Allylation of functionalized aldehydes by potassium allyltrifluoroborate catalyzed by 18-Crown-6 in aqueous media

Article abstract of DOI:10.3390/molecules171214099

An efficient method for the allylation of aldehydes containing a broad range of functional groups using potassium allyltrifluoroborate is described. The reaction utilizes a catalytic amount of 18-C-6 in biphasic media under open atmosphere and room temperature to provide the corresponding homoallylic alcohols in high yields and without the necessity of any subsequent purification.

Full text of DOI:10.3390/molecules171214099

Molecules 2012, 17, 14099-14110; doi:10.3390/molecules171214099
OPEN ACCESS
molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Communication
Allylation of Functionalized Aldehydes by Potassium
Allyltrifluoroborate Catalyzed by 18-Crown-6 in Aqueous Media
Fernanda C. G. Barbosa, Juliano C. R. Freitas, Caio F. Melo, Paulo H. Menezes and
Roberta A. Oliveira *
Departamento de Química Fundamental, Universidade Federal de Pernambuco,
Av. Jornalista Aníbal Fernandes, s/n - Cidade Universitária, Recife – PE, 50740-560, Brazil
*
Author to whom correspondence should be addressed; E-Mail: roberta.aoliveira@ufpe.br;
Tel.: +55-81-2126-7473; Fax: +55-81-2126-8442.
Received: 25 September 2012; in revised form: 19 November 2012 / Accepted: 23 November 2012 /
Published: 28 November 2012
Abstract: An efficient method for the allylation of aldehydes containing a broad range of
functional groups using potassium allyltrifluoroborate is described. The reaction utilizes a
catalytic amount of 18-C-6 in biphasic media under open atmosphere and room
temperature to provide the corresponding homoallylic alcohols in high yields and without
the necessity of any subsequent purification.
Keywords: potassium allyltrifluoroborate; allylation; 18-crown-6
1
. Introduction
The addition of allylic organometallics to aldehydes is an important method for C-C bond formation [1],
while the product obtained from this reaction, an homoallylic alcohol, is an analogue of the compound
obtained from the aldol addition of metal enolates [2]. In addition, the introduced alkene moiety can be
readily converted into the corresponding aldehyde for further carbon-carbon homologation; or can be
selectively epoxidized to introduce a new chiral center [3].
The general approaches to prepare homoallylic alcohols are based on the use of an allylic
organometallic (e.g., Li [4], Mg [5], Mn [6], Zn [7], Pb [8], Bi [9], Ce [10], In [11], Sn [12] and many
others [13–17]), organometalloid derivatives (e.g., B [18–20], Si [21]) and electrochemical based
methods [22]. However, in some cases, these reagents are expensive and difficult to handle due to their
Lewis base character. Alternative methods based on the Barbier reaction were also developed [23,24].

Molecules 2012, 17
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These methods avoid the previous preparation of the allylic organometallics, however, the use of
zero valent metals can cause metal oxide (or hydroxide) precipitation and Rieke metals and some
chlorosilanes are also sensitive to the reaction media.
Organoboron compounds have proved to be very useful in the allylation of carbonyl compounds
because of their easy formation and stability and to date, several methods for the allylation of carbonyl
compounds employing allyl boronic acids or boronic esters were developed [18–20].
Potassium allyltrifluoroborates have proven to be a good option to replace allylboronic acids and
allylboronate esters in allylation reactions, providing many advantages over the latter reagents [25–28].
These compounds are stable, easy to handle, compatible with several functional groups and can be stored
for a long time. Several methods for the allylation of carbonyl compounds using allylic trifluoroborates
promoted by a variety of Lewis acids [29–31] or palladium-catalysts [32] have been described. However,
the search for an easy and reliable method for the allylation of aldehydes, that could be performed in
an open flask with substrates containing a broad range of functional groups would be desirable, while
some of the previously described methods for the allylation of aldehydes present drawbacks such as
the price of catalysts [33] and the need to use anhydrous conditions [34].
In addition, the development of methods focusing on environmentally benign reaction media has
become particularly prominent [35,36] and the use of water as (co)-solvent, which would seem to be
the best option due to its simplicity and very low cost, is still a challenge.
