Chiral Bisdiphenylphosphine Dioxides Bearing a Bis(triazolyl) Backbone as Promising Lewis Bases for Asymmetric Organocatalysis

Article abstract of DOI:10.1002/ejoc.201800317

Two chiral C₂-symmetric diphenylphosphine dioxides bearing an original bis(triazolyl) backbone were prepared starting from inexpensive and readily available precursors. The key step involves the simultaneous formation of five bonds in one chemi

Full text of DOI:10.1002/ejoc.201800317

A Journal of
Accepted Article
Title: Chiral bisdiphenylphosphine dioxides bearing an original
bis(triazolyl) backbone as promising Lewis bases for asymmetric
organocatalysis
Authors: Nicolas SEVRAIN, Jean-Noël VOLLE, Jean-Luc PIRAT,
Tahar AYAD, and David Virieux
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201800317
Link to VoR: http://dx.doi.org/10.1002/ejoc.201800317
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10.1002/ejoc.201800317
European Journal of Organic Chemistry
FULL PAPER
Chiral bisdiphenylphosphine dioxides bearing an original
bis(triazolyl) backbone as promising Lewis bases for asymmetric
organocatalysis
Nicolas Sevrain,[a] Jean-Noel Volle,[a] Jean-Luc Pirat,[a] Tahar Ayad*[a],[b] and David Virieux*[a]
Abstract: Two chiral C2-symmetric diphenylphosphine dioxides
bearing an original bis(triazolyl) backbone were prepared starting
from inexpensive and readily available precursors. The key step
of our approach involves the simultaneous formation of 5 bonds
in one chemical step with 100% atom efficiency through a Copper
catalyzed tandem [3+2] cycloaddition/dimerization reaction.
Interestingly, these chiral inducers exhibited good to excellent
catalytic activities as chiral Lewis base organocatalysts promoting
useful stereoselective reactions.
oxides can be readily obtained through straightforward oxidation
of commercially available chiral phosphines. Indeed, only few
examples of chiral phosphine oxide catalysts are known in
literature;[7] and these studies mainly rely on the use of bis-
(diphenylphosphinoyl)-binaphthyl dioxides (BINAPO) derived
from the popular BINAP. To the best of our knowledge, the first
true organocatalytic reaction catalyzed by chiral phosphine oxides
was disclosed in 2005 by Nakajima and co-workers[8], when (S)-
BINAPO catalyzed the addition of allyltrichlorosilane to aldehydes.
Shortly after this seminal work, a very limited number of chiral
phosphine oxides mostly derived from known phosphines have
been reported and used as Lewis bases in several chemical
processes including asymmetric allylation of aldehydes,[9] aldol
reactions,[10] ring-opening of meso-epoxides,[11] Abramov−type
phosphonylation of carbonyl compounds[12] and Morita-Baylis-
Hillman reaction.[13] Despite some notable successes, most of
these catalysts resulted in low to moderate catalytic activities.
Therefore, the development of more effective chiral phosphine
oxides with new structural and/or electronic features remains a
challenge.
Recently, we committed to develop a program dedicated to
the design and the utilization of new chiral phosphorus ligands,
that resulted in the development of a highly convergent and atom
economic synthetic route toward enantiopure C2-symmetric
diphenylphosphine dioxides bearing an original bis(triazolyl)
backbone. Such derivatives were obtained through a tandem Cu-
mediated Huisgen reaction–oxidative coupling.[14] Gratifying, it
turned out that those ligands are effective Lewis bases for SiCl4-
mediated enantioselective Abramov-type phosphonylation of
aldehydes with trialkyl phosphites.[15] Considering these
encouraging results, we thus decided to extend the use of this
new class of ligands as chiral Lewis bases in other relevant
synthetic transformations. In this context, we wish to report herein,
the full investigation of our studies regarding the asymmetric
allylation and reductive aldol reactions of aldehydes promoted by
enantiopure bis(triazolyl)bisphosphine dioxide organocatalysts 3.
