Highly selective and robust palladium-catalyzed carbon-carbon coupling between allyl alcohols and aldehydes via transient allylboronic acids

Article abstract of DOI:10.1002/ejoc.200600530

The highly regio- and stereoselective coupling of allyl alcohols with aldehydes could be achieved with 5 mol-% of SeCSe pincer complex catalyst and p-toluenesulfonic acid in the presence of diboronic acid. The transformations have a broad synthetic scope, and the high yields were obtained without the use of an inert atmosphere and carefully dried solvents. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.

Full text of DOI:10.1002/ejoc.200600530

SHORT COMMUNICATION
DOI: 10.1002/ejoc.200600530
Highly Selective and Robust Palladium-Catalyzed Carbon–Carbon Coupling
between Allyl Alcohols and Aldehydes via Transient Allylboronic Acids
Nicklas Selander,[a] Sara Sebelius,[a] Cesar Estay,[a] and Kálmán J. Szabó*[a]
Keywords: Aldehydes / Allylation / Boron / Electrophilic substitution / Palladium
The highly regio- and stereoselective coupling of allyl
alcohols with aldehydes could be achieved with 5 mol-% of
SeCSe pincer complex catalyst and p-toluenesulfonic acid in
the presence of diboronic acid. The transformations have a
broad synthetic scope, and the high yields were obtained
without the use of an inert atmosphere and carefully dried
solvents.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2006)
Catalytic allylation of the carbonyl carbon of aldehydes plex catalyst 4[2h] and p-toluenesulfonic acid (5) (Schemes 2,
with allyl alcohols is one of the most attractive transforma- 3 and 4; Tables 1 and 2). These reactions can be performed
tions in palladium chemistry.[1,2a–2d] In practical implemen- as an operationally simple one-pot sequence under mild
tations, the allylation reaction is initiated by a palladium- conditions (typically 40 °C–50 °C) in a DMSO/MeOH mix-
catalyzed conversion of allyl alcohols to allylmetal species. ture. Allylation of the aldehyde substrates occurs via the
This conversion is mediated by SnCl2,[2a] BEt3,[2b] Et2Zn[2c] allylboronic acids formed from the allyl alcohols and 3
and indium[2d] salts (Scheme 1). Subsequently, the al- (Scheme 5). When the reaction is carried out in the absence
lylmetal species undergoes electrophilic allylation with the of the aldehyde component, allylboronic acids 7 can be ob-
aldehyde substrate.[2e–2g] As these transformations involve served and isolated after conversion to their corresponding
a two-step procedure with a Lewis acid and/or reductive allyl boronates.[3] Because transient allylboronic acids 7[3]
organometallic reagent, the functional group tolerance of and the other reactants, including catalyst 4, are stable in
the reaction is usually limited. With the use of function- the presence of air, moisture, weak acids and bases, the re-
alized allyl alcohols, a further issue is the control of the actions can be carried out without the use of an inert atmo-
stereoselectivity of the process, which is highly dependent sphere and in standard quality solvents. Diboronic acid (3)
on the applied organometallic reagent and on the steric is a nonreductive reagent with very weak (if any) Lewis acid
bulk of the allylic substituent. Although there are many ex- character, and therefore, many functionalities, including
cellent procedures described in the literature,[1,2a–2d] it is still ethoxycarbonyl/methoxy (Scheme 3; Table 2, Entries 2–10),
a challenge to find highly selective and robust methods for nitro (Table 1, Entry 5; Table 2, Entries 5 and 8) and cyano
the palladium-catalyzed coupling of various allyl alcohols groups (Tables 1 and 2, Entry 4), are tolerated. Palladium
(including both cyclic and acyclic ones) with aliphatic and catalyst 4 is compatible with all of these groups and aro-
aromatic aldehydes.
matic bromides as well (Tables 1 and 2, Entry 3). Allylation
of 2e (Tables 1 and 2, Entry 6) represents a particularly
good example of the functional group tolerance of this re-
action, as the aldehyde functionality of 2e could be selec-
tively converted without affecting its keto moiety.
The regioselectivity[4] of the reaction is excellent as both
linear, 1a, and branched, 1b–d, allyl alcohols give the
branched allylic products 6a–j. At elevated temperatures
and with the use of 50 mol-% of 5, product 6k undergoes
Scheme 1. Allylation of aldehydes by in situ generated allylmetal
species. M = Sn, B, Zn and In.
We have now found that allyl alcohols 1a–g react readily lactonization[5c] to provide 6l as a final product of the one-
with aldehydes 2a–i in the presence of diboronic acid (3), pot sequence (Scheme 3).
catalytic amounts (5 mol-%) of easily accessible pincer com-
In the described processes (Schemes 2, 3 and 4), homoal-
lylic alcohol products 6a–i and 6m–v were obtained as sin-
gle diastereomers. The reactions of acyclic allyl alcohols 1a–
c afford the anti products, as the transformations proceed
via allylboronic acids 7,[3] in which the geometry of the
double bond is trans.[4] The reaction proceeds readily and
[a] Dept. Organic Chemistry, Stockholm University,
10691 Stockholm, Sweden
E-mail: kalman@organ.su.se
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
Eur. J. Org. Chem. 2006, 4085–4087
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4085

