Asymmetric synthesis of α-amino-1,3-dithianes via Chiral N -phosphonyl imine-based umpolung reaction without using chromatography and recrystallization

Article abstract of DOI:10.1021/jo200070d

A series of α-amino-1,3-dithianes have been synthesized via the asymmetric Umpolung reaction of 2-lithio-1,3-dithianes with chiral N-phosphonyl imines in good chemical yields (up to 82%) and good to excellent diastereoselectivities (>99:1). The manner by

Full text of DOI:10.1021/jo200070d

ARTICLE
pubs.acs.org/joc
Asymmetric Synthesis of r-Amino-1,3-dithianes via Chiral
N-Phosphonyl Imine-Based Umpolung Reaction Without Using
Chromatography and Recrystallization
Padmanabha V. Kattamuri,† Teng Ai,† Suresh Pindi,† Yinwei Sun,‡ Peng Gu,‡ Min Shi,*,‡ and Guigen Li*,†
†Department of Chemistry & Biochemistry, Texas Tech University, Lubbock, Texas 79409-1061, United States
‡State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354
Fenglin Lu, Shanghai 200032, P. R. China
S Supporting Information
b
ABSTRACT: A series of R-amino-1,3-dithianes have been synthesized
via the asymmetric Umpolung reaction of 2-lithio-1,3-dithianes with
chiral N-phosphonyl imines in good chemical yields (up to 82%) and
good to excellent diastereoselectivities (>99:1). The manner by which
chiral N-phosphonyl imines are slowly added into the solution of
2-lithio-1,3-dithiane was found to be crucial for achieving excellent
diastereoselectivity. The current synthesis was proven to follow the
GAP chemistry (group-assistant-purification chemistry) process, which
avoids traditional purification techniques of chromatography or recrys-
tallization, i.e., the pure chiral R-amino-1,3-dithianes attached with the
chiral N-phosphonyl group were readily obtained by washing the solid
crude products with hexane or a mixture of hexaneꢀethyl acetate.
’ INTRODUCTION
reactions5ꢀ9 can be performed by following the GAP chemistry
process. Furthermore, the asymmetric catalysis using achiral
N-phosphonyl imines as electrophiles has also been proven to
undergo the GAP chemistry process, which was shown by the
asymmetric catalytic Strecker reaction.5 In this GAP Strecker
reaction, achiral N-phosphonyl imines were subjected to react
with Et2AlCN in the presence of three types of catalysts:
free amino alcohols,5b primary free natural amino acids,5a and
BINOLs.5b All of these catalysis processes resulted in excellent
chemical yields and enatioselectivities under convenient condi-
tions. This reaction represented the first use of achiral N-
phosphonyl imines and Et2AlCN as a nonvolatile and inexpen-
sive cyanide source in asymmetric catalysis. The GAP chemistry
process has also been proven to be effective for this catalysis. The
achiral N-phosphonyl auxiliary can be readily cleaved under mild
acidic conditions and recycled via extraction with n-butanol to
afford a quantitative recovery of N,N0-bis(naphthalen-1-yl-
methyl)ethane-1,2-diamine for future reuse.
In the meanwhile, the asymmetric synthesis of enantiomeri-
cally pure R-amino aldehydes and R-amino ketones have become
an active topic in synthetic chemistry, as they serve as valuable
versatile building blocks for organic and medicinal research.10ꢀ13
It is well-known that R-amino carbonyl compounds are relatively
sensitive to racemization and self-condensation conditions, even
when the amino group is protected by various protecting
groups.14 These problems are usually avoided or minimized by
The development of economic, greener, and environmentally
friendly synthetic methodologies has been a great challenge in
modern organic chemistry.1ꢀ4 So far, general reagents, particu-
larly chiral reagents that enable organic synthesis to be performed
without the use of traditional purifications via chromatography or
recrystallization, have not been established.5 However, this concept
would encourage the synthetic community to make more effort to
search for greener reagents and related reactions to better serve
academia and the pharmaceutical industry. It would substantially
minimize the use of energy, starting materials, and manpower as to
save nature’s resources.
In the past several years, we have established new chiral
reagents of N-phosphonyl and N-phosphinyl amides and imines
and have successfully applied them to various asymmetric
reactions,5ꢀ9 such as asymmetric aza-Darzen reaction,6a asym-
metric aza-Henry reaction,6b asymmetric Mannich reaction,6d,7b
asymmetric additions of allylmagnesium bromides,6c asymmetric
synthesis of N-phosphonyl propargyl amines,8 and asymmetric
synthesis of N-phosphonyl β-amino Weinreb amides.7 On
the basis of the results of the above reactions, we proposed a
new concept of GAP chemistry (group-assistant-purification
chemistry)5 which can avoid traditional purification using chro-
matography and recrystallization; i.e., the pure chiral amino
products attached with the chiral N-phosphonyl groups can
be readily obtained by washing their solid crude products with
hexane or a mixture of hexaneꢀethyl acetate. After this concept
was generated, we re-examined and confirmed that all 13 chiral
N-phosphonyl and N-phosphinyl imine-based asymmetric
Received: January 28, 2011
Published: March 15, 2011
r
2011 American Chemical Society
2792
dx.doi.org/10.1021/jo200070d J. Org. Chem. 2011, 76, 2792–2797
|

The Journal of Organic Chemistry
ARTICLE
Scheme 1
Table 2. Asymmetric Addition of Lithio-1,3-dithianes to N-
Phosphonyl Iminesa
Table 1. Optimization of N-Protecting Groups of Phospho-
entry
imine
R1
R2
product
yield (%) b
dr c
nyl Iminesa
1
2
1a
1a
1a
1b
1b
1b
1c
1c
1d
1d
1e
1e
1f
H
H
H
H
6a
6b
6c
6d
6e
6f
82
78
75
80
77
73
75
70
79
80
77
74
75
74
85
>99:1
94:6
Me
Ph
H
3
81:19
>99:1
90:10
81:19
>99:1
92:8
4
4-F
5
4-F
Me
Ph
H
6
4-F
7
4-Me
4-Me
4-Cl
4-Cl
4-Br
4-Br
3-Br
3-Br
4-OBn
6g
6h
6i
8
Me
H
9
>99:1
91:9
10
11
12
13
14
15
Me
H
6j
6k
6l
>99:1
92:8
entry
substrate
R
product
yield (%)b
drc
Me
H
6m
6n
6o
92:8
1
2
3
4
5
1a
2a
3a
4a
5a
isopropyl
3-pentyl
6a
82
71
32
81
70
>99:1
87:13
95:5
1f
Me
H
91:9
7a
1g
>99:1
cyclohexyl
benzyl
8a
a Reaction conditions: 0.1 mmol of imine, 0.2 mmol of 1,3-dithiane, 0.22
mmol of base, 2 mL of solvent, ꢀ30 to ꢀ78 °C to rt. b Isolated yields.
c Diastereoselectivities were determined by 31P NMR analysis of crude
products.