Introduction
The design and synthesis of new chiral Lewis base catalysts that
are able to promote enantioselective reactions with high levels of
chemical efficiency and stereocontrol is a topic of primary
importance in modern organic chemistry. Over the past decade,
a wide range of chiral Lewis bases have been developed. Among
them, enantiopure phosphoramides,[1] formamides,[2] N-oxides,[3]
and sulfoxides[4] are probably the most popular and have found
widespread applications as organocatalysts promoting
stereoselective reactions in good to excellent stereoselectivities.[5]
For instance, Lewis base catalyzed asymmetric reactions
involving hypervalent silicate intermediates, where both the
electrophilicity and nucleophilicity of the adduct are enhanced,
have received increasing attention in recent years.[6]
Mechanistically, the above-mentioned Lewis bases are thought to
activate silicon atom in electron donors such as silane derivatives,
while conventional Lewis acid catalysts activate heteroatoms in
electron acceptors such as carbonyl groups. Chiral phosphine
oxides, thanks to a Lewis base character derived from the highly
polarized P=O bond, are also able to coordinate silanes, thereby
generating hypervalent silicate species. Quite surprisingly, they
have been very scarcely explored as chiral Lewis base
organocatalysts in stereoselective reactions. This is even more
surprising if, one thinks that enantiomerically pure phosphine
Results and Discussion
[a]
[b]
Institut Charles Gerhardt − CNRS UMR 5253, AM2N, Ecole
Supérieure de Chimie de Montpellier, 8 rue de l’Ecole Normale,
34296 Montpellier CEDEX 5, France
Our synthetic approach to enantiopure bis(triazolyl)bisphosphine
dioxides 3 is outlined in Scheme 1. Diphenylethynylphosphine
oxide 1[16] and alkyl azides 2[17] chosen for our study were readily
prepared on multigram scale from cheap and commercially
available precursors according to known literature procedures.
With the aforementioned compounds 1 and 2 in hand, the key
copper catalyzed tandem [3+2] cycloaddition/dimerization
E-mail: david.virieux@enscm.fr
PSL Research University, Chimie ParisTech − CNRS, Institut de
Recherche de Chimie Paris, 75005 Paris, France
E-mail: tahar.ayad@chimieparistech.psl.eu
Supporting information for this article containing experimental
procedures and characterization data for all new compounds is
available on the WWW under http://dx.doi.org/10.1002/cctc.200xxxx.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800317
European Journal of Organic Chemistry
FULL PAPER
reaction was then explored.[14, 18] We found that the yields of the
desired oxidatively coupled bis(triazole) compounds 3, as well as
the product distribution of this Huisgen reaction–oxidative
coupling is highly dependent on both the reaction conditions and
the nature of the alkyl azide partner employed. Indeed, after
considerable screening, bis(triazolyl)bisphosphine dioxide
product 3a was isolated in 49% yield, along with some
monotriazole derivatives (not shown)[19] by using 1 equivalent of
CuBr in the presence of 3 equivalents of Cs2CO3 and benzyl azide
Having established an efficient route to chiral dioxide
ligands 3a-b, attention was then focused on the evaluation of their
catalytic properties as Lewis base organocatalysts in
enantioselective processes such as asymmetric allylation[9] and
reductive aldol reactions.[20] In the first set of experiments, we
studied the effect of the solvent and additives on the
stereochemical outcome of the asymmetric addition of
allyltrichlorosilane 4 to benzaldehyde 5a catalyzed by 10 mol% of
organocatalyst (S)-3a in the presence of diisopropylethylamine at
room temperature for 6 h.
at 0.25
M substrate concentration in a 1:1 mixture of
acetonitrile/water under air atmosphere at room temperature.
Unfortunately, the above-mentioned conditions proved to be not
suitable for the synthesis of the more constrained
bis(triazolyl)bisphosphine dioxide 3b, leading to somewhat
disappointing results in terms of both yield and product distribution.
