Modularly evolved 2-aminodmap/squaramides as highly active bifunctional organocatalysts in Michael addition

Article abstract of DOI:10.1021/jo5022597

We report a new family of chiral bifunctional acid/base type organocatalysts, 2-aminoDMAP/Squaramides, which are proved to be highly active (1 mol % cat. loading) promoters in conjugate addition of dibenzoylmethane to various trans-β-nitroalkenes. Steric demand of the catalysts was clearly seen by a set-by-set modulation of the squaramide unit through electronic and steric factors. The synergistic cooperation of 2-aminoDMAP "uperbase" and sterically encumbered squaramide (H-bond donor) enabled complete conversion of a range of reactants into corresponding Michael adducts in a couple of hours with exquisite selectivities (up to 98% ee).

Full text of DOI:10.1021/jo5022597

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Article
Modularly Evolved 2-AminoDMAP/Squaramides as Highly
Active Bifunctional Organocatalysts in Michael Addition
Cihangir Tanyeli
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/jo5022597 • Publication Date (Web): 24 Dec 2014
Downloaded from http://pubs.acs.org on December 30, 2014
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Modularly Evolved 2-AminoDMAP/Squaramides as Highly
Active Bifunctional Organocatalysts in Michael Addition
Journal: The Journal of Organic Chemistry
Manuscript ID: joꢀ2014ꢀ022597.R2
Manuscript Type: Article
Date Submitted by the Author: 12ꢀDecꢀ2014
Complete List of Authors: Iꢁık, Murat; Bingöl University, Metallurgical and Materials Science
Unver, M. Yagiz; Middle East Technical University, Chemistry
Tanyeli, Cihangir; Middle East Technical University, Chemistry
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Modularly Evolved 2ꢀAminoDMAP/Squaramides as Highly
Active Bifunctional Organocatalysts in Michael Addition
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Murat Iꢀık,†,‡ M. Yagiz Unver,† and Cihangir Tanyeli*,†
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†Department of Chemistry, Middle East Technical University, 06800 Ankara, Turkey and
‡Department of Metallurgical and Materials Engineering, Bingöl University, 12400 Bingöl,
Turkey.
tanyeli@metu.edu.tr
O
O
O
O
O
O
Ph
Ph
N
H
N
H
Ph
Ph
NH
NO2
Ar
NO2
Me2N
Ar
N
1 mol%
15 examples
ee up to 98%
2-aminoDMAP / Squaramide
Superbase & H-bond Donor
ABSTRACT
We report a new family of chiral bifunctional acid/base type organocatalysts, 2ꢁ
aminoDMAP/Squaramides, which are proved to be highly active (1 mol% cat. loading)
promoters in conjugate addition of dibenzoylmethane to various transꢁβꢁnitroalkenes. Steric
demand of the catalysts was clearly seen by a setꢁbyꢁset modulation of the squaramide unit
through electronic and steric factors. The synergistic cooperation of 2ꢁaminoDMAP
“superbase” and sterically encumbered squaramide (Hꢁbond donor) enabled complete
conversion of a range of reactants into corresponding Michael adducts in a couple of hours
with exquisite selectivities (up to 98% ee).
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INTRODUCTION
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Asymmetric organocatalysis offers unique performance advantages over transition metalꢁ and
enzymeꢁbased protocols, and thus has encouraged thousands to design a myriad of catalyst
examples.1 Bifunctional acid/base organocatalysis—cooperative activation of substrates—has
received considerable attention in this endeavor.2 transꢁCyclohexaneꢁ1,2ꢁdiamine and
chincona alkaloids hold prominent places as “privileged”3 chiral scaffolds to that end with the
majority of efforts focused on exploring novel Hꢁbond donor entities.4 Integration of novel
Brønsted bases into these organic catalysts, on the other hand, can considerably raise their
potential and may open new avenues towards “ideal catalysis”.5 Unsuprisingly, this gap has
been partially filled by the emerging use of organic superbase6 catalysts, examples of which
include amidines (2ꢁaminopyridines7 and 2ꢁaminoDMAP8), guanidines,9 phosphazenes,10 and
similar molecular architectures.11 Building upon these precedents, our latest work involved
the straightforward preparation of 2ꢁaminoDMAP/Sulfonamides and their application as
highly selective bifunctional acid/base type organocatalysts.8d Yet, our most notable
achievement in that work was the development of a direct, oneꢁstep, and selective monoꢁNꢁ
pyridylation of transꢁ(R,R)ꢁcyclohexaneꢁ1,2ꢁdiamine to build a 2ꢁaminoDMAP—Lewis basic
core—unit thereof. Our interest in this superbasic module, which was elegantly made use of
at first hand by Wulff group8a is mainly due to its stronger basicity than the commonly
encountered trialkylamine alternatives (Figure 1).
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Figure 1. Pronucleophile activation by 2ꢁaminoDMAP superbases
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This is in part because a strong base would deprotonate the pronucleophile at an enhanced
rate, thereby ensuring rapid conversion of substrates into products, and simultaneously would
yield lower catalyst loading as a bonus. The other equally important result of this
manipulation would be the stronger and/or tighter binding of the nascent nucleophile with the
resulting 2ꢀaminopyridinium ion (mimicking ureas) through double coordination, which, in
turn, is anticipated to result in higher asymmetry induction once chirally wellꢁdecorated.
Squaramides, on the other hand, display unique performance characteristics as hydrogenꢁbond
donor catalysts in a diverse array of asymmetric reactions and evolve abundantly as described
in the highly influential work by Rawal and coworkers.12 The strong activation of
electrophiles by squaramides is attributed at least partly to their double proton donor capacity,
rigidity and unique Hꢁbond spacing/angle.4c Apart from these appealing features, from a
synthetic chemist’s perspective, their modular nature coupled with their ease of preparation
makes them a favorite among other wellꢁrecognized alternatives.12–14 All these builtꢁin
advantages may therefore stimulate the development of more productive catalysts that are also
highly stereoselective and timeꢁ and costꢁeffective for sustainable catalysis.5,15 In this article,
we describe a series of 2ꢁaminoDMAP/Squaramides and their modular evolution through
electronic and steric fit, which results in a very fruitful interplay of the catalaphores in
asymmetric conjugate addition.
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RESULTS and DISCUSSION
Preparation of the catalysts is very straightforward, as depicted in Scheme 1.
Scheme 1. Synthesis of 2ꢁaminoDMAP/Squaramides 2a–k.
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The synthesis of mixedꢁsquaramates follows oneꢁtoꢁone mixing of diethyl squarate with the
desired amine at room temperature in dichloromethane.12 Subsequently, these mixedꢁ
squaramates were coupled to the easily accessible chiral 2ꢁaminoDMAP base (1)8d by simply
stirring them in methanolic dichloromethane for 48 h. All eleven examples of 2ꢁ
aminoDMAP/Squaramides 2a–k shown in Scheme 2 were produced by the aforementioned
route comprising just two high yielding steps.
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Scheme 2. Catalyst tuning on squaramide unita–c
aReactions were carried out in 0.2 M concentration of transꢁβꢁnitrostyrene (4a) with 3 equiv
b
c
of dibenzoylmethane (3). Time for complete conversion. Enantiomers were separated by
HPLC using the chiral stationary phase. *All our efforts to synthesize tritylamine bearing
mixedꢁsquaramate failed. See experimantal part for a detailed discussion.
