Rh-catalyzed enantioselective conjugate addition of arylboronic acids with a dynamic library of chiral tropos phosphorus ligands

Article abstract of DOI:10.1002/chem.200600960

A library of 19 chiral tropos phosphorus ligands, based on a free-to-rotate (tropos) biphenol unit and a chiral P-bonded alcohol (11 phosphites, 1-P(O)₂O to 11-P(O)₂O) or secondary amine (8 phosphoramidites, 12-P(O)₂N to 19-P(O)₂N). were screened, individually and in combinations of two, in the rhodium-catalyzed asymmetric conjugate addition of arylboronic acids to enones and enoates. High enantioselectivities (up to 99% ee) and excellent yields were obtained in the addition to either cyclic or acyclic substrates. The flexible biphenolic P ligands outperformed the analogous rigid binaphtholic P ligands. Variable-temperature ³¹P NMR studies revealed that the biphenolic ligands are tropos even at low temperature. Only below 190 K was a coalescence observed: upon further cooling, two atropisomers were detected. The Rh homocomplexes ([Rh(L^a)₂]⁺) were also studied: in general, a single doublet (P-Rh coupling) was observed in the case of the biphenolic phosphite ligands, over the temperature range 380-230 K, demonstrating their tropos nature in the rhodium complexes even at low temperatures. On the other hand, the phosphoramidites showed different behaviors depending on the structure of the ligand and on the nature of the rhodium source. The spectrum at 230 K of the mixture of [Rh(acac)(eth)₂] (eth = C₂H₄) with phosphite 6-P(O)₂O and phosphoramidite 19-P(O)₂N (the most enantioselective ligand combination in the conjugate addition reaction) revealed the presence of four homocomplexes (total approximately 40%: [Rh(6-P(O)₂}₂], [Rh{(aR)-19-P(O)₂N}₂], [Rh((aS)-19-P(O)₂N) ₂], [Rh((aR)-19-P(O)₂N}((aS)-19-P(O)₂N}]) and one heterocomplex, [Rh{6-P(O)₂O){(aR)-19-P(O)₂NJ] (approximately 60%) In the heterocomplex, the biphenol-derived phosphite is free to rotate (tropos) while the biphenol-derived phosphoramidite shows a temperature-dependent tropos/atropos behavior (coalescence temperature = 310 K).

Full text of DOI:10.1002/chem.200600960

FULL PAPER
DOI: 10.1002/chem.200600960
Rh-Catalyzed Enantioselective Conjugate Addition of Arylboronic Acids
with a Dynamic Library of Chiral tropos Phosphorus Ligands
Chiara Monti,[a] Cesare Gennari,*[a] and Umberto Piarulli*[b]
Abstract: A library of 19 chiral tropos
phosphorus ligands, based on a free-to-
rotate (tropos) biphenol unit and a
chiral P-bonded alcohol (11 phosphites,
1-P(O)2O to 11-P(O)2O) or secondary
amine (8 phosphoramidites, 12-P(O)2N
to 19-P(O)2N), were screened, individ-
ually and in combinations of two, in
the rhodium-catalyzed asymmetric con-
jugate addition of arylboronic acids to
enones and enoates. High enantioselec-
tivities (up to 99% ee) and excellent
yields were obtained in the addition to
either cyclic or acyclic substrates. The
flexible biphenolic P ligands outper-
formed the analogous rigid binaphthol-
coalescence observed; upon further
cooling, two atropisomers were detect-
mixture of [RhACTHEURNG(acac)ACTHRE(UNG eth)2] (eth=
C2H4) with phosphite 6-P(O)2O and
phosphoramidite 19-P(O)2N (the most
enantioselective ligand combination in
the conjugate addition reaction) re-
vealed the presence of four homocom-
plexes (total approximately 40%: [Rh-
ed.
The
Rh
homocomplexes
([Rh(La)2]+) were also studied: in gen-
eral, a single doublet (P–Rh coupling)
was observed in the case of the biphe-
nolic phosphite ligands, over the tem-
perature range 380–230 K, demonstrat-
ing their tropos nature in the rhodium
complexes even at low temperatures.
On the other hand, the phosphorami-
dites showed different behaviors de-
pending on the structure of the ligand
and on the nature of the rhodium
source. The spectrum at 230 K of the
AHCTREUNG
AHCTREUNG
19-P(O)2N}] (approximately 60%) In
the heterocomplex, the biphenol-de-
rived phosphite is free to rotate
(tropos) while the biphenol-derived
phosphoramidite shows a temperature-
dependent tropos/atropos behavior (co-
alescence temperature=310 K).
ic
P
ligands. Variable-temperature
Keywords: asymmetric catalysis
·
31P NMR studies revealed that the bi-
phenolic ligands are tropos even at low
temperature. Only below 190 K was a
atropisomerism · enones · NMR
spectroscopy · P ligands · rhodium
Introduction
and Hayashi, has become the method of choice for the ste-
reoselective introduction of an aryl or a vinyl group in the b
position of a variety of electron-deficient olefins (including
enones, nitroolefins, a,b-unsaturated esters, amides, phos-
phonates, and sulfones).[1] Excellent enantioselectivities
were obtained using both bidentate (binap,[2] segphos,[3] chir-
aphos,[4] P-phos,[5] diphosphonites,[6] bisphosphanes,[7] amido-
monophosphanes,[8] chiral dienes,[9] deguPhos,[10] cyrhe-
trenes,[11]) and more recently monodentate ligands (binaph-
tholic phosphoramidites), which may contain, besides the
stereogenic axis, additional stereogenic elements (stereocen-
ters).[12]
The asymmetric rhodium-catalyzed conjugate addition of
aryl- and vinylboronic acids, originally reported by Miyaura
[a] Dr. C. Monti, Prof. Dr. C. Gennari
Dipartimento di Chimica Organica e Industriale
Centro di Eccellenza C.I.S.I.
Università degli Studi di Milano
Istituto di Scienze e Tecnologie Molecolari (ISTM) del CNR
Via G. Venezian 21, 20133 Milano (Italy)
Fax : (+39)02-5031-4072
E-mail: cesare.gennari@unimi.it
A library of 19 chiral tropos phosphorus ligands, based on
a flexible (tropos)[13] biphenol unit and a chiral P-bonded al-
cohol (11 phosphites) or secondary amine (8 phosphorami-
dites), was recently synthesized in our laboratories and used
in the rhodium-catalyzed asymmetric hydrogenation of pro-
chiral olefins.[14] These ligands exist as a mixture of two rap-
idly interconverting diastereomers, La and La’, differing in
[b] Prof. Dr. U. Piarulli
Dipartimento di Scienze Chimiche e Ambientali
Università degli Studi dellꢀInsubria
Via Valleggio 11, 22100 Como (Italy)
Fax : (+39)031-238-6449
E-mail: umberto.piarulli@uninsubria.it
Supporting information for this article is available on the WWW
under http://www.chemeurj.org/ or from the author.
