A mild dihydrobenzooxaphosphole oxazoline/iridium catalytic system for asymmetric hydrogenation of unfunctionalized dialins

Article abstract of DOI:10.1002/anie.201408929

Air-stable P-chiral dihydrobenzooxaphosphole oxazoline ligands were designed and synthesized. When they were used in the iridium-catalyzed asymmetric hydrogenation of unfunctionalized 1-aryl-3,4-dihydronaphthalenes under one atmosphere pressure of H₂, up to 99:1 e.r. was obtained. High enantioselectivities were also observed in the reduction of the exocyclic imine derivatives of 1-tetralones.

Full text of DOI:10.1002/anie.201408929

Angewandte
Chemie
DOI: 10.1002/anie.201408929
P,N Ligands
A Mild Dihydrobenzooxaphosphole Oxazoline/Iridium Catalytic
System for Asymmetric Hydrogenation of Unfunctionalized Dialins**
Bo Qu,* Lalith P. Samankumara, Shengli Ma, Keith R. Fandrick, Jean-Nicolas Desrosiers,
Sonia Rodriguez, Zhibin Li, Nizar Haddad, Zhengxu S. Han, Keith McKellop, Scott Pennino,
Nelu Grinberg, Nina C. Gonnella, Jinhua J. Song, and Chris H. Senanayake
Abstract: Air-stable P-chiral dihydrobenzooxaphosphole oxa-
zoline ligands were designed and synthesized. When they were
used in the iridium-catalyzed asymmetric hydrogenation of
unfunctionalized 1-aryl-3,4-dihydronaphthalenes under one
atmosphere pressure of H2, up to 99:1 e.r. was obtained. High
enantioselectivities were also observed in the reduction of the
exocyclic imine derivatives of 1-tetralones.
dronaphthalenes are known to be difficult substrates and the
current literature methods often require high pressures, and
very few dialin substrates have been reported.[4] Buchwald
and co-workers reported the titanocene-catalyzed asymmet-
ric hydrogenation of unfunctionalized olefins under high H2
pressures (up to 136 atm) over long reaction times.[5] More
recently Pfaltz and co-workers demonstrated that chiral
P,N ligands, when complexed with iridium, can reduce certain
cyclic unfunctionalized dihydronaphthalenes with good to
high enantioselectivities.[6] Again, this catalytic system gen-
erally required 50 atm of pressure of H2 and was applied to
only a handful of substrates. To develop a scalable and
economical synthesis of our target molecules, a mild and
reactive catalytic system was required. Herein, we describe
our work on the development of a novel ligand series for the
asymmetric hydrogenation of unfunctionalized 1-aryl dialins
and it proceeds under only one atmosphere of H2.
S
ubstituted tetralins,[1] especially those containing stereo-
genic centers, have been widely utilized in the design and
synthesis of biologically active compounds.[2] Recently we
were interested in an efficient synthetic route to a family of
chiral, unfunctionalized 1-aryl-substituted tetralins in an
optically pure form (Scheme 1). One of the most direct
Recently, we reported the design and synthesis of a series
of pyridyl-based BoQPhos ligands and their utility in the
asymmetric hydrogenation of unfunctionalized alkenes.[7] As
part of the study, we demonstrated that asymmetric hydro-
genation of a phenyl-substituted dialin could be achieved with
a moderate, yet promising 88:12 e.r. (Scheme 1). In the search
for a more stereoselective ligand system, we envisioned the
incorporation of a chiral oxazoline motif into the design of
our next generation P,N ligands for the hydrogenation of
unfunctionalized 1-aryl-3,4-dihydronaphthalenes.
Scheme 1. Enantioselective synthesis of 1-aryl tetralins. cod=1,5-cyclo-
octadiene.
