Design and synthesis of new chiral phosphorus-olefin bidentate ligands and their use in the rhodium-catalyzed asymmetric addition of organoboroxines to N-sulfonyl imines

Article abstract of DOI:10.1039/c1cc11823d

Novel chiral phosphorus-olefin bidentate ligands have been synthesized in a few steps from a readily available enantiopure compound. These ligands have been applied to a rhodium-catalyzed asymmetric addition of organoboroxines to N-sulfonyl aldimines, achieving high yield and enantioselectivity.

Full text of DOI:10.1039/c1cc11823d

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COMMUNICATION
Design and synthesis of new chiral phosphorus–olefin bidentate ligands
and their use in the rhodium-catalyzed asymmetric addition of
organoboroxines to N-sulfonyl iminesw
Ryo Shintani,* Rintaro Narui, Yosuke Tsutsumi, Sayuri Hayashi and Tamio Hayashi*
Received 31st March 2011, Accepted 12th April 2011
DOI: 10.1039/c1cc11823d
Novel chiral phosphorus–olefin bidentate ligands have been
synthesized in a few steps from a readily available enantiopure
compound. These ligands have been applied to a rhodium-
catalyzed asymmetric addition of organoboroxines to N-sulfonyl
aldimines, achieving high yield and enantioselectivity.
Enantioselective synthesis of chiral compounds under the
catalysis of transition-metal complexes coordinated with chiral
ligands is one of the most powerful methods in modern
synthetic organic chemistry, and the design and the synthesis
of new chiral ligands are very important for advancement of
asymmetric catalysis. Traditionally, chiral ligands for late
transition-metals are based on phosphorus- and/or nitrogen-
Fig. 1 (a) Previously developed chiral phosphine–olefin ligand A.
coordination, and several ligands are known to be highly
effective for various asymmetric transformations.1 As concep-
(b) Newly designed chiral phosphorus–olefin ligand B.
tually new chiral ligands, a series of chiral dienes have been
To solve this synthetic problem while keeping the good
chiral environment around the olefin, here we describe the
development of a new class of P–olefin ligands B based on
1-(diphenylphosphino)-2,5-dihydro-1H-pyrrole as illustrated
in Fig. 1b. These ligands are designed to coordinate to transition-
metals in a bidentate fashion by the phosphorus atom and the
olefin as was the case for ligands A, and the coordination face
of the olefin is supposed to be controlled by the stereogenic
carbon center substituted with the X group on the dihydro-
pyrrole ring. Thus, to avoid the unfavorable steric interaction
of the X group, bre-face of the olefin would preferentially
coordinate to a metal (M) and thereby the substituent on the
olefin (R) effectively dictates the chiral environment around
the metal.
developed in the past decade, proving that good chiral environ-
ments can be created around olefin ligands.2 Although these
chiral dienes can provide highly active catalysts in some cases
such as the rhodium-catalyzed 1,4-addition reactions, coordi-
nation ability of dienes to transition-metals is generally weaker
than that of phosphorus-based ligands, thereby limiting the
potential application of these attractive chiral ligands.
To enhance the utility of chiral olefin ligands with increased
coordination ability to transition-metals, several research
groups3 including ours4 described the use of chiral phosphine–
olefin hybrid ligands. For example, we reported the development
of structurally compact phosphine–olefins A, which have a
bicyclo[2.2.1]heptene backbone with high rigidity (Fig. 1a),
and demonstrated that they provide highly active and stereo-
selective catalysts for the rhodium-catalyzed asymmetric 1,4-
addition of arylboronic acids to electron-deficient olefins.4a,c
Despite the attractive features of these ligands, the major
drawback of A is the long synthetic scheme involving a step
of optical resolution of the two enantiomers using chiral HPLC.
As an initial member of chiral phosphorus–olefin ligands B,
we targeted (S)-1a, the synthesis of which commenced with
the readily available allylamine derivative (S)-25 in a straight-
forward manner (Scheme 1). Thus, N-alkylation of (S)-2 with
2-methyl-2-propenyl bromide, followed by ruthenium-catalyzed
ring-closing metathesis,6 gave (S)-3a in 93% yield over two
steps. Removal of the tert-butoxycarbonyl group and the
subsequent N-phosphination with chlorodiphenyl phosphine
completed the synthesis of (S)-1a in 79% yield from (S)-3a.
Chiral P–olefins (S)-1b and (S)-1c having a benzyloxymethyl
group and a phenyl group on the olefin, respectively, were also
prepared from (S)-2 in good overall yield by following the
same synthetic scheme for (S)-1a.
Department of Chemistry, Graduate School of Science, Kyoto
University, Sakyo, Kyoto 606-8502, Japan.
