Table 3: Rhodium-catalyzed 1,2-addition of aryl boronic acid to ketone.
Figure 2. Energy profile for the transmetalation of the Stille coupling.
The relative free energies and potential energies (in parentheses)
obtained from the DFT calculations are given in kcalmolÀ1. Plain
typeface L=1b, italic L=AsPh3, bold L=1a.
Entry
10
11
Ligand
T [8C]
Yield [%][a]
1
2
3
4
5
6
7
8
10a
10a
10a
10a
10a
10a
10b
10c
10d
10e
10e
10e
10e
10e
11a[b]
11a[b]
11a[b]
11a[b]
11a[b]
11a[b]
11a[b]
11a[c]
11a[b]
11a[c]
11b[c]
11c[c]
11d[c]
11e[b]
none
40
40
40
40
40
40
40
20
30
20
20
20
20
20
0 (12aa)
0 (12aa)
35 (12aa)
72 (12aa)
2 (12aa)
94 (12aa)
91 (12ba)
99 (12ca)
81 (12da)
98 (12ea)
95 (12eb)
96 (12ec)
94 (12ed)
93 (12ee)
(Æ)-binap[d]
(Æ)-3c
(Æ)-3d
(Æ)-3 f
(Æ)-3a
(Æ)-3a
(Æ)-3a
(Æ)-3a
(Æ)-3a
(Æ)-3a
(Æ)-3a
(Æ)-3a
(Æ)-3a
[L(I)PdPh] (A), the isomer with cis arrangement of L and I
was not obtained in all cases. The overall relative energy
profile (A–D) of the 1a system is smaller than those of the
other systems. In particular, the activation barrier of the 1a
system (30.9 kcalmolÀ1) is significantly lower than that of the
corresponding AsPh3 or 1b systems (34.6 and 37.8 kcalmolÀ1,
respectively), thus indicating that highly electron-poor 1a
electronically accelerates the transmetalation step. However,
similar electron-poor ligand 1e showed no LAE in the Stille
coupling (Table 2, entries 6 and 11 vs. 1). 31P NMR spectros-
copy revealed that a large amount of 1e was not complexed
with Pd in the reaction mixture.[23] In the 1a system, no
inhibitory effect of excess ligand was observed (Table 2,
entry 2 vs. 7) although the effect was apparent in the 1b
system (Table 2, entry 5 vs. 10).[23] The results show that the
lower s-donating ability of 1a enables it to control the
electronic properties of the catalyst while avoiding catalyst
inactivation caused by coordination of additional ligands.[26]
The BFPy phosphane ligand accelerated the rhodium-
catalyzed 1,2-addition of aryl boronic acid to an unactivated
ketone. Although many examples of similar reactions using
aldehyde have been reported, this type of 1,2-addition to a
ketone had been limited, except for a few examples,[27] to
activated ketones,[28] intramolecular reactions,[28] and the side
reaction of 1,4-addition to an enone.[29] Furthermore, the
exceptional successful cases[27] required high reaction temper-
atures (80–1208C), a long reaction times (10–24 h), an
equivalent amount of additive, and aryl boron derivatives
instead of aryl boronic acid. The reaction of acetophenone
(10a) with three equivalents phenylboronic acid (11a) in the
presence of 1.5 mol% [{RhOH(cod)}2] and 3 mol% (Æ)-3a in
toluene/H2O gave 94% yield of 1,1-diphenylethanol (12aa)
when the reaction was carried out at 408C for 1 h without any
additives (Table 3, entry 6). It is obvious that the large LAE of
(Æ)-3a can be attributed to its electronic effect. [{RhOH-
(cod)}2] (1.5 mol%) showed no catalytic activity (Table 3,
entry 1) and further addition of (Æ)-binap or (Æ)-3 f resulted
in no acceleration (Table 3, entries 2 or 5). The Rh catalyst
with electron-poor phosphanes (Æ)-3c and 3d gave the
product in poor to moderate yields (Table 3, entries 3 and
4). The Rh/(Æ)-3a catalyst provided an excellent yield of the
product in the reactions with other ketones and aryl boronic
acids when allowed to react for 1 h at a temperature between
20 and 408C (Table 3, entries 7–14). The reaction mechanism
9
10
11
12
13
14
[a] Yield of isolated product. [b] 3 equiv was used. [c] 2 equiv was used.
[d] binap=2,2’-bis(diphenylphosphanyl)-1,1’-binaphthyl.
is presumed to be similar to that of Rh- or Pd-catalyzed 1,2-
addition to an aldehyde[27a] involving the transmetalation of
À
11 to Rh, insertion of 10 into the Rh Ar bond and then
hydrolysis to give 12. Because an excess amount of 11 was
required, the rate-determining step is assumed to be the
insertion step,[30] and highly electron-poor 3a is expected to
substantially accelerate the insertion.[5] As a result, an
efficient Rh-catalyzed 1,2-addition of aryl boronic acids to
unactivated ketones near room temperature was achieved
using highly electron-poor ligand (Æ)-3a without any addi-
tives. We are currently making efforts to develop the
asymmetric variants.[31]
Highly enantioselective catalysis using (R)-3a was achie-
ved in the asymmetric arylation of aryl imine (Table 4).[32,33]
The reaction of N-tosylimine 13 with one equivalent 11a in
the presence of 0.025 mol% [{RhCl(C2H4)2}2] (0.05 mol%
Rh) and 0.05 mol% (R)-3a in toluene/H2O with 20 mol%
KOH at 20 8C for 1 h gave N-tosylamine (S)-14 in 98% yield
and with 98% ee (Table 4, entry 1). When 0.008 mol% Rh/
(R)-3a was used, the TOF was 6900 hÀ1 (Table 4, entry 2).
This value is notable because similar known catalytic
reactions using activated imine required 1.5–3 mol% catalyst
loading, a longer reaction time (3–12 h, typically TOF
< 10 hÀ1 [34]), and higher reaction temperature.[32,33] The catal-
ysis using (R)-binap or (R)-3 f gave no product under these
conditions (Table 4, entries 4 and 7). Although the use of the
electron-poor phosphanes (R)-3c or (R)-3d showed accept-
able TOF values (Table 4, entries 5 and 6), the values were
much lower than that obtained with (R)-3a. Ultimately, the
Angew. Chem. Int. Ed. 2011, 50, 10703 –10707
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