Chiral N-tert-butanesulfinyl α,β-unsaturated ketimine: A simple and highly effective olefin/sulfinimide hybrid ligand for asymmetric 1,4-additions

Article abstract of DOI:10.1039/c1ob05971h

One novel type of chiral olefin/sulfinimide hybrid ligands has been developed through a simple one-step condensation of α,β-unsaturated ketones with tert-butanesulfinamide and utilized successfully for rhodium-catalyzed asymmetric conjugated additions to furnish the desired adducts in high yields with excellent ee's.

Full text of DOI:10.1039/c1ob05971h

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Chiral N-tert-butanesulfinyl a,b-unsaturated ketimine: a simple and highly
effective olefin/sulfinimide hybrid ligand for asymmetric 1,4-additions†
Xiangqing Feng,a Beibei Wei,b Jing Yang*b and Haifeng Du*a
Received 16th June 2011, Accepted 5th July 2011
DOI: 10.1039/c1ob05971h
One novel type of chiral olefin/sulfinimide hybrid ligands
has been developed through a simple one-step condensation
of a,b-unsaturated ketones with tert-butanesulfinamide and
utilized successfully for rhodium-catalyzed asymmetric con-
jugated additions to furnish the desired adducts in high yields
with excellent ee’s.
Chiral olefin ligands have become one type of important
ligands for asymmetric catalysis.1 Numerous chiral dienes,2
phosphorus/olefin,3 and nitrogen/olefin4 hybrid ligands have been
well developed and successfully utilized for various transition-
metal-catalyzed asymmetric reactions. However, hybrid olefin
ligands contained other coordination elements have rarely been
reported. Until very recently, Knochel,5 Xu,6 and our group7 inde-
pendently and simultaneously reported the development of chiral
Fig. 1 Chiral olefin/sulfur ligands developed recently.
hybrid sulfur-olefin ligands 1–3 for rhodium-catalyzed asymmetric
1,4-additions (Fig. 1).8 Promising activity and selectivity have been
achieved for this novel type of ligands. Interestingly, both ligands
2a and 3 were employed the chiral tert-butanesulfinamide as the
key moieties.9,10 Because of the intriguing features such as the
readily available chiral source and the ease of synthesis, further
exploring tert-butanesulfinamide incorporated novel olefin ligands
is important and attractive.
rhodium-catalyzed asymmetric conjugated additions (Scheme 1).
Herein, we wish to report our efforts on this subject.
In our previous work, we found that the sulfur chirality of
ligands 3 played a crucial role for the observed high enantiose-
lectivity, while the allyl carbon chirality had little impact on both
activity and selectivity.7 This would suggest that elimination of
this stereochemical element might have no effect on the outcome.
Hence, we envisaged that ligands 3 could be simplified as more
practical ligands 4 which could be easily prepared by a one-step
condensation of chiral tert-butanesulfinamide with a variety of
a,b-unsaturated ketones or aldehydes. In addition, we predict that
ligands 4 would still maintain high activity and selectivity for
Scheme 1 Strategy for the development of chiral olefin/sulfinimide
hybrid ligands.
Initially, a well-known compound11 4a obtained by the conden-
sation of chalcone with (R)-tert-butanesulfinamide was subjected
to Rh(I)-catalyzed asymmetric 1,4-addition to evaluate the effect
of directly using N-tert-butanesulfinyl a,b-unsaturated ketimine
as ligand. It was found that the reaction of phenylboronic
acid (6a) and 2-cyclohexenone (5a) went smoothly to furnish
product 7a in quantitative conversion with 92% ee (Scheme 2).
In comparison with the previously reported ligand 3b, under the
same conditions, ligand 4a gave a better reactivity with only a
slightly lower ee (Scheme 2). This promising result encouraged
us to prepare a variety of chiral olefin/sulfinimide hybrid ligands
by a one-step condensation of (R)-tert-butanesulfinamide with
a,b-unsaturated ketones or an aldehyde according to the well
established methodology (Fig. 2).11,12
aBeijing National Laboratory of Molecular Sciences, CAS Key Labo-
ratory of Molecular Recognition and Function, Institute of Chemistry,
Chinese Academy of Sciences, Beijing, 100190, China. E-mail: haifengdu@
iccas.ac.cn; Fax: +86-10-62554449; Tel: +86-10-62652117
bState Key Laboratory Chemical Resource, College of Life Science and
Technology, Beijing University of Chemical Technology, Beijing, 100029,
China. E-mail: yangjingbuct@gmail.com; Fax: +86-10-64427578; Tel: +86-
10-64427578
† Electronic supplementary information (ESI) available: The procedure for
Rh(I)-catalyzed conjugated addition and the characterization and data for
the determination of enantiomeric excess of addition products along with
the NMR spectra. See DOI: 10.1039/c1ob05971h
Further study on the optimization of the reaction conditions
showed that the enantioselectivity could be improved to 97%
when the reaction of 2-cyclohexenone (5a) and phenylboronic
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Table 2 Rhodium-catalyzed asymmetric 1,4-additiona
Product (7)d Yield (%)e ee (%)f
Entry Boronic acid (6)
1
2
R = H
R = Me
90
99
96
96
Scheme 2 Initial study with chiral olefin/sulfinimide hybrid ligand.
