Table 1. Results of the addition reaction of arylboronic acid with various
aldehydes.[a]
effectively with 2d to furnish substituted diarylmethanols
3bd–3hd in 93, 93, 84, 92, 97, 96, and 75% yield, respective-
ly (Table 1, entries 20–26). These results clearly indicate that
the present addition reaction shows excellent tolerance to-
wards Br, F, CHO, Me, and OMe functional groups. The cat-
alytic reaction also worked very well with alkenylboronic
acid. Thus, (E)-1-phenylvinyl boronic acid (1i) reacted with
2d to afford allylic alcohol 3id in 78% yield (Table 1,
entry 27).
The great importance of chiral secondary alcohols in or-
ganic synthesis prompted us to explore the enantioselective
addition of organoboronic acids with aldehydes. Phenylbor-
onic acid (1a) and 2d were used as the model substrates in
this study. Cobalt catalyst CoI2 (5 mol%), a bidentate chiral
ligand (5 mol%), and K2CO3 (1.5 equiv) in THF were used
in the reaction. Various bidentate chiral ligands, including
(R)-Prophos, (R)-Tol-BINAP, (S)-BINAP, (S,S)-Chiraphos,
(S)-BINOL, (R,R)-Ph-BPE, (R)-Quinap, (R)-MOP, (S,S)-
DIPAMP, (R)-Monophos, (R,R)-BDPP, and (S,S)-DIOP,
were examined (for the structure of chiral ligands and de-
tailed optimization studies, see the Supporting Information).
Among them, (R,R)-BDPP is most effective, affording (S)-
diarylmethanol 3ad in 98% yield with an ee value of 94%
(Table 2, entry 3).[11] Other ligands provided 3ad in 44–86%
yields with an ee value of 10–67%. Under the reaction con-
ditions, (S,S)-BDPP provided the other enantiomer (R)-dia-
rylmethanol 3ad in 95% yield with an ee of 93% (Table 2,
Entry Substrates
Product Yield[b] [%]
1
2
3
4
5
6
7
8
1a: R1 =H; 2a: R=4-CN-C6H4
3aa
3ab
3ac
3ad
3ae
3af
3ag
3ah
3ai
96
97
93
98
89
92
82
80
96
84
73
75
75
67
57
76
69
78
79
93
93
84
92
97
96
75
78
1a: R1 =H; 2b: R=4-NO2-C6H4
1a: R1 =H; 2c: R=4-CHO-C6H4
1a: R1 =H; 2d: R=4-CO2Me-C6H4
1a: R1 =H; 2e: R=4-CF3-C6H4
1a: R1 =H; 2 f: R=4-F-C6H4
1a: R1 =H; 2g: R=3-F-C6H4
1a: R1 =H; 2h: R=2-F-C6H4
1a: R1 =H; 2i: R=4-Cl-C6H4
1a: R1 =H; 2j: R=4-Br-C6H4
1a: R1 =H; 2k: R=Ph
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
3aj
3ak
3al
1a: R1 =H; 2l: R=1-napthyl
1a: R1 =H; 2m: R=2-napthyl
1a: R1 =H; 2n: R=4-Me-C6H4
1a: R1 =H; 2o: R=4-OMe-C6H4
1a: R1 =H; 2p: R=4-pyridinyl
1a: R1 =H; 2q: R=2-furyl
3am
3an
3ao
3ap
3aq
3ar
3as
3bd
3cd
1a: R1 =H; 2r: R=2-thienyl
1a: R1 =H; 2s: R=cyclohexyl
1b: R1 =4-Br; 2d: R=4-CO2Me-C6H4
1c: R1 =4-F; 2d: R=4-CO2Me-C6H4
1d: R1 =4-CHO; 2d: R=4-CO2Me-C6H4 3dd
1e: R1 =4-Me; 2d: R=4-CO2Me-C6H4
3ed
1 f: R1 =4-OMe; 2d: R=4-CO2Me-C6H4 3 fd
1g: R1 =2-OMe; 2d: R=4-CO2Me-C6H4 3gd
1h: R1 =4-vinyl; 2d: R=4-CO2Me-C6H4 3hd
entry 4). Another cobalt catalyst, CoACHTNUTRGNENUG(acac)2/ACHTUNGTREN(NGUN R,R)-BDPP, in
THF without base is also effective, giving chiral (S)-3ad in
92% yield and 89% ee.