E-mail: shintani@kuchem.kyoto-u.ac.jp, thayashi@kuchem.kyoto-u.ac.jp;
Fax: +81-75-753-3988; Tel: +81-75-753-3983
w Electronic supplementary information (ESI) available: Experimental
procedures and compound characterization data. CCDC 819417. For
ESI and crystallographic data in CIF or other electronic format see
DOI: 10.1039/c1cc11823d
c
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Scheme 1 Synthesis of chiral P–olefins (S)-1. Conditions: (a) NaH,
2-methyl-2-propenyl bromide, DMF, rt; 95%; (b) cat. Grubbs 2nd,
C6H6, 60 1C; 98%; (c) CF3CO2H, CH2Cl2, rt; 95%; (d) (i) NaOHaq
then Et2O extraction, (ii) Ph2PCl, Et3N, THF, 0 1C to rt; 83%.
Having established the synthesis of (S)-1, we carried out
a complexation experiment of (S)-1a (31P NMR: 43.5 ppm;
1H NMR: 5.24 ppm for the olefin H in benzene-d6) with
Rh(acac)(C2H4)2 in benzene at 30 1C, and found that only
one species 4 was newly generated (85% yield; eqn (1)). This
complex showed a doublet at 127.9 ppm (J = 202 Hz) in
31P NMR and the olefin H of (S)-1a was upfield-shifted to
3.75 ppm in 1H NMR, indicating that both the phosphorus and
the olefin were directly bound to rhodium. Recrystallization of
this complex from benzene/pentane afforded single crystals
suitable for X-ray crystallographic analysis.7 As shown in
Fig. 2, (S)-1a does act as a P–olefin bidentate ligand to rhodium
and the olefin indeed coordinates with its bre-face to keep the
benzyl group on the dihydropyrrole ring away from rhodium,
effectively accomplishing the initial design of this novel ligand.
In addition, it shows that two phenyl groups on the phosphorus
atom are symmetrically projected, and the chiral environment
around the rhodium is effectively constructed by the steric
difference between the two substituents (Me and H) on the
olefin.
Fig. 2 X-Ray crystal structure of complex 4 with thermal ellipsoids
drawn at the 50% probability level (carbon atoms of the acac moiety and
hydrogen atoms are omitted for clarity). Selected bond lengths (A) and
angles (1): Rh–P = 2.1683(9), Rh–Ca = 2.138(4), Rh–Cb = 2.075(4),
Rh–O1 = 2.085(2), Rh–O2 = 2.046(3), P–N = 1.746(3), P–C2 =
1.820(4), P–C3 = 1.816(4), Ca–Cb = 1.409(6), C1–Ca = 1.516(6),
+O1–Rh–O2 = 89.66(12), +P–Rh–Ca = 82.08(11), +P–Rh–Cb =
82.62(11), +Ca–Rh–Cb
+C1–Ca–Cb = 127.1(3).
= 39.04(16), +Rh–Ca–C1 = 114.3(2),
outcome and the structure of a Rh/(S)-1 complex in Fig. 2, the
stereochemical pathway for eqn (2) with Rh/(S)-1c can be
rationalized as shown in Fig. 3. Thus, the phenylrhodium
species has a trans-relationship between the phenyl group and
the olefin ligand, and imine 5a approaches the rhodium with
its re-face at the cis-position of the olefin ligand to give (R)-6a
with high selectivity.4a,c,8b
ð1Þ
To investigate the potential of these ligands (S)-1 in asymmetric
catalysis, we chose to explore the rhodium-catalyzed addition
of organoboroxines to N-tosyl aldimines.8 As shown in
eqn (2), a reaction of N-tosyl imine of 4-chlorobenzaldehyde
(5a) with phenylboroxine (3.0 equiv. B) in the presence of Rh/
(S)-1a (5 mol%) at 60 1C gave the desired addition product
(6a) in 76% yield with 81% ee. The change of the olefin
substituent from methyl to benzyloxymethyl ((S)-1b) did not
show much difference (80% yield, 82% ee), but the use of the
phenyl-substituted ligand (S)-1c significantly improved the
reaction outcome (90% yield, 97% ee). Because this reaction
is known to be better catalyzed by Rh/diene complexes than
by Rh/bisphosphine complexes,8b these results indicate that
rhodium complexes bearing phosphorus–olefin hybrid ligands
(S)-1 display a similar reactivity to that of Rh/diene complexes
rather than Rh/bisphosphine complexes. In addition, the
result using (S)-1c turned out to be almost identical to that
with ligand (7R)-7,4 a type A phosphine–olefin ligand having a
phenyl group on the olefin, demonstrating that (S)-1 is indeed
a simplified surrogate of our previously developed ligands.
