MnI2-catalyzed regioselective intramolecular iodoamination of unfunctionalized olefins

Article abstract of DOI:10.1016/j.tet.2016.09.038

MnI₂-catalyzed intramolecular iodoamination of unfunctionalized olefins was reported. Interaction of MnI₂with N-alkenyl amine/sulfonamide gave [sbnd]NRMnI which produced a [sbnd]CH₂MnI intermediate via intramolecular amino

Full text of DOI:10.1016/j.tet.2016.09.038

Tetrahedron 72 (2016) 7170e7178
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Tetrahedron
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MnI2-catalyzed regioselective intramolecular iodoamination of
unfunctionalized olefins
*
Hui Sun, Bin Cui, Gong-Qing Liu, Yue-Ming Li
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University,
Tianjin, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 31 July 2016
Received in revised form 16 September 2016
Accepted 19 September 2016
Available online 21 September 2016
MnI2-catalyzed intramolecular iodoamination of unfunctionalized olefins was reported. Interaction of
MnI2 with N-alkenyl amine/sulfonamide gave eNRMnI which produced a eCH2MnI intermediate via
intramolecular aminometallation of C]C double bond. Reductive elimination of eCH2I from eCH2MnI
produced iodomethyl heterocycle with the release of Mn(0) which was confirmed by XPS and XRD
experiments.
Ó 2016 Elsevier Ltd. All rights reserved.
Keywords:
Iodoamination
Iodoamidation
MnI2
Unfunctionalized olefin
Reductive elimination
1. Introduction
organocatalytic bromoamination15 as well as transition metal-
catalyzed intramolecular haloamination reactions.16
Vicinalhaloamineshaveplayedimportantroleinorganicchemistry
and medicinal chemistry. They have appeared as subunits of several
natural products1 and have been used as key functional groups in
mechanism-based antitumor drugs.2 Under certain conditions, vicinal
haloamines can be converted to aziridines3 from which different
structures can be constructed,4 and dehalogenation of the vicinal
haloamines can also be a useful supplemental method for hydro-
aminationreactions.5Inaddition,vicinalhaloaminesespecially3-halo-
and2-halomethylheterocycleshavebeenusedaskeyintermediatesfor
the synthesis of a variety of alkaloids6 and pharmaceuticals.7 Further,
a variety of chiral ligands8 and organocatalysts9 can be prepared using
3-halo-and2-halomethylheterocyclesasimportantstartingmaterials.
For these reasons, continued efforts have been made toward the
chemo- and stereoselective synthesis of vicinal haloamines.10
In our previous studies we found that Cu(II) alone was able to
promote chloro- and bromoamination of unfunctionalized olefins,
leading to chlorine and bromine-containing heterocycles in good to
excellent isolated yields.17 Functionalized heterocycles could be
obtained via subsequent nucleophilic substitution reactions.
However, the derivatization would require high temperature due to
the poor leaving group properties of both chloride and bromide
anions. Later, we found that PhI(OAc)2 was a viable promoter for the
reactions, and iodoamination of different substrates were realized
in high isolated yields. The iodo-group could be readily derivatized
under mild conditions (Scheme 1).18
While haloamination of activated C]C double bond has been re-
alized both chemo- and stereoselectively,11 there still exists the space
ofdevelopmentforintramolecularhaloaminationofunfunctionalized
olefins. In addition to the well-developed conventional functional
group transformation reactions,12 a variety of cyclization reactions
havealsobeendevelopedfortheconstructionof2-halomethyl-and3-
haloheterocycles. These methods include free radical cyclization of N-
chloramines,13 electrophilic cyclization of alkeneamines(imines),14
* Corresponding author. Fax: þ86 22 23507760; e-mail address: ymli@nankai.
Scheme 1. Derivatization of 2-iodomethylpyrrolidine compounds.
edu.cn (Y.-M. Li).
http://dx.doi.org/10.1016/j.tet.2016.09.038
0040-4020/Ó 2016 Elsevier Ltd. All rights reserved.

H. Sun et al. / Tetrahedron 72 (2016) 7170e7178
7171
Table 2
The problem associated with our previous methods is the amount
Screening of solvents and iodide sourcesa
of reaction promoters used. So far, it is difficult to carry out these
reactions catalytically, and stoichiometric amount Cu(II) or
PhI(OAc)2 would have to be applied irrespective of whatever
halide sources were used. Considering the potential application
of iodine-containing heterocycles in the construction of bi-
ologically interesting structures, we decided to develop a new
method for intramolecular iodoamination of unfunctionalized
olefins. In this paper we wish to report our recent progress on
Mn(II)-catalyzed intramolecular iodoamination of unfunctional-
ized olefins.
Entry Solvent
MnI2 (equiv) Iodide source (equiv) (2aþ3a):1a/2a:3ab
1
2
3
4
Toluene
MeOH
EtOH
MeCN
DCE
1
d
>99:1 (7:1)
94:6 (7:1)
>99:1 (8:1)
97:3 (8:1)
97:3 (7:1)
98:2 (8:1)
55:45 (8:1)
65:35 (6:1)
79:21 (6:1)
98:2 (8:1)
97:3 (10:1)
90:10 (8:1)
77:23 (8:1)
32:68 (7:1)
97:3 (10:1)
65:35 (7:1)
NR.
1
d
1
d
1
d
5
1
d
6
Et2O
1
d
7
8
CH2Cl2
THF
1
d
1
d
2. Results and discussion
9
EtOAc
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
1
d
10
11
12
13
14
15c
16c
17d
0.5
0.2
0.2
0.2
0.2
0.2
0.2
d
d
Based on our understanding of transition metal-mediated
amination reactions, a variety of metal iodides were screened
and MnI2 gave the most promising results.19 In the presence of
stoichiometric amount of MnI2, cyclization of N-benzyl 2,2-
diphenyl-4-penten-1-amine (1a) proceeded readily, giving 6-
endo-trig product 1-benzyl-3,3-diphenyl-5-iodopiperidine (2a)
NaI$2H2O (4)
NaI(4)
KI(4)
Py$HI(4)
NaI$2H2O(4)
NaI$2H2O(2)
NaI$2H2O
and
5-exo-trig
product
1-benzyl-2-iodomethyl-4,4-
a
Reactions were carried out with 0.25 mmol of 1a at room temperature for 24 h.
diphenylpyrrolidine (3a) in a ratio of 88:12. Isolation of 2a and
3a was difficult due to the easy inter-conversion of these two iso-
mers via aziridium intermediate.20
Iodide sources: 4 equiv, solvent (1 mL).
b
Based on crude 1H NMR analysis of the reaction mixtures.
c
Reaction temperature¼35 ꢁC.
d
NR.¼no reaction.
Different control experiments were then carried out to verify if
the reaction was promoted by MnI2, or by I2 formed via possible
oxidation of Iꢀ (Table 1).21 Iodine was indeed able to promote the
reaction. However, the reaction was significantly suppressed after
the addition of potassium thiosulfate. When MnI2 was used as the
reaction promoter, complete conversion of the substrate was ob-
served either in argon atmosphere or in open air, and potassium
thiosulfate showed less effect on the course of the reaction. These
results indicated that the reactions were promoted by MnI2 rather
than molecular iodine.
After the validation of Mn(II)-promoted intramolecular iodoa-
mination reaction, different solvents were tested to find a suitable
medium for the reaction.19 Preliminary results indicated that tol-
uene, alcoholic solvents (methanol, ethanol), acetonitrile, di-
chloroethane and diethyl ether could all be used as reaction media
(Table 2). Ethanol was used for further study due to the safety issue
and its good performance.
Next, studies were carried out to develop an Mn(II)-catalyzed
intramolecular iodoamination reaction. Reactions with catalytic
amount of MnI2 and different iodide sources were carried out, and
NaI was found to be the most suitable iodide source.19 Both anhy-
drous and sodium iodide dihydrate were tested as the iodide
source, and no significant difference was observed in the presence
of 20 mol % of MnI2 (Table 2, entries 11 and 12). Other iodide
sources such as potassium iodide or pyridine hydroiodic acid salt
gave low conversions under this condition (Table 2, entries 13 and
14). Reducing the amount of iodide source NaI$2H2O resulted in the
decrease of the conversion of the substrate (Table 2, entry 16).
Sodium iodide alone was unable to promote the reaction (Table 2,
entry 17), indicating the important role played by MnI2.
After establishing a general method for Mn(II)-catalyzed intra-
molecular iodoamination of 1a, different substrates were tested to
study the scope of the reaction. Up to 96% yields were observed for
4-penten-1-amine substrates, and up to 95% isolated yields were
observed for 5-hexen-1-amine substrates.19
During the study we found that gray powder was always formed
when the reaction was carried out with stoichiometric amount of
MnI2. This gray powder was not soluble in any organic solvents, nor
was it soluble in any aqueous alkaline solutions. However, the solid
was soluble in acidic solutions, along with the release of gas bub-
bles. XPS experiment on the obtained gray powder indicated that it
contained manganese (0).19 Further XRD experiment confirmed
that this gray solid was manganese (0).
