Cinchona alkaloid squaramide catalyzed enantioselective hydrazination/cyclization cascade reaction of α-isocyanoacetates and azodicarboxylates: Synthesis of optically active 1,2,4-triazolines

Article abstract of DOI:10.1021/jo401585v

An efficient enantioselective hydrazination/cyclization cascade reaction of α-substituted isocyanoacetates to azodicarboxylates catalyzed by Cinchona alkaloid derived squaramide catalysts has been investigated, affording the optically active 1,2,4-triazol

Full text of DOI:10.1021/jo401585v

Article
pubs.acs.org/joc
Cinchona Alkaloid Squaramide Catalyzed Enantioselective
Hydrazination/Cyclization Cascade Reaction of α‑Isocyanoacetates
and Azodicarboxylates: Synthesis of Optically Active 1,2,4-Triazolines
Mei-Xin Zhao,*,†,‡ Hong-Lei Bi,† Hao Zhou,† Hui Yang,† and Min Shi*,†,§
†Key Laboratory for Advanced Materials and Institute of Fine Chemicals, East China University of Science and Technology, 130 Mei
Long Road, Shanghai 200237, People’s Republic of China
‡CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190,
People’s Republic of China
§State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354
Fenglin Road, Shanghai 200032, People’s Republic of China
S
* Supporting Information
ABSTRACT: An efficient enantioselective hydrazination/
cyclization cascade reaction of α-substituted isocyanoacetates
to azodicarboxylates catalyzed by Cinchona alkaloid derived
squaramide catalysts has been investigated, affording the
optically active 1,2,4-triazolines in excellent yields (up to
99%) and good to excellent enantioselectivities (up to 97% ee)
under mild conditions.
derived from cinchonine.8 In light of this, the development of
an efficient catalyst to improve the enantioselectivity of this
hydrazination/cyclization cascade reaction was very necessary.
INTRODUCTION
■
Nitrogen-containing heterocycles constitute a major family of
pharmaceuticals and agrochemicals with a very long history,
because they often exhibit interesting biological activities.1
Over the past decades, hydrogen-bonding-promoted asym-
metric organocatalysis has attracted intense research effort.14
While the 1,2,4-triazole moiety is an important structural motifs
Especially, chiral thiourea or squaramide catalysts, incorporat-
ing the thiourea or squaramide moiety as powerful hydrogen
bond donors in different chiral scaffolds, have been identified as
goldmines in H-bonding-involved bifunctional activation
and is present in a wide array of compounds that have antiviral,
anticancer, anti-inflammatory, and anticonvulsant properties,2
the saturated 1,2,4-trizaolines belong to an underutilized class
of heterocycles and have received considerable attention only
processes to lead to high enantioselectivity and diastereose-
recently. Various synthetic approaches for the synthesis of
lectivity.14 On the basis of the concept of bifunctional H-
1,2,4-triazole derivatives using amino acids,3 oxazoles,4
imidazopyridines,5 N-[(trimethylsilyl)methyl]iminium triflates,6
bonding catalysis and the earlier successes in the asymmetric
additions of α-isocyanoacetates 1,10,11e,h,12,13e,f we envisioned
oxazolones,7 isocyanoacetates,8 and azodicarboxylates have
that the addition of α-isocyanoacetates to azodicarboxylates
may be realized in the presence of bifunctional chiral tertiary
amine−thiourea or −squaramide catalysts. α-Isocyanoacetates 1
with two electron-withdrawing substituents at the α-position
(an isocyanide group and a carboxylic group) can be easily
deprotonated by tertiary amine, and the azodicarboxylates may
been developed during the past 20 years. Among them, the
participation of α-substituted isocyanoacetates 1 in hydrazina-
tion/cyclization cascade reactions with azodicarboxylates has
been shown to be a promising strategy, leading to 1,2,4-
triazolines 3 bearing a quaternary C3 carbon atom containing a
carboxylic acid functional group and a hydrogen atom
substituent at C5 in excellent yields under mild conditions.8
be activated by the H-bonding donor through double H bonds.
Thus, the synergistic interactions of bifunctional catalysis would
Although isocyanoacetates have been proven to be irreplaceable
ensure high stereoselectivity in the hydrazination/cyclization
building blocks for the synthesis of numerous important classes
cascade reactions (Scheme 1). While Feng et al. had reported
of chiral nitrogen heterocyclic compounds by asymmetric
addition with many electrophiles,9 such as nitroolefins,10
very recently the catalytic asymmetric cyclization of α-alkyl-
carbonyl compounds,11 imines,12 and α,β-unsaturated carbonyl
substituted isocyanoacetates with azodicarboxylates using a
chiral iron(II) complex as the catalyst,15 to the best of our
compounds,13 the enantioselective hydrazination/cyclization
cascade reaction with azodicarboxylates has not been very
successful, and excellent yields (>95%) and moderate
enantioselectivities (up to 60% ee) were obtained by employing
phase-transfer conditions (K3PO4−toluene) and a catalyst
knowledge, there is no example of a highly efficient
Received: July 24, 2013
Published: August 19, 2013
© 2013 American Chemical Society
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Scheme 1. Proposed Organocatalytic Reaction of α-
Substituted Isocyanoacetate and Azodicarboxylate
Table 1. Catalyst Screening for Enantioselective
Hydrazination/Cyclization Cascade Reaction of
Isocyanoacetate 1a with Azodicarboxylate 2a
a
b
entry
cat. 3
time (h)
yield (%)
ee (%)
1
3a
3b
3c
3d
3e
3f
72
72
66
66
12
12
12
12
16
12
13
40
11
15
44
98
98
99
99
99
99
76
−21
8
2
3
−11
−13
−51
89
4
5
6
7
3g
3h
3i
81
8
81
organocatalytic system for this kind of reaction. As a part of our
ongoing interest in enantioselective addition reactions of
isocyanoacetates with unsaturated compounds for the synthesis
of polysubstituted chiral heterocycles,11h,13d we describe herein
the Cinchona alkaloid derived squaramide catalyzed enantiose-
lective hydrazination/cyclization cascade reaction of a broad
range of α-isocyanoacetates with azodicarboxylates, affording
the chiral 1,2,4-triazolines in high yields and uniformly excellent
enantioselectivities.