1i: (E)-styryl; 2d: R=4-CO2Me-C6H4
3id
[a] Unless otherwise mentioned, all of the reactions were carried out by
using arylboronic acid 1 (1.20 mmol), aldehydes 2 (1.00 mmol), Co(acac)2
(5 mol%), dppe (5 mol%), and THF/CH3CN (1:1) at 808C for 12 h.
In the presence of CoI2 (5 mol%)/ACTHNUTRGNEUNG(R,R)-BDPP (5 mol%)
AHCTUNGTRENNUNG
and K2CO3 (1.5 equiv) in THF, the reaction of various sub-
stituted aldehydes with phenylboronic acid (1a) were then
examined (Table 2). Electron-withdrawing groups, 4-CN-
(2a), 4-NO2- (2b), 4-CO2Me- (2d), and 4-CF3-substituted
(2e) benzaldehydes afforded chiral (S)-diarylmethanols 3aa,
3ab, 3ad, and 3ae in excellent 97, 95, 98, and 97% yield
with 92, 93, 94 and 92% ee, respectively (Table 2, entries 1–
3, 5). As expected, if CoI2/ACTHNUTRGNE(UNG S,S)-BDPP was employed as the
catalyst, the reaction of 1a with 2d afforded the correspond-
ing (R)-3ad in 93% ee (Table 2, entry 4). Similarly, by using
[b] Isolated yields.
tion.[15] For example, 4-F (2 f), 3-F (2g), 2-F (2h), 4-Cl (2i),
and 4-Br (2j) also reacted efficiently with 1a to give the cor-
responding diarylmethanols 3af–3aj in good to excellent
yields (Table 1, entries 6–10). Similarly, benzaldehyde (2k),
1-napthaldehyde (2l) and 2-napthaldehyde (2m) underwent
addition reaction with 1a to afford products 3ak–3am in
good yields (Table 1, entries 11–13). Benzaldehydes contain-
ing electron-donating groups, such as 4-Me (2n) and 4-OMe
(2o) also gave addition products 3an and 3ao albeit in mod-
erate yields (Table 1, entries 14 and 15). Heterocyclic alde-
hydes, including 4-formylpyridine (2p), 2-formylfuran (2q),
and 2-formylthiophene (2r) also reacted efficiently to give
addition products 3ap–3ar in 76, 69, and 78% yields, respec-
tively (Table 1, entries 16–18). Aliphatic aldehyde, cyclohex-
anecarbaldehyde (2s), also effectively participated in the ad-
dition reaction affording product 3as in 79% yield (Table 1,
entry 19).
CoI2/ACTHNURTGNEU(GN R,R)-BDPP as the catalyst, 4-F- (2 f), 4-Cl- (2i), and
4-Br-substituted (2j) benzaldehydes provided (S)-diarylme-
thanols 3af, 3ai, and 3aj in excellent 95–97% yield with 99,
93, and 96% ee, respectively (Table 2, entries 6–8). Likewise,
1-naphth- (2l) and 2-naphthaldehyde (2m), 4-methyl (2n),
4-methoxybenzaldehyde (2o), and 2-formylthiophene (2r)
gave (S)-diarylmethanols 3al, 3am, 3an, 3ao, and 3ar, re-
spectively, in 77–90% yield with 86–93% ee (Table 2, en-
tries 9–13). A 2-naphthyl and 2-thienyl group on the alde-
hyde substrate appears to lower the ee value slightly com-
pared with other aryl groups used. In a similar manner, cy-
clohexanecarbaldehyde (2s) yielded (R)-3as in 84% yield
with 97% ee (Table 2, entry 14). It is interesting to note that
in the present chiral addition reaction with base, even elec-
tron-rich-substituted, heteroaromatic and aliphatic alde-
hydes provided the corresponding addition products in ex-
To further explore the scope of the addition reaction, vari-
ous substituted organoboronic acids were examined with
methyl 4-formyl benzoate (2d). 4-Bromo- (1b), 4-fluoro-
(1c), 4-formyl- (1d), 4-methyl- (1e), 4-methoxy- (1 f), 2-me-
thoxy- (1g) and 4-vinylphenylboronic (1h) acids all reacted
8990
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2010, 16, 8989 – 8992