A simple synthetic approach to allylated aromatics via the Suzuki-Miyaura cross-coupling reaction

Article abstract of DOI:10.1055/s-2005-871569

The Pd-catalyzed cross-coupling reaction of aromatic iodides and bromides with allylboronic acid esters (2a,b) in the presence of CsF gave allylated aromatics. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-871569

LETTER
1877
A Simple Synthetic Approach to Allylated Aromatics via the Suzuki–Miyaura
Cross-Coupling Reaction
Synthetic
A
pp
a
roach to A
l
m
lylated Aromatics basivarao Kotha,* Manoranjan Behera, Vrajesh R. Shah
Department of Chemistry, Indian Institute of Technology-Bombay, Powai, Mumbai – 400 076, India
Fax +91(22)25723480; E-mail: srk@chem.iitb.ac.in
Received 20 April 2005
have become one of the most popular methods for access-
Abstract: The Pd-catalyzed cross-coupling reaction of aromatic
iodides and bromides with allylboronic acid esters (2a,b) in the
presence of CsF gave allylated aromatics.
ing biaryls. More specifically, the Suzuki–Miyaura (SM)
cross-coupling reaction using aryl boronic acids has
2
0
emerged as one of the most widely used reactions. SM
Key words: allylation, palladium, boron, cross-coupling reaction,
Suzuki coupling
2
2
cross-coupling reaction generally involves sp –sp
2
3
21
coupling whilst sp –sp coupling is also known and is
2
3
equally important. However, sp –sp coupling is relative-
ly less explored. Generally, sp –sp SM cross-coupling
involves use of 9-BBN and these types of reactions are
three-component systems where the alkylboranes or B-
alkyl-9-BBN derivatives are generated in situ by hydro-
boration.
2
3
1
The allylation reaction is one of the most studied trans-
2
2
formations in organic synthesis, because the newly intro-
duced carbon–carbon double bond is a useful tool for
bringing together complex fragments in total synthesis.2–4
Development of various catalytic metathesis processes,
5
In contrast to aryl boronic acids, the palladium-catalyzed
cross-coupling reactions of allyl boronic acid or esters are
relatively poorly described. In this regard, Occhiato et al.
reported the Suzuki reaction of vinyl triflates, generated
from six- or seven-membered N-alkoxycarbonyl lactams,
such as ring-closing metathesis (RCM) and cross-
6
metathesis as effective strategies in organic synthesis has
prompted many researchers to think about the methods for
the introduction of an allyl group in different situations.7
Moreover, the introduction of an allyl group in the target
molecule provides an opportunity for other synthetic
with allyl boronic acids and esters under THF/Na CO ,
2
3
23
8
Pd(PPh ) Cl conditions. In a thorough literature survey,
transformations. In addition, many natural products pos-
3 2
2
we found only a brief mention of reactions of al-
sess an allyl- or propenylbenzene fragment as a structural
2
4
9
lyl(dimethoxy)borane in the presence of aqueous NaOH
and Pd(Ph P) Cl and a preliminary report on the use of B-
element. Matteis and co-workers studied the role of the
allyl group in drug design and they found drugs contain-
3
2
2
25
allyl-9-borobicyclo[2.2.1]nonane (B-allyl-9-BBN). The
ing one or two allyl substituents depress the activity of
1
0
latter methodology is rather limited in scope because the
catalase and the levels of cytochrome P-450. Also suit-
ably positioned allyl groups can act as dienophiles in the
9
-BBN is very expensive and also air sensitive. Moreover,
1
1
many of the recent developments of the SM cross-cou-
pling reaction have focused on usage of other metal cata-
lysts rather than expanding the range of organoboron
coupling partners, which should be an equally important
endeavor. Herein, we report a suitable palladium-cata-
lyzed protocol for the allylation (Scheme 1) of aromatic
iodides and bromides using allylboronic acid esters 2a,b
Diels–Alder reaction as exemplified in the hapalindole
1
2
alkaloids synthesis.
Direct allylation of aromatics by electrophilic aromatic
substitution reaction is not an attractive option.13 For
example, Friedel–Crafts (FC) allylation of aromatics us-
ing allyl halides or allyl alcohol in the presence of an acid
catalyst usually gives a complex mixture, from further
reaction of the initial products and the yields of the mono-
(
Figure 1) to give allylated aromatics.
1
4,15
allylated product are very low.
I
I
NHCHO
NHCHO
CO2C2H5
Allylation with the aid of cross-coupling methodologies
has allowed the organic chemist to achieve greater con-
2a
(i)
CO2C2H5
1
6,17
trol.
In this respect, Heck reported that aryl palladium
salts prepared in situ from arylmercuric salts and LiPdCl2
reacts with allylic halides at room temperature to produce
allylaromatic derivatives. In another report, Migita et al.
detailed the successful catalytic allylation of aryl halides
1
3
1
8
Scheme 1 (i) CsF, Pd(PPh ) , THF, reflux.
3 4
with allyltri-n-butyltin (ATBT) in the presence of Pd(0).19 Initially, several reaction conditions were explored for the
In recent times, Pd(0)-catalyzed cross-coupling reactions allylation reaction using ATBT in the presence of palladi-
um catalysts such as Pd(Ph P) Cl , PdCl (CH CN) ,
3
2
2
2
3
2
Pd(PPh3)4 and PdCl (dba) . When compound 1 was
treated with ATBT in the presence of Pd(0)/THF, the
SYNLETT 2005, No. 12, pp 1877–1880
Advanced online publication: 07.07.2005
0
1
.0
8
.2
0
0
5
2
3
26
DOI: 10.1055/s-2005-871569; Art ID: D10405ST
diallylated product 3 was obtained along with some
©
Georg Thieme Verlag Stuttgart · New York