Chem. Eur. J. 2007, 13, 1547 – 1558
ꢁ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1547

the conformation of the biphenol unit (Scheme 1). Upon
complexation with Rh, the ligand (La in equilibrium with
La’) should give rise to three different species, namely
Feringa and co-workers,[12b,17] we used a combination of two
of these ligands (La in equilibrium with La’ and Lb in equilib-
rium with Lb’) and generated a dynamic in-situ library,[18]
with up to ten different species theoretically present in solu-
tion: [Rh(La)(La)], [Rh(La)
plexes with La and La’), [Rh(Lb)(Lb)], [Rh(Lb)
(Lb’)(Lb’)] (homocomplexes with Lb and Lb’), and
[Rh(La)(Lb)], Rh(La)(Lb’)], [Rh(La’)(Lb)], [Rh(La’)(Lb’)]
(La’)], [Rh(La’)
ACHTREUNG ACHTREUNG ACHTREUNG
AHCTREUNG
A
ACHTREUNG
A
G
A
ACHTREUNG
(heterocomplexes). Although, in principle, each species
could be present and catalyze the reaction, one of them
could predominate over the others, determining the direc-
tion and the extent of the enantioselectivity.
Results and Discussion
Scheme 1. Chiral phosphorus ligands based on a chiral P-bonded alcohol
or secondary amine and a flexible (tropos) P-bonded biphenol unit.
Asymmetric 1,4-addition of arylboronic acids to enones and
enoates: The library of 11 biphenolic phosphites and eight
biphenolic phosphoramidites was screened initially in the
conjugate addition of phenylboronic acid to 2-cyclohexe-
none (20A), as a benchmark reaction, by using 1.5 mol%
[Rh(La)(La)], [Rh(La)(La’)], [Rh(La’)(La’)]. These three dia-
ACHTREUNG ACHTREUNG ACHTREUNG
stereomeric species, which might be interconverting, are
generated in proportions which most probably differ from
the statistical value (1:2:1). In this paper we report highly
enantioselective rhodium-catalyzed conjugate additions of
arylboronic acids to a variety of a,b-unsaturated carbonyl
derivatives (cyclic and acyclic enones, a,b-unsaturated lac-
tones and esters) by using a dynamic library of chiral phos-
phorus ligands, and characterize the tropos/atropos nature of
the ligands in the rhodium complexes by 31P NMR spectros-
copy.[15] Following the lead of Reetz and co-workers[16] and
(eth)2Cl}2][19] and a total of 6 mol% of ligands (Rh/L=
[{RhACHTREUNG
1:2) (Scheme 2). The reaction was performed using KOH
(1equiv) as base, [20] in a 10:1 dioxane/water solution at
room temperature overnight; a few selected results are pre-
sented in Table 1, entries 1–7 (see the Supporting Informa-
tion for the complete screening results). In general, when
the chiral ligands were used individually (homocombina-
tions) the phosphites gave more efficient and enantioselec-
1548
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ꢁ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2007, 13, 1547 – 1558

Arylboronic Acids
FULL PAPER
entry 5; 19-P(O)2N 36% ee, entry 2). The mismatched com-
binations gave (S)-3-phenylcyclohexanone (22Aa) in
70% ee (100% yield) with phosphoramidite 18-P(O)2N and
phosphite 6-P(O)2O (Table 1, entry 4), and 87% ee (100%
yield) with phosphoramidite 18-P(O)2N and phosphite 9-
P(O)2O (Table 1, entry 7), showing that it is the phosphor-
AHCTREaUNG midite which determines the absolute configuration of the
reaction product. Again, the synergistic effect of the hetero-
combination is remarkable.
Scheme 2. Rh-catalyzed conjugate addition of arylboronic acids to 2-cy-
clohexenone (20A).
The ee enhancements with
Table 1. Rh-catalyzed conjugate addition of arylboronic acids to 2-cyclohexenone (20A): selected results.[a]
these ligands are notable and
generally higher than those ob-
tained using combinations of
binaphtholic phosphites or
phosphoramidites.[12b,16,17]
The scope of this reaction
was then investigated using
various arylboronic acids, with
2-cyclohexenone (20A) as the
substrate (Table 1, entries 8–
29; see the Supporting Infor-
mation for the complete
screening results).
Entry
ArB(OH)2
T [8C]
L[a]
L[b]
Product
Conv. [%][b]
ee [%][b]
Abs. conf.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22[c]
23[c]
24[c]
25
26
27
28
29
21a
21a
21a
21a
21a
21a
21a
21b
21b
21b
21b
21b
21b
21c
21c
21d
21d
21d
21d
21e
21e
21e
21e
21e
21 f
21 f
21g
21g
21g
23
23
23
23
23
23
23
23
23
23
23
23
23
23
23
23
23
23
23
23
80
23
23
23
23
80
23
23
23
6-P(O)2O
19-P(O)2N
6-P(O)2O
6-P(O)2O
9-P(O)2O
9-P(O)2O
9-P(O)2O
6-P(O)2O
19-P(O)2N
6-P(O)2O
9-P(O)2O
9-P(O)2O
9-P(O)2O
6-P(O)2O
18-P(O)2N
6-P(O)2O
19-P(O)2N
6-P(O)2O
6-P(O)2O
6-P(O)2O
6-P(O)2O
6-P(O)2O
19-P(O)2N
6-P(O)2O
6-P(O)2O
6-P(O)2O
6-P(O)2O
19-P(O)2N
6-P(O)2O
6-P(O)2O
19-P(O)2N
19-P(O)2N
18-P(O)2N
9-P(O)2O
19-P(O)2N
18-P(O)2N
6-P(O)2O
19-P(O)2N
19-P(O)2N
9-P(O)2O
18-P(O)2N
19-P(O)2N
6-P(O)2O
18-P(O)2N
6-P(O)2O
19-P(O)2N
19-P(O)2N
18-P(O)2N
6-P(O)2O
6-P(O)2O
6-P(O)2O
19-P(O)2N
19-P(O)2N
6-P(O)2O
6-P(O)2O
6-P(O)2O
19-P(O)2N
19-P(O)2N
22Aa
22Aa
22Aa
22Aa
22Aa
22Aa
22Aa
22Ab
22Ab
22Ab
22Ab
22Ab
22Ab
22Ac
22Ac
22Ad
22Ad
22Ad
22Ad
22Ae
22Ae
22Ae
22Ae
22Ae
22Af
22Af
22Ag
22Ag
22Ag
100
100
100
100
100
100
100
100
50
70
36
95
70
28
91
87
42
52
83
23
75
70
41
42
64
6
92
60
58
18
63
nd
85
nd
nd
75
41(
99
(R)-(+)
(R)-(+)
(R)-(+)
(S)-(À)
(R)-(+)
(R)-(+)
(S)-(À)
(+)
(+)
(+)
(+)
95
100
100
100
100
100
100
50
97
95
50
57
100
0
95
0
0
100
90
100
(À)
(+)
(R)-(+)
(S)-(À)
(R)-(+)
(R)-(+)
(R)-(+)
(S)-(À)
(+)
(+)
(+)
–
(+)
In general, the combination
of phosphite 6-P(O)2O and
phosphoramidite
19-P(O)2N
proved to be the most efficient
and enantioselective; as for
the arylboronic acids, high
yields and excellent ee values
were obtained with the elec-
tron-rich p-anisylboronic (21d)
and p-tolylboronic (21g) acids.