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Herein, we selected a conjugate addition reaction to test the efficacy of the catalysts. Indeed,
Michael addition reactions are typically clean and take place in a clickable manner so that
they are the most prominent platform for the evaluation of de novo bifunctional
organocatalysts to construct carbon–carbon and carbon–heteroatom bonds.2b,2e,12a At the
outset of the optimization works, reactions were found to proceed best in toluene by
employing 2 mol% catalyst loading at room temperature (Scheme 2). The first set of catalysts
(2a–b) were devised to explore the effect of small acidity differences they had no significant
impact on selectivities or reaction times, but were reasonably selective (64% ee; 2b). To our
surprise, the next set (2c–d), originally intended to investigate the impact of secondary
chirality on the squaramide unit, provided almost equal enantioselection, but with a dramatic
positive jump (+20%) in the same sense of chirality induction in each. Considered together,
these results suggest two important implications concerning the nature of catalysts: both the
same sense of selection (reꢁface attack in both) and the equally higher selectivities obtained
by catalysts 2c–d, (1) indicate that the chirality of the products depends entirely on that of the
vicinal diamine scaffold, and (2) nominate the substitutionꢁpattern around the modulated
amine as a strong chirality control element. Thereby, catalysts 2e–l were proposed further to
fulfill the steric demand required. Similar stereochemical outcomes obtained by catalysts 2e–f
support the aboveꢁmentioned inference as well. Among the squaramides derived from the
amines neighboring secꢁcarbon (2c–h), while the distinguished selectivity of the 2ꢁadamantyl
amine derived squaramide 2h (87% ee) can be attributed to its rigidꢁsteric bulk, the noticeable
drop in selectivity by means of the benzhydryl derivative 2g is, however, hard to speculate on.
The highest levels of selectivity (up to 89% ee) were achieved by decorating the squaramide
unit with tertꢁcarbon (3°) bearing amines as can be anticipated by the evolving design. In
stark contrast, the only aromatic amine bearing catalyst (2k), and probably the most acidic of
all, afforded a sluggish reaction with a significant loss of enantioselectivity (50% ee).
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Findings presented in scheme 2 clearly demonstrated the superiority of both 2ꢁadamantylꢁ
and 1ꢁadamantylꢁunitꢁincorporating catalysts over the rest. To decide the best, we carried out
some additional comparative experiments (1 mol% vs. 2 mol% cat. loadings of 2j and 2h) in
model reaction of 3 and 4a. To this end, we first fixed the reaction temperature to 5°C to
eliminate its fluctuations. Although reaction times were doubled by doing so, a bit increasedꢁ
selectivities were obtained (2 mol% 2j: 89% ee in 3 h, 1 mol% 2j: 90% ee in 5 h; 2 mol% 2h:
88% ee in 2 h, 1 mol% 2h: 89% ee in 4 h). As a result, we selected structurally rigid and
sterically congested 1ꢁadamantyl amine bearing squaramide 2j as the catalyst and decided to
use it at 1 mol%. In order to demonstrate the generality of the optimized reaction conditions,
various nitroolefins were subjected to this reaction (Table 1).
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Table 1. Substrate Scopea
O
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1 mol%
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NO2
Toluene, 5 °C
Ar
NO2
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4a−o
5a−o
entry
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timeb (h) yieldc (%) eed (%)
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aReactions were carried out in 0.2 M concentration of transꢀβꢀnitroalkenes 4a–o with 3 equiv
of dibenzoylmethane (3). bTime for complete conversion. cIsolated yields. dEnantiomers were
separated by HPLC using the chiral stationary phase.
Gratifyingly, most were typically completed in a couple of hours with excellent
enantioselectivities and in reasonable yields. The stereoselectivity and chemical yield of
conjugate additions (entries 1–15 of Table 1) were apparently insensitive to the substitution
pattern around the aromatic ring (oꢀ, mꢀ, or pꢀ) of nitroalkenes, as well as the electronic
nature, whether electronically activated (entries 2–6, and 15) or deactivated (entries 7–14).
Remarkably, both oꢁfluoroꢁ and pꢁfluoroꢁaryl substituted substrates (4j and 4k) gave 95% ee.
It is notable that all the substrates presented in Table 1 were transformed into highly
enantiomerically enriched Michael adducts (enantiomeric ratios >90:10) in highly acceptable
reaction times and yields. The absolute configuration of chiral adduct 5i was assigned as R by
literature16 comparison of its specific rotation, and HPLC analysis but those of the rest were
assigned, albeit tentatively, in analogy.18 In other words, asymmetry transfer by means of 2j
was assumed to involve a reꢁface addition of dibenzoylmethane to all prochiral nitroolefins
listed in Table 1 (see Figure 2).
We tested catalytic activity of 2j also in conjugate addition of malononitrile (6a), methyl
acetoacetate (6b), acetylacetone (6c) and several malonates (6d‒f) to nitrostyrene 4a under
optimized reaction conditions (Scheme 3). Malononitrile gave a fast reaction but yielded a
racemic mixture of 7a, proving the worst nucleophile among all. The highest stereoselectivity
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was obtained with acetylacetone, 80% ee with complete conversion in 9 h. Reaction with
methyl acetoacetate produced a pair of diastereomers almost in equal ratios (53/47) but with
moderate enantioselectivities in reasonable time and yields in each. With malonates 6d‒f, we
did not observe any noticeable conversion at 1 mol% catalyst loading, so we raised loadings
to 2 mol%, and this time, diisopropyl malonate (6f) was the only nucleophile to give reaction,
albeit with mild conversion and enantioselectivity (50% ee at 50% yield in 24 h). The slowest
reactions of malonate esters, even lack thereof (6d‒e), can be attributed to the relatively
higher pKa values of their methylene protons, although the only reaction with diisopropyl
malonate remains a mystery.
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Scheme 3. Screening of nucleophiles (3 + 6a‒f)
In a previous report of Michael addition of dibenzoylmethane to nitroalkenes, Tan et al.
presented a cinchona alkaloid derived primary amine as the organocatalyst with very
impressive selectivities, but the protocol required as much as 15 mol% of the catalyst to
complete the reaction within a reasonable time (Scheme 4).16
Scheme 4. A literature comparison of 2j in catalysis of 3 + 4a
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Those authors somewhat circumvented this drawback by recycling their catalyst. Scheme 3
shows a performance comparison of 2j with its literature precedents in the particular reaction
between 3 and 4a; and fairly exclusive of 2j, all the others suffer from being either sluggish or
in need of high catalyst loadings, although all are almost equally selective and high yielding.
In light of this comparative structure‒activity analysis, we are convinced that the stronger
basic unit of 2j (2ꢁaminoDMAP) compared to the rest (allꢁtertꢁamine) is the key factor for the
observed rate enhancements. Indeed, our present protocol essentially complements that of Tan
et al. with its unique opportunities, such as low catalyst loading (only 1 mol%), faster
reactions, and low solvent dependence. The descriptive model displayed in Figure 2 aims to
solidify the putative function of each module18 of 2ꢁaminoDMAP/Squaramide 2j in this
particular asymmetric reaction.
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Figure 2. Putative bifunctionality of 2j
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According to this model, upon (partial) deprotonation, dibenzoylmethane may bind doubly to
the correspondingly formed 2ꢁaminopyridinium moiety to stabilize the carbanion formed. On
the other side, nitroalkene is supposed to be activated through wellꢁoriented double Hꢁ
bonding by the donor squaramide coordinating point. We think that this two doublyꢁ
coordinative activation on each side of the catalyst leads to highly strong binding of the
reactants with the catalyst and thereby keeps them in close proximity to the chiral pocket, so
that it may partly explain the marked selectivities and fast reactions observed.
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CONCLUSION
In summary, the setꢁbyꢁset modulation driven design herein paved the way for successful
organocatalyst generation that costs to develop only a handful of candidates—2ꢁ
aminoDMAP/Squaramides 2a–k. While outperforming selectivities (up to 98% ee) of 2j can
be largely ascribable to the rigidꢁsteric bulk (1ꢁadamantyl group) it carries on the squaramide
unit, the high activity (1 mol% cat. loading, high yields in short reaction times) of the catalyst
apparently emanates mainly from the double coordinative nature of squaramide and 2ꢁ
aminopyridine fragments, in which the former is thought to activate transꢁβꢁnitroalkenes and
the latter to stabilize the formed βꢁdiketonate anion. Enantioselectivity of the catalysts is
found to be insensitive to the additional introduction of chiral units through the end caps of
squaramides. 2ꢁAminoDMAP superbaseꢁderived catalysts are greatly promising for “ideal
catalysis” with their outstanding performances described herein and so are the focus of our
current research.
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EXPERIMENTAL
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In this section, the synthetic procedures and structural characterization of novel compounds
(2a–k, 5f–h, and 5j–l) are reported only. They are listed in order of appearance. For those
present in the literature, relevant citations are given where appropriate. Compound 2ꢁ
aminoDMAP 18d and mixedꢁsquaramates12a were prepared according to published procedures.