Further reducing the catalyst loading led to a drop of substrate
conversion, and only 20% of 1a was converted (2a:3a¼9:1) when
the reaction was carried out with 10 mol % of MnI2 under oth-
erwise identical conditions. We reasoned that this was possibly
due to the slow conversion of Mn(0) to Mn(II), and this problem
would be tackled with the addition of acid additive. The acid
additive should be such that it could react with Mn(0) to re-
generate Mn(II), and strong interaction of the additive with the
substrate should be avoided. To this end, several solid acid ad-
ditives were tested for their capability to convert Mn(0) to Mn(II),
and sodium bisulfate gave the most promising results.19 In the
presence of 10 mol % of MnI2, 2.5 equiv of sodium bisulfate, and
4 equiv of NaI$2H2O, intramolecular iodoamination of 1a pro-
ceeded readily, leading to 6-endo-trig product 2a and 5-exo-trig
product 3a in 95% yield (2a:3a¼7:1) (Scheme 2a). A control ex-
periment with 10 mol % of Mn powder under otherwise identical
conditions also provided products in 81% yield (2a:3a¼10:1)
(Scheme 2b).
Table 1
Validation of MnI2-catalyzed intramolecular iodoamination of 1aa
Ph
Ph
Ph
Ph
Ph
Ph
+
I
MnI2 (1 equiv)
NBn
NHBn
N
Toluene, r. t.
open air, 24 h
1a
3a
2a 88:12
Bn
I
Entry
Promoter
Condition
Additive
(2aþ3a):1a/2a:3ab
1
2
3
4
5
MnI2
MnI2
MnI2
I2
Ar
Air
Ar
Air
Ar
d
>99:1 (8:1)
>99:1 (7:1)
72:28 (8:1)
93:7 (8:1)
d
K2S2O3
d
I2
K2S2O3
24:76 (7:1)
a
Reaction conditions: 1a (0.25 mmol), promoter (1 equiv), additive (1 equiv),
toluene (1 mL), room temperature, 24 h.
b
Based on 1H NMR analysis of the reaction mixtures.

7172
H. Sun et al. / Tetrahedron 72 (2016) 7170e7178
Table 4
MnI2-catalyzed intramolecular iodoamination of 5-hexen-1-amine substratesa
EtOH, MnI2,
NaHSO4, NaI·2H2O
R1
R1
R1
R1
R2
NHR2
N
35 °C, 48 h
I
4
5
Entry
Substrate
R1
R2
Bn
Yield (%)b
1
2
3
4
5
6
7
8
4a
4b
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
4q
4r
4s
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
e(CH2)5ꢀ
Me
Ph
e(CH2)5ꢀ
Me
93
91
94
81
85
88
88
64
88
89
83
94
4-MeOBn
4-i-PrBn
4-MeBn
4-FBn
4-ClBn
4-BrBn
p-MeOOCBn
4-CNBn
4-NO2Bn
i-Pr
Bn
Bn
Ts
Ts
Ts
Ts
Scheme 2. Control reaction of 1a in the presence of MnI2/Mn powder and sodium
bisulfate.
This result led to the optimized reaction condition with 10 mol %
of MnI2 as the catalyst, and sodium bisulfate as the additive to assist
the conversion of Mn(0) to Mn(II). In the presence 10 mol % of MnI2,
4 equiv of sodium iodide dihydrate and 2.5 equiv of sodium bi-
sulfate, both 4-penten-1-amine substrates and 5-hexen-1-amine
substrates could be converted to the corresponding products with
good isolated yields (Tables 3 and 4).
9
10
11
12
13
14
15
16
17
83
87c (92)d
81c (91)d
73c (83)d
53c (64)d
As shown in Table 3, the reactions generally proceeded readily,
leading to iodoamination products in good to excellent isolated
yields. When N-benzyl substrates were used, 6-endo-trig com-
pounds (N-benzyl-3-iodopiperidines, 2a-2i) were obtained as the
final products, along with small amount of 5-exo-trig N-benzyl-2-
iodomethylpyrrolidines (entries 1e9). The amount of 5-exo-trig
products decreased with the reduce of the size of 3,3-
disubstituents, and in some cases the 6-endo-trig products could
be isolated as the sole isomers (entries 10 and 11). When the amino
groups in the substrates were tosylated, only 5-exo-trig products
(2-iodomethylpyrrolidines, 3l-3o) were obtained (entries 12e15).
These results also indicated that the 5-exo-trig products were
formed at first. When the nitrogen atoms contained N-alkyl sub-
stituents, the products underwent fast isomerization through
aziridinium intermediates, giving thermodynamically stable 6-
H
a
All reactions were carried out with 0.25 mmol of 4, 0.025 mmol MnI2 (10% mol),
1 mmol NaI$2H2O (4 equiv) and 0.625 mmol NaHSO4 (2.5 equiv) in EtOH (1 mL) at
35 ꢁC for 48 h.
b
Isolated yields.
c
Reaction time¼96 h, reaction temperature¼45 ꢁC.
d
Reaction time¼96 h, reaction temperature¼35 ꢁC, catalyst loading¼20 mol %.
endo-trig 3-iodopiperidines as the final products. When the amino
groups were tosylated, the nucleophilicity of the nitrogen atoms
was reduced, and the conversion of 5-exo-trig 2-
iodomethylpyrrolidines to 6-endo-trig 3-iodopiperidines was dif-
ficult.
Under
such
conditions,
5-exo-trig
N-tosyl
2-
iodomethylpyrrolidines could be isolated as the final products of
the reactions. Further, when o-allylaniline N-sulfonamide 1p was
used, N-sulfonyl 2-iodomethylindoline 3p could also be obtained in
moderate isolated yield (entry 16). Substrates with acetoxyl, ben-
zoyl or Boc groups on nitrogen atoms failed to react.19 Thorpe-
Ingold effect22 showed some impact on the reactions, but most
reactions still produced the corresponding cyclization products in
good to excellent isolated yields.
To determine the skeleton of the products, compound 2c was
subjected to X-ray diffraction experiment. The ORTEP drawing
clearly showed a typical chair conformation with two phenyl
groups at both e- and a-positions of the six-membered ring. Iodo-
and p-chlorobenzyl groups also resided at the e-positions of the six-
membered ring (Fig. 1).
Table 3
MnI2-catalyzed intramolecular iodoamination of 4-penten-1-amine substratesa
R1
R1
R1
R1
R1
R1
EtOH, MnI2, NaHSO4
NaI.2H2O
I
I
NHR2
+
N
N
R2
2
R2
35 °C, 48 h
3
1
Entry
Substrate
R1
R2
Yield (2þ3)b/(2:3)c
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
1m
1n
1o
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
e(CH2)5ꢀ
Me
H
Ph
e(CH2)5ꢀ
Me
H
Bn
95 (7:1)
60 (7:1)
74 (6:1)
83 (8:1)
87 (10:1)
94 (7:1)
94 (7:1)
4-FBn
4-ClBn
4-BrBn
4-MeBn
4-MeOBn
4-CNBn
4-NO2Bn
Bn
Bn
Bn
Ts
Ts
96 (7:1)
9
85 (20:1)
91 (2j only)
85 (2k only)
94 (3l only)
93 (3m only)
87 (3n only)
81 (3o only)
10
11
12d
13d
14d
15d
Ts
Ts
I
16d
67 (3p only)
Fig. 1. ORTEP drawing of compound 2c with thermal ellipsoids at 30% probability.
Hydrogen atoms were omitted for clarity.
1p
Ts
N
Ts
N
H
a
Next, our attention turned to the 5-hexen-1-amine substrates,
and the results were presented in Table 4. The reactions showed
high selectivity for 6-exo-trig products. 2-Iodomethylpiperidines
were obtained in all cases, and conversion of 2-
iodomethylpiperidines to the corresponding 3-iodoazepanes
Reactions were carried out with 0.25 mmol of 1, 0.025 mmol MnI2 (10 mol %),
1 mmol NaI$2H2O (4 equiv) and 0.625 mmol NaHSO4 (2.5 equiv) in EtOH (1 mL) at
35 ꢁC for 48 h.
b
Isolated yields.
Based on NMR integration of the isolated products.
Reaction time¼96 h.
c
d

H. Sun et al. / Tetrahedron 72 (2016) 7170e7178
7173
was not observed. The 2-iodomethylpiperidine structure was also
confirmed with X-ray diffraction experiment (Fig. 2). When N-
sulfonamides were subjected to the same reaction, longer re-
action time and higher reaction temperature were generally re-
quired (entries 14e17).
intramolecular hydroamination product was significantly sup-
pressedwhencyclohexenewasaddedto clearany possible HIformed
during the reaction (Scheme 5). These results supported the possible
release of HI during the interaction of MnI2 with the substrate.
Scheme 5. Possible formation of HI during the reaction.
To further study the possible release of HI, control reactions of 4a
in the absence and presence of bases were carried out (Table 5).
While sodium carbonate was ineffective to accelerate the intra-
molecular iodoamination reaction of 4a (Table 5, entry 2), signifi-
cant rate enhancement was observed when the reaction was carried
out in the presence of potassium phosphate (Table 5 entry 3).
Fig. 2. ORTEP drawing of compound 5g with thermal ellipsoids at 30% probability.
Hydrogen atoms were omitted for clarity.
Table 5
The effect of base on the course of the reactiona
Iodoamination of 4a was also scaled up to prove the scalability
of the current protocol. The reaction was carried out under the
optimized reaction conditions, and the expected product 5a was
obtained in 90% isolated yield (Scheme 3).
Ph
MnI2 (1 equiv), EtOH
Bn additive, 35 °C
Bn
Ph Ph
H
N
Ph
N
I
4a
5a
Entry
Additive (equiv)
5a:4ab
1
2
3
d
1.6:1
1.2:1
6:1
Na2CO3 (1)
K3PO4 (2/3)
a
Reactions were carried out with 0.25 mmol of substrate and 1 equiv of MnI2 in
EtOH (1 mL). Reaction time¼5 h.
b
Scheme 3. Scale-up of the reaction.