In particular, the 19-P(O)2N/6-
P(O)2O combination gave
(3R)-3-(4-methoxyphenyl)cy-
–
–
(R)-(+)
R)-(+)
(R)-(+)
[a] Standard reaction conditions for the library screening: (La + Lb)/[{Rh
hexenone=0.06:0.015:2:1:1. [b] Yields and ee values were determined by chiral GC or HPLC (see the Sup-
porting Information). [c] 5 mol% [{Rh(eth)2Cl}2] and a total of 20 mol% of ligands.
AHCTRE(UNG eth)2Cl}2}]/ArB(OH)2/KOH/2-cyclo-
clohexanone
92% ee (97% yield; Table 1,
entry 18); (3S)-3-(4-methoxy-
(22Ad)
in
AHCTREUNG
phenyl)cyclohexanone (22Ad)
was obtained in 60% ee with
tive catalysts than the phosphoramidites. However, the en-
antiomeric excesses were only moderate and the best ee was
70% with phosphite 6-P(O)2O (Table 1, entry 1). Mixtures
of a phosphite and a phosphoramidite (heterocombinations)
gave reduced yields and ee values in comparison with the
phosphite alone, in all combinations except those containing
either phosphoramidite 18-P(O)2N or 19-P(O)2N. In these
heterocombinations, considerably higher ee values and quan-
titative yields were obtained. In particular, (R)-3-phenylcy-
clohexanone (22Aa) was obtained in 95% ee (100% yield)
with phosphoramidite 19-P(O)2N and phosphite 6-P(O)2O
(Table 1, entry 3), and in 91% ee (100% yield) with phos-
phoramidite 19-P(O)2N and phosphite 9-P(O)2O (Table 1,
entry 6). In the latter case, the synergistic effect of the heter-
ocombination with respect to the corresponding homocom-
binations is worth an additional 55% ee (9-P(O)2O 28% ee,
the mismatched pair 18-P(O)2N/6-P(O)2O (Table 1,
entry 19). (3R)-3-(4-Methylphenyl)cyclohexanone (22Ag)
was obtained in 99% ee (100% yield) using the combination
phosphoramidite 19-P(O)2N/phosphite 6-P(O)2O (Table 1,
entry 29). Again, the synergistic effect of this heterocombi-
nation with respect to the corresponding homocombinations
is remarkable (6-P(O)2O 75% ee, entry 27; 19-P(O)2N
41% ee, entry 28). 1-Naphthylboronic (21b) and p-chloro-
phenylboronic (21e) acids also afforded the expected prod-
ucts with good ee values; with the ligand combination 19-
P(O)2N/6-P(O)2O, 3-(1-naphthyl)cyclohexanone (22Ab) was
obtained in 83% ee (95% yield, entry 10), and 3-(4-chloro-
phenyl)cyclohexanone (22Ae) was obtained in 85% ee
(95% yield, entry 24). In contrast, m-nitrophenylboronic
acid (21 f) did not react. This observation parallels the lack
of reactivity of electron-poor arylboronic acids reported by
Chem. Eur. J. 2007, 13, 1547 – 1558
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1549

C. Gennari, U. Piarulli et al.
Minnaard and co-workers in the Pd-catalyzed conjugate ad-
dition reaction.[21] o-Tolylboronic acid (21c) gave moderate
ee values and complete conversions when the chiral ligands
were used individually (homocombinations, entries 14 and
15), while use of the heterocombinations did not result in
any enhancement of the ee values. The use of phenylborox-
ine[22] did not lead to any ee enhancement; on the contrary,
a slight decrease in the enantioselectivity was observed in
all cases: for example, 6-P(O)2O gave (R)-3-phenylcyclohex-
anone (22Aa) in 60% ee (compare entry 1, 70% ee), while
the combination 19-P(O)2N/6-P(O)2O gave 22Aa in 90% ee
(compare entry 3, 95% ee).
The effect of the substrate was then evaluated: the varia-
tion of the ring size was investigated by using all the homo-
combinations and several heterocombinations with 2-cyclo-
pentenone (20B) and 2-cycloheptenone (20C) (see Table 2
for selected results and the Supporting Information for the
complete screening). The best results were again obtained
using the heterocombination containing 6-P(O)2O and the
2,5-diphenylpyrrolidine phosphoramidite 19-P(O)2N. This
matched combination afforded (R)-3-phenyl-cyclopentanone
(22Ba) in 73% ee and 95% yield (Table 2, entry 1) and (R)-
3-phenyl-cycloheptanone (22Ca) in 90% ee and 97% yield
(Table 2, entry 2).
Acyclic enones were also screened (see Table 2 for select-
ed results and the Supporting Information for the complete
screening). In these cases, the homocombination of phos-
phite 6-P(O)2O worked better than the heterocombinations.
For example, (4R)-4-phenylpentan-2-one (22Ea, entry 5)
and 4-phenyloctan-2-one (22Ha, entry 12) were obtained in
reasonable ee (75–76%), albeit with incomplete conversions.
In contrast, (4S)-5-methyl-4-phenylhexan-2-one (22Fa,
entry 6) and (4R)-4-phenylnonan-2-one (22Ia, entry 15)
were obtained in high ee (93% and 92%, respectively) and
with good yields (90% and 100%, respectively). The conju-
gate addition of p-anisylboron-
ic acid (21d) to 4-phenyl-3-
buten-2-one (20G) required a
higher reaction temperature
(808C) to proceed to comple-
tion: 22Gd was obtained in
good ee (80%, entry 10).
To study whether the range
of substrates could be expand-
ed beyond enones, a,b-unsatu-
rated lactone 20D was subject-
ed to the same reaction condi-
Table 2. Rh-catalyzed conjugate addition of arylboronic acids to substrate 20: selected results.[a]
Entry Substrate ArB(OH)2 T [8C] L[a]
L[b]
Prod. Conv. [%][b] ee [%][b] Abs. conf.
