One step synthesis of chiral olefins via asymmetric diamination and their applications as ligands for rhodium (I)-catalyzed 1, 4-additions

Article abstract of DOI:10.1002/adsc.200900693

A variety of acyclic chiral dienes were synthesized in a single step via palladiums-cata-lyzed asymmetric allylic and homoallylic C-H di-amination of terminal olefins. The applications of such simple dienes as steering ligands for rhodi-um(I)-catalyzed as

Full text of DOI:10.1002/adsc.200900693

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DOI: 10.1002/adsc.200900693
One Step Synthesis of Chiral Olefins via Asymmetric
Diamination and their Applications as Ligands for Rhodium(I)-
Catalyzed 1,4-Additions
Xichao Hu,a Ziping Cao,a Zhaoqun Liu,a Yazhou Wang,a and Haifeng Dua,*
a
Beijing National Laboratory of Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function,
Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, Peopleꢀs Republic of China
Fax : (+86)-10-6255-4449; e-mail: haifengdu@iccas.ac.cn
Received: October 5, 2009; Published online: February 19, 2010
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.200900693.
Abstract: A variety of acyclic chiral dienes were
synthesized in a single step via palladium(0)-cata-
À
lyzed asymmetric allylic and homoallylic C H di-
amination of terminal olefins. The applications of
such simple dienes as steering ligands for rhodi-
ACHTUNGTRENNUNGum(I)-catalyzed asymmetric 1,4-additions afforded
the corresponding adducts in excellent yields and
Scheme 1. Developing acyclic chiral diene ligands based on
1,5-hexadiene skeleton.
up to 85% ee.
Keywords: acyclic chiral dienes; asymmetric cataly-
sis; asymmetric diamination; conjugated addition;
diene ligands
Chiral olefins have proven to be excellent steering li-
gands for asymmetric catalysis, and some of them
even exhibit a distinct advantage over other types of
ligands to afford higher reactivities and/or enantiose-
lectivities.[1,2] With lots of effort devoted to this lately
Scheme 2. Rh(I)-catalyzed asymmetric 1,4-additions with 1
or 2 as ligand.
emerging area, a few fantastic chiral chelating diene have the potential to become a class of promising li-
ligands bearing bicyclic frameworks have been suc- gands in the future. Herein, we wish to report our ef-
cessfully developed.[3–6] The bicyclic structures of forts on this subject.
these ligands play a crucial role in the asymmetric re-
In our previous work, when two hydroxy groups
actions, but also partially result in some difficulties in were introduced into the achiral 1,5-hexadiene skele-
ligand synthesis. Hence, exploring novel, effective, ton, a simple chiral chain diene ligand 2 was success-
and accessible chiral dienes is still one of the most im- fully achieved, which suggests that other types of
portant subjects in this field.[2b] Inspired by the fact chiral dienes containing 1,5-hexadiene skeletons are
that 1,5-hexadiene (1) has an ability to act as a steer- also candidate ligands. We envisioned that introduc-
ing ligand, very recently, we reported that a simple tion of imidazolidin-2-one backbones to 1,5-hexadiene
chiral acyclic diene 2 (Scheme 1) can be employed as may provide a good opportunity to develop novel
an effective ligand for promoting Rh(I)-catalyzed diene ligands (3) for asymmetric catalysis
asymmetric 1,4-additons with encouraging yields and (Scheme 1).[10] The combination of flexible terminal
ees (Scheme 2),[7,8] which demonstrates that the com- olefins and rigid imidazolidin-2-one frameworks in
plexes formed between Rh and a flexible diene are ligand 3 and how it might affect asymmetric induction
stable enough to ensure asymmetric induction.[9] Be- is interesting. Therefore, building the chiral imidazoli-
cause of the convenient synthesis, chiral acyclic dienes din-2-one frameworks became one of the key points.
Adv. Synth. Catal. 2010, 352, 651 – 655
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Scheme 3. One-step synthesis of acyclic chiral diene via
Pd(0)-catalyzed asymmetric diamination of 1,5-hexadiene.
Recently, Shiꢀs group successfully developed a
novel diamination methodology,[11–13] which provides
an efficient and powerful protocol for us to construct
the chiral imidazolidin-2-one backones of diene li-
gands. As shown in Scheme 3, chiral diene (S,S)-3a
can be synthesized in one step via Pd(0)-catalyzed
Figure 2. Rh(I)-catalyzed asymmetric 1,4-additions of phe-
nylboronic acid (5) to 2-cyclohexenone (4) with selected
chiral diene ligands 3.[15]
À
asymmetric allylic and homoallylic C H diamination
of 1,5-hexadiene with di-tert-butyldiaziridinone (7) as
the nitrogen source,[12d] and its X-ray structure is ents were introduced conveniently to give chiral
shown in Figure 1.[14] The ee of 3a can be further im- dienes 3c–f (Figure 2). When using different 1,5-
proved to >99% after recrystallization from n- dienes as starting materials, ligands 3g–i containing
hexane. Chiral diene 3a was then used as a ligand in one di- or tri-substituted double bond can also be pre-
the reaction of 2-cyclohexenone (4) and phenylboron- pared via asymmetric diamination.[12] Ligands 3a–i
ic acid (5) with [RhClACTHNUGTRNE(UNG C2H4)2]2 (5 mol% Rh) as a cat- were then investigated by subjecting them to Rh(I)-
alyst precursor in dioxane/MeOH (v/v=10/1), we catalyzed 1,4-addition of phenylboronic acid (5) to 2-
were pleased to find that quantitative conversion and cyclohexenone (4) in dioxane/MeOH (v/v=10/1) at
up to 85% ee can be achieved (Figure 2).
508C for 3 h, and all the results are summarized in
Encouraged by this result, further studies on modi- Figure 2. It was found that most of chiral diene-modi-
fications of 3a were undertaken to look for more ef- fied Rh(I) catalysts can promote this reaction well to
fective ligands. The tert-butyl groups of 3a can be afford the desired products in 16 to >99% conver-
easily and cleanly removed by treating with trifluoro- sions and 6–85% ees. Our studies showed that the
acetic acid (TFA) at 808C according to literature substituents on nitrogen (3a–f) have an obvious
methods to afford 3b,[12] subsequently, other substitu- impact on both reactivity and enantioselectivity. Li-
gands containing one disubstituted double bond led
to poor conversions and ees, while ligands bearing a
trisubstituted double bond gave no desired product,
presumably because of the steric bulkiness.[16] Overall,
3a was found to be the best ligand to give both the
highest conversion and enantioselectivity.
The substrate scope was further studied, and some
of the results are summarized in Table 1. It was found
that chiral diene 3a-modified Rh catalysts can pro-
mote these reactions with moderate to excellent reac-
tivities (51–99% yields) and moderate to good enan-
tioselectivities (55–85% ees) (Table 1, entries 1–9, 11).
Addition of meta- or para-substituted arylboronic
acids to 2-cyclohexenone (4) under the catalysis of
Rh(I)/3a gave excellent yields and good ees, and bor-
onic acids with electron-donating groups displayed
higher activities (Table 1, entries 4, 6, 8). 1-Naphthyl-
Figure 1. The X-ray structure of 3a.
boronic acid was also an effective substrate for this
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Adv. Synth. Catal. 2010, 352, 651 – 655