Structural characterizations of the new compounds were conducted with the instruments and
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1
methods given below. Liquid H NMR and 13C NMR spectra were recorded on a 400
spectrophotometer using CDCl3, or d6ꢁDMSO as the solvent. Chemical shifts values are
reported in ppm taking tetramethylsilane as the internal standard, and J values are given in
hertz. Spin multiplicities are reported as follows: s (singlet), bs (broad singlet), d (doublet), t
(triplet), q (quartet), dd (doublet of doublet), dt (doublet of triplet), td (triplet of doublet), m
(multiplet). Polarimetric measurements were made by the use of a polarimeter and reported as
follows: [α] ꢁꢀ (c in g per 100 mL, solvent). Enantiomeric excess (ee) values of chiral adducts
were detected by a HPLC system using a Daicell ASꢁH chiral column (0.46 cmØ × 25 cm),
ADꢁH chiral column (0.46 cmØ × 10 cm), OJꢁH chiral column (0.46 cmØ × 25 cm), and IA
chiral column (0.46 cmØ × 25 cm). HRMS data were acquired on a time of flight (TOF)
mass spectrometer. IR spectra of all new compounds were obtained by an IR spectrometer.
Flash column chromatography (FCC) was performed by using glass columns with flash grade
silica gel (230–400 mesh). Reactions were monitored by thin layer chromatography (TLC)
using precoated silica gel plates, visualized by UV light and pꢁanisaldehyde, ninhydrin, and
potassium permanganate stains as appropriate. All organic extracts were dehydrated over
ovenꢁdried MgSO4 or K2CO3 and concentrated by using a rotary evaporator before being
subjected to FCC.
General Procedure for the 2ꢀaminoDMAP/Squaramide Catalysts 2a–k.
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To a one to one (volume) DCM:MeOH solution (1 mL) of (R,R)ꢁconfigurated 2ꢁ
aminoDMAP 1 (47 mg, 0.2 mmol) was added appropriate mixedꢁsquaramate (0.2 mmol) at rt.
The solution was stirred for 48 hours at this temperature. The mixture was directly loaded on
9
to
a
silica gel column and eluted with DCM:MeOH (90:10) to afford 2ꢁ
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aminoDMAP/Squaramides 2a–k (66–84% yield) as solid compounds.
Data for 2a. The use of 3ꢁ(benzylamino)ꢁ4ꢁethoxycyclobutꢁ3ꢁeneꢁ1,2ꢁdione (46 mg, 0.2
mmol) gave compound 2a as pale yellow amorphous solid (60 mg, 72% yield). Mp = 142.5 –
ͧͥ
159.6 °C (decomp.). [α] = –145.1 (c 0.25, CH2Cl2). 1H NMR (400 MHz, d6ꢁDMSO) δ 1.05
ꢁ
– 1.45 (m, 4H), 1.70 (bs, 2H), 1.95 – 2.18 (m, 2H), 2.83 (s, 6H), 3.58 – 3.88 (m, 2H), 4.65
(bs, 2H), 5.56 (s, 1H), 5.88 (bs, 1H), 5.95 (d, J = 6.2 Hz, 1H), 7.20 – 7.35 (m, 5H), 7.58 (bs,
1H). Two protons could not be located. 13C NMR (101 MHz, d6ꢁDMSO) δ 23.6, 24.8, 31.5,
33.0, 46.0, 52.9, 54.2, 56.58, 87.9, 98.3, 126.6, 126.7, 127.9, 138.1, 145.8, 154.7, 158.3,
166.7, 166.9, 181.4, 181.9. HRMS (ESI) calcd for C24H30N5O2 [M + H]+ 420.2400, found
420.2412.
Data for 2b. The use of 3ꢁ(3,5ꢁbis(trifluoromethyl)benzylamino)ꢁ4ꢁethoxycyclobutꢁ3ꢁeneꢁ
1,2ꢁdione (73 mg, 0.2 mmol) gave compound 2b as pale yellow amorphous solid (91 mg,
ͧͥ
ꢁ
1
82% yield). Mp = 162.2 – 173.0 °C. [α]
= –141.7 (c 0.25, CH2Cl2). H NMR (400 MHz,
d6ꢁDMSO) δ 1.09 – 1.55 (m, 4H), 1.71 (bs, 2H), 1.91 – 2.15 (m, 2H), 2.85 (s, 6H), 3.61 –
3.91 (m, 2H), 4.85 (bs, 2H), 5.59 (s, 1H), 5.81 – 6.06 (m, 2H), 7.60 (d, J = 4.4 Hz, 1H), 8.06
(s, 3H). Two protons could not be located. 13C NMR (101 MHz, d6ꢁDMSO) δ 24.3, 25.4,
32.2, 33.8, 45.7, 53.5, 58.0, 62.0, 88.7, 98.8, 121.1, 123.2 (q, J = 272.85), 128.5, 130.4 (q, J =
32.78), 142.4, 146.7, 155.3, 159.2, 167.2, 168.0, 182.1, 182.9. HRMS (ESI) calcd for
C26H26N5O2F6 [M – H]– 554.1991, found 554.1978. IR (neat) 2935, 2860, 1796, 1605, 1526,
1378, 1276, 1168, 1126, 982.
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Data for 2c. The use of (R)ꢁ3ꢁethoxyꢁ4ꢁ(1ꢁphenylethylamino)cyclobutꢁ3ꢁeneꢁ1,2ꢁdione (49
mg, 0.2 mmol) gave compound 2c as colorless amorphous solid (59 mg, 68% yield). Mp =
6
7
8
ͧͥ
ꢁ
1
185.0 – 190.0 °C (decomp.). [α] = –33.4 (c 0.25, CH2Cl2). H NMR (400 MHz, CDCl3) δ
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1.04 – 1.40 (m, 5H), 1.45 (d, J = 6.7 Hz, 3H), 1.55 – 1.70 (m, 2H), 1.86 – 1.95(m, 1H), 1.99 –
2.09 (m, 1H), 2.86 (s, 6H), 3.57 – 3.75 (m, 2H), 5.08 (bs, 1H), 5.44 (d, J = 1.8 Hz, 1H), 5.89
(dd, J = 2.3, 6.4Hz, 1H), 7.13 – 7.33 (m, 5H), 7.48 (d, J = 6.4 Hz, 1H). Two protons could
not be located. 13C NMR (101 MHz, d6ꢁDMSO) δ 23.0, 24.4, 25.4, 32.2, 33.6, 52.5, 53.7,
57.7, 61.7, 88.6, 98.9, 126.0, 127.3, 128.6, 143.4, 146.6, 155.4, 159.1, 166.7, 167.7, 181.7,
182.5. HRMS (ESI) calcd for C25H32N5O2 [M + H]+ 434.2556, found 434.2547. IR (neat)
3158, 2930, 1796, 1640, 1549, 1447, 1375, 1159, 1121, 981, 758, 695.
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Data for 2d. The use of (S)ꢁ3ꢁethoxyꢁ4ꢁ(1ꢁphenylethylamino)cyclobutꢁ3ꢁeneꢁ1,2ꢁdione (49
mg, 0.2 mmol) gave compound 2d as colorless amorphous solid (61 mg, 70% yield). Mp =
ͧͥ
ꢁ
1
194.0 – 203.0 °C. [α] = –103.6 (c 0.25, CH2Cl2). H NMR (400 MHz, d6ꢁDMSO) δ 1.10 –
1.41 (m, 4H), 1.47 (d, J = 6.4 Hz, 3H), 1.60 – 1.76 (s, 2H), 1.90 – 2.10 (m, 2H), 2.83 (s, 6H),
3.59 – 381 (m, 2H), 5.12 (bs, 1H), 5.54 (s, 1H), 5.85 – 6.02 (m, 2H), 7.21 – 7.39 (m, 5H),
7.52 (bs, 1H), 7.57 (d, J = 5.6 Hz, 1H), 7.82 (bs, 1H). 13C NMR (101 MHz, d6ꢁDMSO) δ
23.1, 24.3, 32.1, 33.7, 38.9, 39.1, 39.3, 39.5, 39.7, 39.9, 40.1, 48.6, 52.5, 53.6, 57.6, 88.5,
99.0, 125.9, 127.2, 128.6, 143.5, 146.7, 155.6, 158.8, 166.8, 167.5, 181.7, 182.5. IR (neat)
3152, 2932, 2836, 1796, 1603, 1541, 1446, 1374, 1290, 1160, 757, 696.
