Highly Z-selective asymmetric conjugate addition of alkynones with pyrazol-5-ones promoted by N,N′-dioxide-metal complexes

Article abstract of DOI:10.1002/anie.201109130

Highly selective: The title reaction is achieved with high enantiomeric and geometric control and thermodynamically unstable (Z)-enone derivatives are obtained as the major products (see scheme). The procedure tolerates a wide range of substrates to generate optically active pyrazolones with vinyl-substituted quaternary stereocenters. Copyright

Full text of DOI:10.1002/anie.201109130

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DOI: 10.1002/anie.201109130
Asymmetric Synthesis
Highly Z-Selective Asymmetric Conjugate Addition of Alkynones with
Pyrazol-5-ones Promoted by N,N’-Dioxide–Metal Complexes**
Zhen Wang, Zhenling Chen, Sha Bai, Wei Li, Xiaohua Liu, Lili Lin, and Xiaoming Feng*
The catalytic enantioselective conjugate addition of carbon
nucleophiles to alkynyl carbonyl compounds is an efficient
guanidine catalysts.[5] The highly Z-selective control in the
asymmetric 1,4-addition of acetylenic ketone has not been
achieved yet.
way to construct versatile and useful building blocks because
[1]
=
the newly formed C C bond can be further functionalized.
Recently, we demonstrated that N,N’-dioxide–metal com-
plexes are efficient catalysts for a number of enantioselective
reactions.[6] During the course of developing new asymmetric
transformations, the asymmetric 1,4-addition reaction of
pyrazol-5-ones to alkynones is therefore desirable. Herein,
we present our intensive study on the asymmetric 1,4-addition
of 4-substituted pyrazol-5-ones to alkynones by using N,N’-
dioxide–metal complexes, thus providing the thermodynami-
cally unstable Z isomers in high enantiomeric and geometric
control. In addition, the reaction afforded enantiomerically
enriched pyrazolone isomers with vinyl-substituted quater-
nary stereocenters.[7]
However, in contrast to extensive and fruitful studies on
asymmetric 1,4-addition reactions of electron-deficient
alkenes, investigations of conjugate additions of electron-
deficient alkynes are still limited (Scheme 1).[2] The difficulty
in controlling both E/Z selectivity[3] and enantioselectivity is
Initially, we examined the N,N’-dioxide L1, which was
coordinated in situ with various rare-metal salts to catalyze
the conjugate addition of 4-benzyl-1H-pyrazol-5-one (1a) to
1-phenylprop-2-yn-1-one (2a) in CH2Cl2 at 08C (Table 1).
Gd(OTf)3 and Ho(OTf)3 promoted the reaction smoothly and
gave the thermodynamically stable E isomer (3a) in insuffi-
cient geometric control and moderate enantioselectivity for
Z/E isomers (Table 1, entries 1 and 2). With the assistance of
4 ꢀ molecular sieves and use of L1–Ho(OTf)3 as catalyst, the
yield of the Z isomer exceeded that of E isomer, and the
ee value of the Z isomer could be improved to 91% (Table 1,
entry 3).[8] More interestingly, L1–Sc(OTf)3 catalyst afforded
the Z isomer 3a as the major product, albeit with low yield
(Table 1, entry 4). The addition of 4 ꢀ molecular sieves
increased the yield of product 3a greatly (Table 1, entry 5).
The Z isomer (3a) was stable at room temperature, and the
absolute configuration of the predominated enantiomer
(Table 1, entry 3) was determined to be (Z,S) by X-ray
crystallography (see the Supporting Information for
details).[9]
Encouraged by these results, a series of N,N’-dioxides
were synthesized and combined with scandium triflate to
enhance the Z selectivity and enantioselectivity of the
reaction (Table 1, entries 5–8). The steric effect of the amide
moiety of the N,N’-dioxide ligands played a crucial role on the
enantioselectivity of the reaction (Table 1). The aniline
derived N,N’-dioxide L2 dramatically reduced the enantiose-
lectivity to 19% ee (Table 1, entry 6 versus entry 5). It is
noteworthy that under similar reaction conditions, aliphatic
amine derived N,N’-dioxide L3 showed an notable reversed
enantioinduction and gave (Z,R)-3a as the major product
(> 95:5 Z/E, 86% ee, Table 1, entry 7 versus entry 5). l-
Proline-derived N,N’-dioxide L4 proved to be the most
promising catalyst of those tested with an amino acid
backbone (Table 1, entry 8 versus entry 7). The addition
Scheme 1. Conjugate addition of carbon nucleophiles to alkenes and
alkynyl carbonyl compounds.