9a
77:23
86:14
CH2-1-naphthyl
10a
a Reaction conditions: 0.1 mmol of imine, 0.2 mmol of 1,3-dithiane, 0.22
mmol of base, 2 mL of solvent, ꢀ30 to ꢀ78 °C to rt. b Isolated yields.
c Diastereoselectivities were determined by 31P NMR analysis of crude
products.
’ RESULTS AND DISCUSSION
To continue our projects on chiral N-phosphonyl imine
chemistry and on searching for more practical GAP synthesis
of a series of amino compounds, we investigated the Umpolung
reaction of chiral N-phosphonyl imines with three types of
nucleophilic species: 2-lithio-1,3-dithiane, 2-lithio-2-alkyl-1,3-
dithianes, and 2-lithio-2-phenyl-1,3-dithianes. We found that this
asymmetric Umpolung reaction proceeded smoothly and effi-
ciently under new conditions. In this paper, we would like to
report our results as represented in Scheme 1 and summarized in
Table 1.
As compared with N-sulfinyl imine chemistry, our chiral N-
phosphonyl imines show some unique merits: (1) chiral N-
phosphonamide and N-phosphonyl imines have a higher ther-
molytic stability; (2) multiple sites of their structures can be
readily modified; (3) the N-phosphonyl group in the resulting
amino compounds are inert to oxidative conditions; (4) the N-
phosphonyl group is readily cleavable and the chiral auxiliary
precursor recyclable; (5) it is convenient to determine the
diastereoselectivity by 31P NMR measurement; (6) the N-
phosphonyl imine-based reactions follow the GAP chemistry
process in which traditional purifications of using chromatogra-
phy or recrystallization can be avoided, i.e., the pure chiral R-
amino-1,3-dithianes attached with chiral N-phosphonyl group
protecting their carbonyl groups with 1,3-dithioacetal to give
R-amino-1,3-dithianes that can be selectively deprotected for
further functional manipulations.15 A few years ago, the asym-
metric addition of 2-lithio-1,3-dithianes to sulfinimines (N-
sulfinyl imines) had been successfully conducted by Davis and
our group.16 In the former,16a three examples were studied by
reacting 2-lithio-2-alkyl-1,3-dithiane with N-sulfinyl imine nu-
cleophiles at ꢀ78 °C without the use of any Lewis acid promoter
in yields of 70%ꢀ84% and diastereoselectivity from 92% to
>97% de.7a This reaction has been successfully utilized for the
asymmetric synthesis of polyoxypeptin amino acid (2S,3R)-(ꢀ)-
3-hydroxy-3-methylproline. In the latter,16b N-sulfinyl imine
nucleophiles were subjected to the reaction with 2-lithio-2-
phenyl-1,3-dithiane, a less reactive nucleophile than 2-lithio-2-
alkyl-1,3-dithianes; this decrease in reactivity was attributed to
the electronic delocalization effect from the aromatic phenyl ring
of 2-lithio-2-phenyl-1,3-dithianes. The reaction has to be per-
formed at a higher temperature (ꢀ20 to ꢀ25 °C) in THF in
the presence of Et2AlCl as a Lewis acid promoter.16b Excellent
diastereoselectivities and chemical yields (64ꢀ95%) were
achieved with all individual isomers readily separable via column
chromatography.
2793
dx.doi.org/10.1021/jo200070d |J. Org. Chem. 2011, 76, 2792–2797

The Journal of Organic Chemistry
ARTICLE
Scheme 2
aromatic rings (Table 2, entries 7, 8, and 15) were all found
suitable for this reaction with regard to both chemical yield and
diastereoselectivity. Good yields (74ꢀ85%) and good to excel-
lent diastereoselectivities ranging from 100:24 to >99:1 were
observed. The substituents on 2-lithio-1,3-dithianes also showed
different effects on the diastereoselectivities of the reactions.
Increasing the bulkiness of R2 of 2-lithio-1,3-dithianes (2-lithio-
2-methyl-1,3-dithianes) resulted in lower diastereoselectivities.
For 2-lithio-1,3-dithiane (R2 = H), excellent diastereoselectivities
of >99:1 were obtained with the exception of the 3-Br substituted
N-phosphonyl imine (Table 2, entry 13). 2-Lithio-2-methyl-1,3-
dithiane (R2 = Me) gave good diastereoselectivities of 100:5 to
100:10 for all the substrates that were examined (entries 2, 5, 8, 10,
12, and 14 in Table 2). For 2-lithio-2-phenyl-1,3-dithiane (R2 = Ph),
moderate diastereoselectivities of 100:20 to 100:24 were obtained
(entries 3 and 6, Table 2). As compared with the former two
aliphatic 1-lithio-1,3-dithiane nucleophiles, 2-lithio-2-phenyl-
1,3-dithiane showed lower reactivity due to the electron deloca-
lization effect of the aromatic ring, as mentioned above.
The absolute configuration of the resulting Umpolung adducts
was determined by converting a product (6a) into an authentic
sample.16,17 In this procedure, the N-phosphonyl group was
cleaved by treating with HBr/MeOH at room temperature,
followed by protection of the free amino group using TsCl in
the presence of triethylamine to give a known derivative, 7
(Scheme 2). The optical rotation of 7 was consistent with that
of a known sample with R-configuration. The known compound
7 was obtained with a chemical yield of 83%. In the meanwhile, N,
N-diisopropyl diamine chiral auxiliary was recovered in quanti-
tative yield by one-time extraction of the cleavage mixture with n-
butanol.