9
−79
−61
−65
10
11
3j
3k
a
Unless noted otherwise, all reactions were carried out with
isocyanoacetate 1a (0.12 mmol), azodicarboxylate 2a (0.10 mmol),
and catalyst 3 (10 mol %) in CH2Cl2 (2.0 mL) at 10 °C.
b
Enantiomeric excesses were determined by chiral HPLC analysis.
RESULTS AND DISCUSSION
tivity (Table 1, entries 3 and 4 vs entry 5). Further examination
of Cinchona alkaloid derived squaramide catalysts 3f−k revealed
that the quinine-derived catalyst 3f turned out to be an
excellent catalyst for this hydrazination/cyclization cascade
reaction, leading to the desired 1,2,4-triazoline 4a in 98% yield
along with 89% ee (Table 1, entry 6). Replacing the
bis(trifluoromethyl)phenyl group on the squaramide moiety
of 3f with 4-(trifluoromethyl)phenyl and 4-fluorophenyl groups
gave the desired product 4a in relatively lower yields as well as
lower enantioselectivities, probably due to the weak acidity of
the N−H of the squaramide group of 3g,h (Table 1, entries 7
and 8). Quinidine-derived squaramides 3i−k also promoted
this reaction but gave 4a with opposite absolute configuration
in much lower ee values in comparison to those of the
corresponding quinine-derived catalysts 3f−h (Table 1, entries
9−11).
■
We initiated our study by examining the reaction between
isocyanoacetate 1a and azodicarboxylate 2a in the presence of
various tertiary amine−thiourea or −squaramide catalysts
(Figure 1). As shown in Table 1, Cinchona alkaloid derived
thiourea catalysts 3a,b are not suitable catalysts for this
reaction, affording 1,2,4-triazoline 4a in low yields along with
low enantioselectivities.16 Squaramide catalysts 3c−e with a
chiral cyclohexane-1,2-diamine skeleton were then synthesized
and evaluated (Table 1, entries 3−5). It was found that the
substituents on the nitrogen atoms of the tertiary amine play an
important role in determining the reaction outcome. Different
from dimethyl- and pyrrolidine-substituted catalysts 3c,d, which
also gave 4a in low yields and low enantioselectivities, the
corresponding piperidine-substituted catalyst 3e afforded the
desired product 4a in high yield and moderate enantioselec-
Figure 1. Evaluated catalysts.
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a
In view of the high enantioselectivity, efforts were made to
further optimize the reaction conditions by examining other
parameters such as solvent, temperature, and reactant
concentrations (Table 2). Of the various solvents screened,
Table 3. Scope of Isocyanoacetates 1
a
Table 2. Optimization of Reaction Conditions
b
entry
1 (R1/R2)
1a (Ph/OMe)
4
t (h) yield (%) ee (%)
b
entry
solvent
CH2Cl2
temp (°C) time (h) yield (%) ee (%)
1
4a
4b
4c
4d
4e
4f
12
12
12
12
18
18
12
12
65
65
18
72
72
72
72
99
98
88
98
98
98
76
90
59
99
78
64
n.r.
20
43
93
94
87
89
97
95
85
95
93
96
94
96
n.d.
96
54
2
1b (4-FC6H4/OMe)
1c (4-ClC6H4/OMe)
1d (4-BrC6H4/OMe)
1e (4-MeC6H4/OMe)
1f (4-MeOC6H4/OMe)
1g (3-FC6H4/OMe)
1h (3-MeC6H4/OMe)
1i (2-BrC6H4/OMe)
1j (2-MeC6H4/OMe)
1k (Ph/OBn)
1
2
3
4
5
6
7
8
9
10
10
10
10
10
10
10
10
10
10
10
0
12
12
12
12
18
18
18
12
12
12
12
12
12
12
12
98
98
98
76
67
29
51
28
72
97
98
85
99
99
99
89
91
3
CHCl3
ClCH2CH2Cl
toluene
EA
4
85
5
71
6
35
7
4g
4h
4i
THF
−33
33
8
Et2O
9
CH3OH
CH3CN
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
−39
5
10
11
12
13
14
15
4j
c
4k
4l
10
89
d
1l (Ph/Ot-Bu)
11
93
d
1m (i-Pr/OMe)
4m
4n
4o
12
93
d
1n (Bn/OMe)
13
20
10
10
89
de
,
1o (H/OEt)
14
15
93
d f
−
a
93
Unless noted otherwise, all reactions were carried out with
isocyanoacetate 1 (0.18 mmol), azodicarboxylate 2a (0.15 mmol),
catalyst 3f (3 mol %) and 3 Å MS (30 mg) in 1.5 mL of CHCl3.
a
Unless noted otherwise, all reactions were carried out with
isocyanoacetate 1a (0.12 mmol), azodicarboxylate 2a (0.10 mmol),
b
b
Enantiomeric excesses were determined by chiral HPLC analysis.
and catalyst 3f (10 mol %) in 2.0 mL of solvent. Enantiomeric
c
excesses were determined by chiral HPLC analysis. 4.0 mL of CHCl3
was used. 1.0 mL of CHCl3 was used. 30 mg of 3 Å molecular sieves
d
e
f
important roles in determining the reaction outcomes.
Isocyanoacetates without a substituent or bearing an electron-
donating group on the benzene ring yielded the desired
products in slightly higher yields along with better
enantioselectivities in comparison to the corresponding
substrates with electron-withdrawing groups (Table 3, entries
1, 5, 6, 8, 10 vs entries 2−4, 7, 9). The presence of a substituent
on the ortho position significantly slowed the reaction rate, as
isocyanoacetates 1i,j took a longer reaction time (65 h) to form
4i,j in moderate to high yields along with excellent ee values.