3b
4b
5c
6c
7c
8
R = Ph
96
73
61
57
99
88
98
96
96
94
95
95
R = F
R = CF3
R = Ac
R = CH2OH
9
67
92
Fig. 2 Selected chiral olefin/sulfinimide hybrid ligands.
Table 1 Evaluation of chiral olefin/sulfinimide hybrid ligandsa
Entry
Ligand
Conv (%)b
ee (%)c
10
R = OMe
72
92
1
2
3
4
5
6
7
8
4a
4b
4c
4d
4e
4f
4g
4h
4i
>99
88
40
79
46
86
44
35
17
97
97
94
96
96
96
97
85
65
95
83
NDe
11
R = Me
R = Cl
96
91
90
94
12c
9
10
11
12
4j
4k
4l
44
>99
NRd
13
R = Me
R = F
99
96
a All the reactions were carried out with 2-cyclohexenone (5a) (0.33
mmol), phenylboronic acid (6a) (0.50 mmol), K3PO4·3H2O (0.025 mmol),
[RhCl(C2H4)2]2 (0.005 mmol), ligand (0.012 mmol) in MeOH (1.5 mL)
◦
at 30 C under argon for 4 h. b The conversion was determined by crude
1H NMR. c The ee was determined by chiral HPLC. d No reaction. e Not
14c
15
77
84
96
97
determined.
acid (6a) was carried out under the catalysis of Rh/4a complexes
(3.0 mol %) in MeOH at 30 ◦C for 4 h (Table 1, entry 1). To
search for better ligands, chiral ligands 4b–l were then subjected
to this reaction under the optimal conditions. As shown in
Table 1, the majority of ligands modified rhodium catalysts
can promote this reaction to furnish the desired adduct 7a in
17–99% conversions with 65–97% ee’s (Table 1, entries 2–11).
Ligand 4g derived from (E)-cinnamaldehyde gave 44% conversion
with 97% ee (Table 1, entry 7). Hybrid ligands incorporated
with terminal or tri-substituted olefins can also promote this
reaction (Table 1, entries 9 and 11). While ligand 4l prepared
from 2-cyclohexenone was not a suitable ligand (Table 1, entry
12). After a careful evaluation, ligand 4a proved to be the
16b
48
90
best ligand to afford the highest reactivity and enantioselectivity
(Table 1, entry 1).
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Table 2 (Contd.)
Notes and references
Product (7)d
Yield (%)e
ee (%)f
1 For leading reviews on chiral diene ligands in asymmetric catalysis,
see: (a) F. Glorius, Angew. Chem., Int. Ed., 2004, 43, 3364; (b) J. B.
Johnson and T. Rovis, Angew. Chem., Int. Ed., 2008, 47, 840; (c) C.
Defieber, H. Gru¨tzmacher and E. M. Carreira, Angew. Chem., Int. Ed.,
2008, 47, 4482; (d) R. Shintani and T. Hayashi, Aldrichim. Acta, 2009,
42, 31; (e) C.-G. Feng, M.-H. Xu and G.-Q. Lin, Synlett, 2011, 10,
1345.
Entry
Boronic acid (6)
17
R = H
98
91
2 For selected examples of chiral diene ligands, see: (a) T. Hayashi, K.
Ueyama, N. Tokunaga and K. Yoshida, J. Am. Chem. Soc., 2003, 125,
11508; (b) C. Ficsher, C. Defieber, T. Suzuki and E. M. Carreira, J. Am.
Chem. Soc., 2004, 126, 1628; (c) Z.-Q. Wang, C.-G. Feng, M.-H. Xu
and G.-Q. Lin, J. Am. Chem. Soc., 2007, 129, 5336; (d) T. Gendrineau,
O. Chuzel, H. Eijsberg, J.-P. Genet and S. Darses, Angew. Chem., Int.
Ed., 2008, 47, 7669; (e) Y. Luo and A. J. Carnell, Angew. Chem. Int.
Ed., 2010, 49, 2750; (f) G. Pattison, G. Piraux and H. W. Lam, J. Am.
Chem. Soc., 2010, 132, 14373; (g) Q. Li, Z. Dong and Z.-X. Yu, Org.
Lett., 2011, 13, 1122; (h) X. Hu, M. Zhuang, Z. Cao and H. Du, Org.