Based on NMR analysis of the reaction mixtures.
Mn(III) was known to promote free radical carbolactonization
and related reactions.23 To study the possible pathway of the cur-
rent reaction, iodoamination of 4a was carried out in the presence
of TEMPO (Scheme 4). Preliminary results indicated that this ad-
ditive showed no impact on the reaction, and the free radical
capture was also not observed, possibly ruling out the free radical
pathway of the reaction.
Based on the current results, a preliminary reaction mechanism
was proposed as shown in Scheme 6. Interaction of Mn(II) with
substrate gave intermediate A. HI was released at this stage and this
step could be enhanced upon addition of a suitable base (Table 5,
entry 3). Interaction of Mn with C]C double bond led to the acti-
vation of the latter, and intramolecular nucleophilic attack of ni-
trogen atom on activated C]C double bond proceeded as shown in
B, yielding an aminometallation intermediate C. Reductive elimi-
nation of product D from C occurred, releasing Mn(0), which could
be proved by XPS and XRD experiments. Product D underwent fast
Scheme 4. Reaction of 4a in the presence of free radical capturer.
Tilley et al. showed that a Brønsted acid could be released when
sulfonamide coordinated to a metal salt.24 Bergman et al. pointed out
that acid catalysis was more likely in many metal-catalyzed hydro-
amination and hydroarylation reactions.25 Szolcsanyi et al. detailed
ꢀ
the intramolecular hydroamination of N-tosylalkenylamines using
a variety of metal triflate as catalysts, and concluded that triflic acid
could be the true catalyst for these reactions.26 Sarpong et al. showed
that HI could be used as a viable promoter for intramolecular
hydroamination of unfunctionalized olefins.27 To test if HI was re-
leasedinthe currentreactions, differentsulfonamidesubstrateswere
subjected to the same iodoamination reactions. While only iodoa-
mination product was observed for N-tosyl substrate, iodoami-
nadtion product along with intramolecular hydroamination product
was observed when N-mesyl substrate was subjected to the reaction
under otherwise identical conditions (Scheme 5). Further, the
Scheme 6. A plausible mechanism for MnI2-catalyzed intramolecular iodoamination
reaction.

7174
H. Sun et al. / Tetrahedron 72 (2016) 7170e7178
equilibriumwith E, leading tothe formation of E as the final product,
and Mn(0) was converted to Mn(II) by the action of oxygen or via
reaction with an acid additive, thus completing the catalysis cycle.
When N-benzyl 4-penten-1-amine substrate was subjected to
the reaction, 5-exo-trig product could easily isomerize to 6-endo-
trig product via aziridium iodide intermediate. When N-sulfonyl 4-
penten-1-amine substrate was subjected to the same reaction,
conversion of 5-exo-trig product D to 6-endo-trig product E was
difficult due to the low nucleophilicity of the sulfonylated nitrogen
atom. Under such circumstance, 5-exo-trig 2-iodomethyl hetero-
cyclic product was obtained as the final product. When 5-hexen-1-
amine substrate was subjected to the same reaction, conversion of
6-exo-trig product to 7-endo-trig product was difficult, and 6-exo-
trig compound 5 was obtained as the only product.
by flash column chromatography to give 5a (0.63 g, 90%) as color-
less oil.
4.3.1. 1-Benzyl-5-iodo-3,3-diphenylpiperidine (2a). White solid, m.
p. 47 ꢁCe50 ꢁC. 1H NMR (400 MHz, CDCl3)
d 7.31e6.95 (m,15H), 3.99
(t, J¼11.68 Hz, 1H), 3.58 (d, J¼12.1 Hz, 1H), 3.48 (s, 2H), 3.23 (d,
J¼10.2 Hz, 1H), 3.09 (t, J¼17.6 Hz, 1H), 2.57 (t, J¼12.6 Hz,1H), 2.43 (t,
J¼10.8 Hz, 1H), 2.25 (t, J¼13.9 Hz, 1H). 13C NMR (101 MHz, CDCl3)
d
146.2, 143.6, 135.9, 133.3, 128.2, 127.9, 127.7, 127.2, 127.0, 126.7,
125.3, 124.8, 62.8, 61.0, 60.7, 49.1, 47.7, 22.2, 20.1. HRMSeESI (m/z):
[MþH]þ calcd for C24H24IN: 454.1032; found: 454.1028. The NMR
data were in agreement with reported results.18
4.3.2. 1-(4-Fluorobenzyl)-5-iodo-3,3-diphenylpiperidine (2b). White
solid, mp 105 ꢁCe107 ꢁC. 1H NMR (400 MHz, CDCl3)
d 7.21e6.88 (m,
3. Conclusion
14H), 3.99 (t, J¼11.5 Hz, 1H), 3.55 (d, J¼11.9 Hz, 1H), 3.49e3.37 (m,
2H), 3.20 (d, J¼8.5 Hz,1H), 3.12 (d, J¼12.4 Hz,1H), 2.56 (t, J¼12.6 Hz,
1H), 2.42 (t, J¼10.8 Hz, 1H), 2.26 (d, J¼12.0 Hz, 1H). 13C NMR
In summary, intramolecular iodoamination of unfunctionalized
olefins were realized in the presence of catalytic amount of MnI2,
a suitable iodide source and an acid additive. Both N-substituted
pent-4-en-1-amines and N-substituted hex-5-en-1-amines could
be easily cyclized, leading to 3-iodopiperidines or 2-
iodomethylpyrrolidines in good to excellent isolated yields. The
advantages of the current system include mild and easy-to-operate
reaction conditions, and the easy availability of both the catalyst
and the iodide source. To the best of our knowledge, this is the first
report for reductive elimination of alkyliodide from Mn(II) center.
Development of Mn(II)-catalyzed asymmetric iodohaloamination
and preparation of related heterocycles are in good progress and
the results will be reported in due time.
(101 MHz, CDCl3)
d 147.2, 144.6, 133.4, 133.3, 130.9, 130.8, 128.7,
128.4, 128.2, 126.5, 126.4, 126.1, 115.4, 115.2, 63.9, 61.8, 61.6, 50.2,
48.8, 22.9. 19F NMR (376 MHz, CDCl3)
d
ꢀ115.2. HRMSeESI (m/z):
[MþH]þ calcd for C24H23FIN: 472.0937; found: 472.0929. The NMR
data were in agreement with reported results.18
4.3.3. 1-(4-Chlorobenzyl)-5-iodo-3,3-diphenylpiperidine (2c). White
solid, mp 122 ꢁCe124 ꢁC. 1H NMR (400 MHz, CDCl3)
d 7.23e6.94 (m,
14H), 4.05e3.93 (m, 1H), 3.54 (d, J¼12.0 Hz, 1H), 3.46e3.38 (m, 2H),
3.19 (d, J¼8.6 Hz, 1H), 3.12 (d, J¼12.7 Hz, 1H), 2.55 (t, J¼12.7 Hz, 1H),
2.42 (t, J¼10.9 Hz, 1H), 2.27 (d, J¼12.1 Hz, 1H). 13C NMR (101 MHz,
CDCl3)
d 146.0, 143.4, 135.0, 132.0, 129.4, 127.5, 127.4, 127.3, 127.1,
125.3, 125.2, 124.9, 62.8, 60.9, 60.5, 49.0, 47.5, 21.6. IR (KBr): 3084,
3046, 3025, 2961, 2930, 2815, 2787, 2713, 1951, 1894, 1596, 1491,
1445, 1340, 1184, 1137, 1072, 1061, 1016, 909, 839, 804, 754, 701, 631,
580, 538, 460 cmꢀ1;HRMSeESI (m/z): [MþH]þ calcd for C24H23ClIN:
488.0642; found: 488.0635.
4. Experimental section
4.1. General information
Reactions were carried out using commercially available re-
agents in oven-dried apparatus. 1H and 13C NMR spectra were
recorded on a Bruker DRX 400 spectrometer at 298 K using deu-
terated chloroform as solvent and TMS as the internal reference.
Column chromatography was performed employing 200e300
mesh silica gel. Thin layer chromatography (TLC) was performed on
silica gel GF254. HRMS analyses were carried out with Varian FTICR-
MS 7.0 T.
Crystal data for 2c:
C
24H23ClIN, M¼487.78, monoclinic,
¼90.00ꢁ,
ꢁ
ꢁ ꢁ
3
a¼12.325(3) A, b¼10.604(2) A, c¼16.287(3) A,
a
ꢁ
ꢁ
b
¼91.13(3)ꢁ,
¼90.00 , V¼2128.2(7) A , T¼293(2) K, space group
g
P2(1)/c, Z¼4,
m
(MoK
a
)¼1.639 mmꢀ1, 21,190 reflections measured,
5083 independent reflections (Rint¼0.0391). The final R1 values
were 0.0496 (I>2s
(I)). The final wR(F2) values were 0.1262 (I >
2s
(I)). The final R1 values were 0.0655 (all data). The final wR(F2)
values were 0.1384 (all data). The goodness of fit on F2 was 1.074.
CCDC 1451292.