Variation on the ester moiety was then considered. In
comparison with methyl isocyanoacetate 1a, benzyl isocyanoa-
cetate 1k reacted smoothly with 2a to afford the desired
product 4k in comparable yield and enantioselectivity; while
tert-butyl isocyanoacetates 1l afforded the product 4l in
moderate yield and similar stereoselectivity, even after
prolonged reaction times (72 h), presumably owing to steric
hindrance (Table 3, entries 11 and 12). Moreover, a limitation
was observed with less reactive α-alkyl-substituted or non-
substituted isocyanoacetates. For example, 1n,o are not suitable
for this reaction, affording the corresponding products 4n,o in
moderate yields and moderate to good enantioselectivities by
prolonging the reaction time to 72 h (Table 3, entries 14 and
15). Using α-isopropyl-substituted isocyanoacetate 1m as the
reactant, no reaction occurred under the standard conditions
(Table 3, entry 13).
was added. 3 mol % of catalyst 3f.
chloroform was found to be the best solvent for this cascade
reaction, despite the high yields and similar levels of
enantioselectivity in other chlorinated solvents (Table 2, entries
1−3). Other solvents, whether less polar solvents such as
toluene, EA, ether, and THF or polar solvents, all gave the
corresponding 1,2,4-triazoline 4a in low to moderate yields and
low ee values (Table 2, entries 4−9). The examination of
reactant concentration revealed that increasing the concen-
tration could significantly improve the enantioselectivity of 4a
without sacrificing the yield (Table 2, entries 10 and −11); the
best enantioselectivity for 4a was obtained with a 0.1 M
solution of azodicarboxylate 2a (Table 2, entry 11). The effect
of temperature was also examined, and it was found that
lowering or elevating the reaction temperature led to a decrease
in yield or enantioselectivity, respectively (Table 2, entries 12
and 13). Studies on the effect of additives suggested that
addition of 3 Å molecular sieves could slightly improve the
enantioselectivity of 4a (Table 2, entry 14).17 To our delight,
reducing the catalyst loading to 3 mol % still afforded 4a in
excellent yield with high enantioselectivity (Table 2, entry 15).
Thus, the optimal reaction conditions have been identified as
carrying out the reaction with 1.2 equiv of 1a and 1.0 equiv of
2a in chloroform (0.1 M for 2a) at 10 °C using 3 mol % of 3f as
the catalyst.
In order to investigate the substituent effect of azodicarbox-
ylate on this reaction, several azodicarboxylates with different
ester substituents were subjected to this reaction under the
standard conditions, and the results are summarized in Table 4.
Using DEAD (2b), DIAD (2c), and DBAD (2d) as the
corresponding substrates, the reactions proceeded smoothly to
afford the corresponding products 4p−r in excellent yields
along with good ee values (Table 4, entries 2−4). It should be
also noted that the azodicarboxylate derivative 4-phenyl-1,2,4-
triazoline-3,5-dione (PTAD, 2e) was not suitable for this
Under the optimized conditions, the substrate scope of
isocyanoacetates was investigated and the results of these
experiments are summarized in Table 3. All of the tested α-aryl-
substituted isocyanoacetates 3a−l acted as excellent substrates
to react with azodicarboxylate 2a, affording the corresponding
products 4a−l in moderate to high yields (59−99% yield) along
with good to excellent enantioselectivities (85−97% ee) (Table
3, entries 1−12). However, the electronic and steric properties
of the substituent on the isocyanoacetate benzene ring played
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a
significant deleterious effect on the reactivity and stereo-
Table 4. Scope of Azodicarboxylates 2
selectivity (Scheme 3).
Scheme 3. Enantioselective Hydrazination/Cyclization
Cascade Reaction of 1a with 2a on a Gram Scale
b
entry
2 (R)
4
t (h) yield (%) ee (%)
1
2
3
4
5
2a (R = R = O-t-Bu)
4a
4p
4q
4r
4s
12
12
12
12
72
99
98
95
92
n.r.
93
87
88
85
n.d.
2b, DEAD (R = R = OEt)
2c, DIAD (R = R = O-i-Pr)
2d, DBAD (R = R = OBn)
2e, PTAD (R, R = N-Ph)
a
Unless noted otherwise, all reactions were carried out with
CONCLUSION
isocyanoacetate 1a (0.18 mmol), azodicarboxylates 2 (0.15 mmol),
catalyst 3g (3 mol %), and 3 Å MS (30 mg) in 1.5 mL of CHCl3.
Enantiomeric excesses were determined by chiral HPLC analysis.
■
In conclusion, we have developed an efficient Cinchona alkaloid
squaramide catalyzed enantioselective hydrazination/cyclization
cascade reaction between α-aryl isocyanoacetates and azodi-
carboxylates. A wide variety of α-aryl isocyanoacetates and
azodicarboxylates, with different electronic and steric proper-
ties, were tolerated in this catalytic enantioselective cascade
reaction, leading to optically active 1,2,4-triazolines bearing a
quaternary C3 stereogenic center in good to excellent yields
along with good to excellent enantioselectivities (up to 97%
ee). Investigations aimed at fully understanding the reaction
mechanism and developing more effective enantioselective
addition reactions of isocyanoacetates with other electrophiles
are currently ongoing in our laboratory.
b
reaction; no desired 1,2,4-triazoline derivative was detected
under the optimized reaction conditions by prolonging the
reaction time to 72 h, thus indicating that the presence of a
bulky ester group is crucial for a satisfactory yield and
stereochemical outcome (Table 4, entry 5).
The absolute configuration of 4 was unambiguously assigned
as S by X-ray crystal analysis of product 4d.18 The absolute
configurations of the other products were assigned as well. On
the basis of the above results and the commonly accepted
mechanism for squaramide catalysts, a plausible transition-state
model is proposed as shown in Scheme 2. The carbonyl of
EXPERIMENTAL SECTION
■
Scheme 2. Proposed Transition State Model
General Procedure for the Enantioselective Hydrazination/
Cyclization Cascade Reaction of Isocyanoacetates 1 with
Various Azodicarboxylates 2 Catalyzed by 3f. To a solution of
azodicarboxylates 2 (0.15 mmol), catalyst 3f (2.8 mg, 3 mol %), and 3
Å MS (30 mg) in CHCl3 (1.5 mL) was added isocyanoacetates 1 (0.18
mmol). The resulting mixture was stirred at 10 °C for 12−72 h until
the reaction was complete (monitored by TLC). After concentration,
the residue was directly subjected to flash column chromatography on
silica gel (petroleum ether/ethyl acetate 12/1 as eluent) to furnish the
corresponding adducts 4.