Therefore, further optimizations were required to maximize yield
of 3b. Gratifyingly, we discovered that performing the [3+2]
cycloaddition/dimerization reaction under conditions of high
dilution, which favors the intramolecular at the expense of the
intermolecular oxidative coupling of the two triazole rings, is a
critical parameter for the success of this process. Indeed,
diphenylethynylphosphine oxide 1 (1 equiv.) reacted with 1,2-
bis(azidomethyl)benzene 2b (0.5 equiv.) in the presence of a
stoichiometric amount of CuCl/DIPEA catalyst in acetonitrile at
0.025 M substrate concentration under air atmosphere at room
temperature to give the expected cyclic bis(triazolyl) derivative 3b
in 75% isolated yield along with a tiny amount of the uncyclized
bis(triazole) (not shown).[19] It is worth pointing out that our
Table 1. Optimization of the enantioselective addition of allyltrichlorosilane
4 to benzaldehyde 5a.[a]
Entry
1
Solvent
DCM
DCM
DCM
DCM
CHCl3
Et2O
Additive
none
none
Bu4NI
Bu4NI
Bu4NI
Bu4NI
Bu4NI
Bu4NI
Bu4NI
Bu4NI
Bu4NBr
Bu4NAc
LiI
Conversion [%][b]
Yield[%][c]
65
ee [%][d]
33
22
43
42
26
29
19
14
54
57
40
6
80
65
2[e]
3
52
100
75
91
4[f]
5
63
synthetic
bis(triazolyl)bisphosphine
approach
for
dioxides
the
preparation
involves
of
the
100
78
87
3a−b
simultaneous formation of 5 bonds in one chemical step with
100% atom efficiency. Next, the resolution of racemic 3a−b using
(+)- or (−)-2,3-dibenzoyl tartaric acid (DBTA) as resolving
reagents was realized (Scheme 1). To this end, a chloroformic
solution of racemic 3a−b was slowly added at room temperature
to a molar equivalent amount of DBTA previously dissolved in
ethyl acetate. Both enantiomers of 3a and 3b were obtained on
gram scale in yields ranging from 60 to 80% and ee values
comprised between 99 to 100% from the recrystallized
diastereoisomeric complex by treatment with aqueous potassium
hydroxide solution.
65
6
THF
60
48
7
Toluene
MeCN
EtCN
EtCN
EtCN
EtCN
EtCN
EtCN
EtCN
EtCN
EtCN
70
55
8
100
100
75
94
9
95
10
11
12
13
14
15
16
17
18[g]
55
60
40
50
27
40
30
60
55
70
69
LiBr
45
22
I2
100
100
100
90
82
NaI
91
KI
96
KI
82
[a] All reactions were run using 10 mol % of (S)-3a with 0.5 mmol of
benzaldehyde, 1.2 equiv. of allyltrichlorosilane and 1 equiv. of additive for 6
h. [b] Determined by 1H NMR of crude reaction mixture. [c] Isolated yield. [d]
Determined by HPLC chromatography using a Chiralcel AS-H column.
Absolute configuration was determined to be R by comparison with reported
Scheme 1. Synthesis of enantiopure bis(triazolyl)bisphosphine dioxide
organocatalysts 3a and 3b.
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10.1002/ejoc.201800317
European Journal of Organic Chemistry
FULL PAPER
data. [e] Reaction run with 10 mol% of (S)-3b instead of (S)-3a. [f] Reaction
run at 0 °C for 48 h. [g] Reaction run with 5 mol% of (S)-3a for 24 h.
Table 2. Substrate scope for the enantioselective addition of
allyltrichlorosilane to aldehydes.[a]
From the results depicted in Table 1, it is clear that
bis(triazolyl)bisphosphine dioxide 3a is
a
more efficient
organocatalyst than 3b for this process leading to 6a in 65% and
52% isolated yields and 33 and 22% ee, respectively (entry 1 vs
2).
Berrisford
and co-workers
have
reported
that
tetrabutylammonium salts can dramatically accelerate the
allylation of aldehydes with allyltrichlorosilane.[21] As anticipated,
the use of Bu4NI as additive remarkably increased the catalytic
activity (entry 3, 91% yield, 43% ee). Decreasing the temperature
to 0°C provided 6a in lower yield but with similar enantioselectivity
at the expense of a longer reaction time (entry 4). It was also
found that the reaction could be performed in all solvents tested,
the best catalytic activity in terms of yields and selectivities was
obtained in propionitrile giving 6a in 95% isolated yield with an
encouraging optical purity up to 57% (entry 10). Based on those
results, we then investigated the effect of other additives that may
improve the efficiency of the reaction. For instance, other
ammonium salts such as Bu4NBr and Bu4NAc turned out to be
less effective for this transformation (entries 10 vs 11−12). Similar
poor results were obtained using LiI and LiBr (entries 13−14),
whereas homoallylic alcohol 6a was obtained in good to excellent
yields up to 96% and good enantioselectivities up to 70% using
KI as additive (entries 15−17). Reducing the catalyst loading from
10 to 5 mol% was clearly still effective, although a prolonged
reaction time was required to maintain a comparable level of
selectivity and a satisfying isolated yield of 6a (entry 17 vs 18).
