Et3B-promoted, Pd-catalyzed C-allylation of o-hydroxyacetophenone and its derivatives with allyl alcohols

Article abstract of DOI:10.1016/S0040-4039(01)00381-1

Triethylborane promotes the Pd-catalyzed selective C-diallylation of o-hydroxyacetophenone and C-monoallylation of o-hydroxypropiophenone with a variety of ally alcohols. The reaction proceeds smoothly at 25-50°C and provides the allylation products in excellent yields.

Full text of DOI:10.1016/S0040-4039(01)00381-1

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 3113–3116
Et3B-promoted, Pd-catalyzed C-allylation of
o-hydroxyacetophenone and its derivatives with allyl alcohols
Yoshikazu Horino, Makoto Naito, Masanari Kimura, Shuji Tanaka and Yoshinao Tamaru*
Department of Applied Chemistry, Faculty of Engineering, Nagasaki University, 1-14 Bunkyo-Machi, Nagasaki 852-8521, Japan
Received 8 February 2001; accepted 19 February 2001
Abstract—Triethylborane promotes the Pd-catalyzed selective C-diallylation of o-hydroxyacetophenone and C-monoallylation of
o-hydroxypropiophenone with a variety of ally alcohols. The reaction proceeds smoothly at 25–50°C and provides the allylation
products in excellent yields. © 2001 Elsevier Science Ltd. All rights reserved.
Palladium-catalyzed allylic alkylation of active methyl-
ene compounds such as b-ketoesters and malonates is
an established, efficient method for CꢀC bond forma-
tion reactions.1 In most cases, carboxylic acid esters,
carbonates, phosphates and related compounds of allyl
alcohols have been utilized as the alkylation agents. In
a limited number of cases, however, the reaction has
proven to be successful with direct use of allyl alco-
hols.2 On the other hand, the a-allylic alkylation of
non-stabilized ketones and esters is still to be explored.
The alkylation reported so far is rather sophisticated
and requires both reaction partners to be pre-activated:
allyl alcohols as their ester derivatives and ketones and
esters as their metal and metalloid enolates3 or as their
enol ethers.4
Here we would like to disclose that o-hydroxylphenyl
alkyl ketones and allyl alcohols react to provide the
C-allylation products in excellent yields when they are
treated with Et3B in the presence of a catalytic amount
of Pd(OAc)2. Significantly, no pre-activation of either
reaction partner is required. Thus, the reaction of o-
Pd(OAc)2 (5 mol%)
PPh3 (10 mol%)
OH
O
OH
O
OH
O
+
+
(1)
OH
Et3B (2.4 mmol)
THF (5 mL)
1a
2a
3a
4a
allyl alcohol
product (isolated yield)
ketones
reaction conditions
r.t., 24 h
4a (43%)
3a (1%)
1a (1.2 mmol)
1a (2.4 mmol)
1a (1.2 mmol)
2a (1.0 mmol)
2a (1.0 mmol)
3a (1.0 mmol)
1
2
3
r.t., 24 h
4a (82%)
3a (0%)
r.t., 2 h
4a (80%)
3a (0%)
OH
O
OH
O
OH O
the same as above
(2)
+
+
OH
1a
3b
2b
4b
1a (1.2 mmol)
1a (2.4 mmol)
2b (1.0 mmol)
2b (1.0 mmol)
r.t., 5 h
r.t., 5 h
3b (81%)
3b (83%)
4b (0%)
4b (3%)
4
5
Scheme 1.
Keywords: alcohols; allylation; boron and compounds; palladium and compounds.
* Corresponding author.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00381-1

3114
Y. Horino et al. / Tetrahedron Letters 42 (2001) 3113–3116
hydroxyacetophenone (2a, 1.0 mmol) and allyl alcohol
(1a, 1.2 mmol) in the presence of Et3B (2.4 mmol),
Pd(OAc)2 (0.05 mmol), and PPh3 (0.10 mmol) at room
temperature for 24 h provided mono-3a (1%) and dially-
lation product 4a (43%) with recovery of 2a in 45% yield
(run 1, Scheme 1). The same reaction with 2.4 mmol of
1a provided 4a in 82% isolated yield with no recovery of
2a (run 2, Scheme 1). The selective formation of 4a in
good yield (run 1, Scheme 1; 78% based on 55%
conversion of 2a) suggests that the second alkylation
(3a“4a) proceeds much faster than the first one (2a“
3a). Indeed, the alkylation of 3a with 1a completed in a
remarkably shorter reaction time and provided 4a in
excellent yield (run 3, Scheme 1). o-Hydroxypropiophe-
none (2b) displayed similar reaction features: 2b
smoothly reacted with 1a and provided 3b in good yield
(run 4). Interestingly, a further alkylation of 3b leading
to 4b proceeded to a negligible extent even when the
reaction was undertaken in the presence of an excess
amount of 1a (run 5). All these results indicate that the
present alkylation displays a strong tendency to selec-
tively provide a-disubstituted alkyl ketones.
Table 1. Pd-catalyzed C-diallylation of 2a and C-monoallylation of 2b with allyl alcohols 1b–ha)
% isolated yield of proudcts 3, 4, and 5b)
ketones
allyl alcohol
temp (°C)/time (h)
(% conversion)
run
1
2
1
OH
O
OH
O
25/48
(100)
OH
1b
4c (81)
2a
OH
O
OH
O
Ph
Ph
Ph
25/48; 50/6
(100)
2
2a
Ph
Ph
OH
1c
Ph
4d (80)
5a (10)c)
OH
O
OH
O
25/22
(77)
3
4
1b
1d
3c (83)
2b
2b
OH
O
OH O
25/20
(100)
OH
3d (66)
3d (63)
3d' (24) [1:1.1]d)
3d' (25) [1:1.1]d)
25/20
(100)
5
6
7
2b
2b
2b
OH
1e
OH
O
25/4
(100)
1c
Ph
3e (81)c)
Ph
OH
25/8
(100)
3e (88)c)
1f
OH
O
OH O
25/45; 50/5
(81)
8
9
2b
OH
1g
3f' (11)
3f (83)
OH
O
25/30; 50/8
(100)
2b
OH
1h
3g (96) [1:1.1]d)
a) Typical reaction conditions: A mixture of 1 (2.4 mmol for 2a, 1.2 mmol for 2b), 2 (1.0 mmol), Et3B (2.4 mmol, 1 M solution in hexane),
Pd(OAc)2 (0.05 mmol) and PPh3 (0.10 mmol) in THF (5 ml) was stirred for the period of time and at the temperature indicated in the Table.
b) Isolated yield for the spectroscopically homogenous products (based on conversion).
c) A mixture of 1,6- and 1,4-diphenyl-1,5-hexadienes (24% in run 2, 4% in run 6, 6% in run 7) was also produced.
d) Ratios of two diastereomers determined on the basis of 1H NMR spectra (400 MHz).