probably the reason for the limited amount of studies. In
general, the predominant product is the thermodynamically
stable E isomer, the unstable Z isomer can be transformed
into the E isomer by isomerization after the 1,4-addition
reaction.[2a,d,4] For example, b-dicarbonyl compounds and a-
substituted a-cyanoacetate have both been successfully used
in the asymmetric conjugate additions of alkynes and
furnished preferably the E isomers.[2] Even now, there is
only one example of a highly Z-selective asymmetric 1,4-
addition of 5H-oxazol-4-ones to alkynyl carbonyl compounds,
reported by Sugimura and co-workers who used chiral
[*] Z. Wang, Z. L. Chen, S. Bai, W. Li, Prof. Dr. X. H. Liu, Dr. L. L. Lin,
Prof. Dr. X. M. Feng
Key Laboratory of Green Chemistry & Technology, Ministry of
Education, College of Chemistry, Sichuan University
Chengdu 610064 (China)
E-mail: xmfeng@scu.edu.cn
[**] We acknowledge the National Natural Science Foundation of China
(No. 21021001 and 21172151) and the National Basic Research
Program of China (973 Program: No. 2011CB808600) for financial
support. We also thank Sichuan University Analytical & Testing
Center for NMR analysis.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201109130.
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Table 1: Optimization of 1,4-addition of 4-benzyl-pyrazol-5-one (1a) to 1-
phenylprop-2-yn-1-one (2a) by N,N’-dioxide–metal complexes.[a]
With the established optimized reaction conditions, the
substrate scope of the 1,4-addition reaction of various
pyrazolones and alkynones was examined next. First,
a series of pyrazolone derivatives bearing a benzyl group at
the C4 position were investigated (Table 2). The study
showed that the electronic nature and the position of the
substituents on the aromatic ring of the R group had no
Table 2: Substrate scope of pyrazol-5-ones.[a]
Entry Ligand
Metal
Solvent Yield [%][b] Z/E ratio[c] ee [%][d]
1[e]
2[e]
3
L1
L1
L1
L1
L1
L2
L3
L4
L4
L4
L4
L4
Gd(OTf)3 CH2Cl2
Ho(OTf)3 CH2Cl2
Ho(OTf)3 CH2Cl2
Sc(OTf)3 CH2Cl2
Sc(OTf)3 CH2Cl2
Sc(OTf)3 CH2Cl2
Sc(OTf)3 CH2Cl2
Sc(OTf)3 CH2Cl2
Sc(OTf)3 CHCl3
Sc(OTf)3 CHCl3
Sc(OTf)3 CHCl3
Sc(OTf)3 CHCl3
89
87
92
30
62
35
85
96
97
97
97
98
96
95
33/67
15/85
84/16
90/10
90/10
80/20
>95/5
>95/5
94/6
94/6
94/6
90/10
94/6
<5/95
78 (S)
67 (S)
91 (S)[f]
52 (S)
52 (S)
19 (R)
86 (R)
95 (R)
99 (R)
97 (R)
97 (R)
99 (R)
96 (S)
98 (R)
4[e]
5
Entry
R
t [h]
Yield [%][b]
Z/E[c]
ee [%][d]
1
Bn
36
7
97 (3a)
96 (3b)
93 (3c)
91 (3d)
93 (3e)
92 (3 f)
93 (3g)
94 (3h)
95 (3i)
93 (3j)
96 (3k)
97 (3l)
94 (3m)
93 (3n)
97 (3o)
95 (3p)
92 (3q)
90 (3r)
91 (3s)
90 (3t)
96 (3u)
94/6
92/8
94/6
93/7
94/6
94/6
94/6
91/9
97 (R)
97 (R)
97 (R)
97 (R)
97 (R)
98 (R)
98 (R)
95 (R)
97 (R)
98 (R)
99 (R)
98 (R)
97 (R)
98 (R)
99 (R)
99 (R)
95 (R)
92 (R)
99 (R)
99 (R)
99 (R)