Data for 2e. The use of 3ꢁethoxyꢁ4ꢁ(isoꢀpropylamino)cyclobutꢁ3ꢁeneꢁ1,2ꢁdione (37 mg, 0.2
mmol) gave compound 2e as colorless amorphous solid (59 mg, 80% yield). Mp = 206.6 –
ͧͥ
227.4 °C (decomp.). [α] = –7.1 (c 0.25, DMSO). 1H NMR (400 MHz, d6ꢁDMSO) δ 1.17 (d,
ꢁ
J = 6.3 Hz, 6H), 1.26 – 1.55 (m, 4H), 1.74 (bs, 2H), 1.95 – 2.18 (m, 2H), 2.90 (s, 6H), 3.0 –
3.75 (m, 1H), 3.77 – 3.92 (m, 1H), 4.04 (bs, 1H), 5.59 (bs, 1H), 5.92 (bs, 1H), 6.04 (dd, J =
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2.0, 6.1 Hz, 1H), 7.44 (bs, 2H), 7.65 (d, J = 6.2 Hz, 1H). 13C NMR (101 MHz, d6ꢁDMSO) δ
23.6, 23.8, 30.4, 32.2, 33.6, 34.3, 45.4, 53.7, 56.65, 88.5, 98.9, 146.2, 155.4, 158.9, 167.0,
167.5, 181.7, 182.2. HRMS (ESI) calcd for C20H30N5O2 [M + H] + 372.2400, found 372.2399.
IR (neat) 3367, 3208, 2930, 2858, 1795, 1602, 1403, 1386, 1155, 800.
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Data for 2f. The use of 3ꢁ(cyclohexylamino)ꢁ4ꢁethoxycyclobutꢁ3ꢁeneꢁ1,2ꢁdione (45 mg, 0.2
mmol) compound 2f as colorless amorphous solid (62 mg, 76% yield). Mp = 144.0 – 152.8
ͧͥ
°C. [α] = –66.4 (c 0.25, CH2Cl2). 1H NMR (400 MHz, d6ꢁDMSO) δ 0.99 – 1.37 (m, 10H),
ꢁ
1.39 – 1.50 (m, 1H), 1.50 – 1.66 (m, 4H), 1.66 – 1.83 (m, 2H), 1.83 – 2.06 (m, 2H), 2.78 (s,
6H), 3.61 (bs, 1H), 3.65 – 3.80 (m, 1H), 5.45 (bs, 1H), 5.75 (d, J = 8.0 Hz, 1H), 5.91 (dd, J =
2.1, 6.2 Hz, 1H), 7.33 (bs, 2H), 7.52 (d, J = 6.2 Hz, 1H). 13C NMR (101 MHz, d6ꢁDMSO) δ
23.9, 24.3, 24.8, 32.2, 33.5, 33.7, 51.8, 53.8, 54.9, 57.5, 88.4, 98.9, 146.1, 155.4, 158.8, 167.0,
167.6, 181.6, 182.2. HRMS (ESI) calcd for C23H34N5O2 [M + H]+ 412.2713, found 412.2718.
IR (neat) 3153, 2928, 2854, 1795, 1648, 1525, 1455, 1367, 1159, 981.
Data for 2g. The use of 3ꢁ(benzhydrylamino)ꢁ4ꢁethoxycyclobutꢁ3ꢁeneꢁ1,2ꢁdione (61 mg, 0.2
mmol) gave compound 2g as colorless amorphous solid (70 mg, 71% yield). Mp = 182.3 –
ͧͥ
ꢁ
1
187.5°C (decomp.). [α] = –111.4 (c 0.25, CH2Cl2). H NMR (400 MHz, d6ꢁDMSO) δ 1.11
– 1.56 (m, 4H), 1.62 – 1.81 (m, 2H), 1.94 – 2.16 (m, 2H), 2.85 (s, 6H), 3.65 – 3.78 (m, 1H),
3.79 – 3.93 (m, 1H), 5.58 (s, 1H), 5.88 (bs, 1H), 5.96 (d, J = 4.8 Hz, 1H), 6.36 (bs, 1H), 7.12
– 7.44 (m, 10H), 7.54 (bs, 1H), 7.64 (d, J = 5.1 Hz, 1H), 8.28 (bs, 1H). 13C NMR (101 MHz,
d6ꢁDMSO) δ 24.4, 32.3, 33.8, 38.7, 53.6, 57.9, 60.2, 88.7, 98.9, 127.0, 128.6, 141.9, 142.0,
146.8, 155.3, 159.2, 166.52, 167.8, 181.7, 182.9. HRMS (ESI) calcd for C30H34N5O2 [M +
H]+ 496.2713, found 496.2676. IR (neat) 3150, 2929, 2855, 1797, 1644, 1525, 1262, 986,
695.
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Data for 2h. The use of 3ꢁ(2ꢁadamantylamino)ꢁ4ꢁethoxycyclobutꢁ3ꢁeneꢁ1,2ꢁdione (55 mg, 0.2
mmol) gave compound 2h as pale yellow amorphous solid (64 mg, 69% yield). Mp = 160.1 –
6
7
8
ͧͥ
ꢁ
1
174.0 °C. [α] = –50.9 (c 0.25, DMSO). H NMR (400 MHz, d6ꢁDMSO) δ 1.09 – 1.69 (m,
9
6H), 1.69 – 2.02 (m, 14H), 2.02 –2.23 (m, 2H), 2.91 (s, 6H), 3.78 (s, 1H), 3.93 (bs, 1H), 4.12
(bs, 1H), 5.57 (bs, 1H), 5.74 (bs, 1H), 6.01 (bs, 1H), 7.42 – 7.64 (m, 2H), 7.69 (d, J = 2.4 Hz,
1H). 13C NMR (101 MHz, d6ꢁDMSO) δ 23.0, 23.1, 24.0, 24.9, 25.2, 28.8, 28.9, 31.0, 31.3,
31.4, 32.3, 34.9, 35.0, 35.4, 52.4, 55.6, 56.3, 60.6, 87.3, 97.4, 145.6, 153.8, 158.0, 165.5,
166.3, 180.2, 181.2. HRMS (ESI) calcd for C27H38N5O2 [M + H]+ 464.3026, found 464.3020.
IR (neat) 2904, 2852, 1663, 1581, 1517, 1365, 1292, 1101, 980.
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Data for 2i. The use of 3ꢁ(tertꢁbutylamino)ꢁ4ꢁethoxycyclobutꢁ3ꢁeneꢁ1,2ꢁdione (39 mg, 0.2
mmol) gave compound 2i as pale yellow amorphous solid (56 mg, 73% yield). Mp = 250.4 –
ͧͥ
254.3 °C. [α] = +59.2 (c 0.25, DMSO). 1H NMR (400 MHz, d6ꢁDMSO) δ 1.01 – 1.50 (m,
ꢁ
4H), 1.22 (s, 9H), 1.54 – 1.72 (m, 2H), 1.86 – 2.04 (m, 2H), 2.78 (s, 6H), 3.55 – 3.78 (m, 2H),
5.45 (d, J = 1.8 Hz, 1H), 5.79 (d, J = 8.5 Hz, 1H), 5.92 (dd, J = 2.1, 6.2 Hz, 1H), 7.49 (bs,
2H), 7.52 (d, J = 6.2 Hz, 1H). 13C NMR (100.6 MHz, d6ꢁDMSO) δ 24.3, 30.1, 32.1, 33.4,
52.0, 53.9, 57.6, 88.3, 98.9, 145.6, 155.4, 158.4, 167.6, 168.3, 180.4, 182.3. HRMS (ESI)
calcd for C21H32N5O2 [M + H]+ 386.2556, found 386.2572. IR (neat) 2928, 2855, 1791, 1668,
1520, 1446, 1358, 1300, 1163, 979.