One Step Synthesis of Chiral Olefins via Asymmetric Diamination
Table 1. Rh(I)/3a-catalyzed asymmetric 1,4-additions.[a]
hexenone (4) can proceed smoothly to afford the de-
sired products in good yields and ees (Table 1, en-
tries 3 and 5). However, the reaction between 2-cyclo-
pentenone and phenylboronic acid (5) under the cat-
alysis of Rh(I)/3d only gave a moderate enantioselec-
tivity (Table 1, entry 10).
Entry Substrate
Product[c]
Yield
[%][d]
ee
[%][e]
1
2
3
PhB(OH)2
(PhBO)3
PhBF3K
99
93
51
85
75
80
ACHTUNGTRENNUNG
In conclusion, an acyclic chiral diene 3a prepared in
only one step via Pd(0)-catalyzed asymmetric diami-
nation was found to be highly effective for the Rh(I)-
catalyzed asymmetric conjugated 1,4-additions, and
encouraging results (up to 99% yield and 85% ee)
have been successfully achieved. Although the effi-
ciency, enantioselectivity, and substrate scope still
await further improvement, the facile processes for
synthesis and modification make acyclic chiral dienes
a class of potentially intriguing ligands. Studies
searching for more effective acyclic chiral dienes, elu-
cidating detailed structures of diene-Rh complexes,
and expanding the applications of acyclic chiral diene
ligands in other types of metal-catalyzed asymmetric
reactions are currently underway in our laboratory.
4
5
96
87
80
76
6
98
85
7
8
9
56
96
88
84
78
55
Experimental Section
Preparation of Chiral Diene 3a (Scheme 3)
Diene 3a was prepared according to the literature method
with slight modifications.[12d] Into a 10-mL round-bottom
flask were charged with Pd2ACHTNUTRGENNUG(dba)3 (0.4575 g, 0.5 mmol) and
ligand 8 (1.02 g, 2.2 mmol). The flask was evacuated and
then filled with argon before addition of benzene (1.5 mL,
distilled from sodium). The resulting solution was then im-
mersed into an oil bath (658C), and stirred for 10 min, fol-
lowed by removal of solvents under vacuum at room tem-
perature. To the resulting solid, 1,5-hexadiene (0.82 g,
1.19 mL, 10 mmol) was added, and the reaction mixture was
immersed into an oil bath (658C) with stirring. Then di-tert-
butyldiaziridinone (7) (4.25 g, 25 mmol) was added by sy-
ringe pump at a rate of 5.0 mmolhÀ1for 5 h, and the mixture
was stirred for additional 1 h. After being cooled to room
temperature, the mixture was diluted with diethyl ether, and
sequentially washed with 5% aqueous HCl, water, saturated
brine, and dried over anhydrous Na2SO4. Then the solvent
was removed and the residue was purified by flash chroma-
tography (silica gel, hexanes: ethyl acetate=20:1) to give
the diamination product; further crystallization from n-
hexane gave 3a as a colorless crystal; yield: 1.625 g (65%);
>99% ee; mp 51–528C; [a]2D0: À62.1 (c 0.72, CHCl3). IR
10[b] PhB(OH)2
81
77
43
61
11
PhB(OH)2
[a]
All the reactions were carried out with organoboron re-
agent (0.30 mmol), unsaturated carbonyl compound
(0.20 mmol),
KOH
(0.015 mmol),
[RhClACHTNGUTERN(NUG C2H4)2]2
(0.005 mmol), 3a (0.012 mmol) in dioxane/MeOH) (10/1,
v/v, 0.66 mL) at 508C under argon for 3 h unless other-
wise noted; for entry 2, the reaction was carried out with
organoboron reagent (0.10 mmol).
3d was used instead of 3a.