Synthesis of the phosphine oxazoline LalithPhos ligands
5a–f started with the chiral intermediate 1 (Scheme 2).[8]
Deprotonation followed by CO2(g) afforded the carboxylic
acid after a MeOH quench. After generating the diastereo-
merically pure acid 2, the amide-coupling products were
obtained with various amino alcohols. Both enantiomers of
the cis-1-amino-2-indanols[9] were integrated into the ligand
design, as the conformationally constrained indanyl platform
has been shown as a particularly valuable building block in
a variety of catalytic processes, thus leading to high levels of
asymmetric induction.[10] We anticipated that this bulky and
constrained structure could create an effective chirally
discriminative environment for the asymmetric hydrogena-
tions. The amides 3b–f were synthesized with 65–88% yields
in the presence of EDC/HOBt. The amide 3a was obtained
with the aid of propylphosphonic anhydride (T3P)[11] in 72%
yield. The subsequent cyclization to the oxazolines 4b–d was
achieved under TsCl/Et3N conditions. However, for 3a and
the indanol amides 3e and 3 f, the Lewis acid BF3·Et2O was
required for cyclization.[12] All the amides were isolated in
modest to good yields.
approaches would involve the asymmetric hydrogenation of
the corresponding dialin precursors. However, the enantio-
selective hydrogenation of unfunctionalized alkenes has
proven to be highly challenging, as there are no coordination
groups to complex with the metal center to provide a secon-
dary interaction to position the substrate for enantiofacial
discrimination.[3] In particular, cyclic unfunctionalized dihy-
[*] Dr. B. Qu, Dr. L. P. Samankumara, Dr. S. Ma, Dr. K. R. Fandrick,
Dr. J.-N. Desrosiers, Dr. S. Rodriguez, Dr. Z. Li, Dr. N. Haddad,
Dr. Z. S. Han, K. McKellop, S. Pennino, Dr. N. Grinberg,
Dr. N. C. Gonnella, Dr. J. J. Song, Dr. C. H. Senanayake
Chemical Development
Boehringer Ingelheim Pharmaceuticals, Inc.
900 Ridgebury Road, Ridgefield, CT 06877-0368 (USA)
E-mail: bo.qu@boehringer-ingelheim.com
[**] We thank Dr. Bruce C. Noll of Bruker AXS Inc. for valuable
assistance with the crystallography.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201408929.
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Table 1: Hydrogenation of 1-phenyl-3,4-dihydronaphthalene.[a]
L
Conv. [%][b]
e.r.[b]
5a
5b
5c
5d
5e
5 f
100
100
100
100
80
49:51
96:4[c]
99:1 (R)[d]
95:5
89:11
58:42
4
[a] Reactions performed at 238C for 20 h using 2 mol% of the catalyst in
CH2Cl2 unless specified otherwise. [b] Conversions and e.r. values were
determined by GC using Chiraldex B-PH 30 m, isothermal 1508C.
[c] Isolated in 90% yield. [d] Performed at 108C. The major enantiomer is
R configured.
phenyl moiety afforded the product with an increased
e.r. value of 99:1 at 108C with the opposite chirality. The
ligand 5c is more selective than the phosphine imidazoline
ligands reported lately.[18] The catalyst with the aminoindanyl-
substituted ligand 5e produced an 80% conversion in 89:11
e.r. Surprisingly, the diastereomeric ligand 5 f was ineffective
and low conversion was resulted.
Scheme 2. Synthesis of LalithPhos ligands 5a–f.[19] DMF=N,N-di-
methylformamide, EDC=1-ethyl-3-(3-dimethyl-aminopropyl)carbodi-
imide, LDA=lithium diisopropylamide.
The single-crystal X-ray structure of the catalyst 6d[19]
provided insight into the enantiomeric induction in the
hydrogenation processes. The DFT calculations on the
transition states supported the stereochemical model.[20] The
trisubstituted alkene was found to have one viable binding
mode to the dihydride iridium complex where the dihydro-
naphthalene portion of the olefin is positioned in the open
quadrant of the iridium complex[21] (Figure 1). This arrange-
ment would in turn position the less sterically demanding side
of the alkene with the phenyl substituent in close proximity to
the oxazoline substituent of the ligand. In this capacity, the
complex 6c would expose the Si face of the alkene for the
metathesis hydrogen transfer, thus generating the R configu-
ration of the s-alkyl/iridium intermediate. Furthermore, the
The reduction of the phosphine oxides 4a–f provided the
desired LalithPhos in 70–85% yields (Scheme 2).[15] Another
set of diastereomeric ligands with the phenyl substituent, 5b
and 5c, was also prepared to investigate the influence of the
relative configuration of the substituent chirality on the
oxazoline. No racemization or epimerization of the chiral
centers on the phosphorus or the amino alcohols was
observed during the phosphine oxide reduction. The corre-
sponding cationic iridium tetrakis[3,5-bis(trifluoromethyl)-
phenyl]borate (BArF) complexes were prepared by complex-
ation with [{Ir(cod)Cl}2] and followed by anion exchange with
NaBArF.[16] Both the ligands and the catalysts are stable in air.