Crown ethers have the ability to promote reactions by phase-transfer catalysis solubilizing inorganic
salts in apolar solvents. Because of their remarkable binding properties, many reactions can be
promoted by using these compounds as catalysts. In addition, the study of crown ethers has greatly
contributed to the development of host-guest chemistry and supramolecular chemistry [37].
Herein, we wish to describe an environmentally benign reaction for the synthesis of homoallylic
alcohols based on the reaction of potassium allyltrifluoroborate and aldehydes containing different
functional groups in aqueous media catalyzed by 18-crown-6.
2
. Results and Discussion
Because our initial studies were focused on the development of an optimum set of reaction
conditions, the reaction of 4-nitrobenzaldehyde (1a) and potassium allyltrifluoroborate (2) was
examined to optimize these conditions. Therefore, 1a (1 mmol) and 2 (1.2 mmol) were treated at room
temperature with the appropriate catalyst (10 mol%) using different CH Cl -H O ratios, and the
2
2
2
progress of the reaction was monitored by TLC. The results are presented in Table 1 (all reported
yields in this and other tables are isolated yields).
2 2 2
When a 1:1 mixture of CH Cl –H O was used as the reaction solvent, product 3a was obtained in
good yields, even when the amount of the catalyst was decreased (Table 1, entries 2 and 3). However,
with the variation in the amount of 18-C-6, longer reaction times were required to promote the reaction
(
Table 2, entries 1 and 2). Further decreasing in the amount of catalyst required even longer reaction
times and gave a lower yield.

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Table 1. Effect of solvent and catalyst on the allylation of 4-nitrobenzaldehyde (1a) by
potassium allyltrifluoroborate 2.
Catalyst (mol%)
18-C-6 (1)
Solvent
3a (%)
1
2
3
4
5
6
7
CH
CH
2
2
Cl
Cl
2
2
:H
:H
2
O
O
20
a
18-C-6 (5)
18-C-6 (10)
18-C-6 (10)
18-C-6 (10)
15-C-5 (10)
2
90
CH Cl :H O
94
15
2
2
2
CH Cl
2
2
a
H O
2
80
CH
2
Cl
2
:H
2
O
12
7
-
CH Cl :H O
2
2
2
a
Yield obtained after 30 min of reaction.
Table 2. Allylation of aldehydes 1 with potassium allyl trifluoroborate 2 catalyzed by
1
8-C-6 (10 mol%).
RCHO
Product
Yield (%)
1
2
3
4
5
1a
1b
1c
3a
3b
3c
94
82
80
87
85
1d
1e
3d
3e
6
7
8
1f
1g
1h
3f
3g
3h
86
89
90
9
1i
3i
87

Molecules 2012, 17
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Table 2. Cont.
RCHO
Product
Yield (%)
1
0
1
2
3
4
5
1j
1k
1l
3j
3k
3l
88
1
1
1
1
1
82
89
90
91
86
1m
3m
1n
1o
3n
3o
2 2
When only CH Cl was used as the reaction solvent, lower yields were obtained in the allylation
reaction, probably due to the low solubility of 2 in this solvent (Table 1, entry 4). A similar behavior
was observed when only water was used as the reaction solvent, again due to the low solubility of the
aldehyde in water (Table 1, entry 5). In the absence of 18-C-6, the product was obtained only in 7%
yield after 15 min (Table 1, entry 7) and when 15-C-5 was used as catalyst, lower yields were observed
(
Table 1, entry 6). This fact may be explained by the role of cation solvation by the ligand in size
match-selectivity phenomena, which is widely accepted as the most important factor in controlling
metal ion selectivity for macrocyclic ligands.
With the optimized reaction conditions, we next explored the generality of our method, by
extending the conditions to different aldehydes. The results are listed in Table 2. In all cases, the
reaction took place smoothly to give the corresponding homoallylic alcohols in good yields.
Various differently substituted aldehydes were used in the reaction. The allylation of aldehydes
containing other electron-withdrawing groups gave the corresponding products in high yields (Table 2,
entries 1–6). For example, when 2-, 3- and 4-nitrobenzaldehyde were used, similar yields were observed,
indicating that the substituent position has a little influence in the reaction (Table 2, entries 1–3).