6
7
8
9
2[e]
3
2-MeC6H4CH2
3-MeC6H4CH2
4-MeC6H4CH2
2-MeOC6H4CH2
3-MeOC6H4CH2
4-MeOC6H4CH2
2-ClC6H4CH2
3-ClC6H4CH2
4-ClC6H4CH2
4-BrC6H4CH2
2,4-Cl2C6H3CH2
3,4-Cl2C6H3CH2
2-furanylmethyl
2-thienylmethyl
1-naphthylmethyl
2-naphthylmethyl
Me
36
40
36
36
36
6
30
30
30
6
4
5
6
7
10[g]
11[g,h]
12[g,i]
13[g]
14[g–k]
8[e]
9
ent-L4 Sc(OTf)3 CHCl3
L4 Sc(OTf)3 CHCl3
93/7
10
11
12[e]
13
14[e]
15
16[e]
17
18[e]
19
20
21[e]
90/10
89/11
88/12
92/8
86/14
92/8
89/11
93/7
86/14
87/13
89/11
88/12
[a] Unless otherwise noted, reactions were carried out with ligand
(12 mol%), metal (10 mol%), 1a (0.1 mmol), 2a (0.11 mmol), and
molecular sieves (4 ꢀ, 30 mg) in solvent (1.0 mL) at 08C for 20 hours.
[b] Yield of isolated Z/E-3a. [c] Determined by 1H NMR analysis of the
crude mixture. [d] ee value of the Z isomers determined by chiral HPLC
analysis. [e] Without 4 ꢀ molecular sieves. [f] The absolute configuration
was determined by X-ray analysis. [g] 5 mol% of catalyst, 36 hours.
[h] The catalyst was pre-prepared in the presence of 4 ꢀ molecular sieves.
[i] At 258C for 6 hours. [j] After the 1,4-addition, Ph2MeP (0.3 equiv) was
added for the isomerization (24 h). [k] ee of the E isomer. Tf=trifluor-
omethanesulfonyl.
24
6
30
10
40
10
36
36
10
Et
n-propyl
cyclohexylmethyl
[a] Unless otherwise noted, reactions were carried out under the
optimized reaction conditions at 08C. [b] Yield of isolated Z/E-3.
1
product was obtained in up to 95/5 Z/E ratio and 95% ee
(Table 1, entry 8). A screening of solvents (Table 1, entries 8
and 9) showed that an ee value of 99% could be obtained in
CHCl3 with a little decrease in the Z/E selectivity (Table 1,
entry 9). Notably, when the catalyst loading was lowered to
5 mol%, the reaction performed well with good results
(Table 1, entry 10). Furthermore, the yield, Z/E selectivity,
and enantioselectivity were basically maintained by employ-
ing the catalyst that was prepared before the reaction, thus
facilitating the experimental procedure (Table 1, entry 11).
Excellent enantioselectivity was afforded at 258C, although
the Z/E ratio was somewhat reduced (Table 1, entry 12). The
opposite enantioselectivity was further confirmed by using
the alternative catalyst of d-proline-derived ligand L4
(Table 1, entry 13). In addition, as reported by Shibasaki
and co-workers, Ph2MeP could be added to the Z/E-mixed
adduct 3a for isomerization, thus affording exclusively the
E isomer with 98% ee (Table 1, entry 14).[2d] This is an
efficient and economical method to afford both enantioen-
riched products with complementary geometric configura-
tion. Thus, the optimized reaction conditions for the 1,4-
addition reaction of 4-substituted pyrazol-5-ones to alkynones
included the reaction in CHCl3 and use of 5 mol% of N,N’-
dioxide L4–ScIII complex (Table 1, entry 11).