No detectable oxidations were observed by 31P NMR analysis
when the sample was left open air at ambient temperature for
more than four weeks.
To test the effectiveness of these new ligands towards
asymmetric hydrogenation of 1-aryl-dialins, the iridium com-
plexes 6a–f (Scheme 2) were used as catalysts for the
reduction of 1-phenyl-3,4-dihydronaphthalene to produce
enantiomerically enriched 1-phenyltetralin (Table 1). Com-
plete conversion resulted for the catalysts 6a–d under 1 atm
of H2 pressure. The complexes with different ligands provided
dramatically different enantioselectivities. The unsubstituted
oxazoline 5a was not selective at all. The R-phenyl-substi-
tuted ligand 5b and the R-tert-butyl ligand 5d produced the
enantiomeric ratios of 96:4 and 95:5, respectively. The
absolute configuration of the major enantiomer was desig-
nated as S, as determined by the vibrational circular dichroism
(VCD) analysis.[17] The diastereomeric ligand 5c with the S-
Figure 1. DFT-calculated transition states and stereochemical models.
2
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iridium complex 6b would expose the Re face of the alkene
for the metathesis hydrogen transfer, thus generating the
S configuration of the bound intermediate. A fast reductive
elimination process would then generate the reduced prod-
ucts with switched enantioselectivity.
1-Aryl-3,4-dihydronaphthalenes with various substituents
were then prepared and tested in the hydrogenation reactions
(Table 2). The enantioselectivity increased with an ortho-tolyl
unique reactivity of the aminoindanyl ligand 5e is presumably
due to the special ligand structure of the conformationally
constrained indane platform. 3,4-Dihydro-1,1’-binaphtha-
lenes are generally challenging to prepare because of the
dehydrogenative side reaction to produce binaphtha-
lenes.[22,23] Dihydronaphthalene (7 f; entry 6) was prepared
in 70% yield by Suzuki coupling between 1-naphthyl boronic
acid and the corresponding triflate using the BI-DIME ligand.
Asymmetric hydrogenation of 7 f provided the chiral 1,2,3,4-
tetrahydro-1,1ꢀ-binaphthalene 8 f in 99:1 e.r. No dehydrogen-
ated impurity was observed during the reduction. A similar
e.r. value of 97:3 was obtained with a halogen group at the 6-
position of the dihydronaphthalene 7g (entry 7). A slightly
lower selectivity of 91:9 e.r. was observed with the 6-methoxy
substituted 7h (entry 8). The catalyst is also able to reduce 4-
phenylchromene 7i; the adduct 8i was afforded in 93:7 e.r. in
the presence of the ligand 5c (entry 9).
Table 2: Hydrogenation of 1-aryl-3,4-dihydronaphthalenes.[a]
Entry
1
Alkene
L
e.r.[b]
Ar=2-MeC6H4
7a
5b
5c
5d
5e
5d
5c
5b
5e
5d
97:3
97:3 (R)
These new catalysts were also used in the preparation of 4-
substituted 1-aryl tetralins (Table 3). The dialins 9a,b were
prepared in 55–60% yield from (S)-4-(3,4-dichlorophenyl)-1-
tetralone, a precursor for the synthesis of Sertraline.[1a] With
99:1c
97:3
2
3
4
5
6
Ar=2-OMeC6H4
Ar=4-OMeC6H4
Ar=4-ClC6H4
Ar=2-CO2MeC6H4
Ar=1-naphthyl
7b
7c
7d
7e
7 f
90:10
98:2 (R)
95:5
98:2[d]
Table 3: Hydrogenation of 4-substituted 1-aryl dialins.[a]
>99:1
7
8
9
7g
7h
7i
5b
5c
5c
97:3
91:9 (R)[c]
93:7 (R)
Entry
Ar
L
Conv. [%][b]
d.r.[b]
1
2
3
Ph (9a)
Ph (9a)
o-Tol (9b)
5b
5c
5c
100
100
100
18:82
>99.5:0.5
>99.5:0.5
[a] Reactions performed at 108C for 20 h using 2 mol% of the catalyst in
CH2Cl2. [b] Conversions and e.r. were determined by GC or HPLC using
a chiral stationary phase. Complete conversions unless specified
otherwise. The absolute configuration for the major enantiomer was
obtained from VCD analysis. [c] 238C. [d] 88% conversion under 55 atm
H2.