Y. Horino et al. / Tetrahedron Letters 42 (2001) 3113–3116
3115
O
F
O
NH2 O
OMe O
O
O
HO
2f
2c
2d
2g
2h
HO
2e
Figure 1. A list of acetophenone derivatives that provide no C-allylation products for the reaction with 1a under standard
conditions.
Et
Et
OH
O
B
O
O
Pd
O
H
BEt3
3a
II
Et
I
Et
OH
OH
O
B
4a
O
O
BEt3
Pd(0)
1a•BEt3
2a
III
+
H2O-BEt3
Scheme 2. A plausible catalytic cycle for the Et3B-promoted, Pd-catalyzed C-allylation of 2a with 1a.
Results obtained for the reaction of 2a and 2b with
other allyl alcohols 1b–h (2.4 equiv. for 2a and 1.2
equiv. for 2b) are summarized in Table 1, which reveals
that the present allylative alkylation is successfully
applicable to primary, secondary and tertiary allyl alco-
hols with a wide variety of substitution patterns on the
double bond.5 Regioselectivity is just as is expected for
the reactions via p-allylpalladium complexes as interme-
diates; unsymmetrical allyl alcohols react at the least
substituted allylic termini either exclusively (runs 2, 6
and 7 Table 1) or selectively (runs 4, 5 and 8).
transfer from B to Pd(II), followed by either reductive
elimination from Et2Pd or b-H elimination from
EtPdOAc and/or Et2Pd. Et3B may coordinate to the
oxygen atom of 1a to help it undergo oxidative addition
to Pd(0). Furthermore, a small portion of Et3B may be
hydrolyzed by 1a or 2a to produce an intermediate II.7
The intermediate II would react through its enol form
with p-allylpalladium species I and produce a mixture
of III, H2O–BEt3 and Pd(0) complexes. The thus-
formed III may undergo transesterification with 2a,
regenerating II and liberating 3a. In a similar way, 3a
may be alkylated further to finally provide 4a.
o-Hydroxyphenyl alkyl ketones seem to be unique sub-
strates that undergo the present alkylation; acetophe-
none, m- and p-hydroxyacetophenones were all
unreactive under similar reaction conditions (Fig. 1).
These results suggest the importance of activation of
alkyl ketones through either intramolecular hydrogen
bonding or coordination of some borane species bound
to the o-hydroxyl group. Accordingly, we examined
various o-heteroatom substituted acetophenones (2f–
h).6 However, none of them turned out to be reactive;
2h provided N-allylaminoacetophenone in low yield
(29% based on 31% conversion). As reported recently
from these laboratories,2a the Et3B-promoted, Pd-cata-
lyzed alkylation of malonates with allyl alcohols pro-
ceeds only in the presence of bases such as NaH. In
sharp contrast to this, o-hydroxyphenyl alkyl ketones
smoothly undergoes the alkylation in the absence of a
base even though the acidity of these ketones is
expected to be lower than that of malonates.
The mechanism suggests that the reaction could be
catalytic with respect to Et3B. Indeed, the reactions of
1a (1.2 mmol) and 2b (1.0 mmol) performed with
reduced amounts of Et3B (1.2 and 0.6 mmol) completed
in 5 h at room temperature and provided 3b in 92 and
96% yields, respectively (cf. run 4, Scheme 1). In the
absence of Et3B, no reaction was observed and 2b was
recovered quantitatively.
Acknowledgements
Financial support from the Ministry of Education,
Science, Sports and Culture, Japanese Government,
Grant-in-Aid
for
Scientific
Research
B,
is
acknowledged.
In Scheme 2 our working hypothesis for the present
Pd-catalyzed allylic alkylation using 1a and 2a as typi-
cal reaction partners is outlined, where Et3B serves in
many ways to promote the reaction. Et3B may reduce
Pd(II) to Pd(0) through a few steps: ethyl group(s)
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Y. Horino et al. / Tetrahedron Letters 42 (2001) 3113–3116
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.
.