Inter- and intramolecular additions of 1-alkenylboronic acids or esters to aldehydes and ketones catalyzed by rhodium(I) complexes in basic, aqueous solutions

Article abstract of DOI:10.1055/s-2002-34219

Grignard-type addition reaction of 1-alkenylboronic acids or their esters to aldehydes or ketones were carried out in aqueous MeOH or DME in the presence of KOH (1 equivalent) and an RhCl(dppf) or Rh(OH)(dppf) catalyst (3 mol%). The utility of the protocol was demonstrated in the corresponding intramolecular reaction giving cyclic homoallylic alcohols.

Full text of DOI:10.1055/s-2002-34219

LETTER
1733
Inter- and Intramolecular Additions of 1-Alkenylboronic Acids or Esters to
Aldehydes and Ketones Catalyzed by Rhodium(I) Complexes in Basic,
Aqueous Solutions
Intramolecular
Ad
k
ditions of 1-A
i
lkeny
n
lboronic Acid
o
s/Esters to A
r
ldehyde
i
s
Takezawa, Kenji Yamaguchi, Toshimichi Ohmura, Yasunori Yamamoto, Norio Miyaura*
Division of Molecular Chemistry, Graduate School of Engineering, Hokkaido University, Sapporo 060-8628, Japan
Fax +81(11)7066561; E-mail: miyaura@org-mc.eng.hokudai.ac.jp
Received 23 August 2002
C4H9
Abstract: Grignard-type addition reaction of 1-alkenylboronic ac-
C4H9
C4H9
ids or their esters to aldehydes or ketones were carried out in aque-
ous MeOH or DME in the presence of KOH (1 equivalent) and an
RhCl(dppf) or Rh(OH)(dppf) catalyst (3 mol%). The utility of the
protocol was demonstrated in the corresponding intramolecular re-
action giving cyclic homoallylic alcohols.
B(OR)2
2
RCHO
+
R
R
Rh catalyst
HO
O
1
3
4
2a: B(OR)2 = B(OH)2
Key words: alkenylboron, rhodium catalyst, addition
O
secondary isomerization
2b: B(OR)2
2c: B(OR)2
=
=
B
B
O
O
Metal-catalyzed Grignard-type reaction of main-group or-
ganometallic compounds is attractive as a method for
alkylation of carbonyl compounds that has a potential ap-
plication to asymmetric synthesis using an optically active
metal catalyst. Although insertion of a carbon-heteroatom
-bond into a late metal-carbon bond is rare compared
with that of a carbon-carbon -bond, a catalytic cycle that
occurs by a transmetalation-insertion process was recent-
ly found to be a convenient alternative for alkylation of al-
dehydes or aldimines. It has been shown that the additions
of arylstannanes1 and arylsilanes2 to aldehydes, ketones or
imines are catalyzed by rhodium complexes, Ni(acac)2–
PPh3 catalyzes the methylation of aldehydes with trimeth-
ylaluminum,3 and allylstannanes4 and allylsilanes5 add to
aldehydes and imines in the presence of PdCl2(PPh3)2 or
PtCl2(PPh3)2. Rhodium(I) complexes are efficient cata-
lysts for the addition of aryl- or 1-alkenylboronic acids6,7
or potassium trifluoroborates8 to aldehydes or imines.
Arylrhodium(I) complexes, proposed as an intermediate
of the catalytic cycle, have recently been demonstrated to
insert aldehydes into an aryl-rhodium bond.9
(Bpin)
O
O
2d: B(OR)2
=
B
O
Scheme 1 Rhodium-catalyzed addition to aldehydes
low yields (entry 1). In contrast, the presence of aqueous
KOH had a great accelerating effect as was demonstrated
by Fürstner7 (entries 2–5). The reaction provided a mix-
ture of allylic alcohol and ketone 3 and 4 depending on the
rhodium(I) complexes employed. Since rhodium com-
plexes catalyze the positional isomerization of a double
bond, the reaction was accompanied by a ketone deriva-
tive 4 derived from secondary isomerization of 3. 1-Phe-
nylheptan-1-one was indeed obtained quantitatively when
1-phenyl-2-hepten-1-ol was treated with Rh(acac)/dppf in
aqueous KOH at 80 °C. The related reaction of 1-alkenyl-
silanes also suffered from such secondary isomerization.2b
The added base should contribute to the conversion of an
RhCl or Rh(acac) complex to the corresponding Rh(OH)
species11 that can undergo transmetalation with organobo-
ronic acids.6,10 An Rh(OH)(dppf) complex in situ generat-
ed from [RhOH(cod)]2 and dppf was indeed an excellent
catalyst to selectively yield 3 at room temperature (entry
7), whereas 4 was again the major product at 80 °C (entry
6). Although Rh(OH)(dppf) was found to be a selective
catalyst in a single aqueous medium, a homogeneous sys-
tem using an organic solvent can be advantageous for var-
ious aldehydes. The complex prepared in situ from
[Rh(OH)(cod)]2 and dppf or t-Bu3P gave a catalyst that
was efficient for the synthesis of 3 in a basic, aqueous
MeOH (entries 8 and 9). On the other hand, the corre-
sponding ketone 4 was selectively given at 80 °C in aque-
ous DME (entry 10). Although the reaction of boronic
In connection with our interests in rhodium-catalyzed
reactions of organoboron compounds,6,10 we report here
the alkylation of aldehydes and ketones with 1-alkenyl-
boronic acids or boronic esters. Intermolecular reaction of
1-alkenylboronic acids or esters can be limitedly used for
aldehydes (Scheme 1), whereas analogous addition to
ketones occurred smoothly in the corresponding intra-
molecular version (Scheme 2).