[c] Determined by H NMR analysis of the crude mixture. [d] ee of the
Z isomer determined by chiral HPLC analysis. [e] At 258C. Bn=benzyl.
influence on the enantioselectivity, but a slight influence on
the Z/E selectivity and the reaction rate (Table 2, entries 1–
13). Relatively lower Z/E ratios were obtained with halogen
substituents at ortho or para positions (Table 2, entries 8–13
versus entries 1–7). In addition, substrates bearing a con-
densed ring or heteroaromatic ring at the R substituent were
also suitable substrates for the reaction and afforded the
corresponding products 3n–q with excellent enantioselectiv-
ities and uniformly high Z/E selectivities (86:14–93:7 Z/E, 95–
99% ee; Table 2, entries 14–17). It is worth pointing out that
the catalyst system was also efficient when the R substituent
was a linear alkyl group (Table 2, entries 18–20) or a cyclo-
hexylmethyl group (Table 2, entry 21). The corresponding
adducts 3r–u were generated in good yields with 92–99% ee
and good Z/E selectivities. A comparison with the Cotton
effect in the CD spectra of Z-3a showed that the absolute
configuration of the other Z-isomers was R (see the Support-
ing Information for details).
With these results in hand, a wide range of aromatic,
aliphatic, and heterocyclic alkynone derivatives were inves-
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tigated with 4-benzyl-pyrazol-5-one (1a) as the nucleophile
(Table 3). To our delight, this catalyst system showed
a remarkably broad substrate scope. The desired adducts
were obtained in high yields (85–95%) and good geometric
propose that the carbonyl group of the 4-substituted pyrazol-
5-one 1 would coordinate to the active L4*–ScIII complex to
form an enolate intermediate. Meanwhile, alkynone, which is
structurally similar to enone, coordinated to the central metal
at the favorable position (Scheme 2). Subsequently, the
electrophilic attack of alkynone to the enolate (TS 1) would
afford the corresponding adduct with excellent enantioselec-
tivity.
Table 3: Substrate scope of alkynones.[a]
Entry
R
t [h]
Yield [%][b]
Z/E[c]
91/9
93/7
95/5
91/9
89/11
94/6
ee [%][d]
1[e]
2
3
4
5
2-MeC6H4
3-MeC6H4
4-MeC6H4
2-FC6H4
12
36
48
24
36
30
36
3
95 (4a)
93 (4b)
90 (4c)
93 (4d)
93 (4e)
92 (4 f)
90 (4g)
93 (4h)
94 (4i)
93 (4j)
99 (R)
97 (R)
98 (R)
96 (R)
96 (R)
96 (R)
96 (R)
97 (R)
95 (R)
98 (R)
4-FC6H4
Scheme 2. Proposed catalytic model. TS=transition state.
6
7
4-ClC6H4
4-BrC6H4
4-CF3C6H4
3-CF3C6H4
4-MeOC6H4
93/7
8[e]
9[e]
10[e]
84/16
78/22
>95/5
3
18
According to the reported Z-selective conjugate addition
of carbon nucleophiles to acetylenic esters by using basic
catalysts,[5,11] the nature of the pronucleophile might play
a crucial role on the Z/E selectivity. The electron-donating
R group on electrophile 2 had a positive effect on the Z/E
selectivity (Table 3). Therefore, we postulate a similar inter-
mediate to that of Sugimura and co-workers[5] to rationalize
the sense of geometric induction. One side of the dienolate is
shielded by the pyrazoline ring because of the interaction
between electron-enriched p orbital of dienolate and elec-
tron-deficient carbon atom at the 3 position of the pyrazoline
ring.[12] The protonation process occurs from the other side to
afford the thermodynamically unstable Z isomer.
11[e]
30
91 (4k)
>95/5
99 (R)
12
48
92 (4l)
88/12
91 (R)
13
14
2-naphthyl
2-thienyl
cyclohexyl
n-pentyl
36
30
18
30
24
91 (4m)
92 (4n)
90 (4o)
85 (4p)
96 (4a)
>95/5
89/11
88/12
92/8
98 (R)
96 (R)
97 (R)
98 (R)
99 (R)
15[e]
16[e]
17[e,f]
2-MeC6H4
90/10
[a–e] See the corresponding footnotes in Table 2. [f] The reaction was
carried out on a gram scale in CHCl3 (30 mL) at 258C.
