (d, J¼8.1 Hz, 2H), 7.47 (s, 1H), 7.19 (dd, J¼8.1, 5.2 Hz, 3H), 7.04
130.6, 129.1, 129.0, 128.4, 127.5, 85.0, 47.4, 46.5, 38.9; IR (thin film):
nmax (cmꢂ1)¼2924,1700,1553,1495,1456,1083, 737, 662; HRMS (ESI)
mass calcd for C17H18ClN2O ([MþH]þ): 301.1102. Found 301.1097.
(d, J¼8.2 Hz, 2H), 5.00e4.73 (m, 1H), 3.73 (t, J¼9.0 Hz, 1H),
3.50e3.32 (m, 1H), 2.94 (qd, J¼14.5, 6.1 Hz, 2H), 2.34 (s, 3H); 13C
NMR (100 MHz, CDCl3)
d 161.3, 142.9, 139.2, 133.4, 132.7, 130.7,
129.3, 129.0, 126.4, 78.8, 46.6, 39.2, 21.5; IR (thin film): nmax
(cmꢂ1)¼2924, 1728, 1638, 1457, 1281, 1156, 1080, 878, 810, 709, 580,
551; HRMS (ESI) mass calcd for C17H17ClN2NaO3S ([MþNa]þ):
387.0541. Found 387.0543.
4.1.32. 1-Benzyl-5-(4-bromobenzyl)imidazolidin-2-one (6f0). Yellow
oil, 84% yield. 1H NMR (400 MHz, CDCl3)
d
7.34 (d, J¼8.2 Hz, 2H),
7.30e7.21 (m, 4H), 7.18 (s, 1H), 6.92 (d, J¼8.2 Hz, 2H), 4.87 (dt,
J¼13.9, 7.1 Hz, 1H), 4.30 (s, 2H), 3.83e3.76 (m, 1H), 3.47e3.40 (m,
1H), 2.87 (ddd, J¼19.7, 14.3, 6.3 Hz, 2H); 13C NMR (100 MHz, CDCl3)
4.1.26. 5-(4-Bromobenzyl)-1-tosylimidazolidin-2-one
(6f). White
7.69 (d,
d 161.3, 136.2, 133.7, 131.9, 130.9, 128.9, 128.1, 127.5, 121.4, 83.3, 46.5,
solid, 12% yield, mp 185 ꢀC. 1H NMR (400 MHz, CDCl3)
d
39.5, 29.7; IR (thin film): nmax (cmꢂ1)¼2924, 2855, 1702, 1549, 1454,
1072, 736, 700; HRMS (ESI) mass calcd for C17H18BrN2O ([MþH]þ):
345.0597. Found 345.0594.
J¼8.2 Hz, 2H), 7.40 (s,1H), 7.32 (d, J¼8.2 Hz, 2H), 7.21 (s,1H), 6.99 (d,
J¼8.2 Hz, 2H), 4.95e4.80 (m, 1H), 3.73 (t, J¼9.0 Hz, 1H), 3.45e3.36
(m, 1H), 2.94 (qd, J¼14.5, 6.1 Hz, 2H), 2.35 (s, 3H); 13C NMR
(100 MHz, CDCl3)
d
161.3, 142.9, 139.3, 133.2, 132.0, 131.0, 129.3,
4.1.33. 1-Benzyl-5-(4-(trifluoromethyl)benzyl)imidazolidin-2-one
126.4, 121.5, 46.6, 39.2, 21.5; IR (thin film): nmax (cmꢂ1)¼2921, 1640,
1453, 1282, 1155, 1075, 877, 809, 707, 660, 579; HRMS (ESI) mass
calcd for C17H17BrN2NaO3S ([MþNa]þ): 431.0035. Found 431.0033.
(6g). Yellow oil, 67% yield. 1H NMR (400 MHz, CDCl3)
d 7.48 (d,
J¼7.9 Hz, 2H), 7.27 (dd, J¼14.4, 7.1 Hz, 3H), 7.23e7.15 (m, 4H),
4.93e4.77 (m, 1H), 4.30 (s, 2H), 3.89e3.76 (m, 1H), 3.47 (dd, J¼11.4,
6.7 Hz, 1H), 2.96 (ddd, J¼19.4, 14.1, 6.3 Hz, 2H); 13C NMR (100 MHz,
4.1.27. 1,5-Dibenzylimidazolidin-2-one (6a0). Yellow oil, 88% yield.