On the basis of this result, a six-membered chairlike transition
state was proposed to explain the resulting stereoselectivity
(Figure 1); this model is similar to that of the previous two
asymmetric Umpolung reaction processes. Interestingly, the R
configuration of the final product was in discordance with the
stereochemistry of other enolate addition reactions that were
studied before.5ꢀ9 This is the first example in which the (R,R)-
1,2-cyclohexanediamine auxiliary resulted in the opposite control
of forming chiral N-phosphonyl amine products. This observa-
tion is probably due to the fact that, in nearly all previous
asymmetric reactions, the lithium cation is coordinated unto
the nitrogen of the N-phosphonyl amine reactant. However, in
this reaction, the metal lithium is connected unto the oxygen
atom of N-phosphonyl imine.
Figure 1. Proposed transition state of Umpolung reaction.
were readily obtained by washing the solid crude products with
hexane or a mixture of hexaneꢀethyl acetate.
For this asymmetric Umpolung reaction, the N-phosphonyl
imine was first subjected to the reaction with 2-lithio-1,3-dithiane
at ꢀ78 °C in THF for 12 h. Surprisingly, there was no product
observed under this typical condition. The reaction temperature
was then increased in a range from ꢀ25 to ꢀ20 °C; only a trace
amount of the anticipated Umpolung adduct was observed.
Previously, Et2AlCl has been successfully utilized to promote
the chiral sulfinimine-based asymmetric Umpolung reaction;16b
thus, it was utilized in this system. Interestingly, no obvious
improvement was observed after Et2AlCl and Et2AlI were added
into the reaction mixture. We found that the manner of addition
of the N-phosphonyl imine is very important for this reaction to
occur. Slow addition of N-phosphonyl imine into 2-lithio-1,3-
dithiane solution via a syringe pump was proven to be an efficient
way to consume all imine starting material in good chemical
yield (82%) and excellent diastereoselectivity (>99:1). In fact,
only one isomer was detected by 31P NMR analysis of the crude
product.
Next, N-phosphonyl imines with different N-protecting group
were examined (Table 1) for comparison. Among the five protect-
ing groups, the isopropyl group (Table 1, entry 1) was found to be
the best with regard to both chemical yield and diastereoselectivity.
The cyclohexyl-protected N-phosphonyl imine (Table 1, entry 3)
produced a fairly good diastereoselectivity (100:5), but the chemi-
cal yield was substantially decreased to 32%. Interestingly, the CH2-
1-naphthyl protected imine (Table 1, entry 5), which was proven to
be efficient in some of our previous asymmetric additions of ester
and ketone derived enolates, only produced a moderate yield
(70%) and diastereoselectivity (100:16).
On the basis of the above optimal conditions, the substrate
scope of this Umpolung reaction was examined by using several
N-phosphonyl imines and lithio-1,3-dithianes. N-Phosphonyl
imines containing both electron-withdrawing groups (Table 2,
entries 4ꢀ6 and 9ꢀ14) and electron-donating groups on the
’ CONCLUSION
Chiral N-phosphonyl imines have been found to react with
2-lithio-1,3-dithiane, 2-lithio-2-methyl-1,3-dithiane, and 2-lithio-
2-phenyl-1,3-dithiane without the use of any Lewis acid promo-
ters to produce R-amino-1,3-dithianes in good yields and good to
excellent diastereoselectivities. The manner by which chiral N-
phosphonyl imines are added into the solution of 2-lithio-1,3-
dithiane was found to be crucial for this asymmetric Umpolung
reaction. This reaction provided an easy access to R-amino-1,3-
dithianes as versatile synthetic building blocks. The current
synthesis was proven to follow the GAP chemistry (group-
assistant-purification chemistry) process by avoiding the use of
traditional purifications via chromatography and recrystalliza-
tion, i.e., the pure chiral R-amino-1,3-dithianes attached with the
chiral N-phosphonyl group were readily obtained by washing the
2794
dx.doi.org/10.1021/jo200070d |J. Org. Chem. 2011, 76, 2792–2797

The Journal of Organic Chemistry
ARTICLE
solid crude products with hexane or a mixture of hexaneꢀethyl
1.09 (d, J = 6.6 Hz, 3H), 0.98 (d, J = 6.9 Hz, 3H); 13C NMR (125 MHz,
CDCl3) δ 163.3, 161.3, 136.2, 129.1 (d, J = 8.0 Hz), 115.0, 114.8, 59.9
(d, J = 11.4 Hz), 59.0 (d, J = 9.9 Hz), 58.8, 55.7, 44.1, 43.8 (d, J = 4.5 Hz),
31.5 (d, J = 11.4 Hz), 31.0 (d, J = 9.4 Hz), 30.4, 30.0, 25.5, 24.3 (d, J =
13.3 Hz), 23.9 (d, J = 7.9 Hz), 23.6 (d, J = 3.0 Hz), 19.5, 19.3 (d, J = 2.0
Hz); 31P NMR (202 MHz; CDCl3) δ 23.55; 19F NMR (282.34 MHz;
CDCl3) δ ꢀ114.97; HRMS (ESI) m/z calcd for C23H38FN3OPS2
486.2173, found 486.2174.
acetate.
’ EXPERIMENTAL SECTION
Typical Procedure for the Asymmetric Synthesis of r-
Amino-1,3-dithianes via Chiral N-Phosphonyl Imines. A 30-
mL, oven-dried reaction vial equipped with a magnetic stir bar and a
rubber septum was charged with 1,3-dithiane (0.2 mmol) in THF
(2 mL). The solution was cooled to ꢀ30 °C and n-butyl lithium (0.22
mmol) was added slowly. After 1 h, the temperature of the reaction
mixture was brought to ꢀ78 °C and N-phosphonyl imine (0.1 mmol)
was dissolved in 1 mL of THF and added by means of syringe pump for 1
h. The reaction mixture was stirred overnight while the temperature was
slowly raised to ꢀ30 °C and consequently to rt. After confirming the
completion of the reaction, satd NH4Cl solution was added to quench
the reaction. The aqueous phase was washed with EtOAc (2 ꢁ 10 mL),
and the organic layer was collected, dried over anhydrous Na2SO4, and
concentrated under reduced pressure. Purification of the crude product
was done by simple washing with hexanes or, in some instances, with a
mixture of hexane and ethyl acetate, which is defined as GAP chemistry
by our group.13 The final product was obtained as a white solid. When
the final products are oily liquids, purification by flash column chroma-
tography (solvent system EtOAcꢀhexanes 1:1 to acetoneꢀhexanes 1:1)
was performed.