Data for 2j. The use of 3ꢁ(1ꢁadamantylamino)ꢁ4ꢁethoxycyclobutꢁ3ꢁeneꢁ1,2ꢁdione (55 mg, 0.2
mmol) gave compound 2j as colorless amorphous solid (61 mg, 66% yield). Mp = 254.7 –
ͦͪ
259.0 °C. [α] = –37.7 (c 0.25, DMSO). 1H NMR (400 MHz, d6ꢁDMSO) δ 1.01 – 1.45 (m,
ꢁ
10H), 1.46 – 1.56 (m, 1H), 1.57 – 1.87 (m, 6H), 1.90 – 2.10 (m, 2H), 2.85 (s, 6H), 3.59 –
3.87 (m, 4H), 5.52 (s, 1H), 5.85 (d, J = 7.6 Hz, 1H), 5.99 (dd, J = 2.0, 6.2 Hz, 1H), 7.41 (bs,
2H), 7.59 (d, J = 6.2 Hz, 1H). Two protons could not be located. 13C NMR (101 MHz, d6ꢁ
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DMSO) δ 23.8, 24.3, 24.8, 32.2, 33.5, 33.7, 51.8, 53.8, 54.8, 57.6, 88.4, 98.9, 146.0, 155.4,
158.7, 167.0, 167.5, 181.6, 182.2. HRMS (ESI) calcd for C27H38N5O2 [M + H]+ 464.3026,
found 464.3023. IR (neat) 3321, 3233, 2905, 2855, 1785, 1655, 1519, 1490, 1379, 1307,
1071, 945.
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Data for 2k. The use of 3ꢁ(3,5ꢁbis(trifluoromethyl)phenylamino)ꢁ4ꢁethoxycyclobutꢁ3ꢁeneꢁ
1,2ꢁdione (71 mg, 0.2 mmol) gave compound 2k as pale yellow amorphous solid (91 mg,
ͧͥ
ꢁ
1
84% yield). Mp = 196.7 – 204.0 °C (decomp.). [α] = –325.2 (c 0.25, CH2Cl2). H NMR
(400 MHz, d6ꢁDMSO) δ 1.14 – 1.57 (m, 4H), 1.66 – 1.81 (m, 2H), 1.92 – 2.03 (m, 1H), 2.04 –
2.15 (m, 1H), 2.74 (s, 6H), 3.69 – 3.81 (m, 1H), 3.82 – 3.96 (m, 1H), 5.53 (s, 1H), 5.75 (d, J =
4.9 Hz, 1H), 5.88 (d, J = 8.3 Hz, 1H), 7.48 (d, J = 6.0 Hz, 1H), 7.63 (s, 1H), 7.93 (s, 2H). Two
protons could not be located. 13C NMR (101 MHz, d6ꢁDMSO) δ 24.3, 24.5, 32.1, 33.4, 53.6,
59.6, 88.8, 98.7, 114.3, 117.7, 123.13 (q, J = 272.96 Hz), 131.25 (q, J = 32.2 Hz), 141.2,
146.7, 155.16, 159.4, 162.3, 169.9, 180.3, 184.7. HRMS (ESI) calcd for C25H26N5O2F6 [M +
H]+ 542.1991, found 542.2019. IR (neat) 3322, 2936, 2860, 1792, 1696, 1604, 1529, 1448,
1378, 1276, 1125, 850.
Efforts for the synthesis of precursor of 2l.
The standard procedure failed when the amine was tritylamine even after 48 hour of
stirring.12a Triethyl amine was added as a base in one equivalent next to activate the primary
amine, but no trace of product formation was observed. Then, we tried nucleophile catalysis
as well to promote the reaction using DMAP (10 mol%) in 1,2ꢁdichloroethane, but no
conversion was observed even at reflux. We tried Lewis acid catalysis (Sc(OTf)3, Zn(OTf)2)
too, but fate did not change again.19,20 We reasoned that the unreactivity of tritylamine could
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be attributable to three phenyl rings, which might impose high steric bulkiness thereby
strongly shielding the lone pair electrons on the amine.
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General Procedure for Asymmetric Michael Additions
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To a toluene solution (1.0 mL) of transꢁβꢁnitroalkenes 4a–o (0.20 mmol) was added 2ꢁ
aminoDMAP/Squaramide 2j (0.002 mmol, 0.98 mg or 0.004 mmol, 1.96 mg) and
dibenzoylmethane 3 or active methylene compounds 6a–f (134 mg, 0.6 mmol) at 5 °C.
Stirring was continued till the consumption of limiting reagent (monitored by TLC).
Thereafter, the reaction mixture was directly subjected to flash column chromatography using
1:10 EtOAc:nꢁhexanes as the eluent to afford the conjugate addition products 5a–o.
Data for 5a. The use of (E)ꢀnitrovinylbenzene 4a (0.2 mmol) gave chiral adduct 5a in 92%
yield in 5 hours. Spectroscopic data were reported previously.16 HPLC (ASꢁH, 80:20 nꢁ
hexane:isopropyl alcohol, 1 mL/min, 254 nm): tmajor = 33.8 min, tminor = 24.6 min, 90% ee;
ͦͤ
[α] = –6.5 (c 0.25, CH2Cl2).
ꢁ
Data for 5b. The use of (E)ꢁ1ꢁmethoxyꢁ2ꢁ(2ꢁnitrovinyl)benzene 4b (0.2 mmol) gave chiral
adduct 5b in 70% yield in 6 hours. Spectroscopic data were reported previously.16 HPLC (ASꢁ
H, 80:20 nꢁhexane:isopropyl alcohol, 1 mL/min, 254 nm): tmajor = 20.4 min, tminor = 16.6 min,
ͦͤ
85% ee; [α] = –35.7 (c 1.00, CH2Cl2).
ꢁ
Data for 5c. The use of (E)ꢁ1ꢁmethoxyꢁ3ꢁ(2ꢁnitrovinyl)benzene 4c (0.2 mmol) gave chiral
adduct 5c in 94% yield in 6 hours. Spectroscopic data were reported previously.16 HPLC (ASꢁ
H, 80:20 nꢁhexane:isopropyl alcohol, 1 mL/min, 254 nm): tmajor = 49.6 min, tminor = 64.8 min,
ͥͭ
90% ee; [α] = –16.2 (c 1.00, CH2Cl2).
ꢁ
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Data for 5d. The use of (E)ꢁ1ꢁmethoxyꢁ4ꢁ(2ꢁnitrovinyl)benzene 4d (0.2 mmol) gave chiral
adduct 5d in 70% yield in 6 hours. Spectroscopic data were reported previously.16 HPLC (ASꢁ
H, 80:20 nꢁhexane:isopropyl alcohol, 1 mL/min, 254 nm): tmajor = 49.7 min, tminor = 35.7 min,
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ͦͨ
ꢁ
80% ee; [α] = –17.9 (c 1.00, CH2Cl2).
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Data for 5e. The use of (E)ꢁ1ꢁmethylꢁ4ꢁ(2ꢁnitrovinyl)benzene 4e (0.2 mmol) gave chiral
adduct 5e in 85% yield in 2 hours. Spectroscopic data were reported previously.16 HPLC (ASꢁ
H, 80:20 nꢁhexane:isopropyl alcohol, 1 mL/min, 254 nm): tmajor = 30.6 min, tminor = 23.0 min,
ͦͨ
92% ee; [α] = –13.0 (c 1.00, CH2Cl2).
ꢁ
Data for 5f. The use of (E)ꢁ1ꢁ(benzyloxy)ꢁ4ꢁ(2ꢁnitrovinyl)benzene 4f (0.2 mmol) gave chiral
adduct 5f in 54% yield in 10 hours. HPLC (ASꢁH, 80:20 nꢁhexane:isopropyl alcohol, 1
ͦͤ
ꢁ
mL/min, 254 nm): tmajor = 59.1 min, tminor = 47.9 min, 86% ee; [α] = –22.0 (c 0.25, CH2Cl2).
