P-stereogenic PNP pincer-Pd catalyzed intramolecular hydroamination of amino-1,3-dienes

Article abstract of DOI:10.1039/c4ob02402h

A new P-stereogenic PNP pincer-Pd complex was readily prepared from optically pure 2,6-bis[(boranato(tert-butyl)methylphosphino)methyl]pyridine. It was used in the asymmetric intramolecular hydroamination of amino-1,3-dienes, with the desired products bei

Full text of DOI:10.1039/c4ob02402h

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DOI: 10.1039/C4OB02402H
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ARTICLE TYPE
P-Stereogenic PNP Pincer-Pd Catalyzed Intramolecular
Hydroamination of Amino-1,3-dienes
Zehua Yanga, Chao Xiaa, Delong Liua, Yangang Liua, Masashi Sugiyab, Tsuneo Imamotob,c,* and Wanbin Zhanga,d,*
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
DOI:
A
new Pꢀstereogenic PNP pincerꢀPd complex was readily prepared from optically pure
2,6ꢀbis[(boranato(tertꢀbutyl)methylphosphino)methyl]pyridine. It was used in the asymmetric
intramolecular hydroamination of aminoꢀ1,3ꢀdienes, with the desired products being obtained in good
yields and with excellent regioselectivities and up to moderate enantioselectivities. The absolute
configuration of one of the hydroamination products was determined by Xꢀray crystallography studies.
This simple and efficient procedure can be used for the synthesis of allylꢀtype chiral pyrrolidine
derivatives.
.
the structure of the corresponding 1,3ꢀdienes. Yamamoto
developed an achiral carbaboranylꢀHg catalyzed
Introduction
Chiral pyrrolidine derivatives are valuable and commercially
important chemicals that are prevalent in many biologically
active natural products and pharmaceutical drug candidates.1
The construction of such scaffolds has attracted a great deal of
attention.2 Significant progress has been made in pursuit of this
goal using the direct intramolecular hydroamination of an
amine to an unsaturated C=C bond. This tactic represents the
shortest and most efficient synthetic pathway.2c,2h,2j Among
cycloisomerization of 1,3ꢀdienes, exclusively giving racemic
allylicꢀtype azacycles and cycloalkanes from a range of
sulfonamidodiene substrates.5 Toste reported an asymmetric
catalytic hydroamination using a chiral catalytic system of
Au(I)/menthol. High enantioselectivity as well as good
reactivity was observed with this particular catalytic system,
while a regioisomeric mixture of both propenylꢀtype and
allylicꢀtype products was obtained in most cases.6 As can be
seen, allylicꢀtype compounds can be exclusively obtained in the
hydroamination reactions, however, to the best of our
knowledge, there are no reports relating to asymmetric catalytic
reactions which give allylic type heterocycles as the sole
products.
these strategies, the hydroamination of 1,3ꢀdienes is
a
promising yet challenging option ꢀ the resulting products
possess a preserved C=C bond for further functionalization.
However, it is difficult to control the preferential formation of
one of the two possible regioisomeric products, i.e. the
formation of propenylꢀtype and allylꢀtype isomers (Scheme 1).
Pincerꢀtype metal complexes are structurally stable, possess
a rigid skeleton, and can be used in many transformations.7,8
We have developed a pincerꢀPd complex which can be utilized
in the chemoselective transfer hydrogenation of α,βꢀunsaturated
ketones with high reactivity and selectivity, providing an
attractive methodology for the preparation of saturated ketones
from αꢀenones.9 Following on from the success of the work,
novel Pꢀstereogenic PCP pincerꢀPd complexes were designed
and applied to the asymmetric addition of diarylphosphines to
Scheme 1. Two possible regioisomeric products
The majority of reported diene hydroamination reactions
focus on the formation of propenylꢀtype pyrrolidine
derivatives.3 In contrast, the formation of allylicꢀtype
compounds in such reactions has seldom been explored. Marks
described an organolanthanide catalyzed regioselective
intramolecular hydroamination/cyclization of conjugated
aminodienes to afford both propenylꢀtype and allylicꢀtype
products.4 The regioselectivity of the reaction relies strongly on
nitroalkenes
with
excellent
yields
and
good
enantioselectivities.10 Recently, Michael and coworkers applied
an achiral PNP type pincerꢀPd catalyst to synthesize
allylicꢀtype nitrogen heterocyclic compounds via the
intramolecular hydroamination of aminodienes in high yields.11
We would therefore like to utilize our Pꢀstereogenic
pincerꢀtype catalyst in such reactions for the construction of
a School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan
Road, Shanghai 200240, P. R. China
chiral nitrogen heterocycles. Herein we report
a new
b Organic R&D Department, Nippon Chemical Industrial Co., Ltd.,
Kameido, Kotoꢀku, Tokyo 136ꢀ85 15, Japan
Pꢀstereogenic PNPꢀtype pincerꢀPd complex catalyzed
intramolecular
exclusively
hydroamination
generating enantioenriched
of
aminoꢀ1,3ꢀdienes,
allylicꢀtype
c Department of Chemistry, Graduate School of Science, Chiba
University, Yayoiꢀcho, Inageꢀku, Chiba 263ꢀ8522, Japan
d School of Chemistry and Chemical Engineering, Shanghai Jiao Tong
University, 800 Dongchuan Road, Shanghai 200240, P. R. China
Fax: +86ꢀ21ꢀ5474ꢀ3265; Tel: +86ꢀ21ꢀ5474ꢀ3265; Eꢀmail:
wanbin@sjtu.edu.cn; imamoto@faculty.chibaꢀu.jp
pyrrolidines.
Results and Discussion
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DOI: 10.1039/C4OB02402H
ClCH2CH2Cl
PhCH3
5
6
AgBF4
AgBF4
AgBF4
AgBF4
AgBF4
25
25
25
25
25
> 99 : 1
> 99 : 1
> 99 : 1
> 99 : 1
ꢀ
99
10
6
ꢀ15
ꢀ10
ꢀ10
ꢀ
Synthesis of P-stereogenic PNP type pincer-Pd
complex
Based on the synthesis of the Pꢀstereogenic PCP pincer Pd
complex,10 we adopted the Livinghouse’s deprotection
method12 to prepare the Pꢀstereogenic PNP type pincerꢀPd
complex over two highꢀyielding steps (Scheme 2). Thus, the
boranato groups were removed via the reaction of
(R,R)ꢀ2,6ꢀbis[(boranato(tertꢀbutyl)methylphosphino)methyl]pyr
idine (1)13 with tetrafluoroboric acid diethyl ether in degassed
dry dichloromethane, followed by treatment with degassed
10% Na2CO3 solution to produce the resulting bisphosphine
pyridine 2. The ligand 2 was then reacted directly with
(Me2S)2PdCl2 in degassed dry dichloromethane to form the
Pꢀstereogenic pincerꢀPd complex 3 as an orange solid. The total
yield for the above two steps from 1 to 3 was 90%. The
resulting solid product is stable to air and moisture and requires
no special storage precautions.
7
EtOAc
10
8
acetone
EtOH
21
9
trace
99
10
11
12
13
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
AgBF4 reflux > 99 : 1
5
AgBF4
AgBF4
AgBF4
15
0
> 99 : 1
> 99 : 1
> 99 : 1
98
10
9
95
–20
79
9
a
Reactions of 4a (0.1 mmol) were carried out using 3 (5 mol%) as a
chiral catalyst in the presence of different additives (0.01 mmol) in a
b
1
c
suitable solvent (3 mL) for 24 h. Determined by H NMR spectra.
d
Isolated yield. Determined by chiral HPLC using Daicel ChiralPak
ICꢀ3 column. Cbz = benzyloxycarbonyl.
We next investigated the influence of solvent on the reaction.
All the reactions showed excellent regioselectivities with
allylicꢀtype pyrrolidines being obtained as the sole products.
The desired product was obtained in quantitative yield when
the reaction was carried out in 1,2ꢀdichloroethane but with very
low enantioselectivity (entry 5). Other solvents, such as toluene,
ethyl acetate and acetone, provided low reaction activities and
low enantioselectivities albeit with excellent regioselectivities
(entries 5ꢀ8). The protic solvent ethanol provided only trace
amount of product (entry 9).
Scheme 2. The synthetic route of pincerꢀPd complex
Temperature had an apparent effect on the reaction activities
and enantioselectivities. Reaction under reflux conditions gave
the product with quantitative yield with lower ee (entry 10).