Lett., 2009, 11, 4744; (i) X. Hu, Z. Cao, Z. Liu, Y. Wang and H. Du,
Adv. Synth. Catal., 2010, 352, 651; (j) Z. Cao and H. Du, Org. Lett.,
2010, 12, 2602; (k) Y. Wang, X. Hu and H. Du, Org. Lett., 2010, 12,
5482.
18
R = Me
PhB(OH)2
91
81
89
97
19b
3 (a) P. Maire, S. Deblon, F. Breher, J. Geier, C. Bo¨hler, H. Ru¨egger, H.
Scho¨nberg and H. Gru¨tzmacher, Chem.–Eur. J., 2004, 10, 4198; (b) R.
Shintani, W.-L. Duan, T. Nagano, A. Okada and T. Hayashi, Angew.
Chem., Int. Ed., 2005, 44, 4611; (c) P. Kasa´k, V. B. Arionb and M.
20b
21b
PhB(OH)2
R = n-C3H7
R = n-C5H11
88
84
60
60
a All the reactions were carried out with enone 5 (0.40 mmol), arylboronic
acid 6 (0.60 mmol), K3PO4·3H2O (0.030 mmol), [RhCl(C2H4)2]2 (0.006
mmol), ligand 4a (0.0144 mmol) in MeOH (1.5 mL) at 30 ◦C under argon
for 5 h unless other noted. b 5.0 mol % of catalyst and K3PO4·3H2O (7.5
mol %) as base. c 5.0 mol % of catalyst and CsF (0.6 mmol) as base. d The
absolute configuration was determined by comparing the optical rotation
with the reported one. e Yield based on enone 5. f The ee was determined
by chiral HPLC.
ˇ
Widhalm, Tetrahedron: Asymmetry, 2006, 17, 3084; (d) P. Steˇpnicˇka
and I. C´ısarˇova´, Inorg. Chem., 2006, 45, 8785; (e) R. T. Stemmler and
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Minuth and M. M. K. Boysen, Org. Lett., 2009, 11, 4212; (h) Z. Liu
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Feng, M. Zhuang and H. Du, Org. Lett., 2011, 13, 2164; (j) R. Shintani,
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8 For leading reviews on chiral sulfoxide ligands, see: (a) I. Ferna´ndez
and N. Khiar, Chem. Rev., 2003, 103, 3651; (b) M. C. Carren˜o, G.
Herna´ndez-Torres, M. Ribagorda and A. Urbano, Chem. Commun.,
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9 For leading reviews on tert-butanesulfinamide, see: (a) J. A. Ellman,
T. D. Owens and T. P. Tang, Acc. Chem. Res., 2002, 35, 984; (b) J. A.
Ellman, Pure Appl. Chem., 2003, 75, 39; (c) F. Ferreira, C. Botuha, F.
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2010, 110, 3600.
The substrate scope for ligand 4a in Rh(I)-catalyzed 1,4-
additions was subsequently investigated. As shown in Table 2,
in most cases, it was found that ligand 4a was highly effective
for the reactions between 2-cyclohexenone (5a) and electron-rich
arylboronic acids to give the corresponding products in high
yields with excellent ee’s, but exhibited relatively lower activity for
electron-poor arylboronic acids where 5 mol % of catalyst loading
and/or 1.5 equiv of CsF were required (Table 2, entries 1–14).
Other cyclic enones are also suitable substrates for this reaction
to furnish the corresponding products in 81–98% yields with 89–
97% ee’s (Table 2, entries 17–19). It is worth noting that ligand
4a can be also applied to the Rh(I)-catalyzed asymmetric addition
of phenylboronic acid (6a) to linear enones to give the desired
adducts in good yields with moderate ee’s (Table 2, entries 20, 21).
10 For leading references on chiral ligands incoporated with tert-
butanesulfinamide, see: (a) T. D. Owens, F. J. Hollander, A. G. Oliver
and J. A. Ellman, J. Am. Chem. Soc., 2001, 123, 1539; (b) T. D. Owens,
A. J. Souers and J. A. Ellman, J. Org. Chem., 2003, 68, 3; (c) L. B.
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Conclusion
In summary, a variety of chiral olefin/sulfinimide hybrid ligands
has been successfully developed by a simple one-step conden-
sation of a,b-unsaturated ketones and readily available (R)-tert-
butanesulfinamide. This novel type of ligands exhibited promising
activity and enantioselectivity for rhodium-catalyzed asymmetric
1,4-additions to afford the desired products in high yields with up
to 98% ee. The ease of synthesis and the diverse structures make
this type of ligands attractive for other transition-metal-catalyzed
asymmetric reactions.
Acknowledgements
This work was generously supported by the National Science
Foundation of China (20802079, 21072194), the National Basic
Research Program of China (2010CB833300).
This journal is
The Royal Society of Chemistry 2011
Org. Biomol. Chem., 2011, 9, 5927–5929 | 5929
©