CDCl3) d 161.5, 159.5, 138.1, 135.2, 129.6, 128.9, 128.6, 128.4, 127.8,
1H NMR (400 MHz, CDCl3)
(m, 3H), 7.00 (d, J¼3.7 Hz, 2H), 5.19 (dt, J¼14.1, 7.0 Hz, 1H), 4.33 (s,
d
7.25 (dd, J¼16.8, 9.4 Hz, 4H), 7.19e7.11
127.5, 127.2, 127.1, 125.8, 84.6, 56.9, 47.5, 46.4, 44.3, 39.4, 29.7, 21.7.
IR (thin film): nmax (cmꢂ1)¼2923, 2357, 1696, 1456, 1325, 1117, 1065,

S. Zhu et al. / Tetrahedron 69 (2013) 10375e10383
10383
698; HRMS (ESI) mass calcd for C18H18F3N2O ([MþH]þ): 335.1366.
University (NCET-10-0403), Guangdong NSF (1035106410
1000000), the National Basic Research Program of China (973)
(2011CB808600), SRF for ROCS, State Education Ministry, and the
Fundamental Research Funds for the Central Universities, SCUT
(2012ZZ0038).
Found 335.1363.
4.1.34. Methyl 4-((3-benzyl-2-oxoimidazolidin-4-yl)methyl)-benzo-
ate (6h) and methyl 4-(1-benzyl-2-oxohexahydro-pyrimidin-5-yl)
benzoate (6h0). Yellow oil, 68% yield. 1H NMR (400 MHz, CDCl3)
d
7.88 (d, J¼8.1 Hz, 3H), 7.25 (d, J¼7.0 Hz, 4H), 7.17 (d, J¼4.9 Hz, 3H),
Supplementary data
7.14 (s, 5H), 7.07 (d, J¼7.8 Hz, 3H), 5.52e5.43 (m, 1H), 5.21e5.15 (m,
1H), 4.82 (s, 2H), 4.27 (s, 3H), 4.18 (d, J¼5.8 Hz, 2H), 3.84 (s, 6H),
3.55e3.48 (m, 2H), 3.04 (d, J¼6.1 Hz, 3H); 13C NMR (100 MHz,
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2013.09.097.
CDCl3)
d 166.7, 161.4, 159.6, 139.2, 135.2, 130.1, 129.5, 129.3, 128.9,
128.6,128.3, 127.5, 127.2, 127.1, 84.7, 52.2, 47.5, 46.4, 44.3, 39.6, 29.7;
IR (thin film): nmax (cmꢂ1)¼2927, 2357, 1704, 1550, 1439, 1282, 1107,
701, 530; HRMS (ESI) mass calcd for C19H21N2O3 ([MþH]þ):
325.1547. Found 325.1544.
References and notes
1. (a) Miyata, O.; Nishiguchi, A.; Ninomiya, I.; Aoe, K.; Okamura, K.; Naito, T. J. Org.
Chem. 2000, 65, 6922; (b) Ghosh, A. K.; Thompson, W. J.; McKee, S. P.; Duong, T. T.;
Lyle, T. A.; Chen, J. C.; Darke, P. L.; Zugay, J. A.; Emini, E. A. J. Med. Chem. 1993, 36,
292; (c) Campiani, G.; Nacci, V.; Fiorini, I.; Filippis, M. P. D.; Garofalo, A.; Ciani, S.