To assess the substrate scope, a wide range of diversely
substituted aromatic or heteroaromatic aldehydes were allylated
under the optimized conditions using (S)-3a as organocatalyst
(Table 2). Excepting the reaction of 1-naphthaldehyde 2k,
complete conversions were generally reached and chiral
homoallylic alcohols 6a−m were obtained in yields ranging from
86 to 96%. More specifically, for substrates bearing electron-
donating substituents on the benzene ring such as a methyl or a
methoxy group, the reaction outcomes were negligibly affected by
the position of the substituents giving the target adducts 6a−e in
uniformly high yields and acceptable enantiopurities (entries 2−5,
93−96% yield, 59−60% ee). For substrates bearing electron-
withdrawing substituents such as fluoride, chloride or
trifluoromethyl group, the reaction proceeds smoothly, regardless
of the position of the substituents, leading to the desired products
6f−i with slightly higher asymmetric induction but in lower yields
(entries 6−10, 86−90% yield, 62−67% ee). Similar catalytic
activity was reached with 2-naphthyl derivative 2l, while both
chemical and optical yields dropped significantly for 1-naphthyl
compound 2k. This result can presumably be attributed to the
increased steric hindrance of the 1-naphthyl over 2-naphthyl
group (entries 11 and 12, 96 and 70% yields, 66 and 27% ee,
respectively). Finally, 2-furaldehyde 2m proved to be also a
suitable partner for this reaction, giving 6m in high 89% isolated
yield and good enantioselectivity up to 81% (entry 13). Although
moderated to good enantioselectivities were obtained in this
allylation process, those results clearly illustrated that this new
class of bis(triazolyl)bisphosphine dioxides can act as efficient
chiral Lewis bases in asymmetric catalysis.
Entry
1
Product
Yield [%][b]
94
ee [%][c]
70
6a
6b
6c
6d
93
95
96
59
59
60
2
3
4
6e
6f
94
86
89
60
65
65
5
6
7
8
6g
6h
6i
87
90
88
62
62
67
9
6j
10
11[d]
6k
70
27
6l
96
89
66
81
12
13
6m
[a] All reactions were run using 10 mol % of (S)-3a with 0.5 mmol of aldehyde
derivatives, 1.2 equiv. of allyltrichlorosilane and 1 equiv. of KI for 6 h. [b]
Isolated yield. [c] Determined by HPLC chromatography using a Chiralcel
AS-H or IA columns (see the Supporting Information for details). Absolute
configuration was determined to be R by comparison with reported data. [d]
80% conversion was reached.
Inspired by the report of Nakajima and co-workers,[8] and to
further demonstrate the potential application of (S)-3 as Lewis
base organocatalysts, we next decided to investigate the
diastereo- and enantioselective reductive aldol reaction of
chalcone 7 and various aldehydes 5 in presence of trichlorosilane.
Results from these experiments are presented in Table 3.