Compound 6e. Mp 178ꢀ180 °C; 1H NMR (300 MHz, CDCl3) δ
7.44ꢀ7.40 (m, 2H), 7.04ꢀ6.96 (m, 2H), 4.69ꢀ4.62 (m, 1H),
3.72ꢀ3.60 (m, 2H), 3.20ꢀ3.14 (m, 1H), 2.89ꢀ2.70 (m, 5H),
2.06ꢀ1.97 (m, 4H), 1.71ꢀ1.64 (m, 5H), 1.34ꢀ1.28 (m, 5H), 1.19 (d,
J = 6.9 Hz, 3H), 1.09 (d, J = 6.9 Hz, 3H), 1.04 (d, J = 6.9 Hz, 3H), 0.86 (d,
J = 6.9 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 163.2, 161.2, 137.1,
130.4 (d, J = 7.9 Hz), 114.5, 114.4, 63.4, 59.5 (d, J = 11.9 Hz), 58.9 (d, J =
9.9 Hz), 54.4 (d, J = 9.9 Hz), 53.8, 43.9 (d, J = 3.0 Hz), 43.8 (d, J = 3.9
Hz), 32.0, (d, J = 12.4 Hz), 31.4 (d, J = 9.9 Hz), 30.2 (d, J = 9.9 Hz), 29.7,
29.3, 26.9 (d, J = 6.5 Hz), 26.2, 24.7, 24.3, 23.1 (d, J = 4.0 Hz), 20.7 (d, J =
13.8 Hz), 19.7, 19.1; 31P NMR (202 MHz; CDCl3) δ 24.44, 24.06;
HRMS (ESI) m/z calcd for C24H40FN3OPS2 500.2329, found 500.2332
Compound 6f. 1H NMR (300 MHz, CDCl3) δ 7.68ꢀ7.65 (m, 2H),
7.29ꢀ7.26 (m, 3H), 6.79ꢀ6.74 (m, 4H), 4.86ꢀ4.78 (m, 1H), 3.69ꢀ
3.61 (m, 1H), 3.20ꢀ3.11 (m, 1H), 3.05ꢀ2.85 (m, 2H), 2.69ꢀ2.54 (m,
5H), 2.05ꢀ1.98 (m, 2H), 1.88ꢀ1.85 (m, 2H), 1.72ꢀ1.69 (m, 2H), 1.35ꢀ
1.34 (m, 5H), 1.20ꢀ1.18 (m, 3H), 1.07ꢀ1.01 (m, 5H), 0.95ꢀ0.85
(m, 4H); 13C NMR (125 MHz, CDCl3) δ 163.0, 161.0, 138.1, 135.5
(d, J = 3.0 Hz), 130.5, 128.2, 127.3, 113.7, 113.6, 65.7 (d, J = 9.4 Hz),
65.3, 59.4 (d, J = 3.4 Hz), 59.3 (d, J = 4.5 Hz), 58.9, 58.8, 54.7, 53.8,
44.1 (d, J = 3.0 Hz), 43.8 (d, J = 2.9 Hz), 43.7 (d, J = 4.5 Hz), 43.3 (d,
J = 4.9 Hz), 36.7, 32.0 (d, J = 12.3 Hz), 31.5, (d, J = 13.3 Hz) 29.2,
28.4, 27.5, 27.3, 24.7, 24.4 (d, J = 3.9 Hz), 24.3 (d, J = 3.5 Hz), 24.0 (d,
J = 5.0 Hz), 19.7 (d, J = 2.4 Hz), 19.5 (d, J = 1.9 Hz), 19.3, 18.9; 31P
NMR (202 MHz; CDCl3) δ 24.01, 23.57; 19F NMR (282.34 MHz;
CDCl3) δ ꢀ115.60; HRMS (ESI) m/z calcd for C29H42FN3OPS2
562.2486, found 562.2500.
Compound 6a. Mp 211ꢀ213 °C; 1H NMR (300 MHz, CDCl3) δ
7.43ꢀ7.30 (m, 5H), 4.66 (td, J = 4.5 Hz, J = 10.2 Hz, 1H), 4.36 (d, J = 4.5
Hz, 1H), 3.59ꢀ3.34 (m, 3H), 3.10ꢀ2.90 (m, 1H), 2.79ꢀ2.68 (m, 4H),
2.12ꢀ1.95 (m, 4H), 1.77 (bs, 3H), 1.41ꢀ1.29 (m, 4H), 1.25 (d, J = 6.6
Hz, 3H), 1.19 (d, J = 6.9 Hz, 3H), 1.07 (d, J = 6.9 Hz, 3H), 0.93 (d, J = 6.9
Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 140.4 (d, J = 2.5 Hz), 128.0,
127.5, 59.9 (d, J = 11.3 Hz), 59.4, 59.0 (d, J = 9.9 Hz), 55.5 (d, J = 5.9
Hz), 44.1 (d, J = 3.5 Hz), 43.8 (d, J = 4.9 Hz), 31.5 (d, J = 11.9 Hz), 31.1
(d, J = 9.0 Hz), 30.3, 30.0, 25.6, 24.4 (d, J = 11.9 Hz), 24.0 (d, J = 8.4 Hz),
23.6 (d, J = 3.5 Hz), 19.5, 19.3 (d, J = 2.4 Hz); 31P NMR (202 MHz;
CDCl3) δ 23.71; HRMS (ESI) m/z calcd for C23H39N3OPS2 468.2267,
found 468.2267.
Compound 6g. Mp 220ꢀ223 °C; 1H NMR (300 MHz, CDCl3) δ
7.29ꢀ7.26 (m, 2H), 7.16ꢀ7.14 (m, 2H), 4.61 (td, J = 4.5 Hz, J = 10.5
Hz, 1H), 4.35 (d, J = 4.2 Hz, 1H), 3.55ꢀ3.35 (m, 3H), 3.01ꢀ2.93 (m,
1H), 2.85ꢀ2.67 (m, 5H), 2.34 (s, 3H), 2.11ꢀ1.96 (m, 3H), 1.76 (bs,
3H), 1.36ꢀ1.30 (m, 4H), 1.25 (d, J = 6.9 Hz, 3H), 1.20 (d, J = 6.9 Hz,
3H), 1.07 (d, J = 6.6 Hz, 3H), 0.93 (d, J = 6.9 Hz, 3H); 13C NMR (125
MHz, CDCl3) δ 137.4, 137.1, (d, J = 3.0 Hz), 128.7, 127.2, 59.9 (d, J =
11.4 Hz), 59.1, 59.0 (d, J = 9.9 Hz), 56.0 (d, J = 6.0 Hz), 44.1 (d, J = 3.4
Hz), 43.7 (d, J = 4.9 Hz), 31.5 (d, J = 11.9 Hz), 31.1 (d, J = 8.9 Hz), 30.5,
30.1, 25.6, 24.3 (d, J = 14.3 Hz), 24.0 (d, J = 8.5 Hz), 23.6 (d, J = 3.5 Hz),
21.2, 19.5, 19.2 (d, J = 2.4 Hz); 31P NMR (202 MHz; CDCl3) δ 23.75;
HRMS (ESI) m/z calcd for C24H40N3OPS2 482.2424, found 482.2433.