1
2
3
4
20B
20C
20C
20D
20E
20F
20F
20F
20F
20G
20G
20H
20H
20H
20I
21a
21a
21a
21a
21a
21a
21a
21a
21a
21d
21d
21a
21a
21a
21a
21a
21a
21d
21d
21d
23
23
23
80
23
23
80
23
23
80
80
23
23
23
23
23
23
23
23
23
6-P(O)2O
6-P(O)2O
9-P(O)2O
19-P(O)2N 22Ba
19-P(O)2N 22Ca
19-P(O)2N 22Ca
95
97
97
80
75
90
90
5
73
90
90
50
76
93
80
48
81(
80
67
75
54
63
92
61
80
79
30
71
(R)-(+)
(R)-(+)
(R)-(+)
(R)-(À)
(R)-(À)
(S)-(À)
(S)-(À)
(S)-(À)
S)-(À)
(S)-(À)
(S)-(À)
(À)
19-P(O)2N 19-P(O)2N 22Da
5[c]
6
6-P(O)2O
6-P(O)2O
6-P(O)2O
19-P(O)2N 19-P(O)2N 22Fa
6-P(O)2O
6-P(O)2O
10-P(O)2O 10-P(O)2O 22Gd
6-P(O)2O 6-P(O)2O 22Ha
19-P(O)2N 19-P(O)2N 22Ha
6-P(O)2O
6-P(O)2O
19-P(O)2N 19-P(O)2N 22Ia
6-P(O)2O
6-P(O)2O
6-P(O)2O
6-P(O)2O
6-P(O)2O
22Ea
22Fa
22Fa
7
8
9
10
19-P(O)2N 22Fa
6-P(O)2O
85
22Gd 100
11
12
13
14
15
16
17
18
19
20
85
72
40
50
100
5
97
95
5
tions, but only
a moderate
50% ee was obtained with
phosphoramidite 19-P(O)2N at
808C (entry 4). Better results
were obtained by addition of
p-anisylboronic acid (21d) to
tert-butyl 3-phenylpropanoate
(20J) using phosphite 6-
P(O)2O, with the formation of
22Jd in 79% ee (entry 18).
(À)
19-P(O)2N 22Ha
6-P(O)2O 22Ia
(À)
(R)-(À)
R()-(À)
(R)-(À)
(S)-(+)
(S)-(+)
(S)-(+)
20I
20I
20J
20J
20J
19-P(O)2N 22Ia
6-P(O)2O 22Jd
18-P(O)2N 18-P(O)2N 22Jd
6-P(O)2O
18-P(O)2N 22Jd 100
[a] Standard reaction conditions for the library screening: (La + Lb)/[{Rh
strate=0.06:0.015:2:1:1. [b] Yields and ee values were determined by chiral GC or HPLC (see the Supporting
Information). [c] 2.5 mol% [{Rh(eth)2Cl}2] and a total of 10 mol% of ligands.
ACHTER(UNG eth)2Cl}2}]/ArB(OH)2/KOH/sub-
AHCTREUNG
1550
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ꢁ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2007, 13, 1547 – 1558

Arylboronic Acids
FULL PAPER
NMR studies of the ligands and of their Rh complexes: The
remarkable increase in enantiomeric excess observed when
using combinations of these biphenolic P ligands is rather
puzzling. As we expected (see Introduction), the use of a
combination of two tropos ligands (La in equilibrium with
La’ and Lb in equilibrium with Lb’) generates a dynamic in-
situ library with up to ten different species theoretically
around 197 K and two broad resonances were observed at
183 K, in a relative ratio of 6.7:1. In these two cases, the
free-energy barrier DG° to biphenol rotation was calculat-
ed[23] to be 8.5 kcalmolÀ1 (see the Supporting Informa-
tion).[24]
NMR studies of the Rh complexes—ligand homocombina-
tions: The tropos/atropos nature[13] of the ligands in the rho-
dium complexes was then studied in detail. The metal com-
plexes containing biphenolic tropos ligands (phosphites or
phosphoramidites) were defined as “induced atropisomeric”
by Alexakis[25] and “fluxionally atropisomeric” by Reetz.[16f]
However, no evidence was ever presented regarding their
tropos or atropos nature.[26] The variable-temperature
31P NMR spectroscopy of the rhodium complexes originat-
ing from several ligand homocombinations (2La) and differ-
ent rhodium sources was therefore studied over the temper-
ature range 380–230 K. The temperature could not be low-
ered below 230 K because of signal broadening caused by
the increased viscosity of the sample and precipitation of
the rhodium complexes.
present in solution: [Rh(La)(La)], [Rh(La)
(La’)] (homocomplexes with La and La’), [Rh(Lb)(Lb)],
[Rh(Lb)(Lb’)], [Rh(Lb’)(Lb’)] (homocomplexes with Lb and
Lb’), and [Rh(La)(Lb)], Rh(La)(Lb’)], [Rh(La’)(Lb)], [Rh(La’)-
(Lb’)] (heterocomplexes). These complexes are not formed
(La’)], [Rh(La’)-
ACHRTEUNG ACHTREUGN
ACHTREUNG
A
N
ACHTREUNG
A
N
ACHTREUNG
ACHTREUNG
in the statistical ratio and the library composition should re-
flect their relative stabilities in terms of both electronic
(phosphite/phosphoramidite versus phosphite/phosphite
versus phosphoramidite/phosphoramidite combinations) and
steric effects. To shed light on the “black box” of this cata-
lyst system, we investigated the dynamic behavior of our bi-
phenolic ligands and of their rhodium complexes (precata-
lysts) by variable-temperature 31P NMR spectroscopy. Sever-
al homocomplexes (with the same ligand) and complexes re-
sulting from selected ligand combinations (that is, phosphite
6-P(O)2O/phosphoramidite 19-P(O)2N, the most enantiose-
lective ligand combination in the conjugate addition reac-
tion) were investigated.
In general, a doublet was observed for the rhodium com-
plexes of the phosphites over the temperature range 380–
230 K, using [Rh
onstrates the tropos nature of the biphenolic phosphites in
the [Rh
(acac)(L)2] complexes even at low temperatures.[27]
ACHRTUNEG(acac)ACHTRE(UGN eth)2] as the metal source; this dem-
AHCTREUNG
NMR characterization of the ligands: The ligands were stud-
ied by variable-temperature 31P NMR spectroscopy. At
room temperature a single resonance was observed, which
corresponds to a free-to-rotate (tropos) ligand. The multi-
plicity did not change over the temperature range 380–
210 K. However, by lowering the temperature below 210 K,
the singlet corresponding to the tropos ligand broadened
and eventually split into two signals with coalescence tem-
peratures in the range 200–180 K. In the case of phosphite
4-P(O)2O, for example, the coalescence temperature is
around 190 K (Figure 1). Further cooling (to 183 K) resulted
in the generation of two resolved signals approximately in a
2:1ratio, originating from the two atropisomers. In the case
of phosphite 6-P(O)2O, the coalescence temperature is
For example, a doublet (JP, Rh =296 Hz, [D8]toluene) was ob-
served for the rhodium complex of phosphite 6-P(O)2O over
the temperature range 380–230 K (Figure 2; see the Sup-
porting Information for the 31P NMR spectra).[28]
Figure 2. The tropos nature of the biphenolic phosphite 6-P(O)2O in the
Rh complex.