The absolute configuration was determined by comparing
[b]
[c]
1
(film): n=1691 cmÀ1; H NMR (400 MHz, CDCl3): d=5.97
the optical rotation with the reported one.
Isolated yield.
[d]
[e]
(ddd, J=16.8, 10.0, 8.4 Hz, 2H), 5.22 (d, J=16.8 Hz, 2H),
5.13 (d, J=10.0 Hz, 2H), 3.61 (d, J=8.4 Hz, 2H), 1.34 (s,
18H); 13C NMR (100 MHz, CDCl3): d=158.4, 139.7, 115.9 ,
62.8, 53.3, 28.8.
The ee was determined by chiral HPLC (Chiralpak AD-
H column) unless otherwise stated, Chiralcel OJ-H
column for entry 9, Chiralcel OB-H column for entry 10,
and Chiralcel AS-H column for entry 11.
reaction, but only resulted in relatively lower ee
(Table 1, entry 9). The reactions between potassium
phenyltrifluoroborate or boronate ester and 2-cyclo-
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Representative Procedure for 3a/Rh(I)-Catalyzed
Asymmetric 1,4-Addition of Phenylboronic Acid (5)
to 2-Cyclohexenone (4) (Table 1, entry 1)
To a Schlenk flask charged with phenylboronic acid (5)
(0.0366 g, 0.30 mmol), [RhClACHTNUGRTNE(UNG C2H4)2]2 (0.0019 g, 0.005 mmol,
2.5 mol%), and chiral diene ligand 3a (0.0030 g, 0.012 mmol,
6.0 mol%) was added degassed dioxane (0.60 mL) under
argon. The resulting mixture was heated to 508C and stirred
for 15 min, followed by addition of 2-cyclohexenone (4)
(0.0192 g, 0.20 mmol) and KOH in MeOH (0.015 mmol,
0.25M, 0.060 mL). The reaction mixture was stirred at 508C
for 3 h, solvent was removed under reduced pressure. The
crude residue was purified by flash chromatography on
silica gel (hexanes: ethyl acetate=5:1, v/v) to give the de-
sired product ent-6 as a pale yellow oil; yield: 0.0345 g
(99%); 85% ee; [a]D20: +16.8 (c 0.90, CHCl3). 1H NMR
(400 MHz, CDCl3): d=7.33 (t, J=7.8 Hz, 2H), 7.21–7.26
(m, 3H), 2.98–3.04 (m, 1H), 2.35–2.63 (m, 4H), 2.07–2.18
(m, 2H), 1.75–1.87 (m, 2H); 13C NMR (100 MHz, CDCl3):
d=211.0, 144.4, 128.7, 126.7, 126.6, 49.0, 44.8, 41.2, 32.8,
25.5.
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Acknowledgements
We are grateful to the generous financial support from the
National Science Foundation of China (20802079), Ministry
of Science and Technology (2009ZX09501-018) and the Na-
tional Basic Research Program of China (973 Program,
2010CB833300).
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Adv. Synth. Catal. 2010, 352, 651 – 655

One Step Synthesis of Chiral Olefins via Asymmetric Diamination
[14] For the crystal structures of 3a, see Supporting Infor-
mation. The absolute configuration of 3a was deter-
mined to be S,S judged by its derivative containing one
bromine atom. CCDC 749930 (3a) and CCDC 755622
(derivative of 3a) contain the 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.
[15] All the reactions were carried out with 2-cyclohexe-
none (4) (0.20 mmol), phenylboronic acid (5)
(0.30 mmol), KOH (0.015 mmol), [RhClACTHNUTRGNE(UNG C2H4)2]2
(0.005 mmol), diene ligand (0.012 mmol) in dioxane/
MeOH (10/1, v/v, 0.66 mL) at 508C under argon for
3 h.
[16] Ligands 3g–i were used directly as obtained via asym-
metric diamination without recrystallization.
Adv. Synth. Catal. 2010, 352, 651 – 655
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655