Bicyclic bridgehead phosphoramidite (briphos) ligands with tunable π-acceptor ability and catalytic activity in the rhodium-catalyzed conjugate additions

Article abstract of DOI:10.1021/ol502772m

A new type of bicyclic bridgehead phosphoramidites (briphos) is reported, where the geometrical constraints significantly enhance the π-acceptor ability compared with its monocyclic analogs. The briphos is shown to be highly efficient and tunable for Rh(I

Full text of DOI:10.1021/ol502772m

Letter
pubs.acs.org/OrgLett
Bicyclic Bridgehead Phosphoramidite (Briphos) Ligands with Tunable
π‑Acceptor Ability and Catalytic Activity in the Rhodium-Catalyzed
Conjugate Additions
Ansoo Lee,†,‡ Seihwan Ahn,† Kyungjun Kang,†,‡ Min-Seob Seo,†,‡ Yeonjoon Kim,† Woo Youn Kim,*,†
and Hyunwoo Kim*,†,‡
†Department of Chemistry, KAIST, Daejeon 305-701, Korea
‡Center for Nanomaterials and Chemical Reactions, Institute for Basic Science (IBS), Daejeon 305-701, Korea
S
* Supporting Information
ABSTRACT: A new type of bicyclic bridgehead phosphoramidites (briphos)
is reported, where the geometrical constraints significantly enhance the π-
acceptor ability compared with its monocyclic analogs. The briphos is shown to
be highly efficient and tunable for Rh(I)-catalyzed conjugate additions of aryl
boronic acids to α,β-unsaturated ketones and N-tosyl ketimines.
Although beneficial effects of geometrical constraints have been
continuing goal in the field of transition-metal catalysis is to
Adevelop highly active and selective catalysts for the widely used in transition metal catalysis especially with
commercially available PTA,7 ETPB,8 and proazaphospha-
tranes,9 further modifications such as chiral ligand design10 or
steric and electronic tuning are difficult for the given bicyclic or
cage-shaped P ligands.
We here report a new class of bicyclic bridgehead
phosphoramidite (briphos) ligands (1) based on the
bicyclo[3.3.1]nonane structure (Figure 1b). The geometrical
constraints in briphos with respect to its monocyclic analogs
enhance π-acceptor ability. Furthermore, facile tuning of briphos
leads to (a) highly efficient ligands with dramatic ligand
acceleration effect (LAE), (b) new catalytic reactivity, and (c)
asymmetric induction in Rh(I)-catalyzed conjugate additions of
aryl boronic acids.
pharmaceutical and fine chemical industries.1 One major
research direction is to improve the catalytic performance of
given transition metals by controlling various ligand effects.2 The
phosphorus (P) ligand is a logical first choice to study such ligand
effects due to its wide availability and diversity.3 The reported
methods in this regard include chelate control as well as steric
and electronic control, which were systematically demonstrated
in terms of the bite angle4 and the Tolman cone angle and
electronic parameter.5 Indeed, the concept of tuning the P
ligands has successfully led to the development of highly efficient
transition metal catalysts.1−3
In addition, the geometrical constraints have been used to
modulate the ligand effect. In bicyclic or cage-shaped P ligands,
compared with their acyclic analogs, interesting features such as
increased π−acceptor and decreased σ−donor ability as well as
reduced steric demand have been reported (Figure 1a).6−9
A series of briphos (1) compounds were efficiently prepared
by a three-step procedure, as shown in Scheme 1. Commercially
Scheme 1. Preparation of Briphos (1)
Figure 1. (a) Representative bicyclic or caged phosphorus ligands (b)
design of briphos (1).
Received: September 19, 2014
© XXXX American Chemical Society
A
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Organic Letters
Letter
available 2,2′-dihydroxybenzophenone (2) was reacted with
primary amines to form the corresponding imines (3). We have
demonstrated that the internal hydrogen bonding in 2
significantly accelerates the imine formation, and the imine
products have been used for stereoselective generation of axial
compounds11 and chiral-at-metal complexes.12 The imine
formation smoothly proceeded with a primary alkyl amine,
cyclohexyl amine at ambient temperature, but required elevated
temperature with aniline. For electron-deficient anilines, we
applied microwave radiation in order to improve the product
yields. The resulting imines were conveniently reduced by
NaBH4 to form secondary amines (4), and a series of briphos
compounds (1) were prepared by reaction with 4 and
hexamethylphosphorous triamide (HMPT) in good to moderate
overall yields (33−71%). Briphos 1b was also prepared in
multigram scale (45.8 g) in 31% yield using a modified procedure
(Supporting Information (SI)). In addition to the mild and
scalable reaction conditions, the synthetic procedure for briphos
(1) allows facile tuning of the ligand structures by variation of the
primary amines.