Compound 6h. Mp 182ꢀ184 °C; 1H NMR (300 MHz, CDCl3) δ
7.34ꢀ7.31 (m, 2H), 7.12ꢀ7.10 (m, 2H), 4.68 (t, J = 9.6 Hz, 1H), 3.77ꢀ
3.63 (m, 1H), 3.22ꢀ3.12 (m, 1H), 3.06ꢀ2.97 (m, 1H), 2.92ꢀ2.79 (m,
3H), 2.77ꢀ2.64 (m, 3H), 2.32 (s, 3H), 2.05ꢀ1.88 (m, 4H), 1.73ꢀ1.69
(m, 2H), 1.66 (s, 3H), 1.35ꢀ1.24 (m, 4H), 1.20 (d, J = 6.6 Hz, 3H),
1.06ꢀ1.04 (m, 6H), 0.85 (d, J = 6.9 Hz, 3H); 13C NMR (125 MHz,
CDCl3) δ 137.8, 137.0, 128.6, 128.2, 63.4, 59.3 (d, J = 11.8 Hz), 58.8
(d, J = 9.9 Hz), 54.5, (d, J = 9.9 Hz), 43.7, 31.9 (d, J = 12.4 Hz), 31.4
(d, J = 9.9 Hz), 29.6, 26.8, 26.4, 26.2, 24.8, 24.2, 24.1 (d, J = 3.9 Hz),
21.0, 19.5 (d, J = 1.9 Hz), 19.0; 31P NMR (202 MHz; CDCl3) δ 24.76,
24.11; HRMS (ESI) m/z calcd for C25H42N3OPS2 496.2580, found
496.2588.
Compound 6b. Mp 186ꢀ188 °C; 1H NMR (300 MHz, CDCl3) δ
7.48ꢀ7.44 (m, 2H), 7.34ꢀ7.23 (m, 3H), 4.72 (t, J = 9.3 Hz, 1H),
3.76ꢀ3.67 (m, 1H), 3.22 (t, J = 8.4 Hz, 1H), 2.77ꢀ2.66 (m, 3H),
2.06ꢀ1.84 (m, 4H), 1.74ꢀ1.69 (m, 2H), 1.67 (s, 3H), 1.37ꢀ1.24 (m,
4H), 1.22 (d, J = 6.9 Hz, 3H), 1.08ꢀ1.03 (m, 6H), 0.84 (d, J = 6.9 Hz,
3H); 13C NMR (125 MHz, CDCl3) δ 141.0, 128.8, 127.6, 127.5, 63.8,
59.4 (d, J = 11.9 Hz), 58.9 (d, J = 9.8 Hz), 54.3 (d, J = 9.4 Hz), 43.8 (d, J =
3.0 Hz), 43.7 (d, J = 4.5 Hz), 31.9 (d, J = 11.9 Hz), 31.4 (d, J = 9.9 Hz),
29.6, 26.9, 26.7, 26.2, 24.7, 24.4, 24.3, 24.1 (d, J = 4.5 Hz), 19.6 (d, J = 1.5
Hz), 19.0; 31P NMR (202 MHz; CDCl3) δ 24.66, 24.03.
Compound 6c. 1H NMR (300 MHz, CDCl3) δ 7.72ꢀ7.68 (m, 2H),
7.30ꢀ7.26 (m, 3H), 7.16ꢀ7.10 (m, 3H), 6.84ꢀ6.81 (m, 2H),
4.89ꢀ4.81 (m, 1H), 3.70ꢀ3.60 (m, 1H), 3.19ꢀ3.05 (m, 2H),
2.93ꢀ2.88 (m, 1H), 2.68ꢀ2.55 (m, 4H), 2.04ꢀ2.00 (m, 2H),
1.89ꢀ1.86 (m, 2H) 1.73ꢀ1.69 (m, 2H), 1.32ꢀ1.26 (m, 5H), 1.20 (d,
J = 6.6 Hz, 3H), 1.09ꢀ1.06 (m, 3H), 0.98ꢀ0.95 (m, 3H), 0.91ꢀ0.89 (m,
3H); 13C NMR (125 MHz, CDCl3) δ 139.5, 138.2, 130.8, 129.0, 128.1,
127.3, 127.2, 126.9, 65.9, 59.4 (d, J = 12.4 Hz), 58.9 (d, J = 9.8 Hz), 43.9
(d, J = 3.0 Hz), 43.7 (d, J = 4.5 Hz), 32.0 (d, J = 12.4 Hz), 31.6 (d, J = 9.4
Hz), 29.7, 27.6, 27.4, 24.8, 24.4 (d, J = 6.0 Hz), 19.6, 19.0; 31P NMR (202
MHz; CDCl3) δ 24.19, 23.56; HRMS (ESI) m/z calcd for
C29H43N3OPS2 544.2580, found 544.2590.