Reducing the temperature resulted in both lower yields and ees
(entries 11ꢀ13).
The structure of the pincerꢀPd complex 3 was confirmed by
singleꢀcrystal Xꢀray diffraction (Scheme 2).14 The crystal
structure indicates that there is a rigid and C2ꢀsymmetric stereo
environment around the Pd atom. The large difference between
the small methyl group and the bulky tertꢀbutyl group is
expected to provide efficient stereocontrol for asymmetric
catalysis.
Subsequently, different amine protecting groups were
screened with the aim of improving the enantioselectivities of
the pyrrolidine products (Table 2). Acyl amines were first
examined using 3 as a chiral catalyst in the presence of AgBF4
in dichloromethane at 25 ℃ for 24 h (entries 1ꢀ4). Substrates
bearing carbamate protecting groups, such as Cbz (4a), Boc
(4b) and Fmoc (4c), were successfully converted to their
corresponding hydroamination products in quantitative yields
and with excellent regioselectivities but with no more than 20%
ee (entries 1ꢀ3). Hydroamination of substrate 4d possessing an
acetyl protecting group gave the target product with somewhat
higher enantioselectivity but lower yield (entry 4). Under the
Intramolecular Hydroamination of Amino-1,3-dienes
With complex 3 in hand, intramolecular hydroamination of
Cbzꢀprotected aminodiene 4a was carried out in the presence of
o
additives at 25 C for 24 h (Table 1). When the reaction was
carried out in the presence of AgBF4 in dichloromethane, an
allylicꢀtype pyrrolidine derivative was obtained exclusively in
quantitative yield but with a low enantioselectivity (entry 1). A
low ee value was also observed when AgBF4 was replaced with
same
reaction
conditions,
hydroamination
of
sulfonamideꢀprotected amine 4e gave the desired product with
a relatively high yield and enantiomeric excess, thus providing
us with an opportunity to find a more suitable protecting group
for the substrates (entry 5).
AgSbF6 (entry 2). With AgOTf as an additive, however, both
low yield and enantioselectivity were obtained (entry 3). No
reaction occurred when NaBArF was used as an additive even
after 24 h (entry 4).
Table 2 Screening of the protecting groupa
Table 1 Screening of additive and solventa
Yield (%)b
ee (%)c
14 (ꢀ)
10 (ꢀ)
9 (ꢀ)
Entry Solvent
Additive T (oC) 5a / 6ab Yield (%)c ee (%)d
Entry
PG
5
1
2
3
4
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
AgBF4
AgSbF6
AgOTf
NaBArF
25
25
25
25
> 99 : 1
> 99 : 1
> 99 : 1
ꢀ
99
99
44
nd
14
10
7
1
2
3
4
Cbz (4a)
Boc (4b)
Fmoc (4c)
Ac (4d)
5a
5b
5c
5d
99
99
99
76
ꢀ
22 (ꢀ)
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DOI: 10.1039/C4OB02402H
5
6
PhSO2 (4e)
Ns (4f)
5e
5f
95
55
60
70
72
56
48
20
20
18 (ꢀ)
5 (ꢀ)
7
oꢀMeC6H4SO2 (4g)
mꢀMeC6H4SO2 (4h)
pꢀMeC6H4SO2 (4i)
2,4ꢀMe2C6H4SO2 (4j)
2,5ꢀMe2C6H4SO2 (4k)
2,4,6ꢀMe3C6H4SO2 (4l)
Nps (4m)
5g
5h
5i
29 (ꢀ)
21 (ꢀ)
18 (ꢀ)
33 (ꢀ)
29 (ꢀ)
29 (ꢀ)
25 (ꢀ)
8
9
Yield
(%)b
ee
Entry
1d
R1
H
Product
(%)c
10
11
12
13
5j
5k
5l
30e
23 (ꢀ)
33 (ꢀ)
5n
5m
a
2d
Me
Ph
56
Reactions of 4 (0.1 mmol) were carried out using 3 (5 mol%) as a
chiral catalyst in the presence of AgBF4 (0.01 mmol) in CH2Cl2 (3 mL)
at 25 ℃ for 24 h and all reactions afforded more than 99 : 1
regioselectivities. b Isolated yield. c Determined by chiral HPLC. Boc =
tertꢀbutoxycarbonyl, Ac = acetyl, Fmoc = 9ꢀfluorenylmethoxycarbonyl,
Ns = 4ꢀnitrobenzenesulfonyl, Nps = 1ꢀNaphthalenesulfonyl.
5j
3d
96
97f
99g
62
92
43 (+)
45 (+)
47 (+)
32 (+)
3 (ꢀ)
5o
5o
We subsequently investigated the effect of different
benzenesulfonyl protecting groups on the reaction.
4d
5d
6h
7i
Ph
Ph
Ph
Ph
Hydroamination
of
substrate
4f
possessing
an
electronꢀwithdrawing group led to the desired product with
decreased yield and enantioselectivity (entry 6). Therefore
benzenesulfonyl
protecting
groups
possessing
electronꢀdonating groups were examined. For the
monomethylꢀbenzenesulfonyl aminediene, the oꢀsubstituted
substrates provided the most promising results (entries 7ꢀ9).
Further increase of the steric hindrance of the aromatic ring
5o
5p
improved
the
enantioselectivity
with
2,4ꢀdimethylbenzenesulfonyl protected substrates giving better
enantiomeric excess. (entries 10ꢀ11). However, when
2,4,6ꢀtrimethyl substituted benzenesulfonyl aminodiene was
used, the yield and enantiomeric excess decreased (entry 12). A
naphthylsulfonyl group also used as a protecting group, but the
yield and enantiomeric excess remained low (entry 13).
Therefore, we chose 2,4ꢀdimethylbenzenesulfonyl as the
protecting group for use in following reactions due to its
relatively high enantioselectivity and yield (entry 10).
5q
8d
ꢀ(CH2)3ꢀ
ꢀ(CH2)4ꢀ
52
73
33 (ꢀ)
32 (ꢀ)
Substrates with a different substituted R1 group were
examined using the above optimal reaction conditions (Table 3).
Substrates lacking an R1 group (R1=H) provided the desired
products in low yield and enantiomeric excess (entry 1).
Increasing the steric hindrance improved the reaction activity
and enantioselectivity, and up to 96% yield and 43% ee were
obtained when a phenyl group (4o) was used (entries 2, 3). We
then increased the catalyst loading from 5% to 10 and 20 mol%,
nevertheless up to 47% ee can be obtained (entries 4, 5). Based
on this result, we attempted to construct a similar allylicꢀtype
piperidine derivative and the desired product was obtained in
moderate yield but lower enantioselectivity than the
corresponding pyrrolidine product (entry 6). Products
possessing a quaternary carbon center at the 2ꢀposition of the
pyrrolidine could also be obtained with excellent
regioselectivity but poor enantioselectivity (entry 7). Substrates
with cyclic R1 groups were also utilized providing the
corresponding chiral spiro compounds with promising catalytic
results (entries 8ꢀ11). 2ꢀSubstituted chiral isoindoline could
also be prepared using this Pꢀstereogenic PNP pincerꢀPd
catalyzed intramolecular hydroamination but with a low ee
value (entry 12).
5r
5s
9d
10d
11d
ꢀ(CH2)5ꢀ
ꢀ(CH2)6ꢀ
96
92
35 (ꢀ)
36 (ꢀ)
5t
5u
12d
ꢀC4H4ꢀ
74
9 (+)
5v
a
Reactions of 4 (0.1 mmol) were carried out using 3 (5 mol%) as a
chiral catalyst in the presence of AgBF4 (0.01 mmol) in CH2Cl2 (3
mL) at 25 ℃ for 24 h and all reactions afforded more than 99 : 1
regioselectivities. b Isolated yield. Determined by chiral HPLC. R2
c
d
= H, n = 1. e Stirred for 96 h. f 10 mol% catalyst was used. g 20 mol%
catalyst was used. R2 = H, n = 2. R2 = Me, n = 1. PG =
h
i
Table 3 Substrate scope of the hydroaminationa
2,4ꢀdimethylbenzenesulfonyl.