1
Mp = 156 – 159 °C. H NMR (400 MHz, CDCl3) δ 4.50 (dd, J = 14.2, 7.6 Hz, 1H), 4.75 –
4.97 (m, 4H), 5.73 (d, J = 8.1 Hz, 1H), 6.69 – 6.76 (m, 2H), 7.06 (d, J = 8.7 Hz, 2H), 7.20 –
7.36 (m, 9H), 7.38 – 7.51 (m, 2H), 7.70 (d, J = 7.4 Hz, 2H), 7.80 (d, J = 7.4 Hz, 2H). 13C
NMR (101 MHz, CDCl3) δ 42.4, 59.1, 68.9, 114.2, 126.4, 127.0, 127.55, 127.58, 127.76,
127.80, 127.9, 128.4, 132.7, 133.0, 134.8, 135.2, 134.9, 135.7, 157.5, 192.7, 193.3. HRMS
calcd for C30H25NO5, m/z 479.1733, found 479.1760. IR (neat) 2965, 2960, 1691,1595, 1546,
1513, 1448, 1286, 1117, 1039, 821, 733, 689 cmꢁ1.
Data for 5g. The use of (E)ꢁ1ꢁchloroꢁ2ꢁ(2ꢁnitrovinyl)benzene 4g (0.2 mmol) gave chiral
adduct 5g in 86% yield in 3 hours. HPLC (ASꢁH, 80:20 nꢁhexane:isopropyl alcohol, 1
ͦͤ
ꢁ
mL/min, 254 nm): tmajor = 24.6 min, tminor = 23.1 min, 94% ee; [α] = +31.5 (c 0.25, CH2Cl2).
1
Mp = 110 – 115 °C. H NMR (400 MHz, CDCl3) δ 4.91 – 5.21 (m, 3H), 5.99 (d, J = 6.5 Hz,
1H), 6.97 (t, J = 7.5 Hz, 1H), 7.03 – 7.08 (m, 1H), 7.17 – 7.12 (m, 1H), 7.25 – 7.35 (m, 5H),
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7.46 (t, J = 7.2 Hz, 2H), 7.72 (d, J = 7.6 Hz, 2H), 7.82 (d, J = 7.5 Hz, 2H). C NMR (101
MHz, CDCl3) δ 39.2, 56.1, 74.2, 126.2, 127.61, 127.66, 127.88, 127.92, 128.3, 128.6, 129.4,
132.8, 132.9, 133.1, 133.2, 134.6, 135.2, 192.3, 193.5. HRMS calcd for C23H18ClNO4, m/z
407.0924, found 407.094. IR (neat) 2921, 2850, 1686, 1549, 1447, 1376, 1258, 1179, 756,
684 cmꢁ1.
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Data for 5h. The use of (E)ꢁ1ꢁchloroꢁ3ꢁ(2ꢁnitrovinyl)benzene 4h (0.2 mmol) gave chiral
adduct 5h in 74% yield in 2.5 hours. HPLC (ASꢁH, 80:20 nꢁhexane:isopropyl alcohol, 1
ͥͭ
ꢁ
mL/min, 254 nm): tmajor = 43.9 min, tminor = 24.7 min, 84% ee; [α] = +25.0 (c 1.00, CH2Cl2).
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Mp = 86 – 88 °C. H NMR (400 MHz, CDCl3) δ 4.52 (td, J = 8.2, 5.4 Hz, 1H), 4.80 – 4.98
(m, 2H), 5.74 (d, J = 8.2 Hz, 1H), 7.00 – 7.07 (m, 3H), 7.15 (s, 1H), 7.24 – 7.36 (m, 4H), 7.39
– 7.51 (m, 2H), 7.67 – 7.74 (m, 2H), 7.76 – 7.83 (m, 2H). 13C NMR (101 MHz, CDCl3) δ
42.6, 58.4, 75.9, 125.6, 127.4, 127.5, 127.6, 127.7, 127.9, 128.0, 129.2, 132.9, 133.2, 133.7,
134.6, 134.9, 137.8, 192.4, 192.9, HRMS calcd for C23H18ClNO4, m/z 407.0921, found
407.0941. IR (neat) 2820, 1689, 1656, 1593, 1544, 1446, 1379, 1255, 958, 683 cmꢁ1.
Data for 5i. The use of (E)ꢁ1ꢁchloroꢁ4ꢁ(2ꢁnitrovinyl)benzene 4i (0.2 mmol) gave chiral
adduct 5i in 90% yield in 3 hours. Spectroscopic data were reported previously.16 HPLC (ASꢁ
H, 80:20 nꢁhexane:isopropyl alcohol, 1 mL/min, 254 nm): tmajor = 33.8 min, tminor = 24.6 min,
ͥͭ
ꢁ
89% ee; [α] = –6.5 (c 0.25, CH2Cl2).
Data for 5j. The use of (E)ꢁ1ꢁfluoroꢁ2ꢁ(2ꢁnitrovinyl)benzene 4j (0.2 mmol) gave chiral
adduct 5j in 95% yield in 3 hours. HPLC (OJꢁH, 80:20 nꢁhexane:isopropyl alcohol, 1
ͥͭ
ꢁ
mL/min, 254 nm): tmajor = 53.9 min, tminor = 80.4 min, 95% ee; [α] = –49.1 (c 1.00, CH2Cl2).
Mp = 88 – 91 °C. 1H NMR (400 MHz, CDCl3) δ 4.87 – 4.70 (m, 2H), 5.02 (dd, J = 13.2, 10.2
Hz, 1H), 5.92 (d, J = 8.6 Hz, 1H), 6.82 – 6.91 (m, 2H), 7.01 – 7.09 (m, 1H), 7.16 (dt, J = 7.6,
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1.7 Hz, 1H), 7.24 – 7.36 (m, 4H), 7.39 – 7.50 (m, 2H), 7.75 – 7.80 (m, 2H), 7.80 – 7.85 (m,
2H). 13C NMR (101 MHz, CDCl3) δ 39.9, 57.5, 75.9, 115.9 (d, J = 22.1 Hz), 123.5 (d, J =
13.0 Hz), 124.66, 124.69, 128.58, 128.68, 128.90, 129.1, 130.01, 130.09, 131.3 (d, J = 4.1
Hz), 134.1 (d, J = 17.6 Hz), 135.9 (d, J = 41.7 Hz), 161.1 (d, J = 245.3 Hz), 193.4, 193.8.
HRMS calcd for C23H18FNO4, m/z 391.1220, found 391.1247. IR (neat) 2950, 2945, 1685,
1593, 1555, 1469, 1448, 1258, 1204, 682 cmꢁ1.
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Data for 5k. The use of (E)ꢁ1ꢁfluoroꢁ4ꢁ(2ꢁnitrovinyl)benzene 4k (0.2 mmol) gave chiral
adduct 5k in 75% yield in 7 hours. HPLC (ASꢁH, 80:20 nꢁhexane:isopropyl alcohol, 1
ͦͤ
ꢁ
mL/min, 254 nm): tmajor = 34.1 min, tminor = 23.3 min, 95% ee; [α] = –9.1 (c 0.25, CH2Cl2).
Mp = 115 – 119 °C. 1H NMR (400 MHz, CDCl3) δ 4.55 (td, J = 8.3, 5.3 Hz, 1H), 4.78 – 4.93
(m, 2H), 5.73 (d, J = 8.3 Hz, 1H), 6.76 – 6.86 (m, , 2H), 7.26 – 7.36 (m, 4H), 7.40 – 7.51 (m,
2H), 7.10–7.16 (m, 2H), 7.68–7.73 (m, 2H), 7.78–7.85 (m, 2H). 13C NMR (101 MHz, CDCl3)
δ 42.4, 58.9, 76.5, 114.8, 115.0, 126.2, 127.56, 127.68, 127.75, 127.88, 128.0, 129.0, 129.1,
131.46 (d, J = 4.0 Hz), 133.1 (d, J = 27.3 Hz), 134.96 (d, J = 30.6 Hz), 161.3 (d, J = 247.7
Hz), 192.5, 193.0. HRMS calcd for C23H18FNO4, [M – H]+ 390.1220, found 390.1239. IR
(neat) 2954, 2950, 1690, 2595, 1551, 1509, 1447, 1377, 1258, 970,820, 687 cmꢁ1.
Data for 5l. The use of (E)ꢁ1ꢁbromoꢁ3ꢁ(2ꢁnitrovinyl)benzene 4l (0.2 mmol) gave chiral
adduct 5l in 60% yield in 5 hours. HPLC (ASꢁH, 80:20 nꢁhexane:isopropyl alcohol, 1
ͦͨ
ꢁ
mL/min, 254 nm): tmajor = 46.8 min, tminor = 26.4 min, 83% ee; [α] = –14.6 (c 1.00, CH2Cl2).