we note that the increase of π-acceptor ability by the geometric
constraints (ΔvCO = 10 cm−1) is compatible with that of strong
electron-withdrawing substituents, CF3 (ΔvCO = 11 cm−1),
which suggests that geometric control of ligands can be an
efficient route to modulate ligand properties apart from the
conventional electronic tuning. Decreased basicity of bicyclic
phosphites compared to their monocyclic or acyclic analogs has
been reported.6b,d,8a,c This work represents the first example of
bicyclic phosphoramidite ligands as a platform of geometry-
induced tunable π-acceptor ligands.
Tolman’s electronic parameter, determined by measuring the
CO A1 vibrational frequency of Ni(CO)3L [vCO (A1)], has been
used as an indicator of the donor/acceptor ability of a ligand.5
Perrin et al. showed a linear correlation between computational
vCO (A1) of P ligands in the gas phase and corresponding
experimental values.15a Recently Gusev generalized such a linear
relationship for a series of two-electron ligands.15b In this regard,
we computed vCO (A1) of briphos to investigate their relative
donor/acceptor properties with respect to other known ligands.
In order for direct comparison, we used GAUSSIAN09 at the
same level of DFT with that in ref 15b: the MPW1PW91
functional and 6-311+G(2d) for Ni and 6-311+G(d,p) for all
others.16
In order to examine the ligand property of briphos, we
measured the electronic properties of a series of briphos ligands
(1), as well as their monocyclic analogs 6 and monophos (7),
with results as summarized in Table 1. The σ-donor ability has
Figure 2 shows the computational results. Relative vCO (A1)
values between 1a, 1b, 1f, 5, 6, and 7 for Ni(CO)3L are consistent
Table 1. Ligand Properties
a
b
c
entry
L
R in briphos (1)
δ [ppm]
1J [Hz]
vCO [cm−1
]
Figure 2. Calculated vCO (A1) data for Ni(CO)3L.
1
2
3
4
5
6
7
8
9
5
−
−
−
Cy
128.6
149.8
149.4
98.0
1025
968
2016
2006
2010
2016
2018
2011
2013
2019
2029
6
with those for [RhCl(L)2(CO)] in Table 1, indicating that the
enhanced π-acceptor ability of briphos can be generalized to
other metal complexes. Both monophos (7) and 6 are weaker π-
acceptors than PH3, whereas the three briphos ligands (1a, 1b,
and 1f) as well as 5 turn out to be stronger π-acceptors than PH3.
We stress that briphos, by varying its N-substituent, spans a wide
range of the Tolman electron parameters, which promises its
diverse applicability as a tunable π-acceptor ligand.
7
972
1a
1b
1c
1d
1e
1f
1015
1039
1037
1040
1048
1051
Ph
90.5
3,5-Me2C6H3
3,5-(MeO)2C6H3
3,5-F2C6H3
90.5
90.1
88.7
3,5-(CF3)2C6H3
88.3
c
a
b
31P NMR spectra in CDCl3. 31P−77Se. [RhCl(L)2(CO)].
In order to verify the geometrical features of the briphos, we
compared the crystal structures of briphos (1c) with monophos
(7)17 (Figure 3a and 3b). The sum of three P-centered angles for
briphos is 300.0°, while that for monophos is 303.2°. Despite the
similar total angles, the individual angles for briphos (1c) are
symmetric (100.8°, 99.4°, and 99.8°), whereas those for
monophos (7) are asymmetric (96.0°, 109.5°, and 97.7°).
Moreover, the geometry of briphos is conserved in [Rh(1a)2Cl]2,
where the average total angle is 301.6° and the average individual
angles are 101.0°, 101.5°, and 99.1° (Figure 3c). On the basis of
the variable hybridization calculations of the P atom using the
crystal structures 1c and 7, the geometrical constraints in briphos
result in an increase of the s-character of the P lone pair (SI).