Furthermore, the absolute configuration of 6a obtained in
eqn (2) was determined to be R by comparison of its optical
rotation value with that in the literature.8b On the basis of this
ð2Þ
Under the conditions using Rh/(S)-1c, several N-tosyl imines
derived from sterically and electronically different benzaldehydes
can be effectively phenylated with high enantioselectivity
(94–97% ee; Table 1, entries 1–5). It is worth noting that
the reaction using only 1.0 equiv. B of phenylboroxine
also proceeds with acceptable yield of 71% with the same
level of enantioselectivity (entry 2). In addition, substrates
with heteroaryl, alkenyl, and alkyl groups at the imine carbon
also undergo phenylation to give the corresponding addition
Fig. 3 Proposed stereochemical pathway for the addition of phenyl-
boroxine to 5a catalyzed by Rh/(S)-1c.
c
6124 Chem. Commun., 2011, 47, 6123–6125
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Table 1 Rh/(S)-1c-catalyzed asymmetric addition of organoboroxines
to 5: scope
to N-sulfonyl aldimines, achieving high yield and enantio-
selectivity. Future studies will explore further applications of
these ligands to various transition-metal-catalyzed asymmetric
processes.
Support has been provided in part by a Grant-in-Aid for
Scientific Research (S) (19105002), the Ministry of Education,
Culture, Sports, Science and Technology, Japan.
Entry
5
R0
Product
Yielda (%)
eeb (%)
Notes and references
1
5a
5a
5b
5c
5d
5e
5f
5g
5h
5h
5h
5h
5h
5h
5a
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
(R)-6a
(R)-6a
(R)-6b
(R)-6c
(R)-6d
(R)-6e
(S)-6f
(S)-6g
(S)-6a
(S)-6c
(S)-6h
(S)-6i
(S)-6j
(R)-6f
(R)-6k
90
71
71
90
95
83
73
73
83
87
70
93
86
86
91
97
97
95
97
94
96
97
96
96
96
96
98
96
89
95
1 (a) Phosphorus Ligands in Asymmetric Catalysis 1–3, ed. A. Borner,
¨
2c
3
Wiley-VCH, Weinheim, 2008; (b) Catalytic Asymmetric Synthesis, ed.
I. Ojima, Wiley-VCH, New York, 2nd edn, 2000; (c) Comprehensive
Asymmetric Catalysis I–III, ed. E. N. Jacobsen, A. Pfaltz and
H. Yamamoto, Springer-Verlag, New York, 1999.
4
5
6
2 For reviews, see: (a) R. Shintani and T. Hayashi, Aldrichimica Acta,
2009, 42, 31; (b) C. Defieber, H. Grutzmacher and E. M. Carreira,
7d
8e
9
¨
Angew. Chem., Int. Ed., 2008, 47, 4482; For early reports, see:
(c) T. Hayashi, K. Ueyama, N. Tokunaga and K. Yoshida,
J. Am. Chem. Soc., 2003, 125, 11508; (d) C. Fischer, C. Defieber,
T. Suzuki and E. M. Carreira, J. Am. Chem. Soc., 2004, 126, 1628.
4-ClC6H4
4-MeOC6H4
2-MeC6H4
2-Naphthyl
3-Thienyl
1-Cyclohexenyl
4-MeOC6H4
10
11d
12
13
14
15
3 (a) P. Maire, S. Deblon, F. Breher, J. Geier, C. Bohler, H. Ruegger,
¨
H. Schonberg and H. Grutzmacher, Chem.–Eur. J., 2004, 10, 4198;
¨
¨
(b) E. Piras, F. Lang, H. Ruegger, D. Stein, M. Worle and
¨
¨
¨
¨
H. Grutzmacher, Chem.–Eur. J., 2006, 12, 5849; (c) P. Kasak,
´
¨
a
b
V. B. Arion and M. Widhalm, Tetrahedron: Asymmetry, 2006, 17,
3084; (d) R. T. Stemmler and C. Bolm, Synlett, 2007, 1365;
(e) C. Defieber, M. A. Ariger, P. Moriel and E. M. Carreira, Angew.
Chem., Int. Ed., 2007, 46, 3139; (f) P. Stepnicka, M. Lamac and
Isolated yield. Determined by chiral HPLC with hexane/2-propanol.
The reaction was conducted using 1.0 equiv. B of phenylboroxine.
The reaction was conducted for 24 h in the presence of 0.4 equiv. of
c
d
e
KOH. The reaction was conducted in dioxane/H2O (100/1).