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10.1002/ejoc.201800317
European Journal of Organic Chemistry
FULL PAPER
dioxides 3a‒b as organocatalysts and
2 equivalents of
trichlorosilane as reductant. As outlined in Table 3, the cyclic
bis(triazole) diphenylphosphine dioxide (S)-3b exhibits
significantly higher catalytic activity than (S)-3a for this
transformation, leading to the formation of the syn aldol product
8a as the major diastereoisomer in good yield, high diastereo- and
enantiomeric excesses (entry 1 vs 2, 78 and 84% yield, 93:7 d.r.,
57 and 85% ee, respectively). A brief solvent screening revealed
that the stereochemical outcome of this reductive aldol process is
highly sensitive to the nature of the solvent. Indeed, reaction in
propionitrile gave adduct 8a in good 85% yield, with a high
diastereomeric ratio of 93:7 and an excellent enantioselectivity of
91%, while the use of other solvents such as, THF, ether and
toluene led to much lower catalytic activity (entries 3 vs 4‒6). Thus,
propionitrile was selected as the optimal solvent. Remarkably, it
should be noted that the catalytic activities obtained with this
system are in a similar range than those observed with the most
popular chiral diphosphine dioxide BINAPO for the same
transformation.[8] Next, we set out to investigate the substrate
scope of the reaction of chalcone 7 with a wide range of diversely
substituted aldehydes 5. The reaction proceeds well in most
cases, giving the corresponding syn aldol products 8a‒k in good
to excellent yields, with good to high diastereomeric ratios and,
good to excellent enantiomeric excesses (entries 7‒16). The data
in Table 3 also show that the outcomes of the reaction is largely
influenced by the substitution pattern on the benzene ring of the
aldehyde substrates. For instance, the electron-donating
substituents such as a methoxy or a methyl group at the ortho- or
para-position altered the catalytic activity to a significant extent as
seen from the moderate yields and selectivities observed (entries
7 and 9, 71 and 72% yields, 72:28 and 78:22 d.r., 71 and 75% ee,
respectively). In contrast, and for unknown reasons, significantly
better results were obtained for substrate bearing a methoxy
group at the meta position (entry 8, 80% yield, 93:7 d.r., 92% ee).
A marked increase in the reaction efficiency was observed with
aldehydes bearing an electron-withdrawing groups such as
chlorine or fluorine atoms, giving the desired syn β-hydroxyl
ketones in excellent yields (90 to 92%), high diastereoselectivities
(86:14 and 90:10 d.r.) and excellent enantioselectivities (88 to
93% ee), irrespectively of the substituents’ position (entries 10‒
13). Finally, naphthyl derivatives can also be used as partners, as
demonstrated by the good to excellent results depicted in Table
3. Due to steric constraints, the 1-naphthyl aldol adduct 8i was
produced in lower yield and selectivities compared to the
2-naphthyl adduct 8j (entries 14 and 15). Even more impressive
results were obtained from 2-furanaldehyde, providing the
expected aldo 8k in high 92% yield, with an excellent
diastereoselectivity of 95:5 and an enantioselectivity greater than
99% (entry 16).
Table 3. Optimization and substrate scope for the asymmetric reductive
aldol reaction of chalcone 7 and various aldehydes 5.[a]
Yield
[%][b]
d.r.
syn:anti[c]
ee
[%][d]
Entry
Solvent
Product
1[e]
DCM
DCM
EtCN
THF
8a
8a
8a
8a
8a
8a
8b
8c
8d
8e
8f
78
84
85
52
48
76
71
80
72
90
92
91
90
79
90
92
93:7
57
85
91
88
78
74
71
92
75
94
93
88
91
89
94
99
93:7
2
93:7
3
92:8
4
Et2O
91:9
5
Toluene
EtCN
EtCN
EtCN
EtCN
EtCN
EtCN
EtCN
EtCN
EtCN
EtCN
90:10
72:28
93:7
6
7
8
78:22
90:10
90:10
86:14
88:12
91:9
9
10
11
12
13
14
15
16
8g
8h
8i
8j
95:5
8k
94:6
[a] All reactions were performed using 10 mol % of (S)-3b, 0.5 mmol of
chalcone, 1.2 equiv. of aldehyde and 2 equiv. of trichlorosilane (1 M solution
in DCM) for 16 h. [b] Isolated yield. [c] Determined by 1H NMR of crude
reaction mixture. [d] Determined by HPLC chromatography using a Chiralcel
ID or IB columns (see the Supporting Information for details). [e] 10 mol% of
(S)-3a was used instead of (S)-3b.
Conclusions
In summary, we have developed an efficient, straightforward, and
atom-economic protocol for the synthesis of a new family of chiral
C2-symmetric diphenylphosphine dioxides bearing an original
bis(triazolyl) backbone. The potential of these novel ligands as
Initial reactions were carried out in dichloromethane at
−78 °C for 16 h using 10 mol% of bis(triazolyl)bisphosphine
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10.1002/ejoc.201800317
European Journal of Organic Chemistry
FULL PAPER
N. S. is grateful to the French Ministry of Higher Education and
Scientific Research for financial support.