Compound 6d. Mp 200ꢀ205 °C; 1H NMR (300 MHz, CDCl3) δ
7.41ꢀ7.37 (m, 2H), 7.08ꢀ7.02 (m, 2H), 4.67 (td, J = 4.2 Hz, J = 10.2
Hz, 1H), 4.34 (d, J = 4.2 Hz, 1H), 3.53ꢀ3.32 (m, 3H), 3.00ꢀ2.94 (m,
1H), 2.83ꢀ2.70 (m, 5H), 2.10ꢀ1.99 (m, 4H), 1.82ꢀ1.73 (m, 3H),
1.36ꢀ1.30 (m, 3H), 1.23 (d, J = 6.9 Hz, 3H), 1.18 (d, J = 6.9 Hz, 3H),
Compound 6i. Mp 217ꢀ219 °C; H NMR (300 MHz, CDCl3) δ
1
7.38ꢀ7.31(m, 4H), 4.66 (td, J = 4.2 Hz, J = 10.5 Hz, 1H), 4.34 (d, J = 4.5
Hz, 1H), 3.54ꢀ3.32 (m, 3H), 3.00ꢀ2.90 (m, 1H), 2.83ꢀ2.69 (m, 5H),
2.11ꢀ1.99 (m, 4H), 1.85ꢀ1.71 (m, 3H), 1.36ꢀ1.30 (m, 3H), 1.23 (d,
J = 6.9 Hz, 3H), 1.19 (d, J = 6.6 Hz, 3H), 1.10 (d, J = 6.9 Hz, 3H), 0.99
2795
dx.doi.org/10.1021/jo200070d |J. Org. Chem. 2011, 76, 2792–2797

The Journal of Organic Chemistry
ARTICLE
(d, J = 6.9 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 138.9, 133.6, 128.8,
128.2, 59.9 (d, J = 11.3 Hz), 59.0, 58.9 (d, J = 6.5 Hz), 55.5 (d, J = 6.4 Hz),
44.1 (d, J = 3.0 Hz), 43.8 (d, J = 4.5 Hz), 31.5 (d, J = 11.9 Hz), 31.0 (d, J =
8.9 Hz), 30.4, 30.1, 29.7, 25.5, 24.3 (d, J= 10.9 Hz), 24.0 (d, J= 8.9 Hz), 23.6
(d, J = 3.4 Hz), 19.5, 19.4 (d, J = 2.0 Hz); 31P NMR (202 MHz; CDCl3) δ
23.53; HRMS (ESI) m/z calcd for C23H38ClN3OPS2 502.1877, found
502.1880.
19.1; 31P NMR (202 MHz; CDCl3) δ 24.35, 24.19; HRMS (ESI) m/z
calcd for C24H40BrN3OPS2 560.1529, found 560.1534.
Compound 6o. Mp 192ꢀ194 °C; 1H NMR (300 MHz, CDCl3) δ
7.47ꢀ7.32 (m, 7H), 6.99ꢀ6.95 (m, 2H), 5.08 (s, 2H), 4.62 (td, J = 4.2
Hz, J = 10.8 Hz 1H), 4.35 (d, J = 4.5 Hz, 1H), 3.55ꢀ3.38 (m, 3H), 3.00ꢀ
2.95 (m, 1H), 2.81ꢀ2.67 (m, 5H), 2.12ꢀ2.02 (m, 3H), 1.82ꢀ1.77 (m,
3H), 1.37ꢀ1.29 (m, 4H), 1.26 (d, J = 6.6 Hz, 3H), 1.20 (d, J = 6.9 Hz,
3H), 1.08 (d, J = 6.6 Hz, 3H), 0.94 (d, J = 6.9 Hz, 3 H); 13C NMR (125
MHz, CDCl3) δ 158.4, 136.9, 132.8 (d, J = 2.4 Hz), 128.7, 128.5, 127.9,
127.5, 114.3, 69.9, 60.0 (d, J = 11.9 Hz), 59.1 (d, J = 9.9 Hz), 58.9, 55.9
(d, J = 6.9 Hz), 44.2 (d, J = 2.9 Hz), 43.8 (d, J = 4.9 Hz), 31.5 (d, J = 11.9
Hz), 31.1 (d, J = 9.4 Hz), 30.3, 30.0, 25.6, 24.4, 24.3, 24.0 (d, J = 8.4 Hz),
23.7 (d, J = 2.9 Hz), 19.6, 19.4 (d, J = 2.0 Hz); 31P NMR (202 MHz;
CDCl3) δ 23.68; HRMS (ESI) m/z calcd for C30H45N3O2PS2 574.2686,
found 574.2685.
1
Compound 6j. Mp 197ꢀ199 °C; H NMR (300 MHz, CDCl3) δ
7.39ꢀ7.38 (m, 1H), 7.37ꢀ7.36 (m, 1H), 7.28ꢀ7.23 (m, 2H), 4.68 (t, J =
9.6 Hz, 1H), 3.74 (m, 1H), 3.14ꢀ3.08 (m, 1H), 2.97ꢀ2.61 (m, 7H),
2.04ꢀ1.83 (m, 4H), 1.72ꢀ1.67 (m, 2H), 1.62 (s, 3H), 1.34ꢀ1.23 (m,
4H), 1.19 (d, J = 6.9 Hz, 3H), 1.10 (d, J = 6.9 Hz, 3H), 1.03 (d, J = 6.9 Hz,
3H), 0.84 (d, J = 6.9 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 139.8,
133.2, 130.2, 127.7, 63.4, 59.4 (d, J = 11.8 Hz), 58.9 (d, J = 9.8 Hz), 54.2
(d, J = 9.4 Hz), 43.8 (d, J = 3.5 Hz), 43.7 (d, J = 4.5 Hz), 31.9 (d, J = 11.9
Hz), 31.4 (d, J = 9.9 Hz), 29.2, 26.9, 26.8, 26.2, 24.7, 24.4, 24.3, 24.3, 24.0
(d, J = 3.9 Hz), 19.7 (d, J = 2.0 Hz), 19.0; 31P NMR (202 MHz; CDCl3)
δ 24.36, 24.03; HRMS (ESI) m/z calcd for C24H40ClN3OPS2 516.2034,
found 516.2028.
’ ASSOCIATED CONTENT
Supporting Information. 1H, 13C, 19F, and 31P NMR
S
b
1
Compound 6k. Mp 217ꢀ219 °C; H NMR (300 MHz, CDCl3) δ
spectra of all pure products. This material is available free of
charge via the Internet at http://pubs.acs.org.