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To determine the absolute configuration of the
Scheme 3 Proposed reaction pathway
hydroamination reaction products, an Xꢀray crystallography
study was performed. Recrystallization of 5o from a mixed
solvent system of dichloromethane and nꢀhexane provided a
crystal suitable for single crystal Xꢀray diffraction. Diffraction
data and HPLC analysis showed that the major enantiomer of
the catalytic reaction appears to be the product with the
(S)ꢀabsolute configuration (Figure 1).15
Conclusions
We have prepared a novel Pꢀstereogenic PNP pincerꢀPd
complex from optically pure
2,6ꢀbis[(boranato(tertꢀbutyl)methylphosphino)methyl]pyridine
and used it in the asymmetric intramolecular hydroamination of
aminoꢀ1,3ꢀdienes. The desired products were obtained in high
yields (up to quantitative yield) and with excellent
regioselectivities (> 99
:
1) and up to moderate
enantioselectivities (up to 47% ee). The absolute configuration
of an enantioenriched product was determined by Xꢀray
crystallography studies. A proposed mechanism has been
suggested to explain the excellent regioselectivity of the
intramolecular
hydroamination.
The
observed
enantioselectivities are only moderate, but the results
apparently indicate that the distinct enantioselection occurs at
the reaction site separated by four bonds from the catalyst
metal center.
4. Experimental
General Details
Figure 1. ORTEP diagram for complex 5o (Thermal ellipsoids
are at the 30% probability level)
All air and moisture sensitive manipulations were carried out
with standard Schlenk techniques or in a glove box under
nitrogen atmosphere. Column chromatography was performed
using 200ꢀ300 mesh silica gels. All solvents were refined by
the standard method of solvent manual. The other reagents
were purchased from AdamasꢀBeta Ltd., Energy Chemical Inc.
or J&K Scientific Inc. and used without further purification
unless otherwise specified. The NMR spectra were recorded on
A mechanism has been proposed to explain the excellent
regioselectivity for the intramolecular hydroamination of
aminoꢀ1,3ꢀdienes (Scheme 3). Initially, the chiral pincerꢀtype
catalyst 3 reacts with AgBF4 to give an activated catalytic
molecule A. This cationic palladium species interacts with the
terminal double bond of the aminoꢀ1,3ꢀdiene in close proximity
the methyl group located on the phosphorus atom due to the
strong steric hindrance of the tertꢀbutyl group, affording the
square planar πꢀcomplex B. The intermediate B undergoes an
intramolecular CꢀN bond formation to produce the
η1ꢀallyl–palladium complex C, which is consistent with
Michael’s discovery of the isolated η1ꢀallyl–palladium
intermediate.11 Subsequent protonation and cleavage of the
PdꢀC bond produces the allylicꢀtype Sꢀconfiguration product,
regenerating the catalyst A. In the absence of a bulky
substituent, such as a tertꢀbutyl group, the internal double bond
of the aminoꢀ1,3ꢀdiene can also coordinate to the Pd atom of A,
eventually leading to the undesired propenylꢀtype product.5
Because of the remote distance (four bonds) between the
palladium atom and the reaction site in B, the moderate 43% ee
obtained for the allylicꢀtype pyrrolidine derivative presents a
very promising result.
1
a Varian MERCURY plusꢀ400 (400 MHz, H; 101 MHz, 13C;
162 MHz, 31P) spectrometer with chemical shifts reported in
ppm relative to the residual deuterated solvents, the internal
standard tetramethylsilane or 85% phosphoric acid. Mass
spectrometry analysis was carried out using an electrospray
spectrometer Waters Micromass QꢀTOF Premier Mass
Spectrometer. Melting points were measured with SGW Xꢀ4
micro melting point apparatus. IR spectra were recorded on a
Thermo Scientific Nicolet IS10 infrared spectrometer. Optical
rotations were measured on a Rudolph Research Analytical
Autopol VI automatic polarimeter using a 50 mm pathꢀlength
cell at 589 nm. Enantiomeric excess analyses were performed
on a Shimadzu LCꢀ10Avp HPLC system and using Daicel
Chiralcel ICꢀ3, IE, ODꢀH, OJꢀH, and OZꢀH columns with
nꢀhexane/iꢀpropyl alcohol as a eluent. The Xꢀray diffraction
data were collected on an Oxford Diffraction Gemini A Ultra
diffractometer with graphite monochromator.
Preparation of Catalyst
(R,R)-2,6-Bis[(tert-butylmethylphosphino)methyl]pyridine
(2). A twoꢀnecked flask (20 mL) equipped with a magnetic
stirring bar and
a nitrogen balloon was charged with
(R,R)ꢀ2,6ꢀbis[(boranato(tertꢀbutyl)methylphosphino)methyl]pyr
idine (1) (170 mg, 0.5 mmol) and degassed dry
dichloromethane (3 mL). The flask was immersed in an
iceꢀwater bath, and tetrafluoroboric acid diethyl ether adduct
(HBF4•OEt2, 0.95 mL, 7.0 mmol) was slowly added over 10
min. The iceꢀwater bath was removed and the mixture stirred at
ambient temperature for 2 h, whereupon hydrogen gas was
evolved and a white crystalline solids appeared. The flask was
again immersed in an iceꢀwater bath, and degassed nꢀhexane (5
mL) was added. To this mixture was slowly added a degassed
10% Na2CO3 solution (5 mL), and then the mixture was stirred
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DOI: 10.1039/C4OB02402H
(101 MHz, CDCl3): δ 155.2, 134.8, 117.5, 60.1, 59.2, 56.6,
45.8, 45.0, 39.7, 38.6, 28.8, 26.6, 26.3; HRMS (ESI): calcd. for
C14H26NO2 [M+H]+ 240.1964, found 240.1980; IR (KBr disc)
ν/cmꢀ1: 3361, 2964, 1705, 1511, 1366, 1248, 1171, 1004, 897,
779; HPLC Daicel ChiralPak OJꢀH, nꢀhexane, 210 nm, 1
mL/min, tR1 = 4.4 min (minor), tR2 = 5.1 min (major), ee = 10%;
[α]2D5 = –5.1 (c 0.3, CHCl3).
at 40 ℃ for 30 min. The aqueous layer was removed by using
a syringe, and the nꢀhexane layer was dried over anhydrous
MgSO4 under nitrogen. The nꢀhexane solution was transferred
to another flask filled with nitrogen, and the solvent was
removed under reduced pressure to give 2 as a colourless oil,
which was used in the next step without further purification.
(S,S)-2,6-Bis[(tert-butylmethylphosphino)methyl]pyridine-
palladium(II) dichloride (3). A dichloromethane solution (5
mL) of compound 2 (the entire product obtained by the
procedure described above, ca. 0.5 mmol) was added to a
dichloromethane solution (5 mL) of (Me2S)2PdCl2 (150.8 mg,
0.5 mmol), and the mixture was stirred for 1 h. The solvent was
removed and the residue was washed with ethyl acetate (3 × 5
mL) and dried under vacuum to give complex 3 as a yellow
solid (220 mg, 90% from compound 1). Crystals suitable for
Xꢀray analysis were obtained by diffusion of a concentrated
dichloromethane solution of 3 with ethyl ether. m.p. 247.0 –
(–)-(9H-Fluoren-9-yl)methyl
2-allyl-4,4-dimethylpyrrolidine-1-carboxylate
(5c).
1
Chartreuse oil (35.8 mg, 99%). H NMR (400 MHz, CDCl3,
observed as a mixture of rotamers): δ 7.76 (d, J = 7.4 Hz, 4H,
both), 7.60 (d, J = 7.1 Hz, 4H, both), 7.39 (t, J = 6.9 Hz, 4H,
both), 7.31 (t, J = 7.4 Hz, 4H, both), 5.77 – 5.67 (m, 1H, major),
5.55 – 5.44 (m, 1H, minor), 5.16 – 4.84 (m, 3H, both), 4.69 –
4.50 (m, 1H, major), 4.51 – 4.34 (m, 2H, minor), 4.27 – 4.25 (d,
J = 5.6 Hz, 1H, minor), 3.94 (brs, 1H, major), 3.60 (brs, 1H,
minor), 3.42 (d, J = 10.6 Hz, 1H, minor), 3.34 (d, J = 10.4 Hz,
1H, minor), 2.99 (d, J = 10.4 Hz, 1H, major), 2.90 (d, J = 10.9
Hz, 1H, minor), 2.72 (brs, 1H, major), 2.39 – 2.16 (m, 2H,
both), 2.07 – 1.87 (m, 1H, minor), 1.86 – 1.65 (m, 2H, both),
1.53 – 1.35 (m, 2H, both), 1.08 (d, J = 20.6 Hz, 6H, both), 0.93
(d, J = 29.3 Hz, 6H, both); 13C NMR (101 MHz, CDCl3): δ
155.4, 155.0, 144.2, 144.1, 141.4, 141.3, 134.3, 127.6, 127.0,
125.1, 125.0, 124.7, 124.6, 119.9, 117.5, 117.3, 66.6, 66.3, 59.4,
56.9, 56.2, 47.6, 47.4, 45.5, 44.6, 39.0, 38.1, 37.4, 36.9, 26.5,
26.3, 26.0, 25.9; HRMS (ESI): calcd. for C24H28NO2 [M+H]+
362.2120, found 362.2122; IR (KBr disc) ν/cmꢀ1: 3064, 2952,
2784, 1698, 1449, 780, 758, 733; HPLC Daicel ChiralPak
OJꢀH, nꢀhexane/iꢀPrOH = 90/10, 230 nm, 1 mL/min, tR1 = 9.4
min (major), tR2 = 10.1 min (minor), ee = 9%; [α]2D5 = –5.0 (c
0.4, CHCl3).
