Application of chiral N-tert-butylsulfinyl vinyl aziridines in Rh(i) catalyzed 1,4-addition of aryl boronic acids to cyclic enones

Article abstract of DOI:10.1039/c3cc42673d

Chiral N-tert-butylsulfinyl vinyl aziridine ligands prepared from a readily available (R)-tert-butanesulfinamide have been applied in the rhodium-catalyzed asymmetric 1,4-addition of aryl boronic acids to cyclic enones, which gives high yields and excelle

Full text of DOI:10.1039/c3cc42673d

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Application of chiral N-tert-butylsulfinyl vinyl
aziridines in Rh(I) catalyzed 1,4-addition of aryl
boronic acids to cyclic enones†‡
Cite this: Chem. Commun., 2013,
49, 6433
Received 12th April 2013,
Accepted 29th May 2013
Qian Chen,* Chao Chen, Fang Guo and Wujiong Xia*
DOI: 10.1039/c3cc42673d
www.rsc.org/chemcomm
Chiral N-tert-butylsulfinyl vinyl aziridine ligands prepared from a
readily available (R)-tert-butanesulfinamide have been applied in the
rhodium-catalyzed asymmetric 1,4-addition of aryl boronic acids to
cyclic enones, which gives high yields and excellent enantioselectivities.
Chiral molecules were broadly applied in the field of pharma-
ceuticals, agricultural chemicals, fine chemicals and materials.
Asymmetric synthesis of chiral compounds catalyzed by transition-
metals in the presence of chiral ligands has been proven to be one
Fig. 1 Work proposal of chiral S, olefin-ligands for Rh(I) catalyzed asymmetric
arylation.
of the most efficient approaches.1 The design and synthesis of vinyl aziridines was introduced into the ligands (Fig. 1). To our
novel chiral ligands have therefore been topics of great interest in acknowledgement, efficient approaches for preparing chiral
organic and organometallic chemistry. Among them, the develop- N-tert-butylsulfinyl vinyl aziridines from sulfinimines have been
ment of phosphorus-based chiral ligands has been most exten- established for several years,12–14 however, their utility as chiral
sively investigated.2 Despite these advances, the introduction of ligands in catalytic asymmetric transformations has not been
coordination atoms and/or functional groups other than phos- reported. Herein we describe our discovery of N-tert-butylsulfinyl
phorus would greatly enrich the chiral ligand libraries, and some- vinyl aziridines as efficient hybrid ligands for highly enantio-
times lead to higher enantioselectivity. Among the recently selective rhodium-catalyzed asymmetric 1,4-addition reactions.
developed ligands, chiral dienes, and alkene, P- and/or N-hybrid
We started our research by preparing a variety of N-tert-
ligands have shown novel coordination ability and higher catalytic butylsulfinyl vinyl aziridines according to the procedure established
performance in asymmetric catalysis, and attracted considerable by Stockman et al. (Fig. 2).13,15 Fortunately, both cis- and trans-
attention from several research groups.3–6
diastereomers could be separated by silica gel chromatography.16
Besides these, chiral sulfoxide is also one of the most
With chiral N-tert-butylsulfinyl vinyl aziridines in hand, we chose
important ligands and has been broadly used in asymmetric the Rh-catalyzed 1,4-addition of phenylboronic acid to cyclohexenone
synthesis.7 Thanks for the pioneering work of Dorta’s group who as the model reaction to evaluate their catalytic performance.17 To our
have achieved a significant breakthrough by fixing the sulfoxide gratification, the products were obtained in high yield (95%) and
to the privileged atropisomeric 1,10-binaphthyl backbone,8 the excellent enantioselectivity (96%) in the presence of 3 mol% Rh–cis-1a
subsequent research by groups of Liao, Xu and Du independently complex (Table 1, entry 1). Under the same conditions, a similar
led to the development of chiral tert-butyl sulfoxide- and/or result was obtained when cis-1a was replaced by trans-1a (95% yield
sulfinamide–olefin hybrid ligands and satisfactory results were and 97% ee) (Table 1, entry 2). It should be noted that both ligands
attained (Fig. 1).9–11 It occurs to us that whether the activity and
enantioselectivity of catalytic reaction would be maintained or
improved if a rigid three-membered ring with N-tert-butylsulfinyl
State Key Lab of Urban Water Resource and Environment (SKLUWRE) & Academy of
Fundamental and Interdisciplinary Science, Harbin Institute of Technology, Harbin,
Heilongjiang, 150080, P. R. China. E-mail: chenqian@hit.edu.cn, xiawj@hit.edu.cn;
Fax: +86-451-86403760; Tel: +86-451-86403193
† This paper is dedicated to Professor Kiyoshi Tomioka on the occasion of his
65th birthday.