Aldehydes containing electron-withdrawing groups such as 4-fluorobenzaldehyde (Table 2, entry 4);
4
-bromobenzaldehyde (Table 2, entry 5) and 4-chlorobenzaldehyde (Table 2, entry 6) also gave similar
yields. Other aromatic aldehydes such as β-naphtaldehyde (Table 2, entry 9), benzaldehyde (Table 2,
entry 10) and 4-methylbenzaldehyde (Table 2, entry 11) also gave the homoallylic alcohols in high
yields. When an α,β-unsaturated aldehyde was used, the corresponding 1,2-addition product was
obtained exclusively, proving that the reaction is regioselective (Table 2, entry 8). For aliphatic
aldehydes, the 18-C-6-catalyzed allylation also exhibited high efficiency (Table 2, entry 7). Electron-rich
aldehydes reacted in good yields without influence of the substituent location (Table 2, entries 12–14).
When a heterocyclic aldehyde reacted under the optimized conditions, the corresponding homoallylic

Molecules 2012, 17
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alcohol was obtained in good yield (Table 2, entry 15). We attribute the small differences in the
isolated yields to the different solubilities of reactants and products.
As we can see, this new method has several advantages in comparison to other previously described
approaches. First of all, some methods are based on the use of allyl organometallics. It is known that
these compounds are sometimes not suitable for carbonyl additions due to the deprotonation of the
acidic alpha protons. Because of that the use of nonenolizable aldehydes is required. In addition, to
avoid the Wurtz coupling, the preparation of allylic Grignard reagents requires low temperature and
concentration [38].
The use of less reactive compounds such as allylsilanes [21] and allylstannanes [12] requires Lewis
acids as additives. Although the utility of allylstannanes is further indicated by the commercial
availability of some of them, the toxicity of these compounds makes them inappropriate for the use in
pharmaceutical synthesis [39]. In addition, the removal of tributyltin residues from reaction mixtures is
also a major issue.
On the other hand, among the various allylboron reagents, the use of potassium allyltrifluoroborate
seems to be the best option due to its stability, which also allows the complete characterization of these
salts by heteronuclear NMR analysis [40], and exact mass measurements [41]. Additionally,
organotrifluoroborate salts appear to have low toxicity [42].
Previously described methods for the allylation of aldehydes based on the conversion of potassium
allyltrifluoroborate into the corresponding air and moisture sensitive allyl difluoroborane using
BF Et O [34], or palladium catalysts [32] were reported. However, the use of potassium
3
2
allyltrifluoroborate as the allylating agent without any previous transformation is an important
advantage since it can be used in aqueous media and open atmosphere.
Furthermore, the use of potassium (E)-crotyltrifluoroborate (4) gave selectively the corresponding
anti product 5 in a 96:4 anti:syn ratio, proving that the reaction was also diastereoselective (Scheme 1).
Scheme 1. Crotylation of 4-nitrobenzaldehyde.
OH
BF K
3
4
O
1
8-C-6 (10 mol%)
O N
2
O N
2
CH Cl :H O (1:1)
2
2
2
1a
89%
5
o
25 C, 15 min.
anti:syn
96:4
Finally, to exemplify the utility of the proposed method in the synthesis of natural products, we
applied it to the synthesis of C7-C17 fragment of (−)-macrolactin F [43,44], a 24-membered
macrolactone isolated from a marine Bacillus sp. Sc026 which exhibited antibacterial activity against
Bacillus subtilis and Staphylococcus aureus (Scheme 2).

Molecules 2012, 17
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Scheme 2. Synthesis of C7-C17 fragment of (−)-macrolactin F.
3. Experimental
3.1. General
1
13
3
H-NMR and C-NMR data were recorded in CDCl on a Varian Unity Plus 300 spectrometer. The
chemical shifts are reported as delta (δ) units in parts per million (ppm) relative to the solvent residual
peak as the internal reference. Reactions were monitored by thin-layer chromatography on 0.25 mm E.