N. Selander, S. Sebelius, C. Estay, K. J. Szabó
SHORT COMMUNICATION
Scheme 2.
Scheme 3.
with high diastereoselectivity even for cyclic allyl alcohols
1f–g. In these reactions, the double bond in the cyclic allyl-
boronic acid intermediate has a cis geometry,[3] and thus
the new carbon–carbon bond forms with syn diastereoselec-
tivity.[4] It is remarkable that selective tandem stereocontrol
of the reaction can be achieved from 1g to provide the prod-
uct as a single diastereomer out of the four diastereomeric
products that are possible (Table 2, Entries 2–10). The ex-
cellent stereoselectivity is a consequence of the highly ster-
Scheme 4.
Table 1. Allylation of aldehydes with acyclic allyl alcohols (Scheme 2).[a]
Entry
Alcohol
R1
Aldehyde
R2
Conditions[b]
Product
Yield[c] [%]
1
2[d]
3
4
5
6
7
8
9
1a
1a
1a
1a
1a
1a
1a
1b
1b
1c
1d
Ph
Ph
Ph
Ph
Ph
Ph
Ph
2a
2a
2b
2c
2d
2e
2f
2a
2f
2a
2a
Ph
Ph
40/16
40/48
40/16
40/16
40/16
40/16
50/16
50/16
50/16
40/16
60/16
6a
6a
6b
6c
6d
6e
6f
88
96
93
72
78
75
70
86
76
96
82
4-Br–C6H4
4-CN–C6H4
4-NO2–C6H4
4-CH3CO–C6H4
n-pentyl
Ph
n-pentyl
n-pentyl
CH2OBn
vinyl
6g
6h
6i
n-pentyl
Ph
Ph
10
11
6j
[a] Unless otherwise stated, the reactions of 1, 2 and 3 were conducted in the presence of catalytic amounts of 4 and 5 (both 5 mol-%)
in a DMSO/MeOH mixture. [b] Temperature [°C]/Time [h]. [c] Isolated yield. [d] Compound 5 was not used.
Table 2. Coupling of cyclic allyl alcohols with aldehydes (Scheme 4).[a]
Entry
Alcohol
R1
Aldehyde
R2
Conditions[b]
Product
Yield[c] [%]
1
2
3
4
5
6
7
8
9
1f
1g
1g
1g
1g
1g
1g
1g
1g
1g
H
2a
2a
2b
2c
2d
2e
2f
2g
2h
2i
Ph
Ph
60/16
50/36
50/36
50/36
50/36
50/36
50/36
50/36
50/36
50/36
6m
6n
6o
6p
6q
6r
98
93
72
75
73
78
71
73
78
72
COOMe
COOMe
COOMe
COOMe
COOMe
COOMe
COOMe
COOMe
COOMe
4-Br–C6H4
4-CN–C6H4
4-NO2–C6H4
4-CH3CO–C6H4
n-pentyl
6s
3-NO2–C6H4
6t
6u
6v
H[d]
10
Me[e]
[a] Unless otherwise stated, the reactions of 1, 2 and 3 were conducted in the presence of catalytic amounts of 4 and 5 (both 5 mol-%)
in a DMSO/MeOH mixture. [b] Temperature [°C]/Time [h]. [c] Isolated yield. [d] Paraformaldehyde was used. [e] Paracetaldehyde was
used.
4086
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Eur. J. Org. Chem. 2006, 4085–4087