M.; Greco, G.; Novellino, E.; Williams, D. C.; Zisterer, D. M.; Woods, M. J.; Mihai, C.;
Manzoni, C.; Mennini, T. J. Med. Chem. 1996, 39, 3435; (d) Brandi, A.; Cicchi, S.;
4.1.35. 4-Benzyl-1,3-dioxolan-2-one (8a). Yellow oil, 25% yield. 1H
NMR (400 MHz, CDCl3)
d
7.36 (dt, J¼14.1, 7.0 Hz, 3H), 7.24 (d,
ꢀ
Cordero, F. M.; Goti, A. Chem. Rev. 2003, 103, 1213; (e) Fernandez, J.; Alonso, J. M.;
J¼7.0 Hz, 2H), 4.96 (dt, J¼13.8, 6.9 Hz, 1H), 4.46 (t, J¼8.2 Hz, 1H),
4.24e4.16 (m, 1H), 3.20 (dd, J¼14.2, 6.1 Hz, 1H), 3.02 (dd, J¼14.2,
ꢀ
Andres, J. I.; Cid, J. M.; Díaz, A.; Iturrino, L.; Gil, P.; Megens, A.; Sipido, V. K.; Tra-
banco, A. A. J. Med. Chem. 2005, 48, 1709.
2. (a) Willis, M. C. Chem. Rev. 2010, 110, 725; (b) Deiters, A.; Martin, S. F. Chem. Rev.
2004, 104, 2199; (c) Kim, J. Y.; Livinghouse, T. Org. Lett. 2005, 7, 4391; (d)
Donohoe, T. J.; Lindsay-Scott, P. J.; Parker, J. S.; Callens, C. K. A. Org. Lett. 2010, 12,
1060; (e) Reznichenko, A. L.; Nguyen, H. N.; Hultzsch, K. C. Angew. Chem. 2010,
122, 9168; (f) Ramachary, D. B.; Narayana, V. V. Eur. J. Org. Chem. 2011, 19, 3514;
(g) Guimond, N.; Gorelsky, S. I.; Fagnou, K. J. Am. Chem. Soc. 2011, 133, 6449; (h)
Xu, H. C.; Moeller, K. D. J. Am. Chem. Soc. 2010, 132, 2839; (i) Campbell, J. M.; Xu,
H. C.; Moeller, K. D. J. Am. Chem. Soc. 2012, 134, 18338.
6.8 Hz, 1H); 13C NMR (100 MHz, CDCl3)
99.9, 68.4, 39.6, 29.7.
d 133.8, 129.3, 129.0, 127.6,
4.1.36. 1-Tosylpiperidin-3-ol (9a). 1H NMR (400 MHz, CDCl3)
d 7.57
(d, J¼8.1 Hz, 2H), 7.26 (d, J¼7.9 Hz, 2H), 3.85e3.73 (m, 1H), 3.23 (d,
J¼11.2 Hz, 1H), 3.04 (d, J¼4.6 Hz,1H), 2.72 (dd, J¼13.8, 6.0 Hz,1H), 2.64
(dd, J¼10.8, 7.4 Hz,1H), 2.37 (s, 3H), 2.02 (s,1H),1.78 (ddd, J¼13.4, 6.6,
3.5 Hz,1H),1.67 (dd, J¼14.4, 5.1 Hz, 1H), 1.55 (ddd, J¼17.6,10.9, 6.6 Hz,
3. Nakamura, I.; Yamamoto, Y. Chem. Rev. 2004, 104, 2127.
4. (a) Cochran, B. M.; Michael, F. E. J. Am. Chem. Soc. 2008, 130, 2786; (b) Rosen, B. R.;
Ney, J. E.; Wolfe, J. P. J. Org. Chem. 2010, 75, 2756; (c) Wu, T.; Yin, G. Y.; Liu, G. S. J.
Am. Chem. Soc. 2009, 131, 16354; (d) Liskin, D. V.; Sibbald, P. A.; Rosewall, C. F.;
Michael, F. E. J. Org. Chem. 2010, 75, 6294; (e) McDonald, R. I.; Liu, G.; Stahl, S. S.
Chem. Rev. 2011,111, 2981; (f) Jana, R.; Pathak, T. P.; Jensen, K. H.; Sigman, M. S. Org.
Lett. 2012, 14, 4074; (g) Lu, Z.; Stahl, S. S. Org. Lett. 2012, 14, 1234.