4.2. General procedure for intramolecular iodoamination
4.3.4. 1-(4-Bromobenzyl)-5-iodo-3,3-diphenylpiperidine
To a solution of MnI2 (7.72 mg, 0.025 mmol, 10 mol %) in EtOH
(0.5 mL) was added 1a (81.75 mg, 0.25 mmol, 1 equiv), NaI$2H2O
(185.9 mg, 1 mmol, 4.0 equiv) and NaHSO4 (87.0 mg, 0.625 mmol,
2.5 equiv), followed by another portion of EtOH (0.5 mL). The
resulting mixture was stirred at 35 ꢁC and the reaction was moni-
tored by TLC. After completion of the reaction (48 h), the solvent
was evaporated and the residue was purified by flash column
chromatography to give 2a as colorless oil.
(2d). White solid, mp 83 ꢁCe86 ꢁC. 1H NMR (400 MHz, CDCl3)
d 7.37
(d, J¼8.0 Hz, 2H), 7.25e7.06 (m, 11H), 6.99 (d, J¼7.9 Hz, 2H),
4.05e3.95 (m, 1H), 3.56 (d, J¼12.0 Hz, 1H), 3.49e3.39 (m, 2H),
3.23e3.17 (m, 1H), 3.14 (d, J¼12.6 Hz, 1H), 2.56 (t, J¼12.7 Hz, 1H),
2.44 (t, J¼10.9 Hz, 1H), 2.29 (d, J¼12.1 Hz, 1H). 13C NMR (101 MHz,
CDCl3)
d 147.1, 144.5, 136.6, 131.5, 130.9, 128.6, 128.4, 128.4, 128.2,
126.5, 126.3, 126.0, 63.9, 61.9, 61.6, 50.2, 48.6, 22.7. IR (KBr): 3084,
3058, 3026, 2926, 2883, 2813, 2760, 1591, 1490, 1468, 1445, 1332,
1300, 1263, 1100, 1070, 1053, 1012, 965, 840, 802, 768, 749, 697, 630,
566, 526 cmꢀ1; HRMSeESI (m/z): [MþH]þ calcd for C24H23BrIN:
532.0137; found: 532.0116.
4.3. Scaled-up iodoamination of 4a
To a solution of MnI2 (0.046 mg, 0.15 mmol, 10 mol %) in EtOH
(6 mL) was added 4a (0.5118 g, 1.5 mmol, 1 equiv), NaI$2H2O
(1.118 g, 6 mmol, 4.0 equiv) and NaHSO4 (0.522 g, 3.75 mmol,
2.5 equiv). The resulting mixture was stirred at 35 ꢁC and the re-
action was monitored by TLC. After completion of the reaction
(48 h), water (20 mL) was added and the aqueous portion was
extracted with CH2Cl2 (50 mLꢂ3). The organic portion was washed
with brine, dried over anhydrous sodium sulfate, and concentrated
in vacuo. The solvent was evaporated and the residue was purified
4.3.5. 5-Iodo-1-(4-methylbenzyl)-3,3-diphenylpiperidine
(2e). White solid, mp 123 ꢁCe124 ꢁC. 1H NMR (400 MHz, CDCl3)
d
7.31e6.91 (m, 14H), 4.04e3.95 (m, 1H), 3.59 (d, J¼12.1 Hz, 1H),
3.46 (d, J¼3.8 Hz, 2H), 3.28e3.21 (m, 1H), 3.12 (d, J¼12.5 Hz, 1H),
2.56 (d, J¼12.6 Hz, 1H), 2.43 (t, J¼11.0 Hz, 1H), 2.26 (d, J¼13.4 Hz,
4H). 13C NMR (101 MHz, CDCl3)
d 146.3, 143.6, 135.9, 133.4, 128.2,
127.9, 127.7, 127.3, 127.0, 125.3, 125.3, 124.8, 62.8, 61.0, 60.8, 49.1,
47.8, 22.2, 20.1. IR (KBr): 3047, 3020, 2958, 2930, 2786, 2753, 1596,

H. Sun et al. / Tetrahedron 72 (2016) 7170e7178
7175
1494, 1445, 1340, 1262, 1207, 1106, 1061, 1024, 909, 805, 751, 701,
632, 588, 557, 485 cmꢀ1; HRMSeESI (m/z): [MþH]þ calcd for
C25H26IN: 468.1188; found: 468.1180.
J¼10.5 Hz, 1H), 2.17 (t, J¼24.6 Hz, 2H), 1.86e1.71 (m, 1H), 1.65e1.53
(m, 2H). 13C NMR (101 MHz, CDCl3)
d 137.9, 129.0, 128.3, 127.2, 63.5,
62.5, 52.9, 37.5, 27.1, 22.4. HRMSeESI (m/z): [MþH]þ calcd for
C12H16IN:302.0406; found: 302.0399.
4.3.6. 5-Iodo-1-(4-methoxybenzyl)-3,3-diphenylpiperidine
(2f). White solid, mp 105 ꢁCe107 ꢁC. 1H NMR (400 MHz, CDCl3)
4.3.12. 2-(Iodomethyl)-4,4-diphenyl-1-tosylpyrrolidine (3l). White
solid, mp 177 ꢁCe178 ꢁC. 1H NMR (400 MHz, CDCl3)
7.52 (d,
d
7.26e7.03 (m, 10H), 6.99 (d, J¼7.5 Hz, 2H), 6.79 (d, J¼8.4 Hz, 2H),
d
4.06e3.92 (m, 1H), 3.73 (s, 3H), 3.58 (d, J¼12.1 Hz, 1H), 3.50e3.34
(m, 2H), 3.28e3.17 (m, 1H), 3.12 (d, J¼12.6 Hz, 1H), 2.57 (t,
J¼8.1 Hz, 2H), 7.27e6.96 (m, 12H), 4.37 (d, J¼10.3 Hz, 1H), 3.84e3.74
(m, 1H), 3.67 (d, J¼10.3 Hz, 1H), 3.60 (dd, J¼9.5, 3.0 Hz, 1H),
2.81e2.67 (m, 2H), 2.58 (dd, J¼13.1, 5.2 Hz, 1H), 2.32 (s, 3H). 13C
J¼12.7 Hz, 1H), 2.42 (t, J¼11.0 Hz, 1H), 2.23 (d, J¼12.1 Hz, 1H). 13
C
NMR (101 MHz, CDCl3)
d
157.9, 146.2, 143.6, 129.4, 128.5, 127.7,
NMR (101 MHz, CDCl3) d 144.6,144.4,143.7,133.9,129.8,128.7,128.7,
127.3, 127.0, 125.8, 125.3, 124.8, 112.6, 62.8, 60.6, 54.2, 49.1, 47.8,
22.19. HRMSeESI (m/z): [MþH]þ calcd for C25H26INO: 484.1137;
found: 484.1124. The NMR data were in agreement with reported
results.18
127.4, 126.8, 126.6, 126.5, 126.3, 60.4, 59.2, 52.2, 43.8, 21.6, 11.4.
HRMSeESI (m/z): [MþH]þ calcd for C24H22INO2S:518.0651; found:
518.0640. The NMR data were in agreement with reported results.18
4.3.13. 3-(Iodomethyl)-2-tosyl-2-azaspiro[4.5]decane (3m). White
4.3.7. 4-((5-Iiodo-3,3-diphenylpiperidin-1-yl)methyl)benzonitrile
solid, mp 50 ꢁCe51 ꢁC. 1H NMR (400 MHz, CDCl3)
d
7.66 (d, J¼8.3 Hz,
(2g). White solid, mp 145 ꢁCe148 ꢁC. 1H NMR (400 MHz, CDCl3)
2H), 7.25 (d, J¼8.0 Hz, 2H), 3.70e3.65 (m, 1H), 3.57e3.48 (m, 1H),
3.34e3.27 (m, 2H), 3.09 (d, J¼11.0 Hz, 1H), 2.35 (s, 3H), 1.98e1.84
(m, 1H), 1.48e1.41 (m, 1H), 1.41e1.22 (m, 4H), 1.22e1.06 (m, 3H),
1.06e0.98 (m, 1H), 0.76e0.60 (m, 1H), 0.55e0.46 (m, 1H). 13C NMR
d
7.53 (d, J¼8.1 Hz, 2H), 7.31 (d, J¼8.1 Hz, 2H), 7.23e7.04 (m, 8H),
7.00 (d, J¼7.4 Hz, 2H), 4.08e3.97 (m, 1H), 3.59e3.45 (m, 2H),
3.20e3.12 (m, 1H), 2.56 (t, J¼12.8 Hz, 1H), 2.47 (t, J¼11.1 Hz, 1H),
2.39 (d, J¼12.0 Hz, 1H). 13C NMR (101 MHz, CDCl3)
d
146.9, 144.3,
(101 MHz, CDCl3) d 143.7, 134.7, 129.7, 127.5, 59.3, 41.4, 36.1, 33.9,
143.4, 132.3, 129.7, 128.5, 128.5, 128.3, 126.6, 126.3, 126.2, 118.9,
111.3, 63.8, 62.2, 61.8, 50.2, 48.5, 22.2. IR (KBr): 3083, 3053, 3019,
2949, 2907, 2817, 2797, 2227, 1950, 1811, 1606, 1496, 1467, 1444,
1262, 1197, 1132, 1106, 1063, 1032, 911, 816, 757, 700, 631, 581,
25.8, 23.7, 22.7, 21.6, 13.7. HRMSeESI (m/z): [MþH]þ calcd for
C
17H24INO2S:434.0651; found: 434.0642. The NMR data were in
agreement with reported results.18
548 cmꢀ1
479.0984; found: 479.0981.