One-Pot Reaction for Selective Allylation of Aldehydes with Allyl Alcohols
eoselective formation of the allylboronic acid intermediate[3]
SHORT COMMUNICATION
Experimental Section
and the subsequent selective coupling with the aldehyde
substrate.[4,5]
Allyl alcohol 1 (0.15 mmol) was dissolved in a DMSO/MeOH mix-
ture (0.3:0.3 mL) followed by the addition of diboronic acid (3)
(0.18 mmol), pincer complex 4 (0.0075 mmol, 5 mol-%), p-tolu-
enesulfonic acid (5) (0.0075 mmol, 5 mol-%) and aldehyde 2
(0.18 mmol). This reaction mixture was stirred for the allotted tem-
peratures and times listed in Table 1 and Table 2, and thereafter
quenched with water and extracted with diethyl ether. After evapo-
ration of the ether phase, product 6 was purified by silica gel col-
The reaction presented works smoothly with both aro-
matic and aliphatic aldehydes. As aliphatic aldehydes such
as 2f are somewhat less reactive than their aromatic coun-
terparts 2a–e, a higher reaction temperature (50 °C) was re-
quired for the allylation of 2f compared with that of aro-
matic substrates 2a–e (40 °C). Remarkably, even paraform-
aldehyde (2h) and paracetaldehyde (2i) could be used as al- umn chromatography. The reactions do not require an inert atmo-
sphere or carefully dried solvents. A detailed experimental pro-
cedure and characterization of the products is given in the Support-
ing Information.
dehyde sources (Scheme 4; Table 2, Entries 9–10), and thus
the presented one-pot sequence can be employed for the
homologation of allyl alcohols.
The reactions were performed in the presence of catalytic
amounts of p-toluenesulfonic acid (5). It was shown[3a] that
under the applied reaction conditions the formation of al-
lylboronic acids 7 is considerably accelerated in the presence
of 5, particularly when the allyl alcohol substrates contain
carboxy substituents (1e and 1g). Furthermore, Hall and
coworkers[5c,5d] have shown that Brønsted acids catalyze the
coupling reaction of allylboronates with aldehydes. Thus,
5 catalyzes both crucial steps (Scheme 5) of the coupling
reaction. Nevertheless, certain reactions proceed even in the
absence of acid catalyst 5, for example coupling of 1a with
2a (Table 1, Entry 2). However, this process (Entry 2) takes
much longer (48 h) than the corresponding reaction (En-
try 1) in the presence of 5 (16 h). On the other hand, in the
presence of allylic carboxy substituents (1e and 1g) or a
nitro substituent in the aldehyde component (2d), only
traces of the coupling products are formed without the use
of 5.
Supporting Information (see footnote on the first page of this arti-
cle): Detailed experimental procedures, characterization of the
1
products as well as H- and 13C NMR spectra of 6a-v.
Acknowledgments
This work was supported by the Swedish Natural Science Research
Council (VR) and the IDECAT Network of the European Commu-
nities.
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Scheme 5.
In summary, we have developed a versatile one-pot reac-
tion for the selective allylation of aldehydes with allyl
alcohols, which can be carried out under mild conditions
without the use of an inert atmosphere. The described pro-
cedure is environmentally benign as the byproduct of the
catalytic reaction is the nontoxic boronic acid; the process
is also economical as it employs inexpensive allyl alcohols
as reagents.
Received: June 20, 2006
Published Online: August 2, 2006
Eur. J. Org. Chem. 2006, 4085–4087
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4087