In summary, we have successfully developed the highly Z-
selective asymmetric 1,4-addition reaction of 4-substituted
pyrazolones to alkynones. The reactions were catalyzed by an
N,N’-dioxide–scandium(III) complex to give the optically
active 4-alkenyl-pyrazol-5-ones in high geometric control (Z/
E up to 95/5), high yields (up to 97%), and excellent
enantioselectivities (up to 99% ee). In particular, the
procedure tolerates a relatively wide range of substrates,
and excellent results can be obtained on a gram scale. The
thermodynamically stable E adducts could also be generated
through an isomerization procedure. Given the acceptable
catalyst loading, mild reaction conditions, simple operation,
and the fact that diverse functional groups in the adducts are
ready for further conversion, this strategy may find a promis-
ing application in organic synthesis. Further studies are
underway to investigate the enantiomeric discrimination
and the synthetic utility of the a-alkenylation products.
and enantiomeric control (78/22 to > 95:5 Z/E, 91 to 99% ee).
The electronic properties of the substituent on the aromatic
ring of the alkynone had no obvious effect on the enantio-
selectivity of the reaction (Table 3, entries 1–10), whereas the
Z/E selectivities were reduced and a shorter reaction time was
needed when substrates that contained electron-withdrawing
substituents were used (Table 3, entries 8 and 9 versus
entries 10 and 11). Remarkably, alkynones with two substitu-
ents on the aromatic ring, which were rarely investigated
previously, underwent the reaction smoothly with excellent
results (Table 3, entries 11 and 12). The alkynones bearing
condensed-ring or heteroaryl units also proved tolerable with
respect to enantioselectivity and Z/E selectivity of the
reaction (Table 3, entries 13 and 14). Notably, the alkyl-
substituted alkynones gave predominantly Z adducts 4o
(90% yield, 97% ee) and 4p (85% yield, 98% ee; Table 3,
entries 15 and 16, respectively).
Furthermore, when the reaction of pyrazolone 2a was
carried out on a gram scale with 5 mol% of the chiral
scandium complex, good results with 96% yield (1.488 g),
90:10 Z/E, and 99% ee were still obtained (Table 3, entry 17).
In order to elucidate the reaction process, some control
experiments were performed. The HRMS analysis of the
catalyst and an observed straight linear effect[10] indicate that
the monomeric catalyst might be the main catalytically active
species (see the Supporting Information for details). We
Experimental Section
Typical experimental procedure for 1,4-addition reaction of 4-
substituted pyrazol-5-ones to alkynones: The prepared chiral catalyst
(5 mol%; see Supporting Information) and 4-benzyl-pyrazol-5-one
(1a, 26.4 mg, 0.10 mmol) were stirred in CHCl3 (0.9 mL) under
nitrogen at room temperature for 10 min. Alkynone (2a, 14.3 mg,
0.11 mmol in 0.1 mL CHCl3) was added at 08C. The mixture was
stirred at 08C for 36 h. The Z/E ratio (94/6) was determined by
1H NMR analysis of the crude mixture. Separation by column
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chromatography on silica gel with petroleum ether/ethyl acetate
(12:1!4:1) afforded the desired product Z/E-3a in 97% yield with
97% ee of Z-isomer.
Tetrahedron: Asymmetry 2004, 15, 1373; e) A. V. Malkov, P.
ˇ
´
Kocovsky, Curr. Org. Chem. 2003, 7, 1737; for our work in this
field, see: f) W. Li, X. H. Liu, X. Y. Hao, X. L. Hu, Y. Y. Chu,
W. D. Cao, S. Qin, C. W. Hu, L. L. Lin, X. M. Feng, J. Am. Chem.
Soc. 2011, 133, 15268; g) Z. Wang, Z. G. Yang, D. H. Chen, X. H.