The results of addition of (E)-1-hexenylboronic acid or its
ester to benzaldehyde are summarized in Table 1. The cat-
alysts for addition of arylboronic acids to aldehydes,
RhCl(dppf) and Rh(acac)(dppf),6a resulted in significantly
Synlett 2002, No. 10, Print: 01 10 2002.
Art Id.1437-2096,E;2002,0,10,1733,1735,ftx,en;U05902ST.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214

1734
A. Takezawa et al.
LETTER
Table 1 Reaction Conditionsa
Entry
1
2
Rh catalyst
Additive (equiv) Solvent
Temp/°C
80
Yield/%
2
(3/4)b
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2b
2c
2d
[RhCl(cod)]2/dppf
[RhCl(cod)]2/dppf
[RhCl(coe)2]2/dppf
Rh(acac)(coe)2/dppf
[Rh(cod)2]BF4/dppf
[RhOH(cod)]2/dppf
[RhOH(cod)]2/dppf
[RhOH(cod)]2/dppf
[RhOH(cod)]2/2PtBu3
[RhCl(cod)]2/dppf
[RhCl(cod)]2/dppf
[RhCl(cod)]2/dppf
[RhCl(cod)]2/dppf
none
H2O
(0:100)
(0:100)
(13:77)
(15:85)
(0:100)
(0:100)
(100:0)
(94:6)
2
KOH (6)
KOH (6)
KOH (6)
KOH (6)
none
H2O
80
95
89
62
75
81
77
78
67
80
81
51
0
3
H2O
80
4
H2O
80
5
H2O
80
6
H2O
80
7
none
H2O
25
8
KOH (1)
KOH (1)
KOH (1)
KOH (1)
KOH (1)
KOH (1)
MeOH/H2O (6:1)
MeOH/H2O (6:1)
DME/H2O (6:1)
DME/H2O (6:1)
DME/H2O (6:1)
DME/H2O (6:1)
25
9
25
(99:1)
10
11
12
13
80
(0:100)
(81:19)
(100:0)
80
80
80
a A mixture of benzaldehyde (1 mmol), (E)-1-hexenylboronic acid or ester (2, 2.0 mmol), KOH (0–6 mmol), and a rhodium catalyst (0.03 mmol,
3 mol%) in solvent (3 mL) was stirred for 16 h at the temperature shown in Table 1.
b GC yields.
Table 2 Addition of (E)-1-Hexenylboronic Acid (2a) to Aldehydesa
esters was much slower than that of boronic acid, the
trimethylene glycol ester afforded a comparable yield at
80 °C (entry 11). The pinacol ester resulted in a moderate
yield, and no addition product was obtained for the cate-
chol ester (entries 12 and 13).
Method Aa
Method Bb
Entry
1
Aldehyde
Yield/% (3/4) Yield/% (3/4)
4-MeOC6H4CHO
C6H5CHO
0
0
The addition of (E)-1-hexenylboronic acid to the repre-
sentative aldehydes is shown in Table 2. No addition was
observed for 4-methoxybenzaldehyde even at 80 °C (en-
try 1) due to its high electron density on the aromatic ring.
In contrast, the boronic acid smoothly added to 4-chloro,
4-methoxycarbonyl-, and 4-trifluromethyl derivatives
(entries 3–7) under the conditions optimized for benzalde-
hyde (entry 2). Formation of allylic alcohols 3 predomi-
nated at 25 °C in a basic, aqueous methanol (method A).
On the other hand, the ketones 4 were selectively given at
80–100 °C in a basic, aqueous DME (method B). Addi-
tions of 4-cyano- and 4-nitrobenzaldehyde were strongly
retarded, presumably due to coordination of these polar
functional groups to the metal center (entries 8 and 9).