I. Cısarova, J. Organomet. Chem., 2008, 693, 446; (g) R. Mariz,
´ ´
A. Briceno, R. Dorta and R. Dorta, Organometallics, 2008, 27, 6605;
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2010, 29, 2503; (i) T. Minuth and M. M. K. Boysen, Org. Lett., 2009,
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2010, 3248; (k) Z. Liu and H. Du, Org. Lett., 2010, 12, 3054; See also:
(l) P. S. Pregosin, Chem. Commun., 2008, 4875.
4 (a) R. Shintani, W.-L. Duan, T. Nagano, A. Okada and T. Hayashi,
Angew. Chem., Int. Ed., 2005, 44, 4611; (b) R. Shintani, W.-L. Duan,
K. Okamoto and T. Hayashi, Tetrahedron: Asymmetry, 2005, 16,
3400; (c) W.-L. Duan, H. Iwamura, R. Shintani and T. Hayashi,
J. Am. Chem. Soc., 2007, 129, 2130.
products with similarly high efficiency (96–97% ee; entries 6–8).
With regard to the nucleophilic component, various aryl
groups including 2-naphthyl and 3-thienyl as well as alkenyl
groups can be added to N-tosyl imine of benzaldehyde with
uniformly high enantioselectivity (89–98% ee; entries 9–14).
Highly enantioselective preparation of diarylmethyl sulfona-
mides having substituents on both of the aryl groups is also
possible as exemplified in entry 15 (95% ee).
5 J. R. Luly, J. F. Dellaria, J. J. Plattner, J. L. Soderquist and N. Yi,
J. Org. Chem., 1987, 52, 1487.
We have also begun to explore asymmetric addition of
organoboron nucleophiles to other types of imines under the
catalysis of Rh/(S)-1c. For example, N-nosyl imine of 4-chloro-
benzaldehyde (8) undergoes the addition of phenylboroxine to
give product 9 in 76% yield with 94% ee (eqn (3)).8c,d,9 This
result also confirms the high catalytic activity of Rh/(S)-1
complexes compared to that of Rh/bisphosphine complexes,
which are reported to be ineffective for additions to N-nosyl
imines.8c
6 (a) G. C. Fu, S. T. Nguyen and R. H. Grubbs, J. Am. Chem. Soc.,
1993, 115, 9856; (b) R. H. Grubbs, S. J. Miller and G. C. Fu, Acc.
Chem. Res., 1995, 28, 446; (c) M. Scholl, S. Ding, C. W. Lee and
R. H. Grubbs, Org. Lett., 1999, 1, 953; (d) M. Bujard, A. Briot,
V. Gouverneur and C. Mioskowski, Tetrahedron Lett., 1999, 40,
8785; (e) S. Cren, C. Wilson and N. R. Thomas, Org. Lett., 2005, 7,
3521.
7 CCDC 819417. See also ESIw.
8 For examples of rhodium-catalyzed asymmetric addition of
organoboroxines or organoboronic acids to N-sulfonyl aldimines,
see: (a) M. Kuriyama, T. Soeta, X. Hao, Q. Chen and K. Tomioka,
J. Am. Chem. Soc., 2004, 126, 8128; (b) N. Tokunaga, Y. Otomaru,
K. Okamoto, K. Ueyama, R. Shintani and T. Hayashi, J. Am.
Chem. Soc., 2004, 126, 13584; (c) Y. Otomaru, N. Tokunaga,
R. Shintani and T. Hayashi, Org. Lett., 2005, 7, 307;
(d) K. Okamoto, T. Hayashi and V. H. Rawal, Chem. Commun.,
2009, 4815; (e) H.-F. Duan, Y.-X. Jia, L.-X. Wang and Q.-L. Zhou,
Org. Lett., 2006, 8, 2567; (f) R. B. C. Jagt, P. Y. Toullec,
D. Geerdink, J. G. de Vries, B. L. Feringa and A. J. Minnaard,
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M.-H. Xu and G.-Q. Lin, J. Am. Chem. Soc., 2007, 129, 5336;
(h) K. Kurihara, Y. Yamamoto and N. Miyaura, Adv. Synth. Catal.,
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Chem. Soc., 2000, 122, 976; (j) T. Hayashi, M. Kawai and
N. Tokunaga, Angew. Chem., Int. Ed., 2004, 43, 6125.
ð3Þ
In summary, we have designed and synthesized novel chiral
P–olefin ligands. These ligands can be prepared in a few steps
from a readily available enantiopure compound and act as
bidentate ligands to rhodium. The coordination face of the
olefin is effectively controlled by the chirality embedded in the
ligand framework and we have applied these ligands to a
rhodium-catalyzed asymmetric addition of organoboroxines
9 Unactivated imines such as an N-phenyl imine are not suitable
substrates for the present catalysis.
c
This journal is The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 6123–6125 6125