1
248.3 ℃; H NMR (400 MHz, CDCl3): δ 7.97 (brs, 3H), 4.28
(dt, J = 18.3, 4.1 Hz, 2H), 4.07 (dt, J = 18.3, 4.6 Hz, 2H), 1.74
(vt, J = 3.1 Hz, 6H), 1.26 (vt, J = 8.3 Hz, 18H); 13C NMR (101
MHz, CDCl3): δ 163.7 (vt, J = 4.0 Hz), 141.6 (s), 123.9 (vt, J =
5.7 Hz), 39.6 (vt, J = 10.7 Hz), 32.6 (vt, J = 13.1 Hz), 26.4 (s),
6.1 (vt, J = 12.7 Hz); 31P NMR (162 MHz, CDCl3): δ 46.58;
HRMS (ESI): calcd. for C17H31ClNP2Pd [MꢀCl]+ 452.0655,
found 452.0667; IR (KBr disc) ν/cmꢀ1: 3385, 2958, 1600, 1465,
1369, 1293, 902, 883, 744; [α]2D5 = +97.8 (c 0.8, CHCl3).
General procedure for the intramolecular hydroamination
Complex 3 (2.44 mg, 0.005 mmol) and AgBF4 (1.95 mg,
0.01 mmol) were added to a dry 10 mL Schlenk tube under N2
atmosphere. CH2Cl2 (2 mL) was added by syringe and the
reaction mixture was stirred for 1 h at given temperature. A
solution of the substrate (0.1 mmol) in CH2Cl2 (1 mL) was
added by syringe to the stirring mixture. Stirring was continued
for a predetermined length of time, and the reaction mixture
was filtered through a plug of celite. Purification by column
chromatography (ethyl acetate/petroleum ether) on silica gel
afforded the pure product.
(–)-1-(2-Allyl-4,4-dimethylpyrrolidin-1-yl)ethanone (5d).
1
Colourless oil (13.8 mg, 76%). H NMR (400 MHz, CDCl3,
observed as a mixture of rotamers): δ 5.77 – 5.58 (m, 2H, both),
5.18 – 4.93 (m, 4H, both), 4.13 – 4.06 (m, 2H, both), 3.98 –
3.84 (m, 1H, minor), 3.76 (d, J = 11.5 Hz, 1H, minor), 3.18 –
3.08 (m, 4H, both), 2.84 (d, J = 11.5 Hz, 1H, major), 2.76 –
2.61 (m, 2H, both), 2.53 – 2.36 (m, 1H, minor), 2.36 – 2.20 (m,
2H, both), 2.09 (s, 3H, minor), 2.01 (s, 3H, major), 1.92 – 1.87
(m, 1H, minor), 1.82 – 1.73 (m, 2H, major), 1.56 (dd, J = 12.9,
7.7 Hz, 1H, minor), 1.46 (dd, J = 12.8, 9.0 Hz, 2H, major), 1.09
(d, J = 1.9 Hz, 6H, both), 0.97 (s, 3H, major), 0.94 (s, 1H,
minor); 13C NMR (101 MHz, CDCl3): δ 169.4, 134.6, 133.3,
118.7, 117.7, 61.4, 58.3, 57.4, 56.3, 46.1, 44.5, 40.6, 37.9, 26.9,
26.6, 26.4, 26.2, 23.6; HRMS (ESI): calcd. for C11H20NO
[M+H]+ 182.1545, found 182.1543; IR (KBr disc) ν/cmꢀ1: 2959,
2924, 2855, 1655, 1417, 1260, 1097; HPLC Daicel ChiralPak
ODꢀH, nꢀhexane/iꢀPrOH = 98/2, 210 nm, 1 mL/min, tR1 = 10.1
min (major), tR2 = 12.1 min (minor)], ee = 22%; [α]2D5 = –4.5 (c
0.4, CHCl3).
(–)-Benzyl 2-allyl-4,4-dimethylpyrrolidine-1-carboxylate
(5a).10 Colourless oil (27.1 mg, 99%). 1H NMR (400 MHz,
CDCl3, observed as a mixture of rotamers): δ 7.40 – 7.27 (m,
10H, both), 5.82 – 5.59 (m, 2H, both), 5.26 – 4.95 (m, 8H,
both), 3.94 (m, 2H, both), 3.48 (d, J = 10.6 Hz, 1H, minor),
3.39 (d, J = 10.3 Hz, 1H, major), 2.98 (d, J = 10.6 Hz, 2H,
both), 2.73 (brs, 1H, major), 2.54 (brs, 1H, minor), 2.32 – 2.23
(m, 2H, both), 1.78 (ddd, J = 12.7, 7.4, 1.7 Hz, 2H, both), 1.07
(s, 6H, both), 0.97 (s, 6H, both); 13C NMR (101 MHz, CDCl3):
δ 155.6, 155.3, 137.4, 137.2, 134.6, 134.3, 128.7, 128.1, 128.0,
127.9, 117.8, 117.7, 67.0, 66.7, 59.9, 59.7, 57.2, 56.6, 45.7,
44.9, 39.5, 38.4, 37.6, 37.3, 26.7, 26.2; HPLC Daicel ChiralPak
ICꢀ3, nꢀhexane/iꢀPrOH = 98/2, 210 nm, 1 mL/min, tR1 = 13.3
min (minor), tR2 = 14.0 min (major), ee = 14%; [α]2D5 = –4.0 (c
0.3, CHCl3).
(–)-2-Allyl-4,4-dimethyl-1-(phenylsulfonyl)pyrrolidine
(5e). Colourless oil (26.5 mg, 95%). 1H NMR (400 MHz,
CDCl3): δ 7.88 – 7.83 (m, 2H), 7.61 – 7.48 (m, 3H), 5.73 (ddt,
J = 17.3, 10.2, 7.1 Hz, 1H), 5.18 – 4.99 (m, 2H), 3.75 – 3.61 (m,
1H), 3.22 – 3.06 (m, 2H), 2.87 – 2.72 (m, 1H), 2.50 – 2.36 (m,
1H), 1.64 (ddd, J = 12.7, 7.2, 1.1 Hz, 1H), 1.51 (dd, J = 12.7,
8.9 Hz, 1H), 1.01 (s, 3H), 0.47 (s, 3H); 13C NMR (101 MHz,
CDCl3): δ 138.5, 134.4, 132.7, 129.2, 127.6, 118.1, 61.7, 59.8,
45.7, 40.8, 37.5, 26.5, 25.9; HRMS (ESI): calcd. for
C15H22NO2S [M+H]+ 280.1371, found 280.1368; IR (KBr disc)
ν/cmꢀ1: 2951, 2855, 1464, 1355, 1260, 1165, 1094, 1051, 801,
718, 692, 601, 569; HPLC Daicel ChiralPak IE,
nꢀhexane/iꢀPrOH = 90/10, 230 nm, 1 mL/min, tR1 = 15.6 min
(–)-tert-Butyl
2-allyl-4,4-dimethylpyrrolidine-1-carboxylate
(5b).