5. (a) Fuller, P. H.; Kim, J.; Chemler, S. R. J. Am. Chem. Soc. 2008, 130, 17638; (b)
Paderes, M. C.; Chemler, S. R. Org. Lett. 2009, 11, 1915; (c) Paderes, M. C.;
Chemler, S. R. Eur. J. Org. Chem. 2011, 3679; (d) Zhu, R.; Buchwald, S. L. J. Am.
Chem. Soc. 2012, 134, 12462; (e) Wang, Y. F.; Zhu, X.; Chiba, S. J. Am. Chem. Soc.
2012, 134, 3679; (f) Karyakarte, S. D.; Smith, T. P.; Chemler, S. R. J. Org. Chem.
2012, 77, 7755.
1H), 1.37e1.27 (m, 1H); 13C NMR (100 MHz, CDCl3)
d 143.68, 133.14,
129.71, 127.66, 65.72, 52.56, 46.23, 31.63, 21.77, 21.53.
4.1.37. N-(1-Tosylpiperidin-3-yl)acetamide
(10a). 1H
NMR
(400 MHz, CDCl3)
d
7.56 (d, J¼8.2 Hz, 2H), 7.27 (d, J¼8.0 Hz, 2H),
6.01 (s, 1H), 4.08 (s, 1H), 3.45e3.37 (m, 1H), 3.23 (d, J¼8.2 Hz, 1H),
2.65 (dd, J¼11.6, 2.2 Hz, 1H), 2.45 (dd, J¼15.0, 6.7 Hz, 1H), 2.37 (s,
3H), 1.95 (s, 3H), 1.75e1.61 (m, 2H), 1.60e1.49 (m, 1H), 1.44e1.35 (m,
6. (a) Ball, L. T.; Green, M.; Lloyd-Jones, G. C.; Russell, C. A. Org. Lett. 2010, 12, 4724;
(b) Kitahara, H.; Sakurai, H. J. Organomet. Chem. 2010, 696, 442; (c) Haro, T.;
Nevado, C. Angew. Chem., Int. Ed. 2011, 50, 906; (d) Brenzovich, W. E., Jr.; Bra-
zeau, J.; Toste, F. D. Org. Lett. 2010, 12, 4728.
1H); 13C NMR (100 MHz, CDCl3)
d 169.68, 143.90, 132.83, 129.80,
127.66, 50.65, 46.65, 43.89, 28.08, 23.38, 21.53, 21.12.
4.1.38. 5,5-Diphenyl-1-tosylpiperidin-3-ol (9f). 1H NMR (400 MHz,
7. (a) Widenhoefer, R. A.; Han, X. Q. Eur. J. Org. Chem. 2006, 4555; (b) Zheng, H. J.;
Huo, X.; Zhao, C. G.; Jing, P.; Yang, J.; Fang, B.; She, X. G. Org. Lett. 2010, 13, 6448.
8. (a) Zhang, Z. Z.; Widenhoefer, R. A. Angew. Chem., Int. Ed. 2007, 46, 283; (b)
LaLonde, R. L.; Wang, Z. J.; Mba, M.; Lackner, A. D.; Toste, F. D. Angew. Chem., Int.
Ed. 2010, 49, 598; (c) Butler, K. L.; Tragni, M.; Widenhoefer, R. A. Angew. Chem.,
Int. Ed. 2012, 51, 5175.
9. (a) Melhado, A. D.; Brenzovich, W. E., Jr.; Lackner, A. D.; Toste, F. D. J. Am. Chem.
Soc. 2010, 132, 8885; (b) Brenzovich, W. E., Jr.; Benitez, D.; Lackner, A. D.;
Shunatona, H. P.; Tkatchouk, E.; Goddard, W. A., III; Toste, F. D. Angew. Chem.,
Int. Ed. 2010, 49, 5519.