;
HRMSeESI (m/z): [MþH]þ calcd for C25H23IN2:
4.3.14. 2-(Iodomethyl)-4,4-dimethyl-1-tosylpyrrolidine (3n). White
solid, mp 86 ꢁCe87 ꢁC. 1H NMR (400 MHz, CDCl3)
d
7.67 (d, J¼8.2 Hz,
2H), 7.26 (d, J¼8.0 Hz, 2H), 3.70 (dd, J¼9.5, 2.8 Hz, 1H), 3.66e3.56
(m, 1H), 3.30 (t, J¼9.2 Hz, 1H), 3.20e3.07 (m, 2H), 2.36 (s, 3H), 1.85
(dd, J¼12.8, 7.1 Hz, 1H), 1.52 (dd, J¼12.8, 8.5 Hz, 1H), 0.97 (s, 3H),
4.3.8. 5-Iodo-1-(4-nitrobenzyl)-3,3-diphenylpiperidine (2h). White
solid, mp 149 ꢁCe150 ꢁC. 1H NMR (400 MHz, CDCl3)
d 8.12 (d,
J¼7.5 Hz, 2H), 7.38 (d, J¼7.6 Hz, 2H), 7.26e7.07 (m, 8H), 7.01 (d,
J¼7.5 Hz, 2H), 4.05 (t, J¼10.1 Hz, 1H), 3.65e3.52 (m, 3H), 3.18 (d,
J¼10.6 Hz, 2H), 2.57 (t, J¼13.0 Hz,1H), 2.50 (t, J¼11.1 Hz,1H), 2.42 (d,
0.42 (s, 3H). 13C NMR (101 MHz, CDCl3)
d 143.7, 134.9, 129.8, 127.5,
62.0, 60.1, 47.8, 37.5, 26.0, 25.9, 21.6, 13.3. The NMR data were in
agreement with reported results.28
J¼12.0 Hz, 1H). 13C NMR (101 MHz, CDCl3)
d 146.3, 145.8, 144.4,
143.2, 128.6, 127.4, 127.2, 127.1, 125.5, 125.2, 125.1, 122.6, 62.7, 61.1,
60.4, 49.1, 47.4, 20.9. IR (KBr): 3067, 3026, 2962, 2943, 2910, 2843,
2802, 2450, 1955, 1727, 1601, 1508, 1445, 1344, 1262, 1183, 1107,
1055, 1033, 861, 805, 759, 699, 630, 568, 536 cmꢀ1; HRMSeESI (m/
z): [MþH]þ calcd for C24H23IN2O2: 499.0882; found: 499.0875.
4.3.15. 2-(Iodomethyl)-1-tosylpyrrolidine (3o). White solid, mp
89 ꢁCe90 ꢁC. 1H NMR (400 MHz, CDCl3)
d
7.66 (d, J¼8.2 Hz, 2H), 7.27
(d, J¼8.1 Hz, 2H), 3.72e3.60 (m, 1H), 3.55 (dd, J¼9.7, 3.0 Hz, 1H),
3.47e3.37 (m, 1H), 3.20e3.03 (m, 2H), 2.37 (s, 3H), 1.88e1.68 (m,
3H), 1.52e1.40 (m, 1H). 13C NMR (101 MHz, CDCl3)
d 143.8, 134.1,
129.9, 127.5, 60.7, 50.1, 32.0, 23.9, 21.6, 11.6. The NMR data were in
4.3.9. 2-Benzyl-4-iodo-2-azaspiro[5.5]undecane (2i). Brownish oil.
agreement with reported results.16i
1H NMR (400 MHz, CDCl3)
d 7.36e7.01 (m, 5H), 4.36e4.26 (m, 1H),
3.49 (d, J¼13.4 Hz, 1H), 3.31 (d, J¼13.4 Hz, 1H), 3.24e3.17 (m, 1H),
4.3.16. 2-(Iodomethyl)-1-tosylindoline (3p). White solid, mp
2.71 (d, J¼11.3 Hz, 1H), 2.30 (dd, J¼14.5, 7.4 Hz, 2H), 1.63e1.41 (m,
148 ꢁCe149 ꢁC. 1H NMR (400 MHz, CDCl3)
d
7.57 (d, J¼8.1 Hz, 1H),
4H), 1.38e1.13 (m, 8H). 13C NMR (101 MHz, CDCl3)
d
137.5, 127.5,
7.48 (d, J¼8.2 Hz, 2H), 7.21e7.05 (m, 3H), 7.01e6.91 (m, 2H),
4.33e4.20 (m, 1H), 3.58 (dd, J¼9.7, 3.4 Hz, 1H), 3.17 (t, J¼9.9 Hz, 1H),
2.97e2.80 (m, 1H), 2.76 (dd, J¼16.7, 3.0 Hz, 1H), 2.26 (s, 3H). 13C
127.2, 126.0, 64.0, 61.1, 48.4, 37.3, 37.1, 31.3, 25.6, 23.7, 20.5. IR (KBr):
3083, 3060, 3026, 2924, 2851, 2792, 2756, 1736, 1668, 1602, 1494,
1452,1345, 1262, 1144, 1028, 911, 875, 800, 739, 699, 679, 614 cmꢀ1
;
NMR (101 MHz, CDCl3) d 144.3, 141.2, 134.4, 130.4, 129.8, 128.0,
HRMSeESI (m/z): [MþH]þ calcd for C17H24IN:370.1032; found:
127.1, 125.3, 125.0, 116.8, 62.5, 34.8, 21.6, 11.6. The NMR data were in
370.1023.
agreement with reported results.16i
4.3.10. 1-Benzyl-5-iodo-3,3-dimethylpiperidine (2j). Brownish oil.
4.3.17. 1-Benzyl-2-(iodomethyl)-5,5-diphenylpiperidine (5a). White
1H NMR (400 MHz, CDCl3)
d
7.26e7.09 (m, 5H), 4.36e4.19 (m, 1H),
solid, mp 125 ꢁCe127 ꢁC. 1H NMR (400 MHz, CDCl3)
d 7.42e6.86 (m,
3.46 (d, J¼13.4 Hz, 1H), 3.32 (d, J¼13.4 Hz, 1H), 3.23e3.15 (m, 1H),
2.39 (d, J¼11.1 Hz, 1H), 2.23 (t, J¼11.1 Hz, 1H), 2.09e1.99 (m, 1H),
1.72 (d, J¼11.1 Hz, 1H), 1.64 (t, J¼12.7 Hz, 1H), 0.98 (s, 3H), 0.76 (s,
14H), 3.93 (d, J¼12.8 Hz,1H), 3.38 (dd, J¼10.5, 6.6 Hz,1H), 3.31e3.20
(m, 2H), 3.04 (d, J¼12.8 Hz, 1H), 2.42 (d, J¼12.4 Hz, 1H), 2.33 (dd,
J¼8.4, 4.7 Hz, 1H), 2.24e2.14 (m, 1H), 2.10 (s, 1H), 1.66e1.50 (m, 2H).
3H). 13C NMR (101 MHz, CDCl3)
d
137.4, 127.5, 127.2, 126.0, 63.4,
13C NMR (101 MHz, CDCl3)
d 148.0, 146.4, 138.2, 129.8, 128.6, 128.3,
63.3, 61.0, 50.3, 34.3, 28.1, 23.5. IR (KBr): 3647, 3084, 3061, 3027,
2952, 2796, 2755, 2714, 1601, 1455, 1363, 1306, 1255, 1115, 1074,
1037, 909, 878, 785, 740, 698, 613, 546, 462 cmꢀ1; HRMSeESI (m/z):
[MþH]þ calcd for C14H20IN:330.0719; found: 330.0717.
128.1, 127.8, 127.4, 127.1, 125.9, 125.6, 60.0, 59.6, 58.9, 46.4, 33.3,
28.1, 11.7. IR (KBr): 3084, 3057, 3028, 2949, 2856, 2790, 2742, 1596,
1492, 1445, 1360, 1328, 1262, 1198, 1164, 1095, 1061, 1028, 960, 803,
750, 699, 586, 558 cmꢀ1; HRMSeESI (m/z): [MþH]þ calcd for
C25H26IN: 468.1188; found: 468.1182.