Mp = 102 – 105 °C. 1H NMR (400 MHz, CDCl3) δ 4.51 (td, J = 8.2, 5.2 Hz, 1H), 4.80 – 4.98
(m, 2H), 5.72 (d, J = 8.0 Hz, 1H), 6.99 (t, J = 7.8 Hz, 1H), 7.09 (d, J = 7.7 Hz, 1H), 7.21 (d, J
= 7.9 Hz, 1H), 7.26 – 7.38 (m, 5H), 7.43 – 7.53 (m, 2H), 7.72 (d, J = 7.5 Hz, 2H), 7.80 (d, J =
7.5 Hz, 2H). 13C NMR (101 MHz, CDCl3) δ 42.6, 58.3, 75.9, 121.9, 126.1, , 127.6, 127.7,
127.9, 128.1, 129.4, 130.3, 130.4, 132.9, 133.2, 134.6, 134.9, 138.0, 192.3, 192.9. HRMS
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calcd for C23H18BrNO4, m/z 451.0419, found 451.0443. IR (neat) 2960, 1686, 1539, 1256,
1189, 1176, 958, 799, 771, 711, 666 cmꢁ1.
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Data for 5m. The use of (E)ꢁ1ꢁbromoꢁ4ꢁ(2ꢁnitrovinyl)benzene 4m (0.2 mmol) gave chiral
adduct 5m in 75% yield in 4 hours.Spectroscopic data were reported previously.16 HPLC (ASꢁ
H, 80:20 nꢁhexane:isopropyl alcohol, 1 mL/min, 254 nm): tmajor = 37.0 min, tminor = 26.7 min,
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94% ee; [α] = –16.2 (c 1.00, CH2Cl2).
ꢁ
Data for 5n. The use of (E)ꢁ1ꢁnitroꢁ2ꢁ(2ꢁnitrovinyl)benzene 4n (0.2 mmol) gave chiral adduct
5n in 68% yield in 18 hours. Spectroscopic data were reported previously.16 HPLC (ASꢁH,
80:20 nꢁhexane:isopropyl alcohol, 1 mL/min, 254 nm): tmajor = 32.6 min, tminor = 27.2 min,
ͦͨ
95% ee; [α] = –93.2 (c 1.00, CH2Cl2).
ꢁ
Data for 5o. The use of (E)ꢁ2ꢁ(2ꢁnitrovinyl)furan 4o (0.2 mmol) gave chiral adduct 5o in 58%
yield in 6 hours. Spectroscopic data were reported previously.16 HPLC (ADꢁH, 80:20 nꢁ
hexane:isopropyl alcohol, 1 mL/min, 254 nm): tmajor = 38.4 min, tminor = 48.5 min, 98% ee;
ͥͭ
[α] = –29.5 (c 1.00, CH2Cl2).
ꢁ
Data for 7a. The use of malononitrile 6a (0.2 mmol) gave racemic adduct 7a in 94% yield in
2 hours.
Data for 7b. The use of methyl acetoacetate 6b (0.2 mmol) gave diastereomers of chiral
adduct 7b in 96% yield in 8 hours. Spectroscopic data were reported previously.21 HPLC
(ADꢁH, 95:5 nꢁhexane:isopropyl alcohol, 1 mL/min, 210 nm): tmajor1 = 24.6 min, tminor1 = 16.7
min, 50% ee; tmajor2 = 23.2 min, tminor2 = 30.1 min, 57% ee.
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Data for 7c. The use of acetylacetone 6c (0.2 mmol) gave chiral adduct 7c in 95% yield in 9
hours. Spectroscopic data were reported previously.21 HPLC (ADꢁH, 85:15 nꢁ
hexane:isopropyl alcohol, 1 mL/min, 220 nm): tmajor = 12.2 min, tminor = 9.3 min, 80% ee;.
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[α] = –104.6 (c 0.50, CH2Cl2).
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Data for 7f. The use of diisopropyl malonate 6f (0.2 mmol) gave chiral adduct 7f in 50%
yield in 24 hours. Spectroscopic data were reported previously.22 HPLC (ADꢁH, 80:20 nꢁ
hexane:isopropyl alcohol, 1 mL/min, 210 nm): tmajor = 8.6 min, tminor = 21.0 min, 50% ee.
ͦͤ
[α] = –27.0 (c 1.00, CH2Cl2).
ꢁ
ACKNOWLEDGEMENT
We thank to Dilꢀad Susam very much for conducting some experiments. We are grateful to
TÜBĐTAK for supporting this study (113Z156).
SUPPORTING INFORMATION
1
13
Copies of H NMR and C NMR spectra, and chiral HPLC chromatograms. This material is
available free of charge via the Internet at http://pubs.acs.org.
REFERENCES
1) Berkessel, A.; Gröger, H. Asymmetric Organocatalysis. Wiley VCH: Weinheim, 2005.
(b) Dondoni, A.; Massi, A. Angew. Chem., Int. Ed. 2008, 47, 4638. (c) Macmillan, D.
W. C. Nature 2008, 455, 304. (d) List, B.; Yang, J. W. Science 2006, 313, 1584.
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2) For a clear presentation of this highly emerging field see: (a) Wang, Y.; Deng, L. In
Catalytic Asymmetric Synthesis; Ojima, I. Ed.; 3rd ed.; Wiley VCH: Newyork, 2010,
59ꢁ94. For some seminal works see: (b) Hiemstra, H.; Wynberg, H. J. Am. Chem. Soc.
1981, 103, 417. (c) Sigman, M. S.; Jacobsen, E. N. J. Am. Chem. Soc. 1998, 120,
4901. (d) Corey, E. J.; Grogan, M. J. Org. Lett. 1999, 1, 157. (e) Okino, T.; Hoashi,
Y.; Takemoto, Y. J. Am. Chem. Soc. 2003, 125, 12672.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
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36
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44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
3) Yoon, T. P.; Jacobsen, E. N. Science 2003, 299, 1691.
4) (a) Doyle, G.; Jacobsen, E. N. Chem. Rev. 2007, 107, 5713. (b) Miyabe, H.;
Takemoto, Y. Bull. Chem. Soc. Jap. 2008, 81, 785. (c) Alemán, J.; Parra, A.; Jiang,
H.; Jørgensen, K. A. Chem.—Eur. J. 2011, 17, 6890. (d) Narayanaperumal, S.; Rivera,
D. G.; Silva, R. C.; Paixão, M. W. ChemCatChem 2013, 5, 2756.
5) (a) Gladysz, J. A. Pure Appl. Chem. 2001, 73, 1319. (b) Palomo, C.; Oiarbide, M.;
López, R. Chem. Soc. Rev. 2009, 38, 632.
6) Ishikawa, T. Superbases for Organic Synthesis, Wiley: New York, 2009.
7) (a) Nugent, B. M.; Yoder, R. A.; Johnston, J. N. J. Am. Chem. Soc. 2004, 126, 3418.
(b) Singh, A.; Yoder, R. A; Shen, B.; Johnston, J. N. J. Am. Chem. Soc. 2007, 129,
3466. (c) Singh, A.; Johnston, J. N. J. Am. Chem. Soc. 2008, 130, 5866. (d) Dobish,
M. C.; Johnston, J. N. Org. Lett. 2010, 12, 5744. (e) Davis, T. A.; Wilt, J. C.;
Johnston, J. N. J. Am. Chem. Soc. 2010, 132, 2880. (f) Davis, T. A.; Johnston, J. N.
Chem. Sci. 2011, 2, 1076. (g) Dobish, M. C.; Johnston, J. N. J. Am. Chem. Soc. 2012,
134, 6068. (h) Davis, T. A.; Danneman, M. W.; Johnston, J. N. Chem. Commun. 2012,
48, 5578. (i) Shen, B.; Makley, D. M.; Johnston, J. N. Nature 2010, 465, 1027. (j)
Davis, T. A.; Vilgelm, A. E., Richmond, A.; Johnston, J. N. J. Org. Chem. 2013, 78,
10605.
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8) (a) Rabalakos, C.; Wulff, W. D. J. Am. Chem. Soc. 2008, 130, 13524. (b) Wang, J.;
Feringa, B. L. Science 2011, 331, 1429. (c) Yazıcıoğlu, E. Y.; Tanyeli, C.