CDCl3)
d
7.56 (d, J¼8.2 Hz, 2H), 7.36 (d, J¼7.6 Hz, 2H), 7.23 (t,
J¼7.7 Hz, 4H), 7.18 (t, J¼3.6 Hz, 2H), 7.12 (dd, J¼10.2, 5.2 Hz, 4H),
4.20 (d, J¼12.1 Hz, 1H), 3.78e3.59 (m, 2H), 2.65 (d, J¼12.6 Hz, 1H),
2.52 (d, J¼12.2 Hz, 1H), 2.34 (s, 3H), 2.21 (t, J¼9.5 Hz, 1H), 2.00 (dd,
J¼18.4, 7.9 Hz, 1H), 1.92 (s, 1H); 13C NMR (100 MHz, CDCl3)
d 145.80,
144.19, 143.88, 132.28, 129.83, 128.61, 128.55, 127.76, 127.70, 126.75,
126.71, 126.31, 64.54, 53.93, 52.55, 46.19, 43.21, 21.54.
10. (a) Zhang, G. Z.; Cui, L.; Wang, Y. Z.; Zhang, L. M. J. Am. Chem. Soc. 2010, 132,
1474; (b) Zhang, G. Z.; Luo, Y. D.; Wang, Y. Z.; Zhang, L. M. Angew. Chem., Int. Ed.
2011, 50, 4450.
4.1.39. N-(5,5-Diphenyl-1-tosylpiperidin-3-yl)acetamide
NMR (400 MHz, CDCl3)
(10f). 1H
11. (a) Marion, N.; Gealageas, R.; Nolan, S. P. Org. Lett. 2007, 9, 2653; (b) Powell, A.
B.; Bielawski, C. W.; Cowley, A. H. J. Am. Chem. Soc. 2009, 131, 18232; (c) Paton,
R. S.; Maseras, F. Org. Lett. 2009, 11, 2237; (d) Wang, Y. M.; Kuzniewski, C. N.;
Rauniyar, V.; Hoong, C.; Toste, F. D. J. Am. Chem. Soc. 2011, 133, 12972.
12. (a) Machin, R. R.; Adrio, J.; Carretero, J. C. J. Org. Chem. 2006, 71, 5023; (b) Cui,
D. M.; Zheng, Z. L.; Zhang, C. J. Org. Chem. 2009, 74, 1426; (c) Liu, Y. X.; Xu, W. Q.;
Wang, X. Org. Lett. 2010, 12, 1448; (d) Tkatchouk, E.; Mankad, N. P.; Benitez, D.;
Goddard, W. A.; Toste, F. D. J. Am. Chem. Soc. 2011, 133, 14293; (e) Noey, E. L.;
Luo, Y. D.; Zhang, L. M.; Houk, K. N. J. Am. Chem. Soc. 2012, 134, 1078.
13. (a) Zhu, S. F.; Liang, R. X.; Jiang, H. F. Tetrahedron 2012, 68, 7949; (b) Zhu, S. F.;
Liang, R. X.; Chen, L. J.; Wang, C.; Jiang, H. F. Tetrahedron Lett. 2012, 53, 815; (c)
Zhu, S. F.; Zhang, Z. C.; Huang, X. B.; Jiang, H. F.; Guo, Z. J. Chem.dEur. J. 2013, 19,
4695.
d
7.57 (d, J¼8.0 Hz, 2H), 7.43 (d, J¼7.5 Hz,
2H), 7.27 (dd, J¼16.3, 7.9 Hz, 3H), 7.22e7.17 (m, 4H), 7.12 (t, J¼7.1 Hz,
3H), 5.11 (s, 1H), 4.27 (d, J¼14.9 Hz, 2H), 3.34 (s, 1H), 2.64 (t,
J¼13.0 Hz, 2H), 2.35 (s, 3H), 2.24 (d, J¼11.8 Hz, 1H). 13C NMR
(100 MHz, CDCl3)
d 169.63, 147.91, 143.91, 132.80, 129.92, 129.81,
128.84, 128.68, 127.80, 127.66, 127.59, 126.56, 50.66, 46.66, 45.85,
43.85, 33.70, 28.09, 23.41, 21.54, 21.12.
Acknowledgements
14. For selected reviews: (a) Lucet, D.; Gall, T. L.; Mioskowski, C. Angew. Chem., Int.
Ed. 1998, 37, 2580; (b) Kotti, S. R. S. S.; Timmons, C.; Li, G. Chem. Biol. Drug Des.
2006, 67, 101.
We are grateful for funding from the NNSFC (21172077,
21372086), the Program for New Century Excellent Talents in