Thus, briphos can be a weaker σ-donor and stronger π-acceptor
than its monocyclic analogs in agreement with experiments and
DFT computations.18
been scaled by the coupling constant of 31P−77Se bonds,13 and
the π-acceptor ability has been determined by CO stretch
frequencies of metal complexes.5 Indeed, Cy-briphos (1a) was
characterized to be a weaker σ-donor and stronger π-acceptor
than the monocyclic phosphoramidites 6 and 7 (entries 2−4).
The increased π-acceptor ability of 1a is quite comparable with
that of P(OPh)3 (5) (entry 1). Since Cy-briphos (1a) and 6 have
similar functional groups attached to the P atom, it is quite
remarkable that the electronic properties of phosphoramidite
ligands can be modulated solely using geometrical constraints
(Δ1J (31P−77Se) = 47 Hz, ΔvCO = 10 cm−1).
Moreover, electronic tuning of briphos ligands was performed
using substituted anilines at the meta-position. An electron-
withdrawing group, CF3, greatly enhanced the π-acceptor ability
and lowered the σ-donor ability (Δ1J (31P−77Se) = 12 Hz, ΔvCO
= 11 cm−1), consistent with previous studies14 (entries 5 and 9
for 1b and 1f). For other aryl substituted briphos ligands (1c−e),
subtle changes in electronic properties were observed depending
on the electronic nature of the substituents (entries 6−8). Here
Since π-acceptor ligands are known to facilitate low-valent
metal catalysis, we selected the Rh(I)-catalyzed conjugate
addition of phenyl boronic acid to cyclohexenone as a
benchmark reaction.19 When the reaction was monitored for 1
h at 50 °C, the briphos ligands (1a and 1b) showed a significant
B
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Organic Letters
Letter
Table 2. Rh-Catalyzed Conjugate Addition of Aryl Boronic
a
Acids to α,β-Unsaturated N-Tosyl Ketimines
b
entry
L
8
R1
R2
Ar
yield (%)
1
5
8a
8a
8a
8a
8a
8a
8b
8c
8d
8e
8f
H
H
H
H
H
H
H
H
H
H
H
H
H
H
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
3-MeOC6H4
4-MeC6H4
3-MeC6H4
Ph
0
0
2
7
H
3
1a
1b
1c
1e
1c
1c
1c
1c
1c
1c
1c
1c
1c
1c
1c
H
<5
65
88
21
81
>99
80
4
H
5
H
6
H
7
H
8
H
9
H
c
10
11
12
13
14
15
16
17
H
85
c
H
2-naphthyl
4-ClC6H4
Ph
89
cd
,
8g
8h
8i
H
59
75
88
99
87
65
Figure 3. Crystal structures of (a) briphos (1c), (b) monophos (7), and
(c) [Rh(1b)2Cl]2.
4-F
H
4-F
Ph
8j
4-F
4-Me
H
4-F
Ph
ligand acceleration effect (LAE), while the monocyclic
phosphoramidites (6 and 7) as well as mono- or bidentate
phosphines were inefficient or even inactive (SI).20 In our P
ligand screening, only P(OPh)3 (6) was found to be as effective
as briphos in reasonable agreement with the measured electronic
properties. Remarkably, the tuning of briphos structure showed a
highly efficient ligand as 1e when only 0.1 mol % of
Rh(acac)(C2H4)2 and 0.25 mol % of ligand were used at
ambient temperature (Figure 4).
8k
8l
4-F
Ph
3-NO2
Ph
a
Conditions: Imine (0.2 mmol), ArB(OH)2 (3.0 equiv), [Rh] (3.0
b
mol %), and 1c (7.5 mol %) in 2.0 mL of toluene. Isolated yields.
c
d
The reaction was performed at 50 °C. The reaction was performed
for 10 h.
The utility of briphos is finally verified by asymmetric Rh-
catalyzed conjugate addition of an α,β-unsaturated N-tosyl
ketimine (Scheme 2). A chiral briphos (R)-1g, prepared from
Scheme 2. Asymmetric Conjugate Addition by Chiral Briphos
(1g)
Figure 4. Tuning of briphos ligands for the Rh(I)-catalyzed conjugate
addition of phenylboronic acid under neutral conditions.