Merck silica gel 60 plates (F254) using UV light, vanillin and p-anisaldehyde as visualizing agents.
Potassium allyltrifluoroborate [45] and potassium (E)-crotyltrifluoroborate [34] were prepared
according to the literature procedures.
3
.2. General Procedure for the Allylation of Aldehydes 1a–o with Potassium Allyltrifluoroborate (2)
Catalyzed by 18-C-6
2 2
To a solution of the appropriate aldehyde 1a–o (1.0 mmol) in CH Cl (2 mL) was added 18-C-6
(
(
26 mg, 10 mol%) followed by potassium allyltrifluoroborate (2, 177 mg, 1.20 mmol) and water
2 mL). The biphasic mixture was stirred for 15 minutes, diluted with EtOAc (15 mL) and washed with
CO (3 × 15 mL). The combined organic layers were dried over MgSO
a saturated solution of K
2
3
4
,
filtered and the solvents were removed in vacuo to yield 3a–o [46] without the need of further purification.
1
1
2
4
-(4-Nitrophenyl)but-3-en-1-ol (3a): Yield: 181 mg (94%); H-NMR (CDCl
3
) δ 8.20 (d, J = 8.7 Hz,
H, HAryl), 7.53 (d, J = 8.7 Hz, 2H, HAryl), 5.85–5.71 (m, 1H, CH=CH ), 5.22–5.16 (m, 2H, CH=CH ),
2
2
1
3
2
.86 (dd, J = 7.8, 4.5 Hz, 1H, CHOH), 2.61–2.39 (m, 2H, CHCH ), 2.15 (br s, 1H, OH); C-NMR
(CDCl
3
) δ 151.1, 147.1, 133.1, 126.5, 123.5, 119.5, 72.1, 43.8.
1
1
-(3-Nitrophenyl)but-3-en-1-ol (3b): Yield: 154 mg (82%); H-NMR (CDCl
3
) δ 8.23 (t, J = 1.5 Hz, 1H,
H
Aryl), 8.12 (ddd, J = 8.1, 2.1, 0,9 Hz, 1H, HAryl), 7.69 (d, J = 8.1 Hz, 1H, HAryl), 7.53 (t, J = 8.1 Hz, 1H,
Aryl), 5.86–5.72 (m, 1H, CH=CH ), 5.21–5.15 (m, 2H, CH=CH ), 4.86 (dd, J = 8.1, 5.1 Hz, 1H,
), 2.17 (br s, 1H, OH); C-NMR (CDCl ) δ 148.1, 145.9, 133.2,
31.9, 129.3, 122.4, 120.8, 119.6, 72.0, 43.9.
H
2
2
1
3
CHOH), 2.62–2.42 (m, 2H, CHCH
2
3
1
1
1
1
1
-(2-Nitrophenyl)but-3-en-1-ol (3c): Yield: 158 mg (80%); H-NMR (CDCl
H, HAryl), 7.83 (dd, J = 8.1, 1.5 Hz, 1H, HAryl), 7.67 (td, J = 8.1, 1.2 Hz, 1H, HAryl), 7.42 (td, J = 8.1,
.2 Hz, 1H, HAryl), 5.96–5.82 (m, 1H, CH=CH ), 5.31 (dd, J = 8.4, 3.6 Hz, 1H, CHOH), 5.23–5.17
), 2.75–2.66 (m, 1H, CHCH
) δ 147.7, 139.2, 133.9, 133.4, 128.1, 128.0, 124.3, 119.0, 68.3, 42.8.
3
) δ 7.92 (dd, J = 8.1, 1.2 Hz,
2
1
3
(
m, 2H, CH=CH
2
2 2
), 2.47–2.36 (m, 2H, CHCH and OH); C-NMR
(CDCl
3

Molecules 2012, 17
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1
1
-(4-Fluorophenyl)but-3-en-1-ol (3d): Yield: 144 mg (87%); H-NMR (CDCl ) δ 7.28–7.24 (m, 2H,
3
H
Aryl), 6.96 (t, 2H, J = 8.4 Hz, HAryl), 5.79–5.65 (m, 1H, CH=CH
2
2
), 5.12–5.07 (m, 2H, CH=CH ), 4.66
1
3
(dd, 1H, J = 7.2, 5.7 Hz, CHOH), 2.50–2.38 (m, 2H, CHCH
2
), 1.85 (br s, 1H, OH); C-NMR δ
(
CDCl ) δ 164.1, 139.2, 133.8, 127.1, 118.4, 114.9, 72.3, 43.6.
