Table 1. Comparing Chiral Phosphites and Phosphoramidites
in the Rhodium-Catalyzed Asymmetric Hydroboration of
Styrenea
entry
Rh catalyst
L
X
R1 R2 yield (%) % R ee (%)
1
2
[Rh(cod)Cl]
[Rh(cod)Cl]
[Rh(cod)Cl]
[Rh(nbd)Cl]
[Rh(nbd)Cl]
2
2
2
4a
4b
4c
5a
5b
5c
6a
6a
6a
6a
6b
6c
6c
6c
6c
O
O
N
O
O
N
O
O
O
O
O
N
N
N
N
Ph
13
54
21
21
61
18
95
95
95
94
38
62
66
95
95
65
72
83
44
59
66
89
87
83
78
50
74
64
73
73
5
17
40
11
18
15
84
84
81
75
0
Bn
3
Bn Bn
Ph
Bn
Figure 1. Successful chiral ligands for the rhodium-catalyzed
asymmetric hydroboration of styrene; yield, percent R-isomer, and
its percent enantiomeric excess are given in parentheses.
4
2
2
5
6
[Rh(cod)Cl]
[Rh(cod)Cl]
[Rh(nbd)Cl]
2
Bn Bn
Ph
7
2
8
2
Ph
Chiral monophosphites and phosphoramidites can offer
attractive alternatives to chiral diphosphines and related
chelating ligands as demonstrated, for example, in asym-
9
Rh(nbd)
2
BF
4
Ph
10
Rh(cod) SbF
2
6
Ph
1
1
1
1
2
3
[Rh(cod)Cl]
[Rh(cod)Cl]
2
Bn
2
Bn Bn
Bn Bn
Bn Bn
Bn Bn
25
0
7
7
8
metric hydrogenations. As part of our studies into chiral
[Rh(nbd)Cl]
Rh(nbd) BF
Rh(cod) SbF
2
9
catalyst design, we explored their use in rhodium-catalyzed
14
15
2
4
asymmetric hydroboration.1
0,11
2
6
Our initial studies employed
a
chiral phosphites and phosphoramidites derived from BINOL
Reactions were run in DME at ambient temperature (17 h) in the
presence of powdered 4A molecular sieves using a Rh/L/styrene/PBH ratio
of 1:2.2:100: 120 and followed by oxidation with basic hydrogen peroxide.
The yield, isomer ratio, and enantioselectivity are determined by chiral GC
12
(
4), biaryl derivative 5, and TADDOL (6) in the catalyzed
hydroboration of styrene with pinacol borane (PBH) (Table
). Neither axially chiral scaffold proves very successful
(
cyclosil â) using an internal standard.
1
(
(
entries 1-6). However, a promising result is obtained with
TADDOL)POPh (6a); it affords the branched product in
In light of the promising results obtained with 6a, a more
high yield (95%, 89% R) and good enantioselectivity (84%
ee, S) (entry 7). The presence of coordinating or noncoor-
dinating counterions in the catalyst precursor has little effect
extensive library of TADDOL-derived phosphites and phos-
phoramidites was prepared. Several vinyl arene substrates
1
4
were screened using these ligands; the data obtained for
-chlorostyrene are summarized in Table 2. The yield and
(entries 7-10), a surprising observation in light of mecha-
4
nistic studies indicating the counterion can play a significant
1
3
regioselectivity vary widely with no apparent trend favoring
phosphites or phosphoramidites. Regioselectivity in the
catalyzed reaction has been attributed to a variety of
role. The TADDOL-benzyl phosphite 6b (entry 11) and
the N,N-dibenzylphosphoramidite 6c are much less effective
(entries 12-15).
15
influences, including the nature of the hydroborating reagent
(
8) Bernsmann, H.; van den Berg, M.; Hoen, R.; Minnaard, A. J.; Mehler,
G.; Reetz, M. T.; de Vries, J. G.; Feringa, B. L. J. Org. Chem. 2005, 70,
43-951 and references therein.
9) (a) Takacs, J. M.; Reddy, D. S.; Moteki, S. A.; Wu, D.; Palencia, H.
and the electronic and steric nature of the ligands.16 Sterics
apparently play an important role in our study; for example,
the 1- and 2-naphthyl phosphites 14 and 15 differ greatly,
giving 77% and 8% of the R-product, respectively (entries
9
(
J. Am. Chem. Soc. 2004, 126, 4494-4495. (b) Takacs, J. M.; Chaiseeda,
K.; Moteki, S. A.; Reddy, D. S.; Wu, D.; Chandra, K. Pure Appl. Chem.
8
and 9).
2
006, 78, 501-509.
10) During the course of our work, Alexakis and Micouin reported
(
In terms of enantioselectivity, the methyl and benzyl
phosphites (entries 1 and 2) are unsatisfactory. The (1S,2R)-
promising results using phosphoramidite ligands in the asymmetric iridium-
catalyzed hydroboration of meso-bicyclic hydrazines; see: Alexakis, A.;
Polet, D.; Bournaud, C.; Bonin, M.; Micouin, L. Tetrahedron: Asymmetry
2
005, 16, 3672-3675.
11) (a) Seebach reported the TADDOL-derived methyl phosphinite,
TADDOL)PMe, gives 20% ee in the rhodium-catalyzed hydroboration of
styrene; see: Sakaki, J.; Schweizer, W. B.; Seebach, D. HelV. Chim. Acta
(14) Screening combinatorial mixtures of chiral monodentate ligands has
recently attracted much attention. See: (a) Reetz, M. T.; Sell, T.;
Meiswinkel, A.; Mehler, G. Angew. Chem., Int. Ed. 2003, 42, 790-793.
(b) Pena, D.; Minnaard, A. J.; Boogers, J. A. F.; de Vries, A. H. M.; de
Vries, J. G.; Feringa, B. L. Org. Biomol. Chem. 2003, 1, 1087-1089. (c)
Hartwig, J. Nature 2005, 437, 487-488. No heterocombination of ligands
6a-i and 10-19 gives significantly higher ee than the corresponding
homocombinations shown in Table 2.
(15) Crudden, C. M.; Hleba, Y. B.; Chen, A. C. J. Am. Chem. Soc. 2004,
126, 9200-9201.
(16) Daura-Oller, E.; Segarra, A. M.; Poblet, J. M.; Claver, C.; Fernandez,
E.; Bo, C. J. Org. Chem. 2004, 69, 2669-2680.
(
(
1
993, 76, 2654-2665. (b) Mixed bidentate ligands combining diphe-
nylphosphine and TADDOL-derived phosphites subunits have been used
with success; see: Blume, F.; Zemolka, S.; Fey, T.; Kranich, R.; Schmalz,
H.-G. AdV. Synth. Catal. 2002, 344, 868-883.
(12) Hua, Z.; Vassar, V. C.; Choi, H.; Ojima, I. Proc. Natl. Acad. Sci.
U.S.A. 2004, 101, 5411-5416.
13) Segarra, A. M.; Daura-Oller, E.; Claver, C.; Poblet, J. M.; Bo, C.;
Fernandez, E. Chem. Eur. J. 2004, 10, 6456-6467.
(
3098
Org. Lett., Vol. 8, No. 14, 2006