Fortunately, these reactions proceeded smoothly under
the conditions of method B, by which allylic alcohols 3
were unexpectedly predominated over the formation of
ketones. Additions to aliphatic aldehydes such as cyclo-
hexanecarbaldehyde also gave an alcohol product at 80 °C
(entry 10). Since the boronic acid neutralizes the added
2
78 (94:6)
96 (0:100)
77 (25:75)
82 (0:100)
–
3
4-ClC6H4CHO
4-ClC6H4CHO
4-MeO2CC6H4CHO
4-CF3C6H4CHO
4-CF3C6H4CHO
4-NCC6H4CHO
4-O2NC6H4CHO
cyclo-C6H11CHO
C5H11CHO
72 (97:3)
4c
5
–
69 (91:9)
6
80 (90:10)
89 (17:83)
91 (0:100)
78 (100:0)
60 (85:15)
77 (100:0)
7 (100:0)
7c
8
–
0
0
0
0
9
10
11
a Method A: A mixture of an aldehyde (1.0 mmol), (E)-1-hexenylbo-
ronic acid (2.0 mmol), KOH (1.0 mmol), [RhOH(cod)]2 (0.015 mmol,
3 mol%), dppf (0.03 mmol, 3 mol%) in MeOH/H2O (6:1) (5 mL) was
stirred for 16 at r.t.
b Method B: A mixture of an aldehyde (1.0 mmol), (E)-1-hexenylbo-
base in the form of RB(OH)3K, side-reactions associated ronic acid (2.0 mmol), KOH (1.0 mmol), [RhCl(cod)]2 (0.015 mmol,
3 mol%), dppf (0.03 mmol, 3 mol%) in DME/H2O (6:1) (5 mL) was
with the base, such as saponification of esters (entry 5)
and Cannizzaro reaction of aromatic aldehydes, were not
significant. However, hexanal resulted in 7% yield be-
stirred for 16 h at 80 °C.
c The reactions were carried out at 100 °C.
cause of its high sensitivity to the bases (entry 11).
Synlett 2002, No. 10, 1733–1735 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Intramolecular Additions of 1-Alkenylboronic Acids/Esters to Aldehydes
1735
for 12 h to convert the catechol ester into the pinacol ester. The
product was isolated by chromatography over silica gel with hex-
ane/ethyl acetate (10:1) to give 6 (2.17 g, 82%). H NMR (400
Intermolecular addition of 1-alkenylboronic acids can be
limitedly used for aldehydes; however, the corresponding
intramolecular version can be extended to the addition of
pinacol esters of boronic acids to ketones (Scheme 2).
Rhodium-catalyzed hydroboration of terminal alkynes
with catecholborane (HBcat) is a convenient method12 for
preparation of (Z)-alkenylboronates 6 and 9 desirable for
six- and five-membered cyclization. The reaction requires
the protection of aldehydes, but ketone, ester and amide
derivatives can be directly hydroborated without protec-
tion of the carbonyl group with 97–99% Z-selectivities.
The catechol esters thus synthesized were converted into
pinacol esters 6 and 9 for isolation by chromatography on
silica gel. The intramolecular addition to the carbonyl
group was easily achieved by a Rh(OH)(cod) catalyst in
situ generated from [RhCl(cod)]2 and KOH. Although the
six-membered cyclization afforded an allylic alcohol 7 in
a yield of 91%, the five-membered cyclization was fol-
lowed by dehydration, leading to the formation of three
inseparable tautomers of cyclopentadienes 10.
1
MHz, CDCl3) 6.46 (dt, J = 13.4, 8.1 Hz, 1 H), 5.47 (dt, J = 13.4
Hz, 1.2 Hz 1 H), 2.43 (dd, J = 8.1, 1.2 Hz, 2 H), 2.35 (s, 2 H), 2.13
(s, 3 H), 1.27 (s, 12 H), 1.02 (s, 6 H). 13C NMR (100 MHz, CDCl3):
208.9, 150.5, 82.9, 53.9, 44.4, 34.0, 32.5, 26.9, 24.8. 11B NMR
(128 MHz, CDCl3) 29.64. IR (neat) 1710 cm–1. MS (EI) m/z 266
(M+, 11), 251 (43), 208 (71), 165 (94), 164 (48), 151 (35), 123 (37),
122 (44), 121 (30), 111 (61), 110 (42), 109 (44), 108 (85), 107,
(100), 101 (97). HRMS (EI) calcd for C15H27BO3 266.2053, found
266.2029.