Fig. 2 N-tert-Butylsulfinyl vinyl aziridines applied in Rh(I) catalyzed 1,4-addition
‡ Electronic supplementary information (ESI) available. See DOI: 10.1039/c3cc42673d
of arylboronic acids to enones.
c
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Table 1 Survey of the N-tert-butylsulfinyl vinyl aziridine ligands for Rh catalyzed
Table 2 Rh/trans-1c-catalyzed asymmetric addition of arylboronic acids 5 to
enones 4
asymmetric addition of phenylboronic acids to cyclohexenones
Entry
Ligand
Time (h)
Yielda (%)
eeb (%)
1
2
3
4
5
6
7
8
9c
cis-1a
trans-1a
cis-1b
trans-1b
cis-1c
trans-1c
cis-1d
2
10
10
12
12
8
8
8
95
95
80
95
70
99
99
85
—
96
97
94
96
98
99
96
93
—
Entry Enones ArB(OH)2 Time (h)
6
Yielda (%) eeb (%)
1
2
3
4
5
6
7
8
4a
4a
4a
4a
4a
4a
4a
4a
4b
4b
4b
4b
4b
4c
5a
5b
5c
5d
5e
5f
5g
5h
5a
5c
5d
5h
5i
10
8
8
8
8
8
8
10
8
12
10
8
6aa
6ab
6ac
6ad
6ae
6af
6ag
6ah 99
6ba
6bc
6bd 88
6bh 99
99
99
85
77
70
95
99
99
96
85
98
98
87
96
93
51
85
30
64
41
67
10
12
3
a
b
Isolated yield. Determined by chiral HPLC with hexane–2-propanol.
Trace of the target product.
c
9
85
55
gave the same configuration products, indicating that the stereo-
chemistry of catalytic reaction was determined by the inherent
S-chirality of N-tert-butylsulfinyl vinyl aziridine ligands, and the
independent new chiral carbon center and relative configuration.11c,e
Encouraged by the preliminary results, we hope to further improve
the enantioselectivity of reaction through modifying and optimizing
the structure of ligands. Chiral ligands 1b–3 were thus prepared and
their catalytic efficiencies were examined under the same reaction
conditions. As shown in Table 1, except for ligand 3, all of the chiral
ligands led to the desired product in good yield and excellent
enantioselectivity in 93–99% ee (entries 1–9). The electronic effect
of aryl groups in chiral N-tert-butylsulfinyl vinyl aziridines has no
distinct influence on catalytic activity and enantioselectivity (entries 1
and 3 vs. 5; 2 and 4 vs. 6), whereas the cis-isomer showed a little lower
catalytic activity in spite of maintaining the same high enantio-
selectivity (entry 3 vs. 4 and 5 vs. 6). Notably, trans-1c shows the best
catalytic activity and enantioselectivity (entry 6). Ligand 2 possessing
phenylvinyl that is an internal olefin led to the product with the same
absolute S-configuration as cis-1b (entry 3 vs. 8), which was different
from the phenomenon that the substituted model of olefins could
reverse the absolute configuration of the product observed by Liao
et al.10a and Du et al.11e This result further proves that the stereo-
chemistry of catalytic reaction is governed by S-chirality.11c,e Unfortu-
nately, examination of ligand 3 led to a trace of the target product and
ambiguous mixture (entry 9). However, such a result suggested the
importance of aryl groups in the N-tert-butylsulfinyl vinyl aziridine
ligands for maintaining a high catalytic performance despite that it is
still unclear why aryl groups in the N-tert-butylsulfinyl vinyl aziridine
ligands are critical to the reactivity and selectivity.