[a] See the Supporting Information for the synthesis of alkene 9.
Hydrogenations performed at 108C for 20 h using 2 mol% of the catalyst
in CH2Cl2. [b] Conversions and d.r. were determined by HPLC using
a chiral stationary phase or by 1H NMR analysis. The cis- and trans-
diastereomers were determined by 2D-NMR analysis. Ts=4-toluene-
sulfonyl.
group (7a), presumably because of the added steric hin-
drance. The catalyst with the tert-butyl ligand 5d furnished the
adduct 8a in 99:1 e.r. (entry 1). Catalysts with the ligands 5b,
5c, and indanyl 5e reduced the alkene 7a with the same
enantiomeric ratio of 97:3. Again a reversed enantioselectiv-
ity was observed when using the ligand 5c. The substrate 7b
where o-methyl was replaced by an o-methoxy group,
a slightly compromised e.r. of 90:10 was afforded (entry 2).
When the methoxy group is at the para position of the phenyl
group (7c), the selectivity was restored and the adduct 8c was
produced in 98:2 e.r. (entry 3). In comparison, the para-chloro
adduct 8d was produced in 95:5 e.r. (entry 4). Low conversion
resulted for the alkene 7e with an ortho-methyl ester. The cis-
aminoindanol-derived ligand 5e was the most effective, thus
producing the adduct 8e in 98:2 e.r. However, a high pressure
was required to observe an 88% conversion (entry 5). The
reduced reactivity of the ortho-substituted substrates might
be due to the potential steric interaction with the catalyst. The
both phenyl and o-tolyl substituents at the 1-position, hydro-
genation of 9a and 9b with the ligand 5c afforded a greater
than 99.5:0.5 d.r. favoring the cis-tetrahydronaphthalene 10
(entries 2 and 3). The catalyst with the trans-phenyl ligand 5b,
in contrast, produced the trans-diastereomer 11a as the major
one in 82:18 d.r.
Encouraged by these results, we further investigated the
hydrogenation reaction of related exocyclic ketimines derived
from 1-tetralones. A survey of the literature revealed that
asymmetric hydrogenation of these exocyclic imines using
iridium catalysts generally afforded low enantioselectivities
because the conformational strain, upon coordination to
iridium, in the transition state caused by the cyclic struc-
tures.[24] An encouraging result of iridium-catalyzed enantio-
selective hydrogenation of ketimines was reported by Ding
and co-workers and up to 98% ee was achieved with
a spirophosphine oxazoline ligand.[25]
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To our delight, the LalithPhos/iridium system showed
excellent enantioselectivity towards the exocyclic imine
reduction (Table 4). The imine 12a was successfully reduced
by the Ir/5b catalyst and the chiral amine adduct 13a was
[1] a) F. Zhang, S. Das, A. J. Walkinshaw, A. Casitas, M. Taylor,
M. G. Suero, M. J. Gaunt, J. Am. Chem. Soc. 2014, 136, 8851 –
8854; b) A. Volonterio, M. Zanda, Tetrahedron Lett. 2005, 46,
8723 – 8726.
[2] a) F. Bohlmann, C. Zdero, H. Robinson, R. M. King, Phyto-
chemistry 1979, 18, 1675 – 1680; b) W. M. Welch, A. R. Kraska,
R. Sarges, B. K. Koe, J. Med. Chem. 1984, 27, 1508 – 1515; c) Z.
Xiao, K. F. Bastow, J. R. Vance, R. S. Sidwell, H.-K. Wang, M. S.
Chen, Q. Shi, K.-H. Lee, J. Med. Chem. 2004, 47, 5140 – 5148;
d) E. Rasolofonjatovo, O. Provot, A. Hamze, J. Rodrigo, J.
Bignon, J. Wdzieczak-Bakala, D. Desravines, J. Dubois, J.-D.
Brion, M. Alami, Eur. J. Med. Chem. 2012, 52, 22 – 32.
[3] a) S. Bell, B. Wꢁstenberg, S. Kaiser, F. Menges, T. Netscher, A.