A flask charged with [Rh(cod)Cl]2 (0.007 g, 0.015 mmol) was
flushed with argon. Ethanol (3 mL), 6 (1 mmol), and aq KOH (3 M,
1 ml, 3 mmol) were then added successively. The mixture was
stirred at 60 °C for 1 h. GC analysis shown the formation of 7
1
(91%). H NMR (400 MHz, CDCl3) 5.61–5.66 (m, 1 H), 5.54–
5.57 (m, 1 H), 1.73–1.81 (m, 2 H), 1.48–1.63 (m, 2 H), 1.20 (s, 3 H),
0.98 (s, 3 H), 0.90 (s, 3 H). 13C NMR (100 MHz, CDCl3) 132.4,
127.0, 68.8, 50.4, 38.9, 31.0, 30.9, 29.7, 27.8. IR (neat) 3450 cm–1.
References
(1) (a) Oi, S.; Moro, M.; Inoue, Y. Chem. Commun. 1997, 1621.
(b) Oi, S.; Moro, M.; Ono, S.; Inoue, Y. Chem. Lett. 1998,
83. (c) Hayashi, T.; Ishigedani, M. J. Am. Chem. Soc. 2000,
122, 976.
O
O
OH
H
a, b
c
(2) (a) Oi, S.; Moro, M.; Inoue, Y. Organometallics 2001, 20,
1036. (b) Fujii, T.; Koike, T.; Mori, A.; Osakada, K. Synlett
2002, 298.
91%
82%
Bpin
5
6
7
(3) Ichiyanagi, T.; Kuniyama, S.; Simizu, M.; Fujisawa, T.
Chem. Lett. 1998, 1033.
O
O
(4) (a) Nakamura, H.; Iwama, H.; Yamamoto, Y. J. Am. Chem.
Soc. 1996, 118, 6641. (b) Nakamura, H.; Nakamura, K.;
Yamamoto, Y. J. Am. Chem. Soc. 1998, 120, 4242.
(5) Nakamura, K.; Nakamura, H.; Yamamoto, Y. J. Org. Chem.
1999, 64, 2614.
(6) (a) Sakai, M.; Ueda, M.; Miyaura, N. Angew. Chem. Int. Ed.
1998, 37, 3279. (b) Ueda, M.; Miyaura, N. J. Org. Chem.
2000, 65, 4450. (c) Ueda, M.; Saito, A.; Miyaura, N. Synlett
2000, 1637.
c
a, b
70%
Bpin
88%
O
O
O
NBu2
NBu2
NBu2
10
( three tautomers)
9
8
Scheme 2 Intramolecular addition to ketone carbonyls. Reagents
and conditions: a) HBcat, [RhCl(cod)]2-2-i-Pr3P, Et3N, cyclohexane,
r.t., 2 h; b) pinacol, r.t., 12 h; c) [RhCl(cod)]2, KOH, EtOH, 60 °C, 1 h.
(7) Fürstner, A.; Krause, H. Adv. Synth. Catal. 2001, 343.
(8) Batey, R. A.; Thadani, A. N.; Smil, D. V. Org. Lett. 1999, 1,
1683.
Further studies are in progress to elucidate possible syn-
thetic applications.
(9) Krug, C.; Hartwig, J. F. J. Am. Chem. Soc. 2002, 124, 1674.
(10) (a) Sakai, M.; Hayashi, H.; Miyaura, N. Organometallics
1997, 16, 4229. (b) Takaya, Y.; Ogasawara, M.; Hayashi,
T.; Sakai, M.; Miyaura, N. J. Am. Chem. Soc. 1998, 120,
5579. (c) Sakuma, S.; Sakai, M.; Miyaura, N. J. Org. Chem.
2000, 65, 5951. (d) Itooka, R.; Iguchi, Y.; Miyaura, N.
Chem. Lett. 2001, 722. (e) Sakuma, S.; Miyaura, N. J. Org.
Chem. 2001, 66, 8944.
(11) Grushin, V. V.; Kuznetsov, V. F.; Bensimon, C.; Alper, H.
Organometallics 1995, 14, 3927.
(12) Ohmura, T.; Yamamoto, Y.; Miyaura, N. J. Am. Chem. Soc.
2000, 122, 4990.
Typical Procedures for 6 and 7:
A 25 mL two neck flask equipped with a magnetic stirring bar and
a rubber septum cap was charged with [Rh(cod)Cl]2 (0.07 g, 0.15
mmol) and then flushed with argon. Cyclohexane (30 mL), P-i-Pr3
(0.114 mL, 0.6 mmol), Et3N (1.4 mL, 10 mmol), and catecholbo-
rane (1.20 g, 10 mmol) were successively added. After being stirred
for 30 min, 5 (1.2 mmol) was added in one portion and the mixture
was then stirred at r.t. for 2 h. Pinacol (1.77 g, 15 mmol) in cyclo-
hexane (10 mL) was added. The resulting mixture was stirred at r.t.
Synlett 2002, No. 10, 1733–1735 ISSN 0936-5214 © Thieme Stuttgart · New York