10
11
12
13
14
8
12
6bi
6cc
99
30
5c
a
b
Isolated yield. Determined by chiral HPLC with hexane–2-propanol.
and 4-tert-butylphenyl groups were also introduced into 4a,
affording the corresponding 6 in excellent yield (95–99%) with high
ee (87–96%) (Table 2, entries 6–8). Cyclopentenone 4b was also a
good substrate for this transformation to give the corresponding 6
in high yield (55–99%) with moderate to high ee (entries 9–13).
Furthermore, when linear enone (E)-4-phenylbut-3-en-2-one 4c was
reacted with 4-methoxyphenyl boronic acid, moderate yield and
good enantioselectivity were observed (entry 14).
The absolute configuration of 6aa obtained in this reaction was
determined to be S by comparison of its optical rotation value with
that in the literature.18 On the basis of this outcome, an empirical
stereochemical model can be rationalized as shown in Fig. 3.10b,d,11a,d
Thus, the arylrhodium species has a trans-relationship between the
aryl group and the olefin of trans-1c. To avoid the steric repulsion
between tert-butyl of the ligand and methylene at 5- and/or 6-position
in cyclohexenone 4a, it preferentially approaches the vacant position
of rhodium with its si-face to give (S)-6aa with high selectivity.
Moreover, bidentate coordination of ligand 1 to rhodium requires
the cis relationship between olefin and sulfur, which causes severe
steric repulsion in cis-1 due to the all-cis relationship between olefin,
aryl and sulfinyl groups. This might be the reason for less efficiency
of cis-1 than trans-1 (Table 1).
In conclusion, we have demonstrated that chiralN-tert-butylsulfinyl
vinyl aziridines with a rigid three-membered ring backbone can be
Having identified optimal reaction conditions (Table 1, entry 6),
we next evaluated the substrate scope of this rhodium-catalyzed
asymmetric 1,4-addition. As shown in Table 2, the nature of the
substituent on the phenyl ring of arylboronic acid had very little effect
on the stereoselectivity of the reaction. Aryl groups having electron-
donating and -withdrawing substituted groups, for example,
3-methoxyphenyl, 4-methoxyphenyl, 4-chlorophenyl, and 4-fluoro-
phenyl groups were successfully introduced into 4a, giving
the corresponding 6 with high ee (85–98%) in high yields
(70–99%) (Table 2, entries 2–5). 2-Methylphenyl, 2-naphthyl, Fig. 3 Proposed stereochemical model.
c
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2011, 47, 6123; ( f ) T. Nishimura, Y. Maeda and T. Hayashi, Org.
used as efficient chiral sulfur–olefin hybrid ligands for highly
enantioselective rhodium-catalyzed asymmetric 1,4-addition
reactions. This work presents the first example of application
of N-tert-butylsulfinyl vinyl aziridines as chiral ligands in tran-
sition metal catalysis. The key point to the success was that aryl,
alkenyl, and tert-butyl sulfoxide were correctly installed on the
vertex of the rigid aziridine ring, which favored the coordina-
tion of Rh with olefin and S, and thus accomplished a highly
catalytic activity and stereocontrol performance. Further modi-
fication of more effective chiral sulfur–olefin hybrid ligands
with ring backbones and their applications in other asymmetric
reactions are currently underway in our laboratory.
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