1
878
S. Kotha et al.
LETTER
30
undesired tin impurities, which could not be separated by by its complementary spectral data. To demonstrate the
column chromatography. At this point we thought of us- scope and limitation of this reaction, various aromatic io-
ing an allylboronic acid derivative as a coupling partner. dides, bromides and chlorides were studied and the results
Since the allylboronic acid cyclic ester 2a is commercially of this study are included in Table 1. As indicated in
available, we tested our idea with this allylating agent.
Table 1, the reaction with aromatic iodides with electron-
withdrawing substituents gave moderate to good yields
(
entries 1–7) of cross-coupled products, and with elec-
O
O
OCH3
OCH3
tron-releasing substituted aromatic iodides low yields of
the coupled products were noted (entries 8 and 9). Using
the conditions above, ortho-substitution is tolerated (entry
B
B
2
a
2b
7
) to give the cross-coupled product in high yield. The
cross-coupled products were obtained in good yield
entries 10 and 11) with aryl bromides. However, with
Figure 1
(
The diallylated product 3 was obtained when diiodo com- aromatic chlorides, no cross-coupled products were ob-
pound 1 was treated with boronic ester 2a in the presence served and starting material was recovered (entries 12 and
2
7
32
of Pd(0)/CsF/THF (Scheme 1). Attempts to improve the 13). When boronic acid ester 2b was used as a coupling
yield of the allylated product under different reaction con- partner, the cross-coupled product 7 was obtained in 74%
ditions (e.g., variations in temperature, solvents and vari- yield (entry 14).
ous Pd catalysts) were unsuccessful. The presence of
2
8
CsF appears to be crucial for the success of the coupling
2
9
reaction. Formation of the compound 3 was confirmed
Table 1 List of Various Allylated Aromatics Prepared by the SM Cross-Coupling Reaction
Entry
1
Starting substrates
Coupling products31
Yield (%)
90
I
I
NHCHO
NHCHO
CO2C2H5
CO2C2H5
3
4
2
3
NHBoc
NHBoc
66
47
I
CO2CH3
CO2CH3
CO CH
2
3
CO2CH3
I
I
OCH3
OCH3
539
4
5
6
7
71
88
46a
84
NO2
NO2
6
I
I
COCH3
COCH3
COCH3
7
COCH3
S
S
839
CO CH
2
3
CO2CH3
I
9
8
9
42b
51
I
I
OCH3
OCH3
1
0
1
OCH3
OCH3
1
Synlett 2005, No. 12, 1877–1880 © Thieme Stuttgart · New York