4.3.11. 1-Benzyl-3-iodopiperidine (2k). Brownish oil. 1H NMR
(400 MHz, CDCl3)
J¼13.3 Hz, 2H), 3.05e2.88 (m, 1H), 2.70 (d, J¼8.7 Hz, 1H), 2.43 (t,
d
7.45e7.05 (m, 5H), 4.35e4.04 (m, 1H), 3.45 (q,
4.3.18. 2-(Iodomethyl)-1-(4-methoxybenzyl)-5,5-diphenylpiperidine
(5b). White solid, mp 75 ꢁCe78 ꢁC. 1H NMR (400 MHz, CDCl3)
7.26
d

7176
H. Sun et al. / Tetrahedron 72 (2016) 7170e7178
(t, J¼10.7 Hz, 2H), 7.17e7.06 (m, 6H), 7.06e6.95 (m, 4H), 6.82 (d,
J¼8.6 Hz, 2H), 3.89 (t, J¼10.9 Hz, 1H), 3.74 (s, 3H), 3.40 (dd, J¼10.5,
6.5 Hz, 1H), 3.34e3.19 (m, 2H), 2.98 (d, J¼12.7 Hz, 1H), 2.39 (d,
J¼12.4 Hz, 1H), 2.33 (dd, J¼8.5, 4.6 Hz, 1H), 2.24e2.14 (m, 1H), 2.07
3.40e3.32 (m, 1H), 3.23 (t, J¼10.5 Hz, 2H), 2.96 (d, J¼12.8 Hz, 1H),
2.42e2.27 (m, 2H), 2.26e2.12 (m, 1H), 2.04 (s, 1H), 1.75e1.44 (m,
2H). 13C NMR (101 MHz, CDCl3)
d
163.5, 161.1, 148.0, 146.3, 133.9,
133.9, 131.4, 131.3, 128.6, 128.2, 127.8, 127.1, 126.0, 125.7, 59.9, 59.6,
58.0, 46.4, 33.3, 28.2, 11.9. 19F NMR (376 MHz, CDCl3)
(s, 1H), 1.61e1.48 (m, 2H). 13C NMR (101 MHz, CDCl3)
d
157.8, 146.9,
d
ꢀ115.5. IR
145.3,129.8,129.0,127.5,127.0,126.6,126.0,124.8,124.4, 112.5, 58.5,
58.3, 56.9, 54.2, 45.3, 32.2, 27.0, 10.8. IR (KBr): 3644, 3056, 3018,
2960, 2934, 2906, 2835, 2800, 1663, 1611, 1513, 1445, 1302, 1256,
1177, 1035, 805, 753, 700, 638, 579, 522 cmꢀ1; HRMSeESI (m/z):
[MþH]þ calcd for C26H28INO: 498.1294; found:498.1274.
(KBr): 3058, 3027, 2959, 2935, 2792, 2753, 2730, 1602, 1507, 1494,
1444, 1363, 1321, 1262, 1221, 1086, 1028, 960, 820, 802, 761, 700,
565 cmꢀ1; HRMSeESI (m/z): [MþH]þ calcd for C25H25FIN:486.1094;
found: 486.1092.
Crystal data for 5g:
C
25H25FIN, M¼485.36, monoclinic,
ꢁ
ꢁ ꢁ
3
a¼18.309(4) A, b¼10.301(2) A, c¼24.854(5) A,
a
¼90.00ꢁ,
ꢁ
4.3.19. 2-(Iodomethyl)-1-(3-methoxybenzyl)-5,5-diphenylpiperidine
b
¼111.12(3)ꢁ,
¼90.00 , V¼4372.4(15) A , T¼293(2) K, space group
g
ꢁ
(5c). White solid, mp 138 ꢁCe139 ꢁC. 1H NMR (400 MHz, CDCl3)
C2/c, Z¼8,
m
(MoK
a
)¼1.483 mmꢀ1, 20,834 reflections measured,
d
7.34e6.65 (m, 15H), 3.88 (d, J¼12.9 Hz, 1H), 3.71 (s, 3H), 3.35 (dd,
5167 independent reflections (Rint¼0.0366). The final R1 values
J¼10.4, 6.5 Hz, 1H), 3.25 (t, J¼12.7 Hz, 2H), 2.97 (d, J¼12.9 Hz, 1H),
2.39 (d, J¼12.4 Hz, 1H), 2.29 (t, J¼14.6 Hz, 1H), 2.23e2.11 (m, 1H),
were 0.0447 (I > 2s
(I)). The final wR(F2) values were 0.1222
(I>2s
(I)). The final R1 values were 0.0579 (all data). The final wR(F2)
2.04 (s, 1H), 1.64e1.43 (m, 2H). 13C NMR (101 MHz, CDCl3)
d
159.8,
values were 0.1333 (all data). The goodness of fit on F2 was 1.080.
148.1,146.4,140.1,129.3,128.7,128.2,127.8,127.2,126.0,125.7,122.0,
114.7, 113.5, 60.3, 59.6, 59.0, 55.4, 46.5, 33.5, 28.2, 12.2. IR (KBr):
3563, 3327, 3247, 3161, 3061, 3027, 2944, 2838, 2482, 2378, 2277,
2055, 1950, 1887, 1812, 1757, 1638, 1506, 1493, 1460, 1290, 1245,
1183, 1117, 1036, 912, 840, 761, 712 cmꢀ1HRMSeESI (m/z): [MþH]þ
calcd for C26H28INO: 498.1294; found:498.1294.
CCDC 1451293.
4.3.24. 1-(4-Chlorobenzyl)-2-(iodomethyl)-5,5-diphenylpiperidine
(5h). White solid, mp 108 ꢁCe110 ꢁC. 1H NMR (400 MHz, CDCl3)
d
7.37e6.91 (m, 15H), 3.89 (d, J¼12.9 Hz, 1H), 3.41e3.33 (m, 1H),
3.29e3.15 (m, 2H), 2.98 (d, J¼12.9 Hz, 1H), 2.45e2.28 (m, 2H),
2.25e2.14 (m, 1H), 2.06 (s, 1H), 1.71e1.50 (m, 2H). 13C NMR
4.3.20. 2-(Iodomethyl)-1-(2-methoxybenzyl)-5,5-diphenylpiperidine
(101 MHz, CDCl3) d 146.8, 145.0, 135.6, 132.0, 130.0, 127.4, 127.3,
(5d). White solid, mp 128 ꢁCe129 ꢁC. 1H NMR (400 MHz, CDCl3)
127.0, 126.7, 125.9, 124.9, 124.6, 58.9, 58.4, 57.0, 45.3, 32.2, 27.0, 10.6.
IR (KBr):3087, 3055, 3031, 2963, 2815, 2733, 2609, 1662, 1595, 1491,
d
7.47e6.74 (m, 15H), 3.74 (d, J¼14.0 Hz, 4H), 3.51 (d, J¼13.5 Hz, 1H),
3.42 (t, J¼12.9 Hz, 1H), 3.31 (t, J¼9.1 Hz, 1H), 3.23 (d, J¼12.4 Hz, 1H),
2.63 (d, J¼12.4 Hz, 1H), 2.43e2.25 (m, 2H), 2.14 (dd, J¼16.1, 6.2 Hz,
1447, 1359, 1323, 1197, 1096, 1023, 801, 744, 696, 580, 557 cmꢀ1
;
HRMSeESI (m/z): [MþH]þ calcd for C25H25ClIN:502.0798; found:
1H), 1.73e1.47 (m, 2H) 13C NMR (101 MHz, CDCl3)
d
158.0, 147.9,
502.0792.
146.9, 131.5, 128.4, 128.3, 127.9, 127.8, 127.4, 126.4, 125.7, 125.6,
120.3, 110.5, 59.7, 59.5, 55.4, 52.4, 46.4, 32.7, 27.5, 10.6. IR (KBr):
3559, 3320, 3246, 3150, 3052, 2914, 2829, 2741, 2382, 2281, 1954,
1887, 1827, 1751, 1637, 1603, 1490, 1450, 1376, 1279, 1153, 1124, 1045,
1002, 962, 913, 877, 754, 703 cmꢀ1HRMSeESI (m/z): [MþH]þ calcd
for C26H28INO: 498.1294; found:498.1292.
4.3.25. 1-(4-Bromobenzyl)-2-(iodomethyl)-5,5-diphenylpiperidine
(5i). Brownish oil. 1H NMR (400 MHz, CDCl3)
d 7.77e6.84 (m, 14H),
3.86 (d, J¼13.0 Hz, 1H), 3.42e3.33 (m, 1H), 3.27e3.19 (m, 2H), 2.95
(d, J¼13.0 Hz, 1H), 2.44e2.28 (m, 2H), 2.25e2.12 (m, 1H), 2.04 (d,
J¼7.5 Hz, 1H), 1.68e1.48 (m, 2H). 13C NMR (101 MHz, CDCl3)
d 147.8,
146.1, 137.3, 132.5, 131.4, 130.1, 128.5, 128.1, 127.8, 127.0, 125.7, 121.2,
60.1, 59.6, 58.1, 46.4, 38.3, 28.1, 11.6. IR (KBr): 3055, 3028, 2961,
2926, 2882, 1658, 1595, 1491, 1448, 1360, 1316, 1277, 1071, 1012, 919,
800, 758, 701, 639, 587, 478 cmꢀ1; HRMSeESI (m/z): [MþH]þ calcd
for C25H25BrIN:546.0293; found: 546.0275.
4.3.21. 2-(Iodomethyl)-1-(4-isopropylbenzyl)-5,5-diphenylpiperidine
(5e). White solid, mp 73 ꢁCe77 ꢁC. 1H NMR (400 MHz, CDCl3)
d 7.27
(d, J¼7.8 Hz, 2H), 7.20e7.08 (m, 9H), 7.07e6.98 (m, 4H), 3.90 (d,
J¼12.9 Hz, 1H), 3.44e3.37 (m, 1H), 3.35e3.23 (m, 2H), 3.10 (d,
J¼12.9 Hz, 1H), 2.91e2.81 (m, 1H), 2.48 (d, J¼12.4 Hz, 1H), 2.34 (d,
J¼13.3 Hz, 1H), 2.25e2.11 (m, 2H), 1.67e1.52 (m, 2H), 1.21 (d,
4.3.26. Methyl
methyl)benzoate (5j). Mp 153 ꢁCe155 ꢁC. 1H NMR (400 MHz,
CDCl3)
4-((2-(iodomethyl)-5,5-diphenylpiperidin-1-yl)
J¼6.9 Hz, 6H). 13C NMR (101 MHz, CDCl3)
d 147.9, 147.9, 146.5, 135.4,
129.6, 128.5, 128.0, 127.7, 127.2, 126.2, 125.8, 125.6, 59.7, 59.4, 58.5,
46.4, 33.8, 33.2, 27.9, 24.1, 24.1, 11.4. IR (KBr): 3053, 3027, 2960,
2926, 2872, 1660, 1598, 1495, 1448, 1362, 1276, 1057, 920, 812, 759,
d
7.95 (d, J¼7.9 Hz, 2H), 7.43 (d, J¼7.9 Hz, 2H), 7.19e6.88 (m,
10H), 3.96 (d, J¼13.1 Hz, 1H), 3.83 (s, 3H), 3.39e3.32 (m, 1H),
3.29e3.17 (m, 2H), 3.06 (d, J¼13.1 Hz, 1H), 2.41 (d, J¼12.3 Hz, 1H),
2.34 (d, J¼12.9 Hz, 1H), 2.25e2.13 (m, 1H), 2.08 (s, 1H), 1.69e1.49
701, 638, 588 cmꢀ1
;
HRMSeESI (m/z): [MþH]þ calcd for
C
28H32IN:510.1658; found: 510.1652.