Colorless oil (23.7 mg, 99%). 1H NMR (400 MHz, CDCl3,
observed as a mixture of rotamers): δ 5.75 – 5.65 (m, 2H, both),
5.08 – 5.04 (m, 4H, both), 3.88 (d, J = 5.4 Hz, 1H, minor), 3.79
(d, J = 7.0 Hz, 1H, major), 3.41 (d, J = 10.2 Hz, 1H, minor),
3.27 (d, J = 10.1 Hz, 1H, major), 2.89 (d, J = 10.8 Hz, 2H,
both), 2.67 (brs, 1H, minor), 2.52 (brs, 1H, major), 2.30 – 2.20
(m, 2H, both), 1.75 (ddd, J = 12.6, 7.4, 1.7 Hz, 2H, both), 1.47
(s, 18H, both), 1.06 (s, 6H, both), 0.96 (s, 6H, both); 13C NMR
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Page 6 of 10
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DOI: 10.1039/C4OB02402H
(major), tR2 = 18.3 min (minor), ee = 18%; [α]2D5 = –7.6 (c 0.5,
CHCl3).
yrrolidine (5j). Colourless oil (17.2 mg, 56%). H NMR (400
MHz, CDCl3): δ 7.84 (d, J = 8.7 Hz, 1H), 7.09 – 7.08 (m, 2H),
5.60 (ddt, J = 17.2, 10.3, 7.1 Hz, 1H), 5.02 – 4.90 (m, 2H), 4.03
– 3.93 (m, 1H), 3.37 (dd, J = 10.3, 1.5 Hz, 1H), 2.95 (d, J =
10.3 Hz, 1H), 2.62 (s, 3H), 2.54 – 2.48 (m, 1H), 2.36 (s, 3H),
2.18 – 2.06 (m, 1H), 1.81 (dd, J = 11.9, 6.6 Hz, 1H), 1.52 (dd, J
= 12.7, 8.7 Hz, 1H), 1.06 (s, 3H), 0.95 (s, 3H); 13C NMR (101
MHz, CDCl3): δ 143.0, 137.5, 135.9, 134.1, 133.2, 129.6, 126.6,
117.5, 61.3, 59.0, 45.9, 39.8, 37.6, 26.2, 25.9, 21.2, 20.5;
HRMS (ESI): calcd. for C17H26NO2S [M+H]+ 308.1684, found
308.1681; IR (KBr disc) ν/cmꢀ1: 3076, 2959, 2925, 2870, 1604,
1456, 1318, 1155, 1138, 1062, 923, 618, 590, 549; HPLC
Daicel ChiralPak ICꢀ3, nꢀhexane/iꢀPrOH = 95/5, 230 nm, 1
mL/min, tR1 = 24.9 min (major), tR2 = 26.5 min (minor), ee =
33%; [α]2D5 = –3.0 (c 0.4, CHCl3).
1
(–)-2-Allyl-4,4-dimethyl-1-(4-nitrophenylsulfonyl)
pyrrolidine (5f). Colourless oil (17.8 mg, 55%).1H NMR (400
MHz, CDCl3): δ 8.37 (d, J = 7.9 Hz, 2H), 8.03 (d, J = 7.9 Hz,
2H), 5.76 – 5.61 (m, 1H), 5.17 – 5.02 (m, 2H), 3.81 – 3.74 (m,
1H), 3.16 (dd, J = 35.6, 10.5 Hz, 2H), 2.80 – 2.68 (m, 1H), 2.46
– 2.32 (m, 1H), 1.72 (dd, J = 12.8, 7.3 Hz, 1H), 1.61 – 1.49 (m,
1H), 1.05 (s, 3H), 0.60 (s, 3H); 13C NMR (101 MHz, CDCl3): δ
149.9, 144.7, 133.4, 128.3, 124.2, 118.3, 61.5, 59.9, 45.4, 40.2,
37.6, 25.9, 25.8; HRMS (ESI): calcd. for C15H21N2O4S [M+H]+
325.1222, found 325.1229; IR (KBr disc) ν/cmꢀ1: 2960, 1529,
1350, 1162, 1091, 918, 855, 735, 688, 615, 574; HPLC Daicel
ChiralPak ODꢀH, nꢀhexane/iꢀPrOH = 95/5, 200 nm, 1 mL/min,
tR1 = 13.7 min (major), tR2 = 15.6 min (minor), ee = 5%; [α]D25
= –3.7 (c 0.4, CHCl3).
(–)-2-Allyl-1-(2,5-dimethylphenylsulfonyl)-4,4-dimethylp
1
yrrolidine (5k). Colourless oil (14.8 mg, 48%). H NMR (400
(–)-2-Allyl-4,4-dimethyl-1-(o-tolylsulfonyl)pyrrolidine
(5g). Colourless oil (17.6 mg, 60%). 1H NMR (400 MHz,
CDCl3): δ 7.96 (d, J = 7.0 Hz, 1H), 7.43 (t, J = 7.5 Hz, 1H),
7.30 (t, J = 7.0 Hz, 2H), 5.59 (ddt, J = 17.3, 10.3, 7.1 Hz, 1H),
4.99 – 4.92 (m, 2H), 4.01 (ddd, J = 16.3, 8.9, 3.5 Hz, 1H), 3.41
(dd, J = 10.3, 1.4 Hz, 1H), 2.98 (d, J = 10.3 Hz, 1H), 2.67 (s,
3H), 2.55 – 2.44 (m, 1H), 2.19 – 2.06 (m, 1H), 1.82 (ddd, J =
12.6, 7.4, 1.4 Hz, 1H), 1.53 (dd, J = 12.7, 8.8 Hz, 1H), 1.07 (s,
3H), 0.95 (s, 3H); 13C NMR (101 MHz, CDCl3): δ 138.9, 137.6,
133.9, 132.5, 132.4, 129.3, 126.0, 117.6, 61.3, 59.2, 45.9, 39.8,
37.6, 26.1, 25.8, 20.6; HRMS (ESI): calcd. for C16H24NO2S
[M+H]+ 294.1528, found 294.1520; IR (KBr disc) ν/cmꢀ1: 3065,
2961, 2871, 1641, 1470, 1318, 1156, 1069, 1019, 920, 808, 760,
697, 606, 581, 544; HPLC Daicel ChiralPak ICꢀ3,
nꢀhexane/iꢀPrOH = 90/10, 230 nm, 1 mL/min, tR1 = 13.1 min
(major), tR2 =14.2 min (minor), ee = 29%; [α]2D5 = –5.3 (c 0.4,
CHCl3).
MHz, CDCl3): δ 7.78 (s, 1H), 7.23 (d, J = 7.8 Hz, 1H), 7.17 (d,
J = 7.7 Hz, 1H), 5.61 (ddt, J = 17.2, 10.3, 7.1 Hz, 1H), 5.06 –
4.89 (m, 2H), 4.07 – 3.94 (m, 1H), 3.38 (dd, J = 10.3, 1.5 Hz,
1H), 2.96 (d, J = 10.3 Hz, 1H), 2.61 (s, 3H), 2.57 – 2.46 (m,
1H), 2.37 (s, 3H), 2.20 – 2.07 (m, 1H), 1.81 (ddd, J = 12.6, 7.4,
1.4 Hz, 1H), 1.53 (dd, J = 12.7, 8.7 Hz, 1H), 1.07 (s, 3H), 0.94
(s, 3H); 13C NMR (101 MHz, CDCl3): δ 138.3, 135.8, 134.5,
134.1, 133.2, 132.5, 129.8, 117.6, 61.3, 59.1, 45.9, 39.8, 37.6,
26.2, 25.9, 20.8, 20.1; HRMS (ESI): calcd. for C17H26NO2S
[M+H]+ 308.1684, found 308.1676; IR (KBr disc) ν/cmꢀ1: 2963,
2905, 2871, 2380, 1590, 1573, 1453, 1369, 1067, 1019, 819;
HPLC Daicel ChiralPak ICꢀ3, nꢀhexane/iꢀPrOH = 95/5, 230 nm,
1 mL/min, tR1 = 12.4 min (major), tR2 = 13.9 min (minor), ee =
29%; [α]2D5 = –9.0 (c 0.2, CHCl3).