LETTER
Synthetic Approach to Allylated Aromatics
1879
Table 1 List of Various Allylated Aromatics Prepared by the SM Cross-Coupling Reaction (continued)
Coupling products31
Entry
Starting substrates
Yield (%)
82
1
1
1
1
1
0
Br
Br
Cl
Cl
COCH3
CHO
COCH3
7
1
1
6
7
1
60
–
CHO
CHO
NO2
2
2
2
CHO
NO2
3
–
4c
74
I
COCH3
COCH3
a
b
c
Low yield may be accounted due to the volatile nature of 8.
Based on starting material recovered (ca. 10%).
Allyl dimethyl boronic acid ester 2b was used as a coupling partner.
In conclusion, we have developed a simple methodology
for the synthesis of allylated aromatics starting with aryl
iodides and bromides using the SM cross-coupling
reaction. Aromatic chlorides did not undergo coupling re-
action to give the cross-coupling products. This method-
ology may find useful application in organic synthesis
because of the projected utility of various allylated
aromatics in organic synthesis.
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(
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Acknowledgment
We thank DST, New Delhi for the financial support. M.B. and
V.R.S. thank the CSIR, New Delhi for the award of research
fellowships. We thank the referees for useful suggestions.
(
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20) (a) Kotha, S.; Lahiri, K.; Kashinath, D. Tetrahedron 2002,
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(30) Spectral Data for Compound 3.
–
1
1
5
Mp 64–68 °C. IR (neat): 3404, 1728, 1672 cm . H NMR
via Boranes, Vol. 3; Aldrich Chemical Company Inc.:
Milwaukee, USA, 2003.
(300 MHz, CDCl ): d = 1.40 (t, 3 H, J = 7.4 Hz), 3.21–3.40
(m, 6 H), 3.70 (d, 2 H, J = 14.9 Hz), 4.30 (q, 2 H, J = 7.4 Hz),
3
(
(
21) Molander, G. A.; Yun, C.-S. Tetrahedron 2002, 58, 1465.
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1
3
7.21 (m, 8 H), 8.21 (s, 1 H). C NMR (100 MHz, CDCl3):
d = 14.2, 39.8, 40.7, 62.2, 67.6, 115.8, 128.5, 129.8, 133.7,
137.3, 138.8, 160.8, 172.0. HRMS (FAB): m/z [M + H]+
calcd for C H NO : 392.2226; found: 392.2231.
(
23) Occhiato, E. G.; Trabocchi, A.; Guarna, A. J. Org. Chem.
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5
29
3
3
3
34
35
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37
38
40
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(
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(
(
(
(
(
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29) Representative Experimental Procedure for Cross-
Coupling Reaction.
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A two-neck round-bottom flask was charged diiodo
compound 1 (0.049 mmol), CsF (0.19 mmol), Pd(PPh3)4
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(
5–10 mol%) in THF (3 mL) and stirred for 30 min. Allyl
boronic acid pinacol ester 2a (0.176 mmol) in THF (3 mL)
was added and the resulting reaction mixture was heated to
reflux for 24 h. Then, another portion of CsF (0.19 mmol)
and Pd(PPh ) (5–10 mol%) were added and reaction was
(39) Spectral Data.
–
1
Compound 5: IR (neat): 3020, 1720, 1608, 1502, 1086 cm .
1
H NMR (300 MHz, CDCl ): d = 3.40 (d, J = 6.5 Hz, 2 H),
3
3.81–3.96 (m, 6 H), 5.02–5.09 (m, 2 H), 5.91–6.00 (m, 1 H),
3
4
continued. At the end of the reaction (TLC monitoring), the
reaction mixture was diluted with petroleum ether (bp 60–
6.90 (d, J = 8.7 Hz, 1 H), 7.29 (s, 1 H), 7.60 (d, J = 8.7 Hz,
1
3
1 H). C NMR (75.4 MHz, CDCl ): d = 39.1, 52.1, 56.2,
3
8
0 °C, 10 mL) followed by H O. The layers were separated
112.2, 116.1, 119.8, 131.7, 133.7, 137.2, 157.6, 166.8. MS
2
and the aqueous layer was extracted with petroleum ether
2 × 10 mL). The combined organic layers were washed with
H O (20 mL), brine (20 mL) and dried (Na SO ).
Evaporation of the solvent gave the crude product, which
was purified by silica gel column chromatography. Elution
of the column with 10% EtOAc–petroleum ether gave the
diallylated product 3 (90%) as a white solid which was
characterized by spectral data.
(EI, Q-TOF): m/z calcd for [C H O + Na]: 229.0841;
1
2
12
3
(
found: 229.0850.
Compound 8: IR (neat): n = 1736, 1657, 1268, 1157, 1052
2
2
4
max
–
1 1
cm . H NMR (400 MHz, CDCl ): d = 2.51 (s, 3 H), 3.59 (d,
3
2 H, J = 7.6 Hz), 5.15–5.22 (m, 2 H), 5.90–6.01 (m, 1 H),
1
3
6.84 (d, 1 H, J = 4.0 Hz), 7.55 (d, 1 H, J = 3.6 Hz). C NMR
(75.4 MHz, CDCl ): d = 26.6, 34.9, 117.5, 126.1, 133.0,
3
+
135.2, 142.8, 152.9, 190.6. MS (EI, Q-TOF): m/z [M + H]
calcd for C H OS: 167.0531; found: 167.0530.
9
10
(
40) Liu, Z.; Yasseri, A. A.; Loewe, R. S.; Lysenko, A. B.;
Malinovskii, V. L.; Zhao, Q.; Surthi, S.; Li, Q.; Misra, V.;
Lindsey, J. S.; Bocian, D. F. J. Org. Chem. 2004, 69, 5568.
Synlett 2005, No. 12, 1877–1880 © Thieme Stuttgart · New York