Liu, L. L. Lin, X. M. Feng, Angew. Chem. 2011, 123, 5030;
Angew. Chem. Int. Ed. 2011, 50, 4928; h) K. Zheng, C. K. Yin,
X. H. Liu, L. L. Lin, X. M. Feng, Angew. Chem. 2011, 123, 2621;
Angew. Chem. Int. Ed. 2011, 50, 2573; i) K. Shen, X. H. Liu, G.
Wang, L. L. Lin, X. M. Feng, Angew. Chem. 2011, 123, 4780;
Angew. Chem. Int. Ed. 2011, 50, 4684; j) M. S. Xie, X. H. Chen,
Y. Zhu, B. Gao, L. L. Lin, X. H. Liu, X. M. Feng, Angew. Chem.
2010, 122, 3887; Angew. Chem. Int. Ed. 2010, 49, 3799; k) Y. F.
Cai, X. H. Liu, Y. H. Hui, J. Jiang, W. T. Wang, W. L. Chen, L. L.
Lin, X. M. Feng, Angew. Chem. 2010, 122, 6296; Angew. Chem.
Int. Ed. 2010, 49, 6160; l) Y. L. Liu, D. J. Shang, X. Zhou, Y. Zhu,
L. L. Lin, X. H. Liu, X. M. Feng, Org. Lett. 2010, 12, 180;
m) Y. L. Liu, D. J. Shang, X. Zhou, X. H. Liu, X. M. Feng, Chem.
Eur. J. 2009, 15, 2055; n) D. J. Shang, Y. L. Liu, X. Zhou, X. H.
Liu, X. M. Feng, Chem. Eur. J. 2009, 15, 3678; o) Z. P. Yu, X. H.
Liu, Z. H. Dong, M. S. Xie, X. M. Feng, Angew. Chem. 2008, 120,
1328; Angew. Chem. Int. Ed. 2008, 47, 1308; p) K. Zheng, J. Shi,
X. H. Liu, X. M. Feng, J. Am. Chem. Soc. 2008, 130, 15770.
[7] For reviews of catalytic enantioselective construction of quater-
nary chiral centers, see: a) J. Christoffers, A. Baro, Adv. Synth.
Catal. 2005, 347, 1473; b) E. A. Peterson, L. E. Overman, Proc.
Natl. Acad. Sci. USA 2004, 101, 11943; c) D. J. Ramon, M. Yus,
Curr. Org. Chem. 2004, 8, 149; d) J. Christoffers, A. Baro, Angew.
Chem. 2003, 115, 1726; Angew. Chem. Int. Ed. 2003, 42, 1688.
[8] For leading references on molecular sieves, see: a) J. K. Thomas,
Chem. Rev. 1993, 93, 301; b) M. E. Davis, Acc. Chem. Res. 1993,
26, 111; for a similar molecular sieves effect, see: c) J. Itoh, K.
Fuchibe, T. Akiyama, Angew. Chem. 2008, 120, 4080; Angew.
Chem. Int. Ed. 2008, 47, 4016.
Received: December 24, 2011
Published online: February 3, 2012
Keywords: 1,4-addition · alkynones · asymmetric catalysis ·
.
scandium · Z selectivity
[1] For reviews of conjugate addition reactions, see: a) P. Perlmut-
ter, Conjugate Addition Reactions in Organic Synthesis, Perga-
mon, Oxford, 1992; b) E. N. Jacobsen, A. Pfaltz, H. Yamamoto,
Comprehensive Asymmetric Catalysis, Springer, New York,
1999; c) M. P. Sibi, S. Manyem, Tetrahedron 2000, 56, 8033;
d) N. Krause, A. Hoffmann-Rçder, Synthesis 2001, 171; e) O. M.
Berner, L. Tedeschi, D. Enders, Eur. J. Org. Chem. 2002, 1877;
f) R. Ballini, G. Bosica, D. Fiorini, A. Palmieri, M. Petrini, Chem.
Rev. 2005, 105, 933; g) S. B. Tsogoeva, Eur. J. Org. Chem. 2007,
1701; h) D. Almas¸i, D. A. Alonso, C. Nꢁjera, Tetrahedron:
Asymmetry 2007, 18, 299; i) S. Sulzer-Mossꢂ, A. Alexakis, Chem.