(3S)-1,2-Di-tert-butyl 3-methyl 3-phenyl-1H-1,2,4-triazole-
1,2,3(3H)-tricarboxylate (4a):8 yellow solid; yield 60.0 mg (99%);
mp 138.0−138.3 °C; [α]D20 +69.7 (c 1.00, CH2Cl2) (93% ee); the ee
was determined by HPLC analysis with a Chiralpak AS-H column
(90/10 hexane/i-PrOH; 0.5 mL/min; λ 214 nm; tmajor = 9.92 min;
tminor = 11.59 min); 1H NMR (CDCl3, 400 MHz) δ 1.50 (s, 9H), 1.51
(s, 9H), 3.75 (s, 3H), 7.37−7.40 (m, 3H), 7.637 (s, 1H), 7.644 (d, J =
8.4 Hz, 2H); 13C NMR (CDCl3, 100 MHz) δ 27.9, 28.0, 53.3, 83.6,
84.7, 96.5, 127.2, 128.0, 128.6, 137.6, 146.6, 148.7, 154.1, 168.0; IR
(film) ν 1763, 1758, 1718, 1620, 1450, 1370, 1351, 1290, 1258, 1236,
1153, 1125 cm−1; HRMS (ESI-TOF) m/z [M + H]+ calcd for
C20H28N3O6 406.1978, found 406.1951.
azodicarboxylate is H-bonded to the squaramide motif, while
isocyanoacetate is deprotonated, resulting in a single H-
bonding interaction between the OH group of the enolized
isocyanoacetate and the tertiary amine. Additionally, a weak H-
bonding interaction might be formed concurrently between the
OMe group of the enolized isocyanoacetate and the NH in the
squaramide moiety, which forces the enolized isocyanoacetate
through the Si face to attack the azodicarboxylate from the Si
face, affording the adduct 4a with an S configuration.
Subsequently, a 5-endo-dig cyclization would take place by an
intramolecular reaction between the amine group of the
resulting hydrazine intermediate and the isocyano group to
afford the observed 1,2,4-triazoline 4a.
To further explore the synthetic utility of the current catalyst
system, a gram-scale reaction was also evaluated. The
enantioselective hydrazination/cyclization cascade reaction of
1a with 2a was performed on 3.0 mmol of 2a and 3.6 mmol of
1a with 3 mol % of catalyst 3f. The desired product 4a could be
obtained smoothly in 84% yield and 93% ee after 12 h, without
(3S)-1,2-Di-tert-butyl 3-methyl 3-(4-fluorophenyl)-1H-1,2,4-tria-
zole-1,2,3(3H)-tricarboxylate (4b): white solid; yield 62.0 mg (98%);
mp 115.8−116.2 °C; [α]D20 +71.2 (c 1.00, CH2Cl2) (94% ee); the ee
was determined by HPLC analysis with a Chiralpak AS-H column
(90/10 hexane/i-PrOH; 0.5 mL/min; λ 214 nm; tmajor = 9.30 min;
tminor = 10.34 min); 1H NMR (CDCl3, 400 MHz) δ 1.50 (s, 9H), 1.51
(s, 9H), 3.75 (s, 3H), 7.07 (t, J = 8.4 Hz, 2H), 7.62 (dd, J = 8.8, 5.6
Hz, 2H), 7.65 (s, 1H); 13C NMR (CDCl3, 100 MHz) δ 27.9, 28.0,
53.4, 83.8, 84.9, 96.0, 114.9 (d, J = 21.3 Hz), 129.1 (d, J = 8.4 Hz),
133.5 (J = 2.8 Hz), 146.7, 148.6, 154.1, 162.8 (d, J = 246.0 Hz), 167.9;
19F NMR (CDCl3, 376 MHz) δ −118.4; IR (film) ν 1759, 1717, 1509,
1370, 1291, 1232, 1152, 1124 cm−1; HRMS (ESI-TOF) m/z [M +
H]+ calcd for C20H27FN3O6 424.1884, found 424.1879.
(3S)-1,2-Di-tert-butyl 3-methyl 3-(4-chlorophenyl)-1H-1,2,4-tria-
zole-1,2,3(3H)-tricarboxylate (4c): yellow viscous solid; yield 58.0 mg
20
(88%); [α]D +34.4 (c 1.00, CH2Cl2) (87% ee); the ee was
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determined by HPLC analysis with a Chiralpak AS-H column (90/10
1718, 1620, 1370, 1290, 1252, 1154, 1124 cm−1; HRMS (ESI-TOF)
m/z [M + H]+ calcd for C21H30N3O6 420.2135, found 420.2130.
(3S)-1,2-Di-tert-butyl 3-methyl 3-(2-bromophenyl)-1H-1,2,4-tria-
zole-1,2,3(3H)-tricarboxylate (4i): white solid; yield 43.1 mg (59%);
hexane/i-PrOH; 0.5 mL/min; λ 214 nm; tmajor = 9.12 min; tminor
=
10.36 min); 1H NMR (CDCl3, 400 MHz) δ 1.50 (s, 9H), 1.51 (s, 9H),
3.75 (s, 3H), 7.36 (d, J = 8.8 Hz, 2H), 7.58 (d, J = 8.8 Hz, 2H), 7.65
(s, 1H); 13C NMR (CDCl3, 100 MHz) δ 27.9, 28.0, 53.4, 83.8, 84.9,
96.0, 128.2, 128.7, 134.6, 136.3, 146.9, 148.6, 154.1, 167.7; IR (film) ν
1762, 1719, 1618, 1370, 1290, 1259, 1242, 1154, 1127 cm−1; HRMS
(ESI-TOF) m/z [M + H]+ calcd for C20H27ClN3O6 440.1588, found
440.1583.
20
mp 103.3−104.8 °C; [α]D −7.7 (c 1.00, CH2Cl2) (93% ee); the ee
was determined by HPLC analysis with a Chiralpak AS-H column
(90/10 hexane/i-PrOH; 0.5 mL/min; λ 214 nm; tmajor = 10.80 min;
tminor = 12.96 min); 1H NMR (CDCl3, 400 MHz) δ 1.48 (s, 9H), 1.52
(s, 9H), 3.80 (s, 3H), 7.21 (td, J = 8.0, 1.6 Hz, 1H), 7.35 (td, J = 7.6,
1.2 Hz, 1H), 7.66 (dd, J = 7.6, 0.8 Hz, 1H), 7.67 (s, 1H), 7.71 (dd, J =
8.0, 1.2 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ 27.8, 27.9, 53.3,
83.9, 84.8, 97.0, 122.4, 127.3, 128.5, 130.1, 134.8, 136.0, 146.7, 148.5,
153.6, 166.3; IR (film) ν 1752, 1724, 1617, 1463, 1370, 1291, 1259,
1153, 1134, 1112 cm−1; HRMS (ESI-TOF) m/z [M + H]+ calcd for
C20H27BrN3O6 484.1083, found 484.1088.