Surprisingly, the rhodium complexes of the phosphorami-
dites showed a quite diversified and sometimes abnormal
behavior, depending on the structure of the phosphorami-
dite ligand and on the nature of the rhodium source, as dis-
cussed below.
[Rh
P(O)2N): The 31P NMR spectra of the complex derived from
[Rh(acac)(eth)2] and phosphoramidite 13-P(O)2N (or 12-
P(O)2N) at room temperature showed two doublets in addi-
ACHRTUNEG(acac)ACHTRE(UGN eth)2] and phosphoramidite 13-P(O)2N (or 12-
A
ACHTREUNG
Figure 1. Variable-temperature 31P NMR spectra of ligand 4-P(O)2O.
tion to the doublet originating from complex [LRhACHTREUNG(acac)],
Chem. Eur. J. 2007, 13, 1547 – 1558
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1551

C. Gennari, U. Piarulli et al.
which was visible at ligand/Rh ratios ꢀ 2:1. The ratio of the
two doublets varied, depending on the solvent used, be-
tween 1.5:1 ([D2]dichloromethane) and 3:1([D 8]toluene),
but was constant with the temperature over the range 380–
210 K, and was independent of the ligand/rhodium ratio
(Figure 3).
amidite Rh complexes are caused by the biphenol atropiso-
merism: in fact three diastereomeric complexes (aR,aR;
aS,aS; aR,aS) would be expected in this case. Moreover, in
the atropisomeric (aR,aS) complex the two phosphorus
atoms are diastereotopic and would couple with rhodium
and with each other, giving origin to two doublets of dou-
blets (dd) and not to a single doublet (see the relevant dis-
cussion below, next section).
Alternatively, two different complexes, namely [Rh-
AHCTREUNG
(acac)(L)2] and [Rh(L)4]+, could account for the observed
two doublets. However, this explanation does not fit with:
1) the absence of dependence of the two signals on the Rh/
L ratio, and 2) the magnitude of the Rh–L coupling constant
[29]
JP, Rh
.
Furthermore, all attempts to identify an [Rh(L)4]+
complex by ESI-HRMS were unsuccessful (whereas [Rh-
(acac)(L)2] was always clearly visible). We tentatively ex-
plain the two doublets as the signals of the expected square-
planar monomeric complex [Rh(acac)(L)2] (with tropos li-
AHCTREUNG
AHCTREUNG
gands) and of a dinuclear complex containing bridging li-
gands.[30,31]
[Rh
18-P(O)2N: The 31P NMR spectra of the rhodium complex
derived from [Rh(acac)(eth)2]] and either phosphoramidite
ACHRTUNEG(acac)ACHTRE(UGN eth)2] and either phosphoramidite 19-P(O)2N or
Figure 3. 31P NMR spectra ([D2]dichloromethane) at 298 K of the rhodi-
um complexes of ligand 13-P(O)2N, using [RhACHTERNGU(acac)ACHRTE(UGN eth)2] (two doublets:
A
ACHTREUNG
*
and ”), varying the ligand/rhodium ratio.
19-P(O)2N or 18-P(O)2N showed a typical coalescence be-
havior. In fact, the spectrum at 380 K (Figure 5, top trace)
The 31P NMR spectra of the complexes derived from [Rh-
(acac)(eth)2] and phosphoramidites 14-P(O)2N (or 15-
A
ACHTREUNG
P(O)2N) and 16 P(O)2N (or 17-P(O)2N) showed, in each
case, a doublet at room temperature, which was not broad-
ened by cooling to 230 K. However, when the temperature
was lowered an additional doublet was detected, showing
that in these cases also an additional species is present and
that the two doublets are accidentally isochronous at room
temperature (see the Supporting Information).
A control experiment carried out using [RhACTHERNGU(acac)ACHTRE(UGN eth)2]
and the (S)-binaphthol-derived phosphoramidite 23-P(O)2N
(Figure 4) (an analogue of phosphoramidite 13-P(O)2N)
showed a single sharp doublet over the same temperature
range.
However, we tend to exclude the possibility that the two
doublets observed in the spectra of the biphenolic phosphor-
Figure 5. Variable-temperature 31P NMR spectra ([D8]toluene) of the
rhodium complexes of ligand 19-P(O)2N, with [RhACTHERG(NU acac)CAHTRE(UNG eth)2] as the
rhodium source. At 230 K, [Rh{(aS)-19-P(O)2N}{(aR)-19-P(O)2N}] gives
*
two dds
(
), whereas the doublets of [Rh{(aR)-19-P(O)2N}2] and
[Rh{(aS)-19-P(O)2N}2] are isochronous (”).
consists of a doublet (d=152.0 ppm, JP, Rh =294 Hz), which,
upon cooling, broadens and coalesces at 320 K (Figure 5,
middle trace). Further cooling results in the generation of
multiple species which at 230 K give origin to a sharp dou-
blet (d=154.6 ppm, JP, Rh =290 Hz) and two doublets of dou-
blets (d=152.4 ppm,
JP, Rh =291.8 Hz,
JP,P =95 Hz; d=
149.5 ppm, JP, Rh =289.5 Hz, JP, P =95 Hz) (Figure 5, bottom
trace). This can be interpreted as the formation of three dia-
stereomers (aR,aR; aS,aS; aR,aS) differing in the configura-
tion at the two atropisomeric biphenols (which can be aR or
aS), while the configuration of the two amine stereocenters
Figure 4. 31P NMR spectrum ([D2]dichloromethane) at 298 K of the rho-
dium complex of binaphtholic ligand 23-P(O)2N, using [RhACTHERNGU(acac)ACHRTE(UGN eth)2].
1552
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Arylboronic Acids
FULL PAPER
Scheme 3. The atropos nature of the biphenolic phosphoramidite 19-
P(O)2N in the Rh complex, at low temperature (230 K).
Figure 6. Variable-temperature 31P NMR spectra ([D8]toluene) of the
rhodium complex of ligand 25-P(O)2N, with [RhACHTERNGU(acac)AHCRTE(UGN eth)2] as the rho-
dium source.
is clearly fixed (2S,5S) (Scheme 3). The two diastereomers
aR,aR and aS,aS, where the two phosphorus atoms are ho-
motopic, give rise to two doublets (P–Rh coupling), which
are accidentally isochronous.
[RhCAHTERU(GN nbd)2]ACHTER[UNG BF4] (nbd=norbornadiene) or [RhACHTUER(GN cod)2]ACHTREUNG[BF4]
In contrast, the aR,aS diastereomer in which the two
phosphorus atoms are diastereotopic and couple with rhodi-
um and with the other phosphorus, gives origin to two dou-
blets of doublets (dd). The free-energy barrier DG° to bi-
phenol rotation in [D8]toluene, calculated from the dd sig-
nals,[23], is 14.4Æ0.2 kcalmolÀ1 (coalescence temperature
TC =320 K), while in [D2]dichloromethane DG° is 13.0Æ
0.2 kcalmolÀ1 (TC =290 K).