Pfaltz, Science 2006, 311, 642 – 644; b) J. J. Verendel, O. Pꢂmies,
M. Diꢃguez, P. G. Andersson, Chem. Rev. 2014, 114, 2130 – 2169;
c) X. Cui, K. Burgess, Chem. Rev. 2005, 105, 3272 – 3296.
[4] D. H. Woodmansee, M.-A. Mꢁller, M. Neuburger, A. Pfaltz,
Chem. Sci. 2010, 1, 72 – 78.
[5] R. D. Broene, S. L. Buchwald, J. Am. Chem. Soc. 1993, 115,
12569 – 12570.
[6] a) M. G. Schrems, A. Pfaltz, Chem. Commun. 2009, 6210 – 6212;
b) A. Franzke, F. Voss, A. Pfaltz, Tetrahedron 2011, 67, 4358 –
4363.
[7] B. Qu, L. P. Samankumara, J. Savoie, D. R. Fandrick, N. Haddad,
X. Wei, S. Ma, H. Lee, S. Rodriguez, C. A. Busacca, et al., J. Org.
Chem. 2014, 79, 993 – 1000.
Table 4: Hydrogenation of exocyclic N-aryl-dihydronaphthalene ketimi-
nes.[a]
Entry
Imine
Ar
R
L
e.r.[b]
1
2
3
4
5
12a
12b
12b
12c
12c
Ph
H
H
H
5b
5b
5c
5b
5c
97:3 (13a)
>99:1 (13b)
98:2 (14b)
>99:1 (d.r.) (13c)
98:2 (d.r.) (14c)
o-Tol
o-Tol
o-Tol
o-Tol
(S)-3,4-Cl2C6H3
(S)-3,4-Cl2C6H3
[a] Reactions performed at 238C for 15 h using 2 mol% of the catalyst in
CH2Cl2 with complete conversions. [b] Conversions and e.r. (or d.r.) were
determined by HPLC using a chiral stationary phase. The cis- and trans-
diastereomers were determined by 2D-NMR analysis.
[8] a) W. Tang, B. Qu, A. G. Capacci, S. Rodriguez, X. Wei, N.
Haddad, B. Narayanan, S. Ma, N. Grinberg, N. K. Yee, et al.,
Org. Lett. 2010, 12, 176 – 179; b) Z. S. Han, N. Goyal, M. A.
Herbage, J. D. Sieber, B. Qu, Y. Xu, Z. Li, J. T. Reeves, J.-N.
Desrosiers, S. Ma, et al., J. Am. Chem. Soc. 2013, 135, 2474 –
2477.
[9] I. Gallou, C. H. Senanayake, Chem. Rev. 2006, 106, 2843 – 2874.
[10] a) A. K. Ghosh, P. Mathivanan, J. Cappiello, Tetrahedron:
Asymmetry 1998, 9, 1 – 45; b) F. Fache, E. Schulz, M. L.
Tommasino, M. Lemaire, Chem. Rev. 2000, 100, 2159 – 2231.
[11] J. R. Dunetz, Y. Xiang, A. Baldwin, J. Ringling, Org. Lett. 2011,
13, 5048 – 5051.
[12] I. W. Davies, L. Gerena, N. Lu, R. D. Larsen, P. J. Reider, J. Org.
Chem. 1996, 61, 9629 – 9630.
[13] Low yield of 3a is due to the instability of the compound on silica
gel.
[14] The BF3·Et2O conditions are equally effective for the cyclization
of amides 3b–d.
[15] K. Naumann, G. Zon, K. Mislow, J. Am. Chem. Soc. 1969, 91,
2788 – 2789.
formed in 97:3 e.r.[26] The enantiomeric ratio was increased to
greater than 99:1 for imine 12b which had an o-tolyl
substituent on the imine nitrogen atom. Similarly, the
enantiomeric amine product 14b was afforded using the
iridium catalyst derived from the ligand 5c. For the (S)-4-(3,4-
dichlorophenyl)-substituted ketimine 12c, which has chirality
in the backbone, the asymmetric hydrogenation with the
ligand 5b produced the cis-amine 13c in greater than 99:1
d.r., and the trans-amine 14c in 98:2 d.r. with the ligand 5c. It
is noted that the chiral substituent has little effect on the
selectivity, thus indicating a ligand-controlled environment
during the asymmetric hydrogenations.