7.46ꢀ7.42 (m, 2H), 7.27ꢀ7.25 (m, 2H), 4.60 (td, J = 4.5 Hz, J = 10.5
Hz, 1H), 4.30 (d, J = 4.5 Hz, 1H), 3.50ꢀ3.25 (m, 3H), 2.96ꢀ2.89 (m,
1H), 2.78ꢀ2.65 (m, 5H), 2.07ꢀ1.98 (m, 4H), 1.78ꢀ1.73 (m, 3H),
1.29ꢀ1.26 (m, 3H), 1.19 (d, J = 6.6 Hz, 3H), 1.14 (d, J = 6.6 Hz, 3H),
1.05 (d, J = 6.6 Hz, 3H), 0.95 (d, J = 6.9 Hz, 3H); 13C NMR (125 MHz,
CDCl3) δ 139.5, (d, J = 2.9 Hz), 131.1, 129.2, 121.8, 59.9 (d, J = 11.3
Hz), 59.0, 59.0, 58.9, 55.4 (d, J = 6.4 Hz), 44.1 (d, J = 3.0 Hz), 43.8 (d, J =
4.5 Hz), 31.5 (d, J = 11.9 Hz), 31.0 (d, J = 9.4 Hz), 30.4, 30.1, 25.5, 24.3
(d, J = 9.9 Hz), 23.9 (d, J = 8.4 Hz), 23.5 (d, J = 3.5 Hz), 19.5, 19.4 (d, J =
2.0 Hz); 31P NMR (202 MHz; CDCl3) δ 23.49 ; HRMS (ESI) m/z calcd
for C23H37BrN3OPS2 546.1372, found 546.1373.
’ AUTHOR INFORMATION
Corresponding Author
guigen.li@ttu.edu; mshi@mail.sioc.ac.cn.
’ ACKNOWLEDGMENT
We are grateful to the Robert A. Welch Foundation (D-1361),
NIH (R03DA026960), and NSFC (20928001) for their gener-
ous support. The content is solely the responsibility of the
authors and does not necessarily represent the official views of
the National Institute on Drug Abuse or the National Institutes
of Health.
1
Compound 6l. Mp 198ꢀ200 °C; H NMR (300 MHz, CDCl3) δ
7.44ꢀ7.39 (m, 2H), 7.34ꢀ7.30 (m, 2H), 4.67 (t, J = 9.3 Hz, 1H),
3.74ꢀ3.61 (m, 1H), 3.15 (t, J = 9.3 Hz, 1H), 2.97ꢀ2.79 (m, 4H),
2.74ꢀ2.64 (m, 3H), 2.04ꢀ1.81 (m, 4H), 1.72ꢀ1.67 (m, 2H), 1.62 (s,
3H), 1.33ꢀ1.21 (m, 4H), 1.19 (d, J = 6.9 Hz, 3H), 1.10 (d, J = 6.9 Hz,
3H), 1.03 (d, J = 6.6 Hz, 3H), 0.85 (d, J = 6.9 Hz, 3H); 13C NMR (125
MHz, CDCl3) δ 140.3, 130.6, 121.4, 63.4, 59.4 (d, J = 11.9 Hz), 58.9 (d,
J = 9.9 Hz), 54.2 (d, J = 9.4 Hz), 43.8 (d, J = 3.5 Hz), 43.7 (d, J = 4.5 Hz),
31.9 (d, J = 12.4 Hz), 31.4 (d, J = 9.9 Hz), 26.9, 26.7, 26.2, 24.7, 24.4 (d,
J = 9.4 Hz), 24.3, 24.1 (d, J = 4.4 Hz), 19.7 (d, J = 1.4 Hz), 19.0; 31P NMR
(202 MHz; CDCl3) δ 24.40, 24.08; HRMS (ESI) m/z calcd for
C24H40BrN3OPS2 560.1529, found 560.1523.
’ REFERENCES
(1) (a) Schreiber, S. L. Science. 2000, 287, 1964. (b) Frederic, L. -M.;
Thierry, C.; Jean, R. J. Am. Chem. Soc. 2005, 127, 17176. (c) Trost, B. M.
Science 1991, 254, 1471. (d) Wender, P. A.; Gamber, G. G.; Hubbard,
R. D.; Pham, S. M.; Zhang, L. J. Am. Chem. Soc. 2005, 127, 2836. (e)
Snyder, S. A.; Breazzano, S. P.; Lin, R. Y.; Zografos, A. L. J. Am. Chem.
Soc. 2009, 131, 1753.
(2) (a) Tietze, L. F.; Brazel, C. C.; Holsken, S.; Magull, J.; Ringe, A.
Angew. Chem., Int. Ed. 2008, 47, 5246. (b) Huang, Y.; Waljji, A. M.;
Larsen, C. H.; MacMillan, D. W. C. J. Am. Chem. Soc. 2005, 127, 1505.
(c) Yang, J. W.; Fonseca, H. M. T.; List, B. J. Am. Chem. Soc. 2005,
127, 15036.
(3) (a) Tietze, L. F.; Brasche, G.; Gericke, K. M. Domino Reactions in
Organic Synthesis; Wiley-VCH: Weinheim, 2006. (b) Ivanov, A. S. Chem.
Soc. Rev. 2008, 37, 789. (c) de Meijere, A.; von Zezschwitz, P.; Br€ase, S.
Acc. Chem. Res. 2005, 38, 413.
(4) (a) Li, C.-J. Acc. Chem. Res. 2010, 43, 581. (b) Li, C.-J.; Trost,
B. M. Proc. Natl. Acad. Sci. U. S. A. 2008, 105, 13197.
(5) (a) Kaur, P.; Pindi, S.; Wever, W.; Rajale, T.; Li, G. Chem.
Commun 2010, 46, 4330. (b) Kaur, P.; Pindi, S.; Wever, W.; Rajale, T.;
Li, G. J. Org. Chem. 2010, 75, 5144.
(6) (a) Kattuboina, A.; Li, G. Tetrahedron Lett. 2008, 49, 1573. (b)
Kattuboina, A.; Kaur, P.; Ai, T.; Li, G. Chem. Biol. Drug Des. 2008,
71, 216. (c) Kattuboina, A.; Kaur, P.; Nguyen, T.; Li, G. Tetrahedron Lett.
2008, 49, 3722. (d) Han, J.; Ai, T.; Nguyen, T.; Li, G. Chem. Biol. Drug
Des. 2008, 72, 120.