Commun. 2007, 3123; j) J. Christoffers, G. Koripelly, A. Rosiak,
M. Rçssle, Synthesis 2007, 1279.
[2] For selected examples, see: a) M. Bella, K. A. Jørgensen, J. Am.
Chem. Soc. 2004, 126, 5672; b) X. Wang, M. Kitamura, K.
Maruoka, J. Am. Chem. Soc. 2007, 129, 1038; c) Q. Lan, X.
Wang, K. Maruoka, Tetrahedron Lett. 2007, 48, 4675; d) Z. Chen,
M. Furutachi, Y. Kato, S. Matsunaga, M. Shibasaki, Angew.
Chem. 2009, 121, 2252; Angew. Chem. Int. Ed. 2009, 48, 2218;
e) T. B. Poulsen, L. Bernardi, M. Bell, K. A. Jørgensen, Angew.
Chem. 2006, 118, 6701; Angew. Chem. Int. Ed. 2006, 45, 6551. See
also Ref. [5].
[3] For Z-selective racemic 1,4-addition, see: a) C. Jia, W. Lu, J.
Oyamada, T. Kitamura, K. Matsuda, M. Irie, Y. Fujiwara, J. Am.
Chem. Soc. 2000, 122, 7252; b) R. B. Grossman, S. Comesse,
R. M. Rasne, K. Hattori, M. N. Delong, J. Org. Chem. 2003, 68,
871; c) Z. Shi, C. He, J. Org. Chem. 2004, 69, 3669; d) A. J.
Mueller, M. P. Jennings, Org. Lett. 2007, 9, 5327; for an excep-
tional E selectivity, see: e) A. Rubio, J. Ezquerra, Tetrahedron
Lett. 1995, 36, 5823. See also Ref. [11] and [12] for Z-selective
1,4-addition.
[4] The Jørgensen group isolated the Z isomer from the Z/E mixture
by selective decomposition of the E isomer. See Ref. [2a].
[5] T. Misaki, K. Kawano, T. Sugimura, J. Am. Chem. Soc. 2011, 133,
5695.
[9] CCDC 855275 (3a) contains the supplementary crystallographic
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.
[10] a) D. Guillaneux, S. H. Zhao, O. Samuel, D. Rainford, H. B.
Kagan, J. Am. Chem. Soc. 1994, 116, 9430; b) C. Girard, H. B.
Kagan, Angew. Chem. 1998, 110, 3088; Angew. Chem. Int. Ed.
1998, 37, 2922; c) T. Satyanarayana, S. Abraham, H. B. Kagan,
Angew. Chem. 2009, 121, 464; Angew. Chem. Int. Ed. 2009, 48,
456.
[11] a) W. Steglich, P. Gruber, G. Hçfle, W. Kçnig, Angew. Chem.
1971, 83, 725; Angew. Chem. Int. Ed. Engl. 1971, 10, 653; b) H.
Wegmann, G. Schulz, W. Steglich, Liebigs Ann. Chem. 1980,
1736; c) A. Lꢃpez, M. Moreno-MaÇas, R. Pleixats, A. Roglans, J.
Ezquerra, C. Pedregal, Tetrahedron 1996, 52, 8365; d) G.
Guillena, C. Nꢁjera, J. Org. Chem. 2000, 65, 7310.
[6] For reviews on chiral N-oxides in asymmetric catalysis, see:
a) X. M. Feng, X. H. Liu in Scandium: Compounds, Productions
and Applications (Ed.: V. A. Greene), Nova Science New York,
2011, pp. 1 – 48; b) X. H. Liu, L. L. Lin, X. M. Feng, Acc. Chem.
[12] F. Freeman, D. S. H. L. Kim, J. Org. Chem. 1993, 58, 6474 and
ref. [5].
ˇ
´
Res. 2011, 44, 574; c) A. V. Malkov, P. Kocovsky, Eur. J. Org.
Chem. 2007, 29; d) G. Chelucci, G. Murineddu, G. A. Pinna,
Angew. Chem. Int. Ed. 2012, 51, 2776 –2779
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