(m, 2H). 13C NMR (101 MHz, CDCl3)
d 167.1, 147.8, 146.1, 143.8, 129.7,
129.6, 129.3, 128.5, 128.2, 127.8, 127.0, 126.0, 125.7, 60.3, 59.8, 58.6,
52.2, 46.4, 33.3, 28.1, 11.6. IR (KBr): 3084, 3062, 3022, 2946, 2884,
2861, 2810, 2783, 2737, 2702, 1953, 1716, 1607, 1494, 1438, 1310,
4.3.22. 2-(Iodomethyl)-1-(4-methylbenzyl)-5,5-diphenylpiperidine
(5f). White solid, mp 99 ꢁCe102 ꢁC. 1H NMR (400 MHz, CDCl3)
d
7.26 (t, J¼13.3 Hz, 2H), 7.20e7.07 (m, 8H), 7.07e6.98 (m, 4H), 3.91
1198, 1171, 1106, 1017, 958, 874, 796, 768, 699, 564, 496 cmꢀ1
;
(d, J¼12.8 Hz, 1H), 3.45e3.06 (m, 1H), 3.35e3.22 (m, 2H), 3.04 (d,
J¼12.8 Hz, 1H), 2.41 (t, J¼10.5 Hz, 1H), 2.37e2.26 (m, 4H), 2.26e2.16
(m, 1H), 2.12 (d, J¼5.0 Hz, 1H), 1.66e1.52 (m, 2H). 13C NMR
HRMSeESI (m/z): [MþH]þ calcd for C27H28INO2:526.1243;
found:526.1236.
(101 MHz, CDCl3)
d
148.0, 146.4, 136.9, 135.0, 129.6, 128.9, 128.6,
4.3.27. 4-((2-(Iodomethyl)-5,5-diphenylpiperidin-1-yl)methyl)ben-
128.0, 127.7, 127.1, 125.8, 125.5, 59.8, 59.4, 58.5, 46.4, 33.2, 28.0, 21.2,
11.6. IR (KBr): 3084, 3051, 3027, 2955, 2944, 2922, 2780, 2729, 2702,
1805, 1661, 1597, 1494, 1444, 1359, 1325, 1271, 1201, 1164, 1092,
1034, 955, 910, 886, 842, 793, 754, 700, 583, 543 cmꢀ1; HRMSeESI
(m/z): [MþH]þ calcd for C26H28IN:482.1345; found: 482.1339.
zonitrile (5k). White solid, mp 104 ꢁCe107 ꢁC. 1H NMR (400 MHz,
CDCl3)
d
7.54 (d, J¼8.2 Hz, 2H), 7.45 (d, J¼8.1 Hz, 2H), 7.17e6.90 (m,
10H), 3.94 (d, J¼13.4 Hz, 1H), 3.39e3.32 (m, 1H), 3.26e3.17 (m, 2H),
3.05 (d, J¼13.4 Hz, 1H), 2.45 (d, J¼12.2 Hz, 1H), 2.36 (d, J¼13.3 Hz,
1H), 2.29e2.13 (m, 1H), 2.07 (s, 1H), 1.72e1.45 (m, 2H). 13C NMR
(101 MHz, CDCl3)
d 147.7, 145.9, 144.2, 132.1, 130.3, 128.4, 128.2,
4.3.23. 1-(4-Fluorobenzyl)-2-(iodomethyl)-5,5-diphenylpiperidine
127.9, 126.9, 126.1, 125.8, 119.0, 111.2, 60.5, 59.6, 58.5, 46.4, 33.3,
28.2, 11.6. IR (KBr): 3085, 3053, 3020, 2946, 2903, 2873, 2851, 2806,
2228, 1607, 1496, 1446, 1368, 1340, 1296, 1268, 1177, 1129, 1093,
(5g). White solid, mp 110 ꢁCe112 ꢁC. 1H NMR (400 MHz, CDCl3)
d
7.34e7.27 (m, 2H), 7.17e6.86 (m, 12H), 3.87 (d, J¼12.8 Hz, 1H),

H. Sun et al. / Tetrahedron 72 (2016) 7170e7178
7177
1021, 811, 754, 637, 580 cmꢀ1; HRMSeESI (m/z): [MþH]þ calcd for
2H), 4.23e4.11 (m, 1H), 3.52 (d, J¼13.1 Hz, 1H), 3.32e3.19 (m, 1H),
2.94e2.87 (m, 1H), 2.47 (d, J¼13.2 Hz, 1H), 2.36 (s, 3H), 1.95e1.87
(m, 1H), 1.79e1.63 (m, 1H), 1.42e1.06 (m, 12H). 13C NMR (101 MHz,
C
26H25IN2:493.1141; found: 493.1129.
4.3.28. 2-(Iodomethyl)-1-(4-nitrobenzyl)-5,5-diphenylpiperidine
(5l). Mp 135 ꢁCe136 ꢁC. 1H NMR (400 MHz, CDCl3)
8.14 (d,
J¼8.6 Hz, 2H), 7.54 (d, J¼8.5 Hz, 2H), 7.27e6.88 (m, 10H), 4.02 (t,
J¼11.8 Hz, 1H), 3.43e3.36 (m, 1H), 3.33e3.19 (m, 2H), 3.13 (d,
J¼13.5 Hz, 1H), 2.50 (t, J¼14.3 Hz, 1H), 2.39 (d, J¼13.3 Hz, 1H),
2.26e2.17 (m, 1H), 2.10 (s, 1H), 1.81e1.54 (m, 2H). 13C NMR
CDCl3) d 142.2, 136.7, 128.7, 125.9, 52.9, 37.0, 31.4, 29.6, 25.4, 20.7,
d
20.5, 20.4, 20.2, 2.2. IR (KBr): 3029, 2926, 2854, 2668, 1916, 1728,
1598, 1494, 1452, 1341, 1263, 1887, 1160, 1092, 1032, 967, 939, 813,
668, 602, 547 cmꢀ1
.
HRMSeESI (m/z): [MþH]þ calcd for
C18H26INO2S:448.0807; found: 448.0806.
(101 MHz, CDCl3)
d
146.6, 146.3, 145.2, 144.7, 129.2, 127.2, 127.1,
4.3.34. 2-(Iodomethyl)-5,5-dimethyl-1-tosylpiperidine (5r). White
solid, mp 90 ꢁCe91 ꢁC. 1H NMR (400 MHz, CDCl3)
126.8, 125.8, 125.0, 124.7, 122.4, 59.6, 58.6, 57.1, 45.3, 32.2, 27.1, 10.3.
IR (KBr):3081, 3054, 3022, 2961, 2905, 2852, 2805, 1805, 1602, 1517,
1446, 1351, 1263, 1178, 1129, 1106, 1032, 1020, 857, 809, 753, 700,
d
7.63 (d, J¼8.3 Hz,
2H), 7.23 (d, J¼8.0 Hz, 2H), 4.23e4.15 (m, 1H), 3.27e3.13 (m, 2H),
2.94e2.86 (m, 1H), 2.58 (d, J¼13.0 Hz, 1H), 2.36 (s, 3H), 2.02e1.92
(m, 1H), 1.80e1.68 (m, 1H), 1.26e1.16 (m, 2H), 0.83 (s, 3H), 0.76 (s,
634, 581 cmꢀ1
;
HRMSeESI (m/z): [MþH]þ calcd for
C
25H25INO2:513.1039; found: 513.1031.
3H). 13C NMR (101 MHz, CDCl3)
d 142.3, 136.7, 128.7, 125.9, 52.4,
49.9, 30.1, 29.2, 27.8, 22.0, 21.6, 20.5, 1.9. IR (KBr): 3062, 2963, 2868,
1728, 1596, 1469, 1368, 1335, 1307, 1262, 1156, 1106, 1089, 1054, 974,
908, 803, 664, 600, 546 cmꢀ1. HRMSeESI (m/z): [MþH]þ calcd for
4.3.29. 2-(Iodomethyl)-1-isopropyl-5,5-diphenylpiperidine
(5m). White solid, mp 82 ꢁCe83 ꢁC. 1H NMR (400 MHz, CDCl3)
d
7.43e7.00 (m, 10H), 3.43e3.37 (m, 1H), 3.33e3.27 (m, 1H),
C15H22INO2S:408.0494; found: 408.0492.