(–)-2-Allyl-1-(mesitylsulfonyl)-4,4-dimethylpyrrolidine
(5l). Colourless oil (6.4 mg, 20%). 1H NMR (400 MHz, CDCl3):
δ 6.93 (s, 2H), 5.55 (ddt, J = 17.2, 10.4, 7.1 Hz, 1H), 4.96 (d, J
= 10.2 Hz, 1H), 4.90 (d, J = 17.1 Hz, 1H), 4.03 (ddd, J = 11.7,
8.6, 3.6 Hz, 1H), 3.42 (d, J = 10.3 Hz, 1H), 2.88 (d, J = 10.3 Hz,
1H), 2.65 (s, 6H), 2.37 – 2.31 (m, 1H), 2.29 (s, 3H), 2.02 – 1.91
(m, 1H), 1.87 (dd, J = 12.6, 7.6 Hz, 1H), 1.53 (dd, J = 12.6, 8.4
Hz, 1H), 1.07 (s, 6H); 13C NMR (101 MHz, CDCl3): δ 142.2,
139.6, 134.5, 134.2, 131.8, 117.5, 61.1, 58.7, 46.1, 39.5, 37.5,
29.7, 26.3, 26.2, 22.9; HRMS (ESI): calcd. for C18H28NO2S
[M+H]+ 322.1841, found 322.1836; IR (KBr disc) ν/cmꢀ1: 2957,
2925, 2855, 1604, 1457, 1319, 1151, 1059, 918, 851, 800, 672,
593; HPLC Daicel ChiralPak ODꢀH, nꢀhexane/iꢀPrOH = 99/1,
230 nm, 1 mL/min, tR1 = 8.5 min (major), tR2 = 10.1 min
(minor), ee = 29%; [α]2D5 = –3.6 (c 0.4, CHCl3).
(–)-2-Allyl-4,4-dimethyl-1-(m-tolylsulfonyl)pyrrolidine
(5h). Yellowish solid (20.5 mg, 70%). m.p. 56.0 – 57.7 ℃; H
1
NMR (400 MHz, CDCl3): δ 7.69 – 7.61 (m, 2H), 7.44 – 7.34
(m, 2H), 5.74 (ddt, J = 17.3, 10.2, 7.1 Hz, 1H), 5.14 – 5.02 (m,
2H), 3.71 – 3.64 (m, 1H), 3.17 – 3.09 (m, 2H), 2.85 – 2.73 (m,
1H), 2.43 (s, 3H), 2.45 – 2.38 (m, 1H), 1.65 (ddd, J = 12.7, 7.2,
1.1 Hz, 1H), 1.51 (dd, J = 12.7, 8.9 Hz, 1H), 1.02 (s, 3H), 0.50
(s, 3H); 13C NMR (101 MHz, CDCl3): δ 139.0, 138.2, 134.2,
133.2, 128.8, 127.7, 124.5, 117.7, 61.5, 59.5, 45.5, 40.5, 37.3,
26.3, 25.7, 21.4; HRMS (ESI): calcd. for C16H24NO2S [M+H]+
294.1528, found 294.1518; IR (KBr disc) ν/cmꢀ1: 3076, 2959,
2926, 2873, 1641, 1600, 1467, 1348, 1217, 1155, 1097, 1050,
919, 789, 735, 698, 607, 583; HPLC Daicel ChiralPak ICꢀ3,
nꢀhexane/iꢀPrOH = 90/10, 230 nm, 1 mL/min, tR1 = 19.6 min
(major), tR2 = 20.6 min (minor), ee = 21%; [α]2D5 = –22.0 (c 0.1,
CHCl3).
(–)-2-Allyl-4,4-dimethyl-1-(naphthalen-1-ylsulfonyl)pyrro
lidine (5m). Yellowish oil (6.6 mg, 20%). 1H NMR (400 MHz,
CDCl3): δ 8.88 (d, J = 8.6 Hz, 1H), 8.28 (dd, J = 7.4, 1.1 Hz,
1H), 8.07 (d, J = 8.2 Hz, 1H), 7.94 (d, J = 7.9 Hz, 1H), 7.71 –
7.65 (m, 1H), 7.61 (t, J = 7.0 Hz, 1H), 7.58 – 7.53 (m, 1H),
5.66 – 5.53 (m, 1H), 5.05 – 4.92 (m, 2H), 4.05 (ddd, J = 16.3,
8.9, 3.4 Hz, 1H), 3.44 (dd, J = 10.3, 1.3 Hz, 1H), 3.08 (d, J =
10.3 Hz, 1H), 2.66 – 2.62 (m, 1H), 2.32 – 2.18 (m, 1H), 1.75
(ddd, J = 12.6, 7.2, 1.3 Hz, 1H), 1.52 (dd, J = 12.7, 8.9 Hz, 1H),
1.04 (s, 3H), 0.70 (s, 3H); 13C NMR (101 MHz, CDCl3): δ
135.4, 134.3, 134.0, 133.9, 129.4, 129.0, 128.9, 127.9, 126.7,
125.2, 124.1, 117.7, 61.3, 59.2, 45.8, 39.9, 29.7, 26.0, 25.7;
HRMS (ESI): calcd. for C19H24NO2S [M+H]+ 330.1528, found
330.1533; IR (KBr disc) ν/cmꢀ1: 3061, 2960, 2853, 1507, 1371,
1417, 1319, 1262, 1200, 1132, 919, 803, 679, 636, 600, 577,
524; HPLC Daicel ChiralPak ODꢀH, nꢀhexane/iꢀPrOH = 99/1,
230 nm, 1 mL/min, tR1 = 17.8 min (minor), tR2 = 21.3 min
(–)-2-Allyl-4,4-dimethyl-1-tosylpyrrolidine
(5i).6
1
Colourless oil (21.2 mg, 72%). H NMR (400 MHz, CDCl3): δ
7.73 (d, J = 7.6 Hz, 2H), 7.30 (d, J = 8.0 Hz, 2H), 5.79 – 5.68
(m, 1H), 5.14 – 5.01 (m, 2H), 3.69 – 3.62 (m, 1H), 3.19 – 3.06
(m, 2H), 2.81 – 2.76 (m, 1H), 2.42 (s, 3H), 2.44 – 2.35 (m, 1H),
1.64 (dd, J = 12.7, 7.3 Hz, 1H), 1.51 (dd, J = 12.7, 8.7 Hz, 1H),
1.02 (s, 3H), 0.53 (s, 3H); 13C NMR (101 MHz, CDCl3): δ
143.2, 135.4, 134.3, 129.5, 127.4, 117.7, 61.5, 59.5, 45.5, 40.5,
37.2, 26.3, 25.8, 21.5; HPLC Daicel ChiralPak ODꢀH,
nꢀhexane/iꢀPrOH = 99/1, 200 nm, 1 mL/min, tR1 = 10.5 min
(major), tR2 = 11.6 min (minor), ee = 18%; [α]2D5 = –9.4 (c 0.5,
CHCl3).
(–)-2-Allyl-1-(2,4-dimethylphenylsulfonyl)-4,4-dimethylp
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DOI: 10.1039/C4OB02402H
(major), ee = 25%; [α]2D5 = –1.9 (c 0.5, CHCl3).
minor), 4.54 (d, J = 11.7 Hz, 1H, major), 3.87 – 3.82 (m, 2H,
both), 2.98 – 2.92 (m, 2H, both), 2.63 – 2.28 (m, 6H, both),
(–)-2-Allyl-1-(2,4-dimethylphenylsulfonyl)pyrrolidine
(5n). Colourless oil (8.4 mg, 30%). 1H NMR (400 MHz, CDCl3,
observed as a mixture of rotamers): δ 7.82 (d, J = 8.5 Hz, 1H,
major), 7.78 (d, J = 8.0 Hz, 1H, minor), 7.10 (brs, 2H, major),
7.08 (d, J = 6.7 Hz, 2H, minor), 5.74 – 5.59 (m, 1H, major),
5.40 – 5.35 (m, 1H, minor), 5.02 – 4.97 (m, 4H, both), 4.24 –
4.17 (m, 1H, minor), 3.93 – 3.89 (m, 1H, major), 3.36 – 3.32
(m, 2H, both), 3.25 – 3.21 (m, 2H, both), 2.61 (s, 3H, major),
2.57 (s, 3H, minor), 2.45 – 2.38 (m, 1H, major), 2.36 (s, 3H,
major), 2.35 (s, 3H, minor), 2.17 – 2.11 (m, 1H, major), 1.90 –
1.82 (m, 2H, both), 1.81 – 1.70 (m, 2H, both); 13C NMR (101
MHz, CDCl3): δ 143.2, 137.9, 134.7, 134.5 133.3, 132.9, 130.9,
130.2, 129.8, 126.9, 126.6, 126.3, 117.5, 61.4, 59.0, 48.5, 47.9,
40.0, 33.3, 30.4, 29.7, 24.2, 21.2, 20.5; HRMS (ESI): calcd. for
C15H22NO2S [M+H]+ 280.1371, found 280.1378; IR (KBr disc)
ν/cmꢀ1: 2074, 2963, 2925, 2855, 1640, 1604, 1448, 1261, 1062,
1026, 918, 873, 818, 662, 590, 552, 405; HPLC Daicel
ChiralPak ICꢀ3, nꢀhexane/iꢀPrOH = 90/10, 230 nm, 1 mL/min,
tR1 = 29.8 min (major), tR2 = 31.0 min (minor), ee = 23%; [α]D25
= –14.4 (c 0.1, CHCl3).