Lewis bases in organocatalytic stereoselective reactions have
been demonstrated. While organocatalyst 3a was able to promote
the allylation of aldehydes in up to 96% yield and up to 81% ee,
organocatalyst 3b was more efficient in the formation of optically
active β-hydroxyl ketones in high yields (up to 92%) with good to
excellent diastereo- and enantioselectivities (up to 95:5 d.r., 99%
ee) through the reductive aldol reaction of chalcone and
aldehydes in presence of trichlorosilane. Further studies aimed at
Keywords: Allylation • Reductive Aldol Reaction • Lewis Bases •
Organocatalysts • Asymmetric catalysis
[1]
For selected examples, see: a) S. E. Denmark, D. M. Coe, N. E. Pratt, B.
D. Griedel, J. Org. Chem. 1994, 59, 6161; b) S. E. Denmark, R. A.
Stavenger, J. Org. Chem. 1998, 63, 9524; c) S. E. Denmark, X. Su, Y.
Nishigaichi, D. M. Coe, K.-T. Wong, S. B. D. Winter, J. Y. Choi, J. Org.
Chem. 1999, 64, 1958; d) S. E. Denmark, J. Fu, M. J. Lawler, J. Org.
Chem. 2006, 71, 1513; e) S. E. Denmark, Y. Fan, J. Am. Chem. Soc.
2003, 125, 7825; f) S. E. Denmark, G. L. Beutner, T. Wynn, M. D.
Eastgate, J. Am. Chem. Soc. 2005, 127, 3774.
expanding
bis(triazolyl)bisphosphine
organocatalysts in
the
synthetic
dioxides
other relevant
utility
of
as
these
Lewis
enantioselective
new
base
transformations are currently ongoing in our laboratory and will be
reported in due course.
[2]
[3]
[4]
For selected examples, see: a) K. Iseki, S. Mizuno, Y. Kuroki, Y.
Kobayashi, Tetrahedron 1999, 55, 977; b) K. Iseki, S. Mizuno, Y. Kuroki,
Y. Kobayashi, Tetrahedron Lett. 1998, 39, 2767; c) S. B.; Jagtap, S. B.
Tsogoeva, Chem. Commun. 2006, 4747.
Experimental Section
For comprehensive reviews, see: a) G. Chelucci, G. Murineddu, G. A.
Pinna, Tetrahedron: Asymmetry 2004, 15, 1373; b) A. V. Malkov, P.
Kočovskỳ, Eur. J. Org. Chem. 2007, 29; b) P. Koukal, J. Ulč, D. Nečas,
M. Kotora, Top Heterocycl. Chem. 2017, 53, 29.
General Procedure for the Asymmetric Allylation of Aldehydes with
Allyltrichlorosilane Catalyzed by (S)-3a: Diisopropylethylamine (0.32
mL, 1.8 mmol), allyltrichlorosilane 4 (0.087 mL, 0.60 mmol), and a solution
of the desired aldehydes 5 (0.5 mmol) in anhydrous propionitrile (0.5 mL)
were successively added to a solution of (S)- bis(triazolyl)bisphosphine
dioxide 3a (35.8mg, 0.05 mmol, 10 mol%), and potassium iodide (83mg,
0.5 mmol) in anhydrous propionitrile (2 mL) at room temperature. The
reaction progress was monitored by TLC (hexane/AcOEt, 80:20). Upon
completion (e.g. 6 h), the reaction was quenched by 10% of aqueous
NaOH (3 mL) and the mixture was extracted with AcOEt (2x10 mL). The
combined organic layers were successively washed with 5% HCl (10mL),
saturated aqueous NaHCO3 (10 mL), brine (10 mL), dried over anhydrous
MgSO4, filtered, and evaporated under reduced pressure. The residue was
purified by flash column chromatography (silica gel, hexane/AcOEt
gradient from 100:0 to 70:30) to give the corresponding allylic alcohols 6.
The enantiomeric ratios were determined by HPLC using IA or AS-H
Chiralpak columns.