(3S)-1,2-Di-tert-butyl 3-methyl 3-(4-bromophenyl)-1H-1,2,4-tria-
zole-1,2,3(3H)-tricarboxylate (4d): white solid; yield 70.9 mg (98%);
20
mp 140.8−142.2 °C; [α]D +31.5 (c 1.00, CH2Cl2) (89% ee); the ee
was determined by HPLC analysis with a Chiralpak AS-H column
(90/10 hexane/i-PrOH; 0.5 mL/min; λ 214 nm; tmajor = 9.28 min;
tminor = 10.76 min); 1H NMR (CDCl3, 400 MHz) δ 1.50 (s, 9H), 1.51
(s, 9H), 3.75 (s, 3H), 7.51 (s, 4H), 7.64 (s, 1H); 13C NMR (CDCl3,
100 MHz) δ 27.88, 27.93, 53.4, 83.8, 84.9, 96.0, 122.9, 129.0, 131.1,
136.8, 146.8, 148.6, 154.0, 167.6; IR (film) ν 1760, 1718, 1618, 1370,
1290, 1259, 1241, 1154, 1127 cm−1; HRMS (ESI-TOF) m/z [M +
H]+ calcd for C20H27BrN3O6 484.1083, found 484.1087.
(3S)-1,2-Di-tert-butyl 3-methyl 3-(o-tolyl)-1H-1,2,4-triazole-
1,2,3(3H)-tricarboxylate (4j): white solid; yield 62.2 mg (99%); mp
126.0−126.6 °C; [α]D20 +15.4 (c 1.00, CH2Cl2) (96% ee); the ee was
determined by HPLC analysis with a Chiralpak AS-H column (90/10
hexane/i-PrOH; 0.5 mL/min; λ 214 nm; tmajor = 8.51 min; tminor = 9.61
min); 1H NMR (CDCl3, 400 MHz) δ 1.49 (s, 9H), 1.52 (s, 9H), 2.50
(s, 3H), 3.77 (s, 3H), 7.20−7.26 (m, 3H), 7.61 (s,1H), 7.62 (d, J = 7.6
Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ 21.4, 27.9, 28.0, 53.2, 83.6,
84.6, 97.5, 125.6, 126.5, 128.7, 131.8, 134.9, 137.4, 146.0, 148.8, 153.9,
167.3; IR (film) ν 1764, 1756, 1720, 1622, 1457, 1394, 1370, 1291,
1258, 1227, 1155, 1107 cm−1; HRMS (ESI-TOF) m/z [M + H]+ calcd
for C21H30N3O6 420.2135, found 420.2137.
(3S)-1,2-Di-tert-butyl 3-methyl 3-(p-tolyl)-1H-1,2,4-triazole-
1,2,3(3H)-tricarboxylate (4e): yellow viscous solid; yield 61.6 mg
20
(98%); [α]D +41.7 (c 1.00, CH2Cl2) (97% ee); the ee was
determined by HPLC analysis with a Chiralpak AS-H column (90/10
hexane/i-PrOH; 0.5 mL/min; λ 214 nm; tmajor = 9.28 min; tminor
=
10.25 min); 1H NMR (CDCl3, 400 MHz) δ 1.50 (s, 9H), 1.51 (s, 9H),
2.36 (s, 3H), 3.75 (s, 3H), 7.21 (d, J = 8.0 Hz, 2H), 7.53 (d, J = 8.0
Hz, 2H), 7.64 (s, 1H); 13C NMR (CDCl3, 100 MHz) δ 21.2, 27.9,
28.0, 53.3, 83.5, 84.6, 96.5, 127.0, 128.7, 134.7, 138.4, 146.5, 148.7,
154.1, 168.1; IR (film) ν 1763, 1718, 1620, 1370, 1291, 1238, 1154,
1129 cm−1; HRMS (ESI-TOF) m/z [M + H]+ calcd for C21H30N3O6
420.2135, found 420.2133.
(3S)-3-Benzyl 1,2-di-tert-butyl 3-phenyl-1H-1,2,4-triazole-
1,2,3(3H)-tricarboxylate (4k): white solid; yield 56.4 mg (78%); mp
116.2−117.4 °C; [α]D20 +70.9 (c 1.00, CH2Cl2) (94% ee); the ee was
determined by HPLC analysis with a Chiralpak AS-H column (90/10
hexane/i-PrOH; 0.5 mL/min; λ 214 nm; tmajor = 11.21 min; tminor
=
13.16 min); 1H NMR (CDCl3, 400 MHz) δ 1.42 (s, 9H), 1.49 (s, 9H),
5.08 (d, J = 12.4 Hz, 1H), 5.29 (d, J = 12.8 Hz, 1H), 7.24−7.40 (m,
8H), 7.63−7.65 (m, 2H), 7.64 (s,1H); 13C NMR (CDCl3, 100 MHz)
δ 27.87, 27.94, 67.9, 83.5, 84.7, 96.5, 127.2, 127.7, 127.9, 128.1, 128.4,
128.5, 134.9, 137.5, 146.7, 148.7, 154.0, 167.4; IR (film) ν 1759, 1717,
1619, 1456, 1370, 1290, 1259, 1233, 1153, 1126 cm−1; HRMS (ESI-
TOF) m/z [M + H]+ calcd for C26H32N3O6 482.2291, found
482.2286.
(3S)-1,2-Di-tert-butyl 3-methyl 3-(4-methoxyphenyl)-1H-1,2,4-
triazole-1,2,3(3H)-tricarboxylate (4f): white solid; yield 63.9 mg
(98%); mp 116.9−118.1 °C; [α]D20 +40.7 (c 1.00, CH2Cl2) (95% ee);
the ee was determined by HPLC analysis with a Chiralpak AS-H
column (90/10 hexane/i-PrOH; 0.5 mL/min; λ 214 nm; tmajor = 12.18
min; tminor = 15.00 min); 1H NMR (CDCl3, 400 MHz) δ 1.49 (s, 9H),
1.51 (s, 9H), 3.75 (s, 3H), 3.81 (s, 3H), 6.92 (d, J = 8.8 Hz, 2H), 7.56
(d, J = 9.2 Hz, 2H), 7.64 (s, 1H); 13C NMR (CDCl3, 100 MHz) δ
27.9, 28.0, 53.3, 55.3, 83.5, 84.7, 96.3, 113.4, 128.5, 129.8, 146.5, 148.7,
154.1, 159.7, 168.2; IR (film) ν 1762, 1717, 1613, 1514, 1370, 1292,
1240, 1154, 1127 cm−1; HRMS (ESI-TOF) m/z [M + H]+ calcd for
C21H30N3O7 436.2084, found 436.2082.