3
1
1
-(4-Chlorophenyl)but-3-en-1-ol (3e): Yield: 155 mg (85%); H-NMR (CDCl
Aryl), 5.79–5.62 (m, 1H, CH=CH ), 5.13–5.05 (m, 2H, CH=CH ), 4.65 (dd, J = 7.5, 5.4 Hz, CHOH),
.48–2.32 (m, 2H, CHCH ), 2.04 (br s, 1H, OH); C-NMR (CDCl ) δ 142.2, 133.9, 131.1, 128.5,
3
) δ 7.27–7.19 (m, 4H,
H
2
2
1
3
2
1
2
3
27.2, 118.8, 72.5, 43.8.
1
1
2
4
1
-(4-Bromophenyl)but-3-en-1-ol (3f): Yield: 194 mg (86%); H-NMR (CDCl ) δ 7.41 (d, J = 8.7 Hz,
3
H, HAryl), 7.17 (d, J = 8.7 Hz, 2H, HAryl), 5.78–5.64 (m, 1H, CH=CH ), 5.13–5.06 (m, 2H, CH=CH ),
2
2
13
.64 (dd, J = 7.8, 5.4 Hz, CHOH), 2.49–2.32 (m, 2H, CHCH
2
), 1.99 (br s, 1H, OH); C-NMR (CDCl
3
) δ
42.8, 133.9, 131.4, 127.5, 121.2, 118.9, 72.5, 43.8.
1
Non-1-en-4-ol (3g): Yield: 126 mg (89%); H-NMR (CDCl ) δ 5.89-5.76 (m, 1H, CH=CH ), 5.29–5.09
3
2
(
m, 2H, CH=CH
2
), 3.68–3.59 (m, 1H, CHOH), 2.34–2.25 (m, 2H, CHCH
2
), 2.18–2.07 (m, 2H,
CHOH) 1.66 (br s, 1H, OH), 150–1.25 (m, 6H, CH
3
CH
2
CH
2
CH
2
), 0.87 (t, J = 6.3 Hz, 6H, CH
3
CH
2
);
1
3
C-NMR (CDCl
3
) δ 134.9, 118.0, 70.6, 41.9, 36.7, 31.8, 25.3, 22.6, 14.0.
1
(
E)-1-Phenylhexa-1,5-dien-3-ol (3h): Yield: 157 mg (90%); H-NMR (CDCl
3
) δ 7.40–7.21 (m, 5H, HAryl),
6
.61 (dd, J = 15.9, 1.2 Hz, 1H, PhCH=CH), 6.24 (dd, J = 15.9, 6.3 Hz, 1H, PhCH=CH), 5.86 (ddt,
J = 17.1, 10.2, 6.9 Hz, 1H, CH=CH ), 5.22–5.14 (m, 2H, CH=CH ), 4.39–4.33 (m, 1H, CHOH),
) δ 136.5, 133.9, 131.5, 130.2,
2
2
1
3
2.50–2.34 (m, 2H, CHCH
2 3
), 1.78 (br s, 1H, OH); C-NMR (CDCl
1
28.5, 127.6, 126.4, 118.3, 71.6, 41.9.
1
1
-(Naphthalen-2-yl)but-3-en-1-ol (3i): Yield: 172 mg (87%); H-NMR (CDCl
3
) δ 7.86–7.81 (m, 4H,
H
Aryl), 7.53–7.47 (m, 3H, HAryl), 5.84 (ddt, J = 17.1, 10.2, 7.5 Hz, 1H, CH=CH
2
), 5.23–5.14 (m, 2H,
CH=CH ), 4.91 (dd, J = 7.2, 5.1 Hz, 1H, CHOH), 2.61–2.57 (m, 2H, CHCH ), 2.10 (br s, 1H, OH);
2
2
1
3
C-NMR (CDCl
3
) δ 141.2, 134.3, 133.2, 132.9, 128.1, 127.9, 127.6, 126.1, 125.8, 124.2, 123.9, 118.4,
7
3.3, 43.6.