In summary, a series of modular P-chiral dihydrobenzo-
oxaphosphole oxazoline derived Lalithphos ligands were
designed and synthesized. By judicious choice of the ligand
substituents, both enantiomers of 1-aryltetralins could be
produced enantioselectively using the hydrogenation reac-
tions. It is worth noting that the new ligand system has
exhibited significantly enhanced reactivity compared to that
of known systems which allowed the asymmetric hydro-
genation of the challenging unfunctionalized alkenes and
exocyclic ketimines under mild reaction conditions. It was
shown that the chirality on the oxazoline is crucial for the high
enantioselectivity. Further application of these ligands is
under investigation.
[16] A. Lightfoot, P. Schnider, A. Pfaltz, Angew. Chem. Int. Ed. 1998,
37, 2897 – 2899; Angew. Chem. 1998, 110, 3047 – 3050.
[17] T. B. Freedman, X. Cao, R. K. Dukor, L. A. Nafie, Chirality
2003, 15, 743 – 758.
ˇ
[18] C. A. Busacca, B. Qu, N. Gret, K. R. Fandrick, A. K. Saha, M.
Marsini, D. Reeves, N. Haddad, M. Eriksson, J.-P. Wu, et al.,
Adv. Synth. Catal. 2013, 355, 1455 – 1463.
[19] CCDC 1023264 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.
Received: September 9, 2014
Published online: && &&, &&&&
[20] Gaussian 09 (Revision C.01), M. J. Frisch, G. W. Trucks, H. B.
Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, G.
Scalmani, V. Barone, B. Mennucci, G. A. Petersson, et al.,
Gaussian, Inc., Wallingford CT, 2010.
[21] An iridium(III) to iridium(V) model proposed by Burgess and
Hall involving a metathesis-type reaction between the alkene
and a bonded H2 molecule on the iridium center was used for the
basis of this study: a) Y. Fan, X. Cui, K. Burgess, M. B. Hall, J.
Am. Chem. Soc. 2004, 126, 16688 – 16689; b) T. L. Church, R.
Keywords: asymmetric catalysis · imines · iridium · P,N ligands ·
reduction
.
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Rasmussen, P. G. Andersson, Organometallics 2010, 29, 6769 –
6781.
[22] a) C. D. Nenitzescu, M. Avram, J. Am. Chem. Soc. 1950, 72,
3486 – 3490; b) L. E. Miller, D. J. Mann, J. Am. Chem. Soc. 1951,
73, 45 – 48; c) M. Crawford, V. R. Supanekar, J. Chem. Soc. C
1968, 2328 – 2332.
[23] Only one literature report on the synthesis of 7 f is reported, but
without characterization data: C. D. Zotto, J. Wehbe, D. Virieux,
J.-M. Campagne, Synlett 2008, 2033 – 2035.
[24] a) A. Trifonova, J. S. Diesen, P. G. Andersson, Chem. Eur. J.
2006, 12, 2318 – 2328; b) W.-J. Lu, Y.-W. Chen, X.-L. Hou, Adv.
Synth. Catal. 2010, 352, 103 – 107.
[25] Z. Han, Z. Wang, X. Zhang, K. Ding, Angew. Chem. Int. Ed.
2009, 48, 5345 – 5349; Angew. Chem. 2009, 121, 5449 – 5453.
[26] The major enantiomer is S configured as determined from VCD
studies. See the Supporting Information.
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Communications
P,N Ligands
B. Qu,* L. P. Samankumara, S. Ma,
K. R. Fandrick, J.-N. Desrosiers,
S. Rodriguez, Z. Li, N. Haddad, Z. S. Han,
K. McKellop, S. Pennino, N. Grinberg,
N. C. Gonnella, J. J. Song,
Air-stable P-chiral dihydrobenzooxa-
phosphole oxazoline ligands were
was obtained. High enantioselectivities
were also observed in the reduction of the
exocyclic imine derivatives of 1-tetra-
lones.
C. H. Senanayake
&&&& — &&&&
designed and synthesized. When they
were used in the iridium-catalyzed asym-
metric hydrogenation of unfunctionalized
1-aryl-3,4-dihydronaphthalenes under one
atmosphere pressure of H2, up to 99:1 e.r.
A Mild Dihydrobenzooxaphosphole
Oxazoline/Iridium Catalytic System for
Asymmetric Hydrogenation of
Unfunctionalized Dialins
6
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