As a further proof that the coalescence behavior of the
rhodium complex of phosphoramidite 19-P(O)2N (or 18-
P(O)2N) is due to the hindered rotation about the biphenol-
ic axis, and is not ascribable to the conformational proper-
ties of the 2,5-diphenylpyrrolidine moiety, we synthesized
the binaphtholic phosphoramidites 24-P(O)2N and 25-
P(O)2N which are the (R)-binaphthol (or (S)-binaphthol)
(cod=1,4-cyclooctadiene) and phosphoramidites 12-P(O)2N
(or 13-P(O)2N), 14-P(O)2N (or 15-P(O)2N), 16 P(O)2N (or
17-P(O)2N): The 31P NMR spectra of the complexes derived
from [Rh
ACHTRE(UNG nbd)2]ACHERT[UNG BF4] (nbd=norbornadiene) or [RhACHTREUNG(cod)2]-
AHCTREUNG
phosphoramidites 12-P(O)2N (or 13-P(O)2N), 14-P(O)2N (or
15-P(O)2N), 16 P(O)2N (or 17-P(O)2N) showed a single
sharp doublet (JP, Rh =290–300 Hz) over the temperature
range 380–230 K. This demonstrates the tropos nature of
these biphenolic phosphoramidites in the [Rh(L)
[BF4] or [Rh(L)2A(cod)][BF4] complexes, even at low temper-
atures.
2ACHTREUNG(nbd)]-
A
G
ACHTREUNG
[Rh
P(O)2N): With phosphoramidites 18-P(O)2N (or 19-P(O)2N)
and [Rh(cod)2]
[BF4] as the rhodium source, the 31P NMR
ACHRTUNEG(cod)2]ACHTRE[UGN BF4] with phosphoramidites 18-P(O)2N (or 19-
A
ACHTREUNG
spectra of the complex showed broad signals and multiple
species, even at room temperature. This can be attributed
both to the tropos/atropos behavior of these phosphorami-
dites (see the relevant discussion above), and to the pres-
ence of the cod ligand, which can occa-
sionally display a fluxional behavior.[32]
For example, when [RhACHTRENGU(cod)2]ACHTRE[UGN BF4]
and the atropisomeric binaphtholic
phosphoramidite (S)-monophos (26-
P(O)2N) are used, the complex shows a
doublet at 325 K (d=137.7 ppm, JP, Rh
=
247.8 Hz), a broad signal typical of a
coalescence behavior at 300 K, and one
doublet (d=138.6 ppm, JP, Rh =234.1Hz; both cod double
bonds are Rh-bonded and the monophos P atoms are homo-
topic) and two doublets of doublets (d=134.6 ppm, JP,Rh
240.4 Hz, JP, P =36.8 Hz; d=141.0 ppm, JP, Rh =240.7 Hz, JP, P
=
=
38.0 Hz; only one cod double bond is bound to Rh and the
monophos P atoms are diastereotopic) at 230 K (total: ten
lines). Repeating the same experiment with monophos and
analogues of phosphoramidite 19-P(O)2N. The rhodium
complex of phosphoramidite 25-P(O)2N (or 24-P(O)2N)
gave a sharp doublet over the temperature range 380–230 K
(Figure 6).
[Rh
ACHRTUNEG(nbd)2]ACHTRE[UGN BF4] as the rhodium source (in which norborna-
diene is locked in a boat conformation; Figure 7), a clean
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1553

C. Gennari, U. Piarulli et al.
doublets for the phosphite phosphorus of [Rh
A
P(O)2N}] (d=157.7 ppm, dd, P, Rh =303.2 Hz, JP, P
J
=
100.3 Hz), while the signals of the phosphoramidite are
broadened by the coalescence. On cooling to 230 K, the sig-
nals of the phosphoramidite are resolved and two doublets
of doublets of the [RhACTHER{NGU 6-P(O)2O}ACHTRE{UGN 19-P(O)2N}] heterocom-
plex (d=159.5 ppm, dd, JP, Rh =301.5 Hz, JP,P =102.0 Hz; d=
153.2 ppm, dd, JP, Rh =281.9 Hz, JP,P =101.9 Hz) can be ob-
served clearly (Figure 8, bottom trace; see the Supporting
Information for more details). This can be interpreted by
the formation of one of the two possible diastereomers dif-
fering in the configuration at the phosphoramidite atropiso-
meric biphenol (which can be aR or aS), while the phosphite
biphenol remains free to rotate (tropos). The free-energy
barrier DG° to biphenol rotation in the [Rh(La)(Lb)] hetero-
complex in [D8]toluene was calculated to be 14.5Æ
0.2 kcalmolÀ1 (coalescence temperature TC =310 K).[23]
In summary, of the ten possible different precatalysts, we
detected the presence of five species: four homocomplexes
Figure 7. [RhACHTREUNG(nbd)ACHTREUNG(monophos)2]ACHTREU[GN BF4] complex: P atoms are homotopic
31
À
( P NMR spectrum: one doublet with P Rh coupling).
doublet was observed over the temperature range 380–
230 K. Interested researchers should, therefore, be very cau-
tious about the use of [Rh
source for NMR studies.
ACHTRUNEG(cod)2]ACHRTE[UGN BF4] as the rhodium
NMR studies of the Rh complexes—ligand heterocombina-
tions: The rhodium complexes resulting from the combina-
tion of phosphite 6-P(O)2O and phosphoramidite 19-P(O)2N
(the most enantioselective ligand combination in the conju-
gate addition reaction), with [Rh
C
(eth)2] as the rhodi-
(total: approximately 40%) [Rh
P(O)2N}2], [Rh{(aS)-19-P(O)2N}2],
P(O)2N}{aS)-19-P(O)2N}], and one heterocomplex (approxi-
mately 60%) [Rh{6-P(O)2O}{(aR)-19-P(O)2N}] or [Rh{6-
ACHTREUNG
G
ACHTREUNG
P(O)2O}{(aS)-19-P(O)2N}]) (Scheme 4).
To guess reasonably which diastereomer, [RhACHTREUNG{6-
P(O)2O}{(aR)-19-P(O)2N}]
or
[RhACHTER{UNG 6-P(O)2O}{(aS)-19-
P(O)2N}], is the heterocomplex observed at low tempera-
ture, we prepared the (R)- and the (S)-binaphthol analogues
of phosphoramidite 19-P(O)2N (24-P(O)2N and 25-P(O)2N,
respectively) and tested these structurally related ligands
separately and in combination with phosphite 6-P(O)2O in
the conjugate addition reaction. Surprisingly, the combina-
tions of 6-P(O)2O with either the (S)-binaphthol analogue
25-P(O)2N (50% yield, 46% ee, (R)) or the (R)-binaphthol
analogue 24-P(O)2N (70% yield, 72% ee, (R)) were both
considerably less effective than the original biphenol-based
combination (Table 3; compare entries 5–7). On the basis of
these experiments, the heterocomplex observed at low tem-
perature is presumably the [Rh
diastereomer.