(3S)-Tri-tert-butyl 3-phenyl-1H-1,2,4-triazole-1,2,3(3H)-tricarbox-
20
ylate (4l): white solid; yield 43.3 mg (64%); mp 89.2−91.0 °C; [α]D
+92.5 (c 1.00, CH2Cl2) (96% ee); the ee was determined by HPLC
analysis with a Chiralpak AD-H column (98/2 hexane/i-PrOH; 0.5
mL/min; λ 214 nm; tmajor = 26.12 min; tminor = 22.61 min); H NMR
1
(3S)-1,2-Di-tert-butyl 3-methyl 3-(3-fluorophenyl)-1H-1,2,4-tria-
(CDCl3, 400 MHz) δ 1.44 (s, 9H), 1.51 (s, 9H), 1.53 (s, 9H), 7.31−
7.39 (m, 3H), 7.60 (s, 1H), 7.64 (d, J = 7.2 Hz, 2H); 13C NMR
(CDCl3, 100 MHz) δ 27.6, 28.0, 28.1, 83.2, 83.6, 84.5, 97.0, 127.3,
127.7, 128.2, 138.0, 146.2, 148.9, 154.3, 166.3; IR (film) ν 1759, 1717,
1621, 1478, 1369, 1292, 1250, 1147 cm−1; HRMS (ESI-TOF) m/z [M
+ H]+ calcd for C23H34N3O6 448.2448, found 448.2447.
zole-1,2,3(3H)-tricarboxylate (4g): white solid; yield 48.2 mg (76%);
20
mp 102.1−102.5 °C; [α]D +60.6 (c 1.00, CH2Cl2) (85% ee); the ee
was determined by HPLC analysis with a Chiralpak AS-H column
(98/2 hexane/i-PrOH; 0.5 mL/min; λ 214 nm; tmajor = 14.67 min;
tminor = 16.73 min); 1H NMR (CDCl3, 400 MHz) δ 1.50 (s, 9H), 1.51
(s, 9H), 3.75 (s, 3H), 7.03 (tdd, J = 8.0, 2.4, 0.8 Hz, 1H), 7.32−7.38
(m, 2H), 7.44 (dt, J = 8.0, 1.2 Hz, 1H), 7.66 (s, 1H); 13C NMR
(CDCl3, 100 MHz) δ 27.89, 27.94, 53.4, 83.8, 84.9, 95.9, 114.6 (d, J =
23.9 Hz), 115.5 (d, J = 21.3 Hz), 122.9 (d, J = 2.3 Hz), 129.5 (d, J =
7.6 Hz), 140.3 (d, J = 7.5 Hz), 147.0, 148.6, 154.1, 162.4 (d, J = 244.0
Hz), 167.6; 19F NMR (CDCl3, 376 MHz, not-decoupled) δ −113.1
(m); IR (film) ν 1762, 1719, 1616, 1592, 1371, 12921, 1255, 1153,
1120 cm−1; HRMS (ESI-TOF) m/z [M + Na]+ calcd for
C20H26FN3O6Na 446.1703, found 446.1705.
(3S)-1,2-Di-tert-butyl 3-methyl 3-benzyl-1H-1,2,4-triazole-
1,2,3(3H)-tricarboxylate (4n):8 white viscous solid; yield 13.0 mg
20
(20%); [α]D +42.9 (c 1.00, CH2Cl2) (96% ee); the ee was
determined by HPLC analysis with a Chiralpak AD-H column (98/2
hexane/i-PrOH; 0.5 mL/min; λ 214 nm; tmajor = 21.12 min; tminor
=
28.60 min); 1H NMR (CDCl3, 400 MHz) δ 1.29 (s, 9H), 1.46 (s, 9H),
3.33 (d, J = 14.0 Hz, 1H), 3.45 (d, J = 14.0 Hz, 1H), 3.75 (s, 3H),
7.11−7.20 (m, 5H), 7.28 (s, 1H); 13C NMR (CDCl3, 100 MHz) δ
27.6, 27.8, 41.1, 52.8, 82.8, 83.8, 94.9, 126.6, 127.5, 131.1, 133.8, 147.6,
148.1, 153.2, 168.1; IR (film) ν 1760, 1716, 1618, 1457, 1369, 1290,
1259, 1155, 1103 cm−1; HRMS (ESI-TOF) m/z [M + H]+ calcd for
C21H30N3O6 420.2135, found 420.2135.
(3S)-1,2-Di-tert-butyl 3-methyl 3-(m-tolyl)-1H-1,2,4-triazole-
1,2,3(3H)-tricarboxylate (4h): white viscous solid; yield 56.8 mg
20
(90%); [α]D +55.0 (c 1.00, CH2Cl2) (95% ee); the ee was
determined by HPLC analysis with a Chiralpak AS-H column (90/10
(3S)-1,2-Di-tert-butyl 3-ethyl 1H-1,2,4-triazole-1,2,3(3H)-tricar-
20
hexane/i-PrOH; 0.5 mL/min; λ 214 nm; tmajor = 9.41 min; tminor
=
boxylate (4o): pale yellow oil; yield 22.3 mg (43%); [α]D +34.0 (c
13.63 min); 1H NMR (CDCl3, 400 MHz) δ 1.50 (s, 9H), 1.51 (s, 9H),
2.38 (s, 3H), 3.75 (s, 3H), 7.16 (d, J = 7.2 Hz, 1H), 7.28 (t, J = 7.6 Hz,
1H), 7.44 (t, J = 7.6 Hz, 1H), 7.45 (s, 1H), 7.66 (s, 1H); 13C NMR
(CDCl3, 100 MHz) δ 21.5, 27.89, 27.93, 53.2, 83.5, 84.6, 96.5, 124.1,
127.8, 127.9, 129.4, 137.5, 146.5, 148.6, 154.1, 168.0; IR (film) ν 1763,
1.00, CH2Cl2) (54% ee); the ee was determined by HPLC analysis
with a Chiralpak AS-H column (98/2 hexane/i-PrOH; 0.5 mL/min; λ
214 nm; tmajor = 18.47 min; tminor = 20.52 min); 1H NMR (CDCl3, 400
MHz) δ 1.28 (t, J = 7.2 Hz, 3H), 1.50 (s, 9H), 1.53 (s, 9H), 4.21 (q, J
= 7.2 Hz, 2H), 6.07 (s, 1H), 7.70 (s, 1H); 13C NMR (CDCl3, 100
9381
dx.doi.org/10.1021/jo401585v | J. Org. Chem. 2013, 78, 9377−9382

The Journal of Organic Chemistry
Article
MHz) δ 13.9, 27.9, 28.0, 62.0, 83.8, 84.3, 84.6, 148.1, 154.1, 155.5,
166.4; IR (film) ν 1760, 1723, 1609, 1458, 1393, 1369, 1327, 1255,
1145 cm−1; HRMS (ESI-TOF) m/z [M + K]+ calcd for C15H25N3O6K
382.1380, found 382.1385.