The applications of briphos, a tunable π-acceptor ligand, can
be extended to explore new catalytic reactivity. N-Tosyl
ketimines were used to make α-tertiary amines by Rh(I)-
catalyzed 1,2-addition of arylboronic acids,21 arylboroxines,22
potassium organotrifluoroborates,23 or other boron reagents.24
However, 1,2- or 1,4-addition of boronic acids to α,β-unsaturated
N-tosyl ketimines has not been reported despite the structural
similarity of substrates. Only reactive organoaluminum reagents
were used to react with cyclic N-tosyl ketimines in Rh(I)
catalysis.25 Indeed, in our ligand screening, most monodentate or
bidentate phosphorus ligands including phosphoramidite (6)
and phosphite (5) were not active while briphos ligands
selectively promoted 1,4-addition of 4-methoxyphenyl boronic
acid to a N-tosyl ketimine of 1,3-diphenyl-2-propen-1-one
(Table 2, entries 1−6). Further tuning of briphos ligands showed
that 1c is the most active ligand, and thus 1,4-addition of aryl
boronic acids to α,β-unsaturated N-tosyl ketimines was
successfully demonstrated as shown in Table 2.
(R)-1-aminoindane, provided the product with up to 90% yield
and 94% ee. It is remarkable that only one chiral carbon center in
the monodentate P ligand showed such a high level of
stereoinduction. Thus, the briphos can be a new type of chiral
template.
In summary, we prepared a new class of bicyclic bridgehead
phosphoramidite (briphos) ligands under mild, scalable, and
tunable reaction conditions. Owing to geometrical constraints,
the briphos ligands showed enhanced π-acceptor ligand
properties compared with its monocyclic analogs supported by
X-ray crystallography and DFT computations. We demonstrated
that the electronic tuning of briphos ligands provided the
significant ligand acceleration effect (LAE) and new catalytic
reactivity for Rh(I)-catalyzed conjugate additions and the
briphos can be a template for chiral ligand design. The concept
of controlling the ligand property by geometrical constraints will
be applicable to the development of new ligands or catalysts as
exemplified by briphos.
C
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Organic Letters
Letter
(d) Mathey, F. Acc. Chem. Res. 2004, 37, 954. (e) Gilbertson, S. R.;
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ASSOCIATED CONTENT
* Supporting Information
Experimental procedures and spectroscopic, calculation, and
crystallographic details. This material is available free of charge
via the Internet at http://pubs.acs.org.
■
S
(11) Kim, H.; So, S. M.; Yen, C. P.-H.; Vinhato, E.; Lough, A. J.; Hong,
J.-I.; Kim, H.-J.; Chin, J. Angew. Chem., Int. Ed. 2008, 47, 8657.
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AUTHOR INFORMATION
Corresponding Authors
■
*E-mail: wooyoun@kaist.ac.kr.
*E-mail: hwkim@kaist.edu.
Notes
(15) (a) Perrin, L.; Clot, E.; Eisenstein, O.; Loch, J.; Crabtree, R. H.
Inorg. Chem. 2001, 40, 5806. (b) Gusev, D. G. Organometallics 2009, 28,
763.
The authors declare no competing financial interest.
(16) Frisch, M. J. et al. Gaussian 09, Revision A.02.; Gaussian, Inc.:
Wallingford, CT, 2009. See Supporting Information for full reference.
(17) Crystal data of 7 (CCDC 174779) obtained from the Cambridge
Crystallographic Data Centre.
(18) (a) Bent, H. A. Chem. Rev. 1961, 61, 275. (b) Berhal, F.; Olivier,
E.; Martin, C.-H.; Tone, H.; Genet, J.-P.; Ayad, T.; Ratovelomanana-
Vidal, V. Org. Lett. 2011, 13, 2806. (c) Le Boucher d’Herouville, F.;
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(d) Korenaga, T.; Osaki, K.; Maenishi, R.; Sakai, T. Org. Lett. 2009, 11,
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(19) (a) Edwards, H. J.; Hargrave, J. D.; Penrose, S. D.; Frost, C. G.
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(20) P ligands showed no significant additive effect of base (KOH),
while both [Rh(OH)(COD)]2 and [Rh(COD)Cl]2 with the base were
found to be active (Table S1, Supporting Information).
(21) (a) Wang, H.; Li, Y.; Xu, M.-H. Org. Lett. 2014, 16, 3962.
(b) Wang, H.; Jiang, T.; Xu, M.-H. J. Am. Chem. Soc. 2013, 135, 971.
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ACKNOWLEDGMENTS
■
We are grateful to the National Research Foundation of Korea
(NRF 2011-0014197 and 2012R1A1A1004154) and the
Institute for Basic Science (IBS-R004-D1) for supporting this
work. We thank Dr. Alan J. Lough (University of Toronto) for X-
ray analysis.
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