Compound 6m. Mp 168ꢀ170 °C; 1H NMR (300 MHz, CDCl3) δ
7.59 (bs, 1H), 7.46ꢀ7.43 (m, 1H), 7.38ꢀ7.35 (m, 1H), 7.27ꢀ7.21 (m,
1H), 4.69 (td, J = 4.5 Hz, J = 10.5 Hz, 1H), 4.33 (d, J = 4.2 Hz, 1H), 3.55ꢀ
3.29 (m, 3H), 3.12ꢀ2.91 (m, 1H), 2.81ꢀ2.71 (m, 4H), 2.11ꢀ1.94 (m,
3H), 1.78 (bs, 4H), 1.43ꢀ1.29 (m, 4H), 1.22ꢀ1.17 (m, 6H), 1.13 (d, J =
6.6 Hz, 3H), 1.03 (d, J = 6.9 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ
143.1, 130.9, 130.4, 129.5, 126.3, 122.2, 59.9 (d, J = 11.9 Hz), 59.2, 59.0 (d,
J = 9.9 Hz), 55.1 (d, J = 7.0 Hz), 44.1 (d, J = 3.0 Hz), 43.8 (d, J = 5.0 Hz),
31.6, 24.1 (d, J = 8.5 Hz), 23.6 (d, J = 4.0 Hz), 19.5, 19.5, 19.5; 31P NMR
(202 MHz; CDCl3) δ 23.46, 23.64; HRMS (ESI) m/z calcd for C23H38-
BrN3OPS2 546.1372, found 546.1384.
Compound 6n. Mp 180ꢀ182 °C; 1H NMR (300 MHz, CDCl3) δ
7.45ꢀ7.40 (m, 2H), 7.27ꢀ7.21 (m, 1H), 7.23ꢀ7.17 (m, 1H), 4.71 (t, J =
9.6 Hz, 1H), 3.76ꢀ3.67 (m, 1H), 3.22ꢀ3.16 (m, 1H), 2.95ꢀ2.66 (m,
6H), 2.07ꢀ2.00 (m, 3H), 1.98ꢀ1.88 (m, 2H), 1.72 (bs, 2H), 1.67 (s,
3H), 1.32ꢀ1.28 (m, 4H), 1.24 (d, J = 6.9 Hz, 3H), 1.15 (d, J = 6.6 Hz,
3H), 1.08 (d, J = 6.9 Hz, 3 H), 0.93 (d, J = 7.2 Hz, 3H); 13C NMR (125
MHz, CDCl3) δ 143.6, 131.6, 130.5, 129.1, 127.9, 121.8, 63.6, 59.4 (d,
J = 12.4 Hz), 59.9, (d, J = 9.9 Hz), 54.0 (d, J = 9.9 Hz), 43.9 (d, J = 3.5 Hz),
43.8 (d, J = 4.4 Hz), 32.0 (d, J = 11.9 Hz), 31.4 (d, J = 9.9 Hz), 26.9, 26.8,
26.2, 24.6, 24.5 (d, J= 8.9 Hz), 24.3, 24.1 (d, J= 4.0 Hz), 19.8 (d, J = 2.0 Hz),
(7) (a) Kaur, P.; Nguyen, T.; Li, G. Eur. J. Org. Chem. 2009, 912. (b)
Han, J.; Ai, T.; Li, G. Synthesis 2008, 16, 2519. (c) Han, J.; Chen, Z. -X.;
Ai, T.; Li, G. Chem. Biol. Drug Des. 2009, 73, 203. (d) Chen, Z. -X.; Ai, T.;
2796
dx.doi.org/10.1021/jo200070d |J. Org. Chem. 2011, 76, 2792–2797

The Journal of Organic Chemistry
ARTICLE
Kaur, P.; Li, G. Tetrahedron Lett. 2009, 50, 1079. (e) Ai, T.; Li, G. Bioorg.
Med. Chem. Lett. 2009, 19, 3967.
(8) (a) Kaur, P.; Shakya, G.; Sun, H.; Pan, Y.; Li, G. Org. Biomol.
Chem. 2010, 8, 1091. (b) Ai, T.; Han, J.; Chen, Z. X.; Li, G. Chem. Biol.
Drug. Des. 2009, 73, 203. (c) Kattuboina, A.; Kaur, P.; Ai, T.; Li, G. Chem.
Biol. Drug Des. 2008, 71, 216. (d) Ai, T.; Pindi, S.; Kattamuri, P. V.; Li, G.
Sci. China Series B: Chem. 2010, 53, 125.
(9) (a) For chiral N-phosphinyl imine chemistry, see:Pindi, S.; Kaur,
P.; Shakya, G.; Li, G. Chem. Biol. Drug Design 2011, 75, 20. (b) For chiral
N-phosphoryl imine chemistry, see:Sun, H.; Rajale, T.; Pan, Y.; Li, G.
Tetrahedron Lett. 2010, 51, 4403.
(10) (a) Coppola, G., Schuster, H. Asymmetric Synthesis: Construction
of Chiral Molecules Using Amino Acids; Wiley: New York, 1987. For
reviews, see: (a) Reetz, M. T. Chem. Rev. 1999, 99, 1121. (b) Sardina,
F. J.; Rapoport, H. Chem. Rev. 1996, 96, 1825. (c) Reetz, M. T. Angew.
Chem., Int. Ed. Engl. 1991, 30, 1531.
(11) For reviews see:(a) Reetz, M. T. Chem. Rev. 1999, 99, 1121. (b)
Sardina, F. J.; Rapoport, H. Chem. Rev. 1996, 96, 1825. (c) Reetz, M. T.
Angew. Chem., Int. Ed. Engl. 1991, 30, 1531.
(12) Gryko, D.; Chalko, J.; Jurczak, J. Chirality 2003, 15, 514.
(13) For references leading to the asymmetric synthesis of R-amino
ketones, see:Paleo, M. R.; Calaza, M. I.; Sardina, F. J. J. Org. Chem. 1997,
62, 6862.
(14) Lubell, W. D.; Rapoport, H. J. Am. Chem. Soc. 1987, 109, 236.
(15) Yus, M.; Najera, C.; Foubelo, F. Tetrahedron. 2003, 59, 6147.
(16) (a) Davis, F. A.; Ramachandar, T.; Liu, H. Org. Lett. 2004,
6, 3393. (b) Xu, X.; Liu, J. ꢀY.; Chen, D. ꢀJ.; Timmons, C.; Li, G. Eur. J.
Org. 2005, 1805.
(17) Davis, F. A.; Ramachandar, T.; Chai, J.; Skucas, E. Tetrahedron
Lett. 2006, 47, 2743.
2797
dx.doi.org/10.1021/jo200070d |J. Org. Chem. 2011, 76, 2792–2797