Rev. 2003, 72, 69. (e) Xu, Y.; Guo, Q.-X. Heterocycles 2004, 63, 903.
(f) Gupta, L.; Chauhan, P. M. S. Chem. Biol. Interface 2011, 1, 1.
(2) (a) Todoulou, O. G.; Papadaki-Valiraki, A. E.; Ikeda, S.; De
Clercq, E. Eur. J. Med. Chem. 1994, 29, 611. (b) Bekircan, O.; Kahveci,
B.; Kucuk, M. Turk. J. Chem. 2006, 30, 29. (c) Tandon, M.; Barthwal,
J. P.; Bahalla, T. N.; Bhargava, K. P. Indian J. Chem. 1981, 20B, 1017.
(d) Gulerman, N.; Rollas, S.; Kiraz, M.; Ekinci, A. C.; Vidin, A.
Farmaco 1997, 52, 691.
(3) Kolasa, T.; Miller, M. Tetrahedron Lett. 1988, 29, 4661.
(4) (a) Ibata, T.; Isogami, Y.; Tamura, H. Chem. Lett. 1988, 1551.
(b) Hassner, A.; Fischer, B. Tetrahedron 1989, 45, 3535. (c) Shi, X.;
Ibata, T.; Suga, H.; Matsumoto, K. Bull. Chem. Soc. Jpn. 1992, 65, 3315.
(d) Ibata, T.; Suga, H.; Isogami, Y.; Tamura, H.; Shi, X. Bull. Chem.
Soc. Jpn. 1992, 65, 2998.
(5) Anderson, D. J.; Watt, W. J. Heterocycl. Chem. 1995, 32, 1525.
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55, 243.
(7) Saleem, R. S. Z.; Tepe, J. J. J. Org. Chem. 2010, 75, 4330.
(8) Monge, D.; Jensen, K. L.; Marín, I.; Jørgensen, K. A. Org. Lett.
2011, 13, 328.
(3S)-1,2-Diethyl 3-methyl 3-phenyl-1H-1,2,4-triazole-1,2,3(3H)-
tricarboxylate (4p): pale yellow viscous solid; yield 51.3 mg (98%);
20
[α]D +70.8 (c 1.00, CH2Cl2) (87% ee); the ee was determined by
HPLC analysis with a Chiralpak AS-H column (90/10 hexane/i-
PrOH; 0.5 mL/min; λ 214 nm; tmajor = 25.14 min; tminor = 27.65 min);
1H NMR (CDCl3, 400 MHz) δ 1.28 (t, J = 7.2 Hz, 3H), 1.32 (t, J =
7.2 Hz, 3H), 3.76 (s, 3H), 4.20−4.37 (m, 4H), 7.38−7.40 (m, 3H),
7.64−7.66 (m, 2H), 7.74 (s, 1H); 13C NMR (CDCl3, 100 MHz) δ
14.2, 53.6, 63.5, 64.1, 96.9, 127.1, 128.0, 128.8, 137.0, 146.1, 150.1,
155.4, 167.7; IR (film) ν 1762, 1750, 1721, 1621, 1398, 1372, 1328,
1270, 1232, 1012 cm−1; HRMS (ESI-TOF) m/z [M + H]+ calcd for
C16H20N3O6 350.1352, found 350.1348.
(3S)-1,2-Diisopropyl 3-methyl 3-phenyl-1H-1,2,4-triazole-
1,2,3(3H)-tricarboxylate (4q):3 white viscous solid; yield 53.9 mg
20
(95%); [α]D +75.6 (c 1.00, CH2Cl2) (88% ee); the ee was
determined by HPLC analysis with a Chiralcel OD-H column (98/2
hexane/i-PrOH; 0.5 mL/min; λ 214 nm; tmajor = 34.68 min; tminor
=
(9) For a recent review on isocyanoacetates, see: Gulevich, A. V.;
Zhdanko, A. G.; Orru, R. V. A.; Nenajdenko, V. G. Chem. Rev. 2010,
110, 5235.
(10) Guo, C.; Xue, M.-X.; Zhu, M.-K.; Gong, L.-Z. Angew. Chem., Int.
Ed. 2008, 47, 3414.
30.24 min); 1H NMR (CDCl3, 400 MHz) δ 1.26−1.34 (m, 12H), 3.76
(s, 3H), 5.02−5.06 (m, 2H), 7.36−7.40 (m, 3H), 7.65 (dt, J = 6.4, 1.6
Hz, 2H), 7.71 (s, 1H); 13C NMR (CDCl3, 100 MHz) δ 21.6, 21.73,
21.74, 21.9, 53.4, 71.8, 72.5, 96.7, 127.2, 128.0, 128.7, 137.2, 146.2,
149.8, 154.9, 167.7; IR (film) ν 1762, 1750, 1719, 1621, 1450, 1375,
1315, 1275, 1234, 1180, 1102, 1015 cm−1; HRMS (ESI-TOF) m/z [M
+ H]+ calcd for C18H24N3O6 378.1665, found 378.1656.
(11) For selected examples, see: (a) Ito, Y.; Sawamura, M.; Hayashi,
T. J. Am. Chem. Soc. 1986, 108, 6405. (b) Ito, Y.; Sawamura, M.;
Hayashi, T. Tetrahedron Lett. 1987, 28, 6215. (c) Hayashi, T.;
Sawamura, M.; Ito, Y. Tetrahedron 1992, 48, 1999. (d) Hayashi, T.;
Uozumi, Y.; Yamazaki, A.; Sawamura, M.; Hamashima, H.; Ito, Y.