Tetrahedron: Asymmetry 2012, 23, 1694. (d) Isik, M.; Tanyeli, C. J. Org. Chem. 2013,
78, 1604.
10
11
12
13
14
15
16
17
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20
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9) (a) Iyer, M. S.; Gigstad, K. M.; Namdev, N. D.; Lipton, M. J. Am. Chem. Soc. 1996,
118, 4910. (b) Ref. 2(d) herein. (c) Ishikawa, T.; Araki, Y.; Kumamoto, T.; Seki, H.;
Fukuda, K.; Isobe, T. Chem. Commun. 2001, 245. (d) Terada, M.; Ube, H.; Yaguchi,
Y. J. Am. Chem. Soc. 2006, 128, 1454. (e) Yu, Z.; Liu, X.; Zhou, L.; Lin, L.; Feng, X.
Angew. Chem. Int. Ed. 2009, 48, 5195. (f) Sohtome, Y.; Shin, B.; Horitsugi, N.;
Takagi, R.; Noguchi, K.; Nagasawa, K. Angew. Chem., Int. Ed. 2010, 49, 7299. (g)
Sohtome, Y.; Tanaka, S.; Takada, K.; Yamaguchi, T.; Nagasawa, K. Angew. Chem.,
Int. Ed. 2010, 49, 9254. (h) Chen, X.; Dong, S.; Qiao, Z.; Zhu, Y.; Xie, M.; Lin, L.;
Liu, X.; Feng, X. Chem.—Eur. J. 2011, 17, 2583.
10)For a review see: (a) Ishikawa, T.; Kumamoto, T. Synthesis 2006, 737. Selected
examples: (b) Uraguchi, D.; Sakaki, S.; Ooi, T. J. Am. Chem. Soc. 2007, 129, 12392.
(c) Uraguchi, D.; Yoshioka, K.; Ueki, Y.; Ooi, T. J. Am. Chem. Soc. 2012, 134, 19370.
(d) Corbett, M. T.; Uraguchi, D.; Ooi, T.; Johnson, J. S. Angew. Chem., Int. Ed. 2012,
51, 4685. (e) Takeda, T.; Terada, M. J. Am. Chem. Soc. 2013, 135, 15306.
11) (a) Bandar, J. S.; Lambert, T. H. J. Am. Chem. Soc. 2012, 134, 5552. (b) Bandar, J. S.;
Lambert, T. H. J. Am. Chem. Soc. 2013, 135, 11799. (c) Núñez, M. G.; Farley, A. J.
M.; Dixon, D. J. J. Am. Chem. Soc. 2013, 135, 16348.
12)(a) Malerich, J. P.; Hagihara, K.; Rawal, V. H. J. Am. Chem. Soc. 2008, 130, 14416.
(b) Konishi, H.; Lam, T. Y.; Malerich, J. P.; Rawal, V. H. Org. Lett. 2010, 12, 2028.
(c) Zhu, Y.; Malerich, J. P.; Rawal, V. H. Angew. Chem., Int. Ed. 2010, 49, 153. (d)
Qian, Y.; Ma, G.; Lv, A.; Zhu, H.ꢁL.; Zhao, J.; Rawal, V. H. Chem. Commun. 2010,
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46, 3004. (e) Yang, K. S.; Nibbs, A. E.; Türkmen, Y. E.; Rawal, V. H. J. Am. Chem.
Soc. 2013, 135, 16050.
6
7
8
9
13)Recent examples of Squaramides by other groups: (a) Dai, L.; Wang, S.ꢁX.; Chen, F.ꢁ
E. Adv. Synth. Catal. 2010, 352, 2137. (b) W. Yang, D. ꢁM. Du, Org. Lett. 2010, 12,
5450. (c) Ling, J.ꢁB.; Su, Y.; Zhu, H.ꢁL.; Wang, G.ꢁY.; Xu, P.ꢁF. Org. Lett. 2012, 14,
1090. (d) Wang, X.; Yao, W.; Yao, Z.; Ma, C. J. Org. Chem. 2012, 77, 2959. (e)
Yang, W.; Du, D.ꢁM. Chem. Commun. 2011, 47, 12706. (f) Yang, W.; Du, D.ꢁM. Adv.
Syn. Catal. 2011, 353, 1241. (g) Xu, D. Q.; Wang, Y.ꢁF.; Zhang, W.; Luo, S.ꢁP.;
Zhong, A.ꢁG.; Xia, A.ꢁB.; Xu, Z.ꢁY. Chem. —Eur. J. 2010, 16, 4177. (h) Wang, Y.ꢁF.;
Zhang, W.; Luo, S.ꢁP.; Zhang, G.ꢁC.; Xia, A.ꢁB.; Xu, X.ꢁS.; Xu, D.ꢁQ. Eur. J. Org.
Chem. 2010, 4981. (i) Bae, H. Y.; Some, S.; Lee, J. H.; Kim, J.ꢁY.; Song, M. J.; Lee,
S.; Zhang, Y. J.; Song, C. E. Adv. Synth. Catal. 2011, 353, 3196. (j) Min, C.; Han, X.;
Liao, Z. Q.; Wu, X. F.; Zhou, H.ꢁB.; Dong, C. Adv. Synth. Catal. 2011, 353, 2715. (k)
Pansare, S. V.; Paul, E. K. Chem. Commun. 2011, 47, 1027. (l) Wu, X. F.; Min, C.;
Nyamzundui, E.; Zhou, H.ꢁB.; Dong, C. Tetrahedron: Asymmetry 2011, 22, 1640. (m)
Liu, B.; Han, X.; Dong, Z.; Lv, H.; Zhou, H.ꢁB.; Dong, C. Tetrahedron: Asymmetry
2013, 24, 1276. (n) Zhao, M.ꢁX.; Ji, F.ꢁH.; Wei, D.ꢁK.; Shi, M. Tetrahedron 2013,69,
10763. (o) Kasaplar, P.; Riente, P.; Hartmann, C.; Pericàs, M. A. Adv. Synth. Catal.
2012, 354, 2905. (p) Kasaplar, P.; RodríguezꢁEscrich, P.; Pericàs, M. A. Org. Lett.
2013, 15, 3498. (q) Yang, W.; Yang, Y.; Du, D.ꢁM. Org. Lett. 2013, 15, 1190. (r) Loh,
C. C. J.; Hack, D.; Enders, D. Chem. Commun. 2013, 49, 10230. (s) Zhao, M.ꢁX.; Bi,
H.ꢁL.; Zhou, H.; Yang, H.; Shi, M. J. Org. Chem. 2013, 78, 9377.
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14)For reviews on squaramides, see ref. 4c of this work, and Storer, R. I.; Aciro, C. Jones,
L. H. Chem. Soc. Rev. 2011, 40, 2330.
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15)For a review on low catalyst loading, see: Giacalone, F.; Gruttadauria, M.; Agrigento,
P.; Noto, R. Chem. Soc. Rev. 2012, 41, 2406.
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16)Tan, B.; Zhang, X.; Chua, P. J.; Zhong, G. Chem. Commun. 2009, 779.
17)Wang, C.ꢁJ.; Zhang, Z.ꢁH.; Dong, X.ꢁQ.; Wu, X.ꢁJ. Chem. Commun. 2008, 1431.
18)Okino, T.; Hoashi, Y.; Furukawa, T.; Xu, X.; Takemoto, Y. J. Am. Chem. Soc. 2005,
127, 119.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
19)Rostami, A.; Colin, A.; Li, X. Y.; Chudzinski, M. G.; Lough, A. J.; Taylor, M. S. J.
Org. Chem. 2010, 75, 3983.
20)Rostami, A.; Wei, C. J.; Guérin, G.; Taylor, M. S. Angew. Chem., Int. Ed. 2011, 50,
2059.
21) Peng, F.ꢁZ; Shao, Z.ꢁH; Fan, B.ꢁM; Song, H.; Li, G.ꢁP; Zhang, H.ꢁB J. Org. Chem.
2008, 5202.
22) Evans, D. A.; Mito, S.; Seidel, D. J. Am. Chem. Soc. 2007, 129, 11583.
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