1
1
5
2
1
-Phenyl-but-3-en-1-ol (3j): Yield: 130 mg (88%); H-NMR (CDCl
3
) δ 7.36–7.24 (m, 5H, HAryl),
.87–5.73 (m, 1H, CH=CH
2
), 5.19–5.11 (m, 2H, CH=CH
2
), 4.73 (dd, J = 7.5, 5.4 Hz, 1H, CHOH),
1
3
.54–2.47 (m, 2H, CHCH
2
3
), 2.00 (br s, 1H, OH); C-NMR δ (CDCl ) δ 143.8, 134.4, 128.2, 127.3,
25.7, 118.0, 73.2, 43.6.
1
1
-p-Tolyl-but-3-en-1-ol (3k): Yield: 133 mg (82%); H-NMR (CDCl
3
) δ 7.22 (d, J = 7.8 Hz, 2H, HAryl),
), 5.20–5.11 (m, 2H,
), 2.35 (s, 3H, CH ), 1.78 (br s, 1H,
7
.16 (d, J = 7.8 Hz, 2H, HAryl), 5.81 (ddd, 1H, J = 17.1, 10.2, 6.6 Hz, CH=CH
), 4.71 (t, J = 6.6 Hz, CHOH), 2.56–2.48 (m, 2H, CHCH
2
CH=CH
2
2
3
13
OH); C-NMR (CDCl ) δ 140.9, 137.2, 134.6, 129.0, 125.7, 118.2, 73.1, 43.7, 21.1.
3
1
1
-(4-Methoxyphenyl)but-3-en-1-ol (3l): Yield: 158 mg (89%); H-NMR (CDCl
3
) δ 7.77 (d, J = 9.0 Hz,
), 5.68–5.59
2
H, HAryl), 7.37 (d, J = 9.0 Hz, 2H, HAryl), 6.29 (ddt, J = 16.8, 9.9, 6.6 Hz, 1H, CH=CH
2

Molecules 2012, 17
14106
(
(
m, 2H, CH=CH ), 5.17 (t, J = 6.6 Hz, CHOH), 4.29 (s, 3H, OMe), 3.01–2.96 (m, 2H, CHCH ), 2.50
2
3
2
1
br s, 1H, OH); C-NMR (CDCl
3
) δ 158.9, 136.0, 134.6, 127.0, 118.2, 113.7, 72.9, 55.2, 43.7.
1
1
-(3-Methoxyphenyl)but-3-en-1-ol (3m): Yield: 160 mg (90%); H-NMR (CDCl
3
) δ 7.29 (dd, J = 8.1,
7
.8 Hz, 1H, HAryl), 6.97–6.94 (m, 2H, HAryl), 6.84 (ddd, J = 8.1, 2.7, 1.2 Hz, 1H, HAryl), 5.84 (ddt,
), 5.23–5.15 (m, 2H, CH=CH ), 4.74 (dd, J = 7.5, 5.4 Hz, 1H,
CHOH), 3.84 (s, 3H, OMe), 2.56–2.50 (m, 2H, CHCH ), 2.06 (br s, 1H, OH); C-NMR (CDCl
59.6, 145.6, 134.4, 129.3, 118.2, 118.0, 112.9, 111.2, 73.1, 55.1, 43.6.