In the case of the combination of phosphite 6-P(O)2O and
phosphoramidite 18-P(O)2N (the mismatched ligand combi-
ACHTRE{UNG 6-P(O)2O}{(aR)-19-P(O)2N}]
Figure 8. Variable-temperature 31P NMR spectra ([D8]toluene) of the
rhodium complexes resulting from the combination of ligands 6-P(O)2O
and 19-P(O)2N, with [Rh
A
ACHTREUNG
[Rh
A
ACHTREUNG
~
nation in the conjugate addition reaction), with [Rh
(eth)2] as the rhodium source, the low-temperature (230 K)
31P NMR spectrum consisted of the signals attributed to the
ACHTREUNG(acac)-
*
(
), and [RhACHTREUNG{6-P(O)2O}ACHTREUNG{19-P(O)2N}] gives two dds ( ); at 230 K, [RhACHTREUNG
~
~
P(O)2N}2] gives two dds ( ) and a doublet ( ), [Rh
doublet (”), and [Rh{(aR)-19-P(O)2N}{6-P(O)2O}] gives two dds ( ).
ACHTREUNG
AHCTREUNG
*
AHCTREUNG
corresponding
homocombinations
([Rh(La)(La)]
and
ence of all the signals described above due to the
[Rh(La)(La)] and [Rh(Lb)(Lb)] homocomplexes (approxi-
mately 40%) and of the new signals for the [Rh(La)(Lb)]
heterocomplex (approximately 60%). At 375 K (Figure 8,
[Rh(Lb)(Lb)]) plus two sets of two doublets of doublets
(total: 16 lines) attributed to the heterocomplex
[Rh(La)(Lb)]. These are caused by the presence of two dia-
stereomers, [RhACTHERNGU{6-P(O)2O}{(aR)-18-P(O)2N}] and [RhACHTREUNG{6-
top trace), the heterocomplex [Rh
A
{19-P(O)2N}]
P(O)2O}{(aS)-18-P(O)2N}] (ratio 85:15 or 15:85), differing in
the configuration at the phosphoramidite atropisomeric bi-
phenol (Figure 9; see the Supporting Information for more
details). In this case, of the ten possible different precata-
lysts, we detected the presence of six species: four homo-
gives origin to two doublets of doublets (each phosphorus
couples with rhodium and with the other phosphorus),
which can be interpreted as both a tropos phosphite and a
tropos phosphoramidite. At the coalescence temperature
(TC =310 K, Figure 8, middle trace), only the signals belong-
ing to the tropos phosphite are resolved, that is, a doublet of
complexes (total: approximately 28%) [Rh
ACHTRE{UNG 6-P(O)2O}2],
[Rh{(aR)-18-P(O)2N}2], [Rh{(aS)-18-P(O)2N}2], [Rh{(aR)-
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Arylboronic Acids
FULL PAPER
18-P(O)2N}{(aS)-18-P(O)2N}],
and two heterocomplexes (ap-
proximately
P(O)2O}{(aR)-18-P(O)2N}] and
[Rh{6-P(O)2O}{(aS)-18-
P(O)2N}] in relative ratio
72%)
[RhACHTREUNG{6-
AHCTREUNG
a
85:15 or 15:85 (Scheme 5). The
free-energy barrier to the bi-
phenol
rotation
in
the
[Rh(La)(Lb)]
heterocomplex
had the same value as for the
matched pair: in [D8]toluene
DG° =14.5Æ0.2 kcalmolÀ1 (co-
alescence temperature TC =
310 K).
Conclusions
A library of 19 chiral tropos
phosphorus ligands, based on a
free-to-rotate (tropos) biphenol
unit and a chiral P-bonded alco-
hol (11 phosphites, 1-P(O)2O to
11-P(O)2O) or secondary amine
(eight phosphoramidites, 12-
P(O)2N to 19-P(O)2N), were
screened, individually and as
combinations of two, in the rho-
Scheme 4. The rhodium complexes ([RhACHTER(UNG acac)AHCRTE(UGN eth)2] as the rhodium source) that originate from the combina-
tion of phosphite 6-P(O)2O and phosphoramidite 19-P(O)2N, at low temperature (230 K).
Table 3. Rh-catalyzed conjugate addition of phenylboronic acids to 2-cy-
clohexenone.[a]
dium-catalyzed asymmetric conjugate addition of arylboron-
ic acids to enones and enoates. The scope of the reaction
(different boronic acids and substrates) was investigated,
and high enantioselectivities as well as excellent yields were
observed in the addition to cyclic and acyclic a,b-unsaturat-
ed carbonyl derivatives. In particular, in the case of cyclic
enones the best results were obtained using the ligand com-
bination phosphite 6-P(O)2O/phosphoramidite 19-P(O)2N
(99% ee in the conjugate addition of p-tolylboronic acid to
cyclohexenone), while for acyclic substrates, phosphite 6-
P(O)2O alone was preferred. Variable-temperature
31P NMR studies revealed that the biphenolic phosphorus li-
gands are tropos even at low temperature. Only below
190 K was a coalescence observed; upon further cooling,
two atropisomers were detected. The composition and the
dynamic behavior of the rhodium complexes containing
either the single ligands (homocomplexes, [Rh(La)(La)]+) or
the combination of a phosphite and a phosphoramidite (het-
erocomplexes, [Rh(La)(Lb)]+) were studied by variable-tem-
perature 31P NMR spectroscopy. In general, a doublet (P–
Rh coupling) was observed in the case of phosphite ligands
Entry L[a]
L[b]
Conv. [%][b] ee [%][b] Abs. conf.
1
2
3
4
5
6
7
6-P(O)2O
19-P(O)2N 19-P(O)2N 100
6-P(O)2O
100
70
36
40
28
95
72
46
(R)
(R)
(R)
(R)
(R)
(R)
(R)
24-P(O)2N 24-P(O)2N
25-P(O)2N 25-P(O)2N
6-P(O)2O
6-P(O)2O
6-P(O)2O
40
50
19-P(O)2N 100
24-P(O)2N
25-P(O)2N
70
50
[a] Standard reaction conditions for the library screening: (La
+
Lb)/
[{Rh(eth)2Cl}2]/PhB(OH)2/KOH/2-cyclohexenone=0.06:0.015:2:1:1.