1.62 (s, 2H, both), 1.12 (s, 3H, major), 1.02 (s, 3H, minor); 13
C
NMR (101 MHz, CDCl3): δ 154.8, 153.3, 146.2, 146.1, 146.0,
145.9, 137.3, 136.6, 134.1, 133.8, 128.5, 128.5, 128.47, 128.45,
128.44, 128.0, 127.9, 127.8, 127.7, 126.8, 126.7, 126.6, 126.5,
126.3, 126.2, 126.1, 118.8, 118.7, 67.1, 66.3, 63.3, 62.6, 56.8,
56.2, 50.9, 50.4, 50.1, 48.9, 44.5, 43.2, 26.2, 24.9; HPLC
Daicel ChiralPak OZꢀH, hexane/iꢀPrOH = 99/1, 210 nm, 1
mL/min, tR1 = 5.7 min (major), tR2 = 9.2 min (minor), ee = 3%;
[α]2D5 = –10.3 (c 0.6, CHCl3).
(–)-7-Allyl-6-(2,4-dimethylphenylsulfonyl)-6-azaspiro[3.4]
octane (5r). Colourless oil (16.6 mg, 52%). 1H NMR (400
MHz, CDCl3): δ 7.83 (d, J = 8.6 Hz, 1H), 7.10 – 7.08 (m, 2H),
5.70 – 5.56 (m, 1H), 5.04 – 4.94 (m, 2H), 3.93 – 3.84 (m, 1H),
3.43 (d, J = 9.9 Hz, 1H), 3.20 (d, J = 10.1 Hz, 1H), 2.62 (s, 3H),
2.55 – 2.44 (m, 1H), 2.36 (s, 3H), 2.17 – 2.06 (m, 1H), 2.02 –
1.93 (m, 3H), 1.89 – 1.79 (m, 4H), 1.75 (dd, J = 12.7, 6.1 Hz,
1H); 13C NMR (101 MHz, CDCl3): δ 143.5, 142.7, 138.0,
134.7, 133.5, 130.1, 126.9, 117.8, 59.8, 59.1, 44.6, 43.5, 40.2,
32.1, 31.6, 21.5, 20.8, 16.4; HRMS (ESI): calcd. for
C18H26NO2S [M+H]+ 320.1684, found 320.1675; IR (KBr disc)
ν/cmꢀ1: 3075, 2927, 2855, 1641, 1604, 1447, 1317, 1138, 1060,
1024, 968, 919, 819, 662, 590, 554; HPLC Daicel ChiralPak
ICꢀ3, nꢀhexane/iꢀPrOH = 90/10, 230 nm, 1 mL/min, tR1 = 19.1
min (major), tR2 = 20.9 min (minor), ee = 33%; [α]2D5 = –12.6 (c
0.2, CHCl3).
(+)-2-Allyl-1-(2,4-dimethylphenylsulfonyl)-4,4-diphenylp
yrrolidine (5o). White solid (41.4 mg, 96%). m.p. 114.1 –
1
115.7 ℃; H NMR (400 MHz, CDCl3): δ 7.84 (d, J = 8.7 Hz,
1H), 7.33 – 7.16 (m, 10H), 7.09 (d, J = 7.2 Hz, 2H), 5.68 – 5.53
(m, 1H), 5.01 (d, J = 10.1 Hz, 1H), 4.89 (d, J = 17.1 Hz, 1H),
4.31 (d, J = 10.4 Hz, 1H), 4.02 – 3.96 (m, 1H), 3.96 (d, J =
10.4 Hz, 1H), 2.84 (ddd, J = 12.6, 7.2, 0.9 Hz, 1H), 2.56 (s, 3H),
2.55 – 2.49 (m, 2H), 2.39 (s, 3H), 1.99 – 1.86 (m, 1H); 13C
NMR (101 MHz, CDCl3): δ 145.4, 144.6, 143.2, 137.6, 135.7,
134.1, 133.4, 129.6, 128.6, 128.5, 126.7, 126.6, 126.58, 126.52,
118.0, 58.7, 58.0, 52.6, 42.8, 39.1, 21.3, 20.5; HRMS (ESI):
calcd. for C27H30NO2S [M+H]+ 432.1997, found 432.1991; IR
(KBr disc) ν/cmꢀ1: 3060, 3025, 2974, 2925, 1602, 1496, 1447,
1322, 1156, 1059, 1030, 919, 820, 751, 701, 665, 585, 552;
HPLC Daicel ChiralPak ICꢀ3, nꢀhexane/iꢀPrOH = 90/10, 240
nm, 1 mL/min, tR1 = 21.1 min (major), tR2 = 24.2 min (minor),
ee = 43%; [α]2D5 = +11.2 (c 0.1, CHCl3).
(–)-3-Allyl-2-(2,4-dimethylphenylsulfonyl)-2-azaspiro[4.4]
nonane (5s). Colourless oil (24.3 mg, 73%). 1H NMR (400
MHz, CDCl3): δ 7.83 (d, J = 8.7 Hz, 1H), 7.10 – 7.08 (m, 2H),
5.68 – 5.55 (m, 1H), 5.04 – 4.92 (m, 2H), 3.96 – 3.89 (m, 1H),
3.37 (d, J = 10.1, 1H), 3.03 (d, J = 10.1 Hz, 1H), 2.62 (s, 3H),
2.58 – 2.50 (m, 1H), 2.36 (s, 3H), 2.19 – 2.09 (m, 1H), 1.91
(ddd, J = 12.5, 7.4, 1.2 Hz, 1H), 1.65 (dd, J = 12.6, 7.8 Hz, 1H),
1.63 – 1.50 (m, 8H); 13C NMR (101 MHz, CDCl3): δ 143.4,
137.8, 135.8, 134.6, 133.5, 129.9, 126.8, 117.7, 60.0, 59.5, 49.0,
44.2, 40.1, 37.2, 36.6, 25.0, 24.8, 21.5, 20.8; HRMS (ESI):
calcd. for C19H28NO2S [M+H]+ 334.1841, found 334.1831; IR
(KBr disc) ν/cmꢀ1: 3075, 2950, 2864, 1641, 1604, 1570, 1448,
1312, 1138, 1062, 994, 918, 820, 662, 589, 553; HPLC Daicel
ChiralPak IE, nꢀhexane/iꢀPrOH = 95/5, 230 nm, 1 mL/min, tR1
(+)-2-Allyl-1-(2,4-dimethylphenylsulfonyl)-5,5-diphenylpi
1
peridine (5p). Colourless oil (27.6 mg, 62%). H NMR (400
= 24.6 min (major), tR2 = 26.7 min (minor), ee = 32%; [α]D25
=
MHz, CDCl3): δ 7.91 (d, J = 8.0 Hz, 1H), 7.21 (t, J = 7.5 Hz,
2H), 7.13 (d, J = 7.4 Hz, 2H), 7.09 – 7.03 (m, 3H), 6.97 (dd, J
= 14.1, 6.2 Hz, 3H), 6.81 (d, J = 7.2 Hz, 2H), 5.781 – 5.70 (m,
1H), 5.15 – 5.07 (m, 2H), 4.07 – 4.05 (m, 1H), 4.01 (dd, J =
13.4, 2.2 Hz, 1H), 3.47 (d, J = 13.3 Hz, 1H), 2.82 – 2.69 (m,
1H), 2.55 – 2.44 (m, 2H), 2.41 (s, 3H), 2.32 – 2.20 (m, 1H),
2.13 (s, 3H), 1.82 – 1.77 (m, 2H); 13C NMR (101 MHz, CDCl3):
δ 147.5, 143.5, 143.0, 138.8, 134.7, 133.8, 133.6, 130.8, 128.4,
128.1, 127.1, 126.4, 126.3, 126.1, 125.6, 117.6, 51.7, 48.6, 45.7,
33.7, 28.7, 22.7, 21.3, 19.6; HRMS (ESI): calcd. for
C28H32NO2S [M+H]+ 446.2154, found 446.2148; IR (KBr disc)
ν/cmꢀ1: 3076, 2958, 2871, 1730, 1641, 1490, 1464, 1391, 1371,
1318, 1210, 1154, 1069, 957, 818, 700, 614, 535, 465; HPLC
Daicel ChiralPak ICꢀ3, nꢀhexane/iꢀPrOH = 90/10, 240 nm, 1
mL/min, tR1 = 20.4 min (minor), tR2 = 24.0 min (major), ee =
32%; [α]2D5 = +14.7 (c 0.2, CHCl3).