3.20e3.08 (m, 2H), 2.49 (d, J¼12.2 Hz, 1H), 2.34e2.24 (m, 1H),
2.24e2.13 (m, 1H), 2.13e2.05 (m, 1H), 1.60e1.38 (m, 2H), 1.25 (d,
J¼6.7 Hz, 3H), 0.83 (d, J¼6.6 Hz, 3H). 13C NMR (101 MHz, CDCl3)
4.3.35. 2-(Iodomethyl)-1-tosylpiperidine (5s). Yellowish oil. 1H
NMR (400 MHz, CDCl3)
2H), 4.20 (dd, J¼10.5, 5.2 Hz, 1H), 3.68e3.60 (m, 1H), 3.32e3.25 (m,
1H), 3.15 (dd, J¼9.9, 5.1 Hz, 1H), 2.92e2.82 (m, 1H), 2.36 (s, 3H),
2.05e1.97 (m, 1H), 1.50e1.29 (m, 4H), 1.28e1.11 (m, 1H). 13C NMR
d
7.65 (d, J¼8.2 Hz, 2H), 7.23 (d, J¼8.1 Hz,
d
147.9, 145.9, 128.1, 127.0, 126.6, 126.1, 124.9, 124.4, 54.9, 51.6, 47.0,
45.0, 33.0, 27.6, 19.9, 12.6, 11.9. IR (KBr): 3083, 3060, 3023, 2965,
2859, 2010, 1737, 1653, 1598, 1493, 1446, 1360, 1316, 1264, 1194,
1168, 1093, 1017, 802, 758, 702, 630, 559 cmꢀ1; HRMSeESI (m/z):
[MþH]þ calcd for C21H26IN: 420.1188; found: 420.1180.
(101 MHz, CDCl3)
d 143.3, 137.9, 129.8, 127.0, 53.9, 40.6, 26.2, 24.3,
21.6, 17.7, 4.1. IR (KBr):3030, 2941, 2863, 1919, 1726, 1597, 1494, 1447,
1337, 1160, 1091, 1047, 989, 929, 882, 815, 726, 664, 588, 548 cmꢀ1
.
4.3.30. 2-Benzyl-3-(iodomethyl)-2-azaspiro[5.5]undecane
HRMSeESI (m/z): [MþH]þ calcd for C13H18INO2S: 380.0181; found:
(5n). Brownish oil. 1H NMR (400 MHz, CDCl3)
d
7.33 (d, J¼7.4 Hz,
380.0169.
2H), 7.23 (t, J¼7.4 Hz, 2H), 7.16 (t, J¼5.2 Hz, 1H), 3.96 (d, J¼13.1 Hz,
1H), 3.48e3.42 (m, 1H), 3.33 (d, J¼10.5 Hz, 1H), 2.97 (d, J¼13.1 Hz,
1H), 2.53 (d, J¼11.5 Hz, 1H), 1.92e1.78 (m, 2H), 1.73 (d, J¼11.5 Hz,
Acknowledgements
1H), 1.64e1.07 (m, 13H). 13C NMR (101 MHz, CDCl3)
d 138.5, 127.7,
We acknowledge the financial support from National Natural
127.1, 125.7, 59.0, 56.7, 36.3, 32.6, 32.3, 32.0, 26.8, 25.8, 20.6, 12.5. IR
(KBr): 3640, 3059, 3026, 2922, 2852, 2786, 2734, 2610, 1734, 1668,
1602, 1494, 1450, 1359, 1322, 1261, 1196, 1180, 1106, 1072, 1027, 979,
801, 739, 699, 651, 480 cmꢀ1; HRMSeESI (m/z): [MþH]þ calcd for
Science Foundation of China (NSFC 21272121).
Supplementary data
C
18H26IN:384.1188; found: 384.1181.
Supplementary data (Copies of NMR spectra of the products and
X-ray diffraction data of compounds 2c and 5g.) associated with
this article can be found in the online version, at http://dx.doi.org/
10.1016/j.tet.2016.09.038.
4.3.31. 1-Benzyl-2-(iodomethyl)-5,5-dimethylpiperidine
(5o). Brownish oil. 1H NMR (400 MHz, CDCl3)
7.37e7.03 (m, 5H),
d
3.89 (d, J¼13.2 Hz, 1H), 3.48e3.41 (m, 1H), 3.27 (d, J¼10.5 Hz, 1H),
2.94 (d, J¼13.2 Hz, 1H), 2.31e2.20 (m, 1H), 1.90e1.74 (m, 2H), 1.71
(d, J¼11.3 Hz, 1H), 1.50e1.43 (m, 1H), 1.38e1.28 (m, 1H), 1.26e1.13
References and notes
(m, 1H), 0.88 (s, 3H), 0.72 (s, 3H). 13C NMR (101 MHz, CDCl3)
d 138.3,
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hedron 1993, 49, 8645; (b) Kim, W. G.; Kim, J. P.; Kim, C. J.; Lee, K. H.; Yoo, I. D. J.
Antibiot. 1996, 49, 20; (c) Rahbæk, L.; Christophersen, C. J. Nat. Prod. 1997, 60,
175.
2. (a) Friedman, O. M.; Seligman, A. M. J. Am. Chem. Soc. 1954, 76, 658; (b) Bratzel,
R. P.; Ross, R. B.; Goodridge, T. H.; Huntress, W. T.; Flather, M. T.; Johnson, D. E.
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Pors, K.; Shnyder, S. D.; Teesdale-Spittle, P. H.; Hartley, J. A.; Zloh, M.; Searcey,
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127.6, 127.1, 125.7, 61.3, 58.4, 56.7, 34.9, 29.7, 27.5, 27.4, 24.2, 12.2. IR
(KBr): 3301, 3028, 2957, 2870, 2745, 1664, 1605, 1495, 1454, 1402,
1367, 1313, 1263, 1237, 1082, 1031, 915, 804, 751, 701, 651, 600,
534 cmꢀ1; HRMSeESI (m/z): [MþH]þ calcd for C15H22IN:344.0875;
found: 344.0873.
4.3.32. 2-(Iodomethyl)-5,5-diphenyl-1-tosylpiperidine (5p). White
3. (a) Couty, F.; Kletskii, M. J. Mol. Struct.: THEOCHEM 2009, 908, 26; (b) Hayashi,
K.; Kujime, E.; Katayama, H.; Sano, S.; Shiro, M.; Nagao, Y. Chem. Pharm. Bull.
2009, 57, 1142.
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Speybroeck, V.; D’Hooghe, M.; De Kimpe, N.; Ha, H.-J. Chem.dAsian. J. 2014, 9,
1060.
5. (a) De Kimpe, N.; Boelens, M.; Piqueur, J.; Baele, J. Tetrahedron Lett. 1994, 35,
1925; (b) De Smaele, D.; De Kimpe, N. J. Chem. Soc., Chem. Commun. 1995, 2029.
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Back, T. G.; Nakajima, K. J. Org. Chem. 2000, 65, 4543; (d) Hsu, S.-F.; Ko, C.-W.;
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Pulte, A.; Wu, Y.-T. J. Org. Chem. 2012, 77, 9979.
7. (a) Lunsford, C. D.; Cale, A. D., Jr.; Ward, J. W.; Franko, B. V.; Jenkins, H. J. Med.
Chem. 1964, 7, 302; (b) Sturm, P. A.; Cory, M.; Henry, D. W.; McCall, J. W.; Ziegler,
J. B. J. Med. Chem. 1977, 20, 1333; (c) Russell, R. W.; Crocker, A. D.; Booth, R. A.;
Jenden, D. J. Psychopharmacology 1986, 88, 24; (d) Cale, A. D., Jr.; Gero, T. W.;
Walker, K. R.; Lo, Y. S.; Welstead, W. J., Jr.; Jaques, L. W.; Johnson, A. F.; Leonard,
solid, mp 61 ꢁCe62 ꢁC. 1H NMR (400 MHz, CDCl3)
d
7.57 (d, J¼8.3 Hz,
2H), 7.35 (d, J¼7.6 Hz, 2H), 7.30e7.21 (m, 6H), 7.21e7.12 (m, 4H),
4.58 (dd, J¼13.3, 1.9 Hz, 1H), 4.13e4.03 (m, 1H), 3.37 (dd, J¼11.8,
10.0 Hz, 1H), 3.21e3.10 (m, 1H), 2.51e2.36 (m, 4H), 2.29e2.13 (m,
2H), 1.76e1.62 (m, 1H). 13C NMR (101 MHz, CDCl3)
d 146.9, 143.8,
143.3,136.6,129.9,128.6,128.5,127.8,127.5,126.7,126.4,126.2, 53.8,
48.1, 45.7, 28.3, 23.0, 21.6, 2.4. IR (KBr):3057, 3028, 2960, 2869,1725,
1597, 1495, 1446, 1339, 1261, 1185, 1156, 1090, 1030, 947, 878, 803,
754, 701, 669, 580, 546 cmꢀ1. HRMSeESI (m/z): [MþH]þ calcd for
C
25H26INO2S:532.0807; found: 532.0803.
4.3.33. 3-(Iodomethyl)-2-tosyl-2-azaspiro[5.5]undecane
NMR (400 MHz, CDCl3)
7.63 (d, J¼8.3 Hz, 2H), 7.23 (d, J¼8.1 Hz,
(5q). 1H
d

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H. Sun et al. / Tetrahedron 72 (2016) 7170e7178
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Craig, D. C.; Edwards, G. L.; Muldoon, C. A. Synlett 1997, 1441; (c) Kitagawa, O.;
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