Tetrahedron Lett. 1991, 32, 2799. (e) Xue, M.-X.; Guo, C.; Gong, L.-Z.
Synlett 2009, 2191. (f) Sladojevich, F.; Trabocchi, A.; Guarna, A.;
Dixon, D. J. J. Am. Chem. Soc. 2011, 133, 1710. (g) Kim, H. Y.; Oh, K.
Org. Lett. 2011, 13, 1306. (h) Zhao, M.-X.; Zhou, H.; Tang, W.-H.;
Qu, W.-S.; Shi, M. Adv. Synth. Catal. 2013, 355, 1277.
(12) (a) Zhang, Z.-W.; Lu, G.; Chen, M.-M.; Lin, N.; Li, Y.-B.;
Hayashi, T.; Chan, A. S. C. Tetrahedron: Asymmetry 2010, 21, 1715.
(b) Nakamura, S.; Maeno, Y.; Ohara, M.; Yamamura, A.; Funahashi,
Y.; Shibata, N. Org. Lett. 2012, 14, 2960.
(3S)-1,2-Dibenzyl 3-methyl 3-phenyl-1H-1,2,4-triazole-1,2,3(3H)-
20
tricarboxylate (4r): yellow viscous solid; yield 65.4 mg (92%); [α]D
+49.0 (c 1.00, CH2Cl2) (85% ee); the ee was determined by HPLC
analysis with a Chiralpak AD-H column (60/40 hexane/i-PrOH; 0.5
1
mL/min; λ 214 nm; tmajor = 21.81 min; tminor = 26.56 min); H NMR
(CDCl3, 400 MHz) δ 3.45 (s, 3H), 5.18 (d, J = 12.0 Hz, 1H), 5.23 (d,
J = 12.4 Hz, 1H), 5.27 (d, J = 12.0 Hz, 1H), 5.31 (d, J = 12.0 Hz, 1H),
7.33−7.40 (m, 13H), 7.64−7.67 (m, 2H), 7.75 (s, 1H); 13C NMR
(CDCl3, 100 MHz) δ 53.3, 68.9, 69.4, 96.9, 127.1, 128.0, 128.3,
128.47, 125.50, 128.6, 128.79, 128.82, 134.2, 134.8, 136.8, 145.9,
150.2, 155.3, 167.3; IR (film) ν 1758, 1749, 1724, 1622, 1456, 1385,
1328, 1268, 1233, 1213, 1155, 1013 cm−1; HRMS (ESI-TOF) m/z [M
+ H]+ calcd for C26H24N3O6 474.1665, found 474.1662.
́ ́
(13) (a) Arroniz, C.; Gil-Gonzalez, A.; Semak, V.; Escolano, C.;
Bosch, J.; Amat, M. Eur. J. Org. Chem. 2011, 3755. (b) Song, J.; Guo,
C.; Chen, P.-H.; Yu, J.; Luo, S.-W.; Gong, L.-Z. Chem. Eur. J. 2011, 17,
7786. (c) Padilla, S.; Adrio, J.; Carretero, J. C. J. Org. Chem. 2012, 77,
4161. (d) Zhao, M.-X.; Wei, D.-K.; Ji, F.-H.; Zhao, X.-L.; Shi, M. Chem.
Asian J. 2012, 7, 2777. (e) Wang, L.-L.; Bai, J.-F.; Peng, L.; Qi, L.-W.;
Jia, L.-N.; Guo, Y.-L.; Luo, X.-Y.; Xu, X.; Wang, L.-X. Chem. Commun.
2012, 48, 5175. (f) Bai, J.-F.; Wang, L.-L.; Peng, L.; Guo, Y.-L.; Jia, L.-
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2947.
ASSOCIATED CONTENT
* Supporting Information
Figures, a table, and a CIF files giving NMR spectra and HPLC
analysis spectra of compounds 4 and X-ray structural data of
compound 4d. This material is available free of charge via the
Internet at http://pubs.acs.org.
■
S
́
(14) For recent reviews and references cited therein, see: (a) Aleman,
AUTHOR INFORMATION
Corresponding Authors
*M.-X.Z.: fax, +86-21-34201699; e-mail, mxzhao@ecust.edu.cn.
*M.S.: fax, +86-21-64166128; e-mail, Mshi@mail.sioc.ac.cn.
Notes
■
J.; Parra, A.; Jiang, H.; Jørgensen, K. A. Chem. Eur. J. 2011, 17, 6890.
(b) Doyle, A. G.; Jacobsen, E. N. Chem. Rev. 2007, 107, 5713. (c) Yu,
X.; Wang, W. Chem. Asian J. 2008, 3, 516. (d) Akiyama, T. Chem. Rev.
2007, 107, 5744. (e) Connon, S. J. Chem. Eur. J. 2006, 12, 5418.
(f) Taylor, M. S.; Jacobsen, E. N. Angew. Chem., Int. Ed. 2006, 45,
1520. (g) Seayad, J.; List, B. Org. Biomol. Chem. 2005, 3, 719.
(h) Schreiner, P. R. Chem. Soc. Rev. 2003, 32, 289.
The authors declare no competing financial interest.
(15) Wang, M.; Liu, X.; He, P.; Lin, L.; Feng, X. Chem. Commun.
2013, 49, 2572.
(16) In addition to 4a, another unstable compound was formed, and
its structure could not be determined.
(17) The addition of 3Å MS can slightly improve the
enantioselectivity of 4a from 92.6% to 93.4%.
(18) CCDC 948689 (for 4d) contains supplementary crystallo-
graphic 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.
ACKNOWLEDGMENTS
■
We are grateful for financial support from the National Natural
Science Foundation of China (20772030, 21072056,
21272067), the Fundamental Research Funds for the Central
Universities, Scientific Research Foundation for the Returned
Overseas Chinese Scholars, and State Education Ministry.
REFERENCES
■
(1) For selected reviews, see: (a) Franklin, E. C. Chem. Rev. 1935, 16,
305. (b) Bergstrom, F. W. Chem. Rev. 1944, 35, 77. (c) Lichtenthaler,
F. W. Acc. Chem. Res. 2002, 35, 728. (d) Litvinov, V. P. Russ. Chem.
9382
dx.doi.org/10.1021/jo401585v | J. Org. Chem. 2013, 78, 9377−9382