–12.0 (c 0.3, CHCl3).
(–)-3-Allyl-2-(2,4-dimethylphenylsulfonyl)-2-azaspiro[4.5]
1
decane (5t). Colourless oil (33.4 mg, 96%). H NMR (400
MHz, CDCl3): δ 7.83 (d, J = 8.6 Hz, 1H), 7.09 – 7.07 (m, 2H),
5.66 – 5.55 (m, 1H), 5.02 – 4.91 (m, 2H), 3.95 – 3.88 (m, 1H),
3.52 (d, J = 10.6 Hz, 1H), 2.92 (d, J = 10.6 Hz, 1H), 2.61 (s,
3H), 2.54 – 2.45 (m, 1H), 2.35 (s, 3H), 2.16 – 2.06 (m, 1H),
1.89 (dd, J = 12.8, 7.5 Hz, 1H), 1.45 (dd, J = 12.8, 8.4 Hz, 1H),
1.44 – 1.26 (m, 10H); 13C NMR (101 MHz, CDCl3): δ 143.3,
137.8, 136.9, 134.4, 133.5, 129.8, 126.8, 117.8, 59.0, 58.5, 43.8,
41.8, 40.2, 36.6, 34.5, 26.2, 24.0, 23.0, 21.5, 20.8; HRMS (ESI):
calcd. for C20H30NO2S [M+H]+ 348.1997, found 348.1991; IR
(KBr disc) ν/cmꢀ1: 3075, 2923, 2855, 1640, 1604, 1452, 1317,
955, 917, 891, 819, 737, 666, 591, 552; HPLC Daicel
ChiralPak IE, nꢀhexane/iꢀPrOH = 95/5, 230 nm, 1 mL/min, tR1
= 25.0 min (major), tR2 = 27.2 min (minor), ee = 35%; [α]D25
=
(–)-Benzyl
2-allyl-2-methyl-4,4-diphenylpyrrolidine-1-carboxylate
(5q).10 Colourless oil (37.9 mg, 92%). 1H NMR (400 MHz,
CDCl3, observed as a mixture of rotamers): δ 7.47 – 7.12 (m,
30H, both), 5.74 – 5.59 (m, 2H, both), 5.21 (s, 4H, both), 5.03
(d, J = 10.2 Hz, 2H, both), 4.96 (d, J = 17.0 Hz, 1H, major),
4.90 (d, J = 17.0 Hz, 1H, minor), 4.67 (d, J = 11.9 Hz, 1H,
–9.2 (c 0.3, CHCl3).
(–)-3-Allyl-2-(2,4-dimethylphenylsulfonyl)-2-azaspiro[4.6]
undecane (5u). Colourless oil (33.3 mg, 92%). H NMR (400
MHz, CDCl3): δ 7.82 (d, J = 8.6 Hz, 1H), 7.09 – 7.07 (m, 2H),
5.64 – 5.54 (m, 1H), 4.99 – 4.92 (m, 2H), 3.95 – 3.88 (m, 1H),
1
This journal is © The Royal Society of Chemistry [year]
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Organic & Biomolecular Chemistry
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DOI: 10.1039/C4OB02402H
Ed. 2001, 40, 4501ꢀ4503; (d) J. Pawlas, Y. Nakao, M. Kawatsura
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3.48 (d, J = 10.3 Hz, 1H), 2.91 (d, J = 10.3 Hz, 1H), 2.61 (s,
3H), 2.52 – 2.46 (m, 1H), 2.35 (s, 3H), 2.15 – 2.04 (m, 1H),
1.92 (dd, J = 12.6, 7.3 Hz, 1H), 1.60 – 1.41 (m, 12H); 13C
NMR (101 MHz, CDCl3): δ 143.2, 137.7, 136.3, 134.4, 133.5,
129.7, 126.8, 117.8, 60.8, 59.1, 45.7, 44.8, 40.1, 39.1, 37.4,
29.7, 29.6, 24.3, 23.5, 21.5, 20.8; HRMS (ESI): calcd. for
C21H32NO2S [M+H]+ 362.2154, found 362.2150; IR (KBr disc)
ν/cmꢀ1: 3075, 2923, 2855, 1640, 1604, 1460, 1318 1235, 1139,
1060, 1020, 917, 819, 672, 591, 552; HPLC Daicel ChiralPak
ICꢀ3, nꢀhexane/iꢀPrOH = 95/5, 230 nm, 1 mL/min, tR1 = 29.4
min (major), tR2 = 31.3 min (minor), ee = 36%; [α]2D5 = –10.9 (c
0.6, CHCl3).
(+)-Benzyl
1-vinylisoindoline-2-carboxylate
(5v).10
1
Colourless oil (21.7 mg, 74%). H NMR (400 MHz, CDCl3,
observed as a 1:1 mixture of rotamers): δ 7.43 – 7.32 (m, 8H,
both), 7.29 – 7.16 (m, 10H, both), 5.60 – 5.44 (m, 2H, both),
5.31 – 5.14 (m, 4H, both), 5.04 – 4.85 (m, 4H, both), 4.84 –
4.73 (m, 2H, both), 4.60 (d, J = 14.8 Hz, 2H, both), 2.95 – 2.86
(m, 1H, rotamer A), 2.82 – 2.71 (m, 1H, rotamer B), 2.71 –
2.62 (m, 1H, rotamer A), 2.62 – 2.53 (m, 1H, rotamer B); 13C
NMR (101 MHz, CDCl3): δ 154.8, 154.5, 140.3, 140.0, 136.9,
136.7, 136.6, 136.4, 132.9, 132.7, 128.5, 128.4, 128.1, 128.0,
127.9, 127.8, 127.6, 127.5, 127.3, 127.2, 122.8, 122.6, 122.5,
122.3, 118.6, 118.5, 67.1, 66.7, 63.2, 62.6, 52.7, 52.3, 39.6,
38.3; HPLC Daicel ChiralPak ICꢀ3, nꢀhexane/iꢀPrOH = 98/2,
210 nm, 1 mL/min, tR1 = 19.2 min (major), tR2 = 21.1 min
(minor), ee = 9%; [α]2D5 = +0.7 (c 0.3, CHCl3).
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Acknowledgments
This work was partially supported by the National Natural
Science Foundation of China (No. 21172143, 21172145,
21372152 and 21472123), Nippon Chemical Industrial Co., Ltd,
Shanghai Jiao Tong University (SJTU). We thank the
Instrumental Analysis Center of SJTU for HRMS analysis.
Notes and references
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This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00
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DOI: 10.1039/C4OB02402H
[13] T. Miura, H. Yamada, S.ꢀI. Kikuchi and T. Imamoto, J. Org.
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[14] CCDC 1017088 contains the supplementary crystalloꢀgraphic data
for this paper. These data can be obtained free of charge from The
Cambridge
Crystallographic
Data
Centre
via
www.ccdc.cam.ac.uk/data_request/cif.
[15] CCDC 1029920 contains the supplementary crystalloꢀgraphic data
for this paper. These data can be obtained free of charge from The
Cambridge
Crystallographic
Data
Centre
via
www.ccdc.cam.ac.uk/data_request/cif.
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00
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Organic & Biomolecular Chemistry
Page 10 of 10
P-Stereogenic PNP Pincer-Pd Catalyzed Intramolecular Hydroamination
of Amino-1,3-dienes
Zehua Yanga, Chao Xiaa, Delong Liua, Yangang Liua, Masashi Sugiyab,
Tsuneo Imamotob,c,* and Wanbin Zhanga,d,*
+ Cl -
PG
NH
PG
cat.
(5 mol%)/AgBF4 (10 mol%)
R1
R1 ( )n
N
R2
R2
N
R1
R1
Me
t-Bu
Me
CH2Cl2, 25 ℃, 24 h
P
P
Pd
Cl
A new P-stereogenic PNP pincer-Pd complex was readily prepared and
was used in the asymmetric intramolecular hydroamination of
(
)
n
t-Bu
4
5
cat.
22 examples, up to 99% yield, > 99 : 1 regioselecitvity and 47% ee
amino-1,3-dienes, with the desired products being obtained in good yields
and with excellent regioselectivities and up to moderate enantioselectivities.