For selected examples, see: a) S. Kobayashi, C. Ogawa, H. Konishi, M.
Sugiura, J. Am. Chem. Soc. 2003,125, 6610; b) G. J. Rowlands, W. K.
Barnes, Chem. Commun. 2003, 2712; c) I. Fernández, V. Valdivia, B.
Gori, F. Alcudia, E. Álvarez, N. Khiar, Org. Lett. 2005, 7, 1307; d) R. P.
A. Melo, J. A. Vale, G. Zeni, P. H. Menezes, Tetrahedron Lett. 2006, 47,
1829; e) J. R. Fulton, L. M. Kamara, S. C. Morton, G. J. Rowlands,
Tetrahedron 2009, 65, 9134.
[5]
[6]
For a comprehensive review, see: S. E. Denmark, G. L. Beutner, Angew.
Chem., Int. Ed. 2008, 47, 1560.
For reviews, see: a) Y. Orito, M. Nakajima, Synthesis 2006, 9, 1391; b)
M. Benaglia, S. Guizzetti, L. Pignataro, Coord. Chem. Rev. 2008, 252,
492; c) S. Rossi, M. Benaglia, A. Genoni, Tetrahedron, 2014, 70, 2065.
For reviews on asymmetric reactions catalyzed by chiral phosphine
oxides, see: a) M. Benaglia, S. Rossi, Org. Biomol. Chem. 2010, 8, 3824;
b) S. Kotani, M. Sugiura, M. Nakajima, Chem. Rec. 2013, 13, 362.
M. Nakajima, S. Kotani, T. Ishizuka, S. Hashimoto, Tetrahedron Lett.
2005, 46, 157.
[7]
General Procedure for Asymmetric Reductive Aldol Reaction of
Chalcone and Aldehydes with Trichlorosilane Catalyzed by (S)-3b: To
a solution of (S)- bis(triazolyl)bisphosphine dioxide organocatalyst 3b (32
mg, 0.05 mmol, 10 mol%), the desired aldehydes 5 (0.6 mmol), and
chalcone 7 (104 mg, 0.5 mmol) in anhydrous propionitrile (2 mL) was
added dropwise trichlorosilane (ca. 1M CH2Cl2 solution, 1 mmol) at −78 °C.
The reaction was monitored by TLC analysis (hexane/AcOEt, 80:20). After
the chalcone was consumed or no significant change was observed, the
reaction was quenched with saturated aqueous NaHCO3 solution (3 mL).
After addition of AcOEt (5 mL), the mixture was stirred for 1 h, filtered
through a Celite pad and extracted with AcOEt (3x10 mL). The combined
organic layers were washed with brine (10 mL), dried over anhydrous
MgSO4, filtered, and evaporated under reduced pressure. The
diastereomeric ratio syn/anti was determined by 1H NMR spectrum of
crude reaction mixture. The residue was then purified by flash column
chromatography on silica gel using hexane/AcOEt (gradient from 100:0 to
70:30) as eluting solvents to give the desired syn aldol products 8 as the
major products. The enantiomeric excesses were determined by HPLC
using IB or ID Chiralpak columns.
[8]
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Supporting information: Experimental procedures, characterization data,
and copies of the 1H NMR, 13C NMR and HPLC spectra.
Acknowledgements
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European Journal of Organic Chemistry
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10.1002/ejoc.201800317
European Journal of Organic Chemistry
FULL PAPER
Layout 2:
FULL PAPER
Key Topic*
Nicolas Sevrain, Jean-Noel Volle, Jean-
Luc Pirat, Tahar Ayad* and David
Virieux*
Page No. – Page No.
Two new chiral diphenylphosphine dioxides bearing an original bis(triazolyl)
backbone were prepared through a two-step sequence. The key reaction of our
approach involves a copper catalyzed [3+2] cycloaddition/dimerization reaction
leading to the formation of 5 bonds in one chemical step with 100% atom efficiency.
Interestingly, these ligands exhibited good to excellent catalytic activities as chiral
Lewis base organocatalysts promoting useful stereoselective reactions.
*Asymmetric organocatalysis
Chiral bisdiphenylphosphine dioxides
bearing an original bis(triazolyl)
backbone as promising Lewis bases
for asymmetric organocatalysis
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