ACHTREUNG
[b] Yields and ee values were determined by chiral GC (see the Support-
ing Information).
over the temperature range 380–230 K and using [Rh
(eth)2] as the metal source; this demonstrates the tropos
nature of the biphenolic phosphites in the [L2Rh(acac)]
complexes even at low temperatures. The phosphoramidites
showed different behaviors depending on the structure of
the ligand and on the nature of the rhodium sources. In par-
ticular, two different doublets were detected by 31P NMR in
ACHTREUNG(acac)-
AHCTREUNG
Figure 9. 31P NMR spectra ([D8]toluene) at 230 K of the rhodium com-
plexes resulting from the mismatched combination of ligands 6-P(O)2O
ACHTREUNG
and 18-P(O)2N, using [Rh
ACHRTUNEG(acac)ACHTRE(UGN eth)2] as the rhodium source. At 230 K,
~
~
[Rh{18-P(O)2N}2] gives two dds ( ) and a doublet ( ), [RhACHTRE{UNG 6-P(O)2O}2]
A
*
gives a doublet (”), [Rh{(aR)-18-P(O)2N}ACHTER{UNG 6-P(O)2O}] gives two dds (
*
*
*
or ), and [Rh{[(aS)-18-P(O)2N}
ACHTREU{NG 6-P(O)2O}] gives two dds ( or ).
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1555

C. Gennari, U. Piarulli et al.
tion) with [RhACHTRE(UNG acac)ACHTRE(UGN eth)2] as
the rhodium source, the pres-
ence of six of the ten possible
different precatalysts was de-
tected at low temperature: the
four homocomplexes (total: ap-
proximately 28%), and two
heterocomplexes
mately 72%)
P(O)2O}{(aR)-18-P(O)2N}] and
[Rh{6-P(O)2O}{(aS)-18-
(approxi-
[Rh[6-
ACHTREUNG
AHCTREUNG
P(O)2N}] in
a relative ratio
85:15 or 15:85.
From the experimental re-
sults of the Rh-catalyzed conju-
gate addition reactions and
from the 31P NMR studies of
the Rh precatalysts, it is evident
that: 1) the synergistic effect
(resulting in notable ee en-
hancements) of the phosphite
6-P(O)2O/phosphoramidite 19-
P(O)2N ligand heterocombina-
tion is remarkable; and 2) the
flexible biphenolic
outperform the analogous rigid
binaphtholic ligands
(Table 3). These represent em-
P ligands
Scheme 5. The rhodium complexes ([Rh
ed combination of phosphite 6-P(O)2O and phosphoramidite 18-P(O)2N, at low temperature (230 K).
ACHRTEUNG(acac)ACHRTE(UGN eth)2] as the rhodium source) that originate from the mismatch-
P
the homocomplexes of phosphoramidites 12-P(O)2N to 17-
P(O)2N and [Rh(acac)(eth)2], which are possibly due to the
presence of two species, a square-planar monomeric com-
plex and a dinuclear complex containing bridging ligands.
Homocomplexes of the same phosphoramidites 12-P(O)2N
blematic cases of catalyst self-adaptation and tuning, where
the heterocomplexes perform better than the homocomplex-
es, and the conformationally mobile systems perform better
than the rigid ones.
We are now actively investigating the use of combinations
of tropos ligands for other enantioselective reactions.
A
ACHTREUNG
to 17-P(O)2N and either [RhCAHTRE(UGN cod)2]ACHTRE[UGN BF4] or [RhACHTEUG(RN nbd)2]ACHTRE[UGN BF4]
showed the presence of only one doublet and no coales-
cence over the 380–230 K temperature range. Homocom-
plexes of phosphoramidites 18-P(O)2N and 19-P(O)2N with
Experimental Section
[RhACHTREUNG(acac)ACHTREUNG(eth)2] showed a single doublet at 375 K, a coales-
General procedure for the ligand library screening—Rh-catalyzed conju-
gate addition of arylboronic acid to enones: The reaction was performed
using standard Schlenk techniques, under argon. A solution of the ligands
cence at 320 K, and the generation of a sharp doublet and
two doublets of doublets at 230 K. This can be interpreted
as the formation of three diastereomers (aR,aR; aS,aS;
aR,aS) differing in the configuration at the two atropisomer-
ic biphenols. In the most enantioselective ligand combina-
tion in the conjugate addition reaction (that of phosphite 6-
(0.03 equiv, 0.006 mmol La
+
0.03 equiv, 0.006 mmol Lb) and [{Rh-
AHCTRE(UNG eth)2Cl}2] (0.015 equiv, 0.003 mmol, 5.8 mg) in degassed dioxane
(0.5 mL) was stirred for 30 min. A solution of the appropriate arylboronic
acid (2 equiv, 0.4 mmol) in degassed dioxane (0.3 mL) was added, fol-
lowed by a 2m KOH solution in water (1equiv, 0.2 mmol, 0.1mL). A so-
lution of the substrate (1equiv, 0.2 mmol) in dioxane (0.2 mL) was then
added, and the reaction mixture was stirred overnight under argon, at the
appropriate temperature. The reaction mixture was quenched with a sa-
turated aqueous NaHCO3 solution, and extracted with dichloromethane.
The combined organic extracts were dried and concentrated in vacuo to
give the crude product, which was purified by flash chromatography.
P(O)2O and phosphoramidite 19-P(O)2N), with [Rh
ACHTRE(UNG acac)-
ACHTREUNG(eth)2] as the rhodium source, the biphenol-derived phos-
phite is free to rotate (tropos) while the biphenol-derived
phosphoramidite shows a temperature-dependent tropos/
atropos behavior (coalescence temperature=310 K). The
spectrum at low temperature accounts for the presence of
the signals due to four homocomplexes (total: approximate-
ly 40%) [Rh
19-P(O)2N}2], [Rh{(aR)-19-P(O)2N}{(aS)-19-P(O)2N}], and
one heterocomplex [Rh{6-P(O)2O}{(aR)-19-P(O)2N}] (ap-
ACHTREUNG[6-P(O)2O]2], [Rh{(aR)-19-P(O)2N}2], [Rh{(aS)-
Acknowledgements
AHCTREUNG
proximately 60%). In the case of the combination of phos-
phite 6-P(O)2O and phosphoramidite 18-P(O)2N (the mis-
matched ligand combination in the conjugate addition reac-
We thank the European Commission for financial support (R-Evolution-
ary Catalysis (REVCAT) MRTN-CT-2006–035866). We also thank
Merck Research Laboratories (Merckꢀs Academic Development Program
1556
www.chemeurj.org
ꢁ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2007, 13, 1547 – 1558

Arylboronic Acids
FULL PAPER
Award to C.G.) and Università degli Studi di Milano for financial support
and for a postdoctoral fellowship to C.M. (Assegno di ricerca).
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À
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P
a
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Chem. Eur. J. 2007, 13, 1547 – 1558
ꢁ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
1557

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monomeric to dimeric complexes; see: a) H. L. M. Van Gaal,
Received: July 5, 2006
Published online: November 29, 2006
1558
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Chem. Eur. J. 2007, 13, 1547 – 1558