J = 17.1, 10.2, 7.5 Hz, 1H, CH=CH
2
2
1
3
2
3
) δ
1
1
1
-(2-Methoxyphenyl)but-3-en-1-ol (3n): Yield: 162 mg (91%); H-NMR (CDCl ) δ 7.33 (dd, J = 7.5,
3
1
.8 Hz, 1H, HAryl), 7.28 (td, J = 7.5, 1.8 Hz, 1H, HAryl), 6.95 (td, J = 8.4, 1.2 Hz, 1H, HAryl), 6.87 (d,
J = 8.4 Hz, 1H, HAryl), 5.85 (ddt, J = 17.1, 10.2, 7.5 Hz, 1H, CH=CH ), 5.17–5.08 (m, 2H, CH=CH ),
2
2
4
.95 (dd, J = 8.1, 5.1 Hz, 1H, CHOH), 3.84 (s, 3H, OMe), 2.64–2.44 (m, 2H, CHCH
2
), 2.41 (br s, 1H,
1
3
OH); C-NMR (CDCl ) δ 156.2, 135.1, 131.7, 128.2, 126.7, 120.6, 117.4, 110.3, 69.5, 55.1, 41.8.
3
1
1
1
1
2
1
-(Furan-2-ylbut-3-en-1-ol (3o): Yield: 119 mg (86%); H-NMR (CDCl
3
) δ 7.38 (dd, J = 1.8, 0.9 Hz,
H, HHet), 6.33 (dd, J = 2.1, 1.8 Hz, 1H, HHet), 6.25 (dd, J = 2.1, 0.9 Hz, 1H, HHet), 5.81 (ddt, J = 17.1,
0.2, 6.9 Hz, 1H, CH=CH ), 5.23–5.13 (m, 2H, CH=CH ), 4.75 (dd, J = 6.6, 6.3 Hz, 1H, CHOH),
), 2.15 (br s, 1H, OH); C-NMR (CDCl ) δ 155.6; 141.9; 133.6, 118.6,
2
2
1
3
.66–2.60 (m, 2H, CHCH
2
3
10.1, 106.1, 66.9, 40.1.
3
.3. General Procedure for the Crotylation of 1a with Potassium (E)-crotyltrifluoroborate (4)
Catalyzed by 18-C-6
2 2
To a solution of aldehyde 1a (38 mg, 0.25 mmol) in CH Cl (1 mL) was added 18-C-6 (6.5 mg,
1
0 mol%) followed by potassium (E)-crotyltrifluoroborate (4, 49 mg, 0.3 mmol) and water (1 mL). The
biphasic mixture was stirred for 15 min, diluted with EtOAc (15 mL) and washed with a saturated
solution of K CO (3 × 10 mL). The combined organic layers were dried over MgSO4, filtered and the
2
3
solvents were removed in vacuo to yield 5 [47] without the need of further purification.
1
2
-Methyl-1-(4-nitrophenyl)but-3-en-1-ol (5): Yield: 55 mg (89%); H-NMR (CDCl
3
) δ 8.21 (d, J = 8.7 Hz,
), 5.23–5.15
), 4.52 (d, J = 7.2 Hz, 1H, CHOH), 2.47 (sex, J = 7.2 Hz, 2H, CHCH), 2.17 (br s, 1H,
2
H, HAryl), 7.51 (d, J = 8.7 Hz, 2H, HAryl), 5.75 (ddd, J = 16.8, 10.5, 8.1 Hz, 1H, CH=CH
2
(
m, 2H, CH=CH
2
1
3
OH), 0.94 (d, J = 7.2 Hz, 3H, CH
3
3
); C-NMR (CDCl ) δ 15.0, 139.4, 127.8, 123.4, 118.1, 76.9, 46.5,
2
5.0, 16.5.
3
.4. General Procedure for the Allylation of Compound 6 with Potassium Allyltrifluoroborate (2)
Catalyzed by 18-C-6
To a solution of 6 (150 mg, 0.5 mmol) in CH Cl (1.5 mL) was added 18-C-6 (13 mg, 10 mol%)
2
2
followed by potassium allyltrifluoroborate (2, 89 mg, 0.60 mmol) and water (1.5 mL). The biphasic
mixture was stirred for 15 minutes, diluted with EtOAc (15 mL) and washed with a saturated solution
2 3
of K CO (3 x 15 mL). The combined organic layers were dried over MgSO4, filtered and the solvents
were removed in vacuo to yield 7 (138 mg, 85%) without the need of further purification.

Molecules 2012, 17
14107
1
(
5S,7Z,9E)-5-(Methoxymethoxy)-11-(tetrahydro-2H-pyran-2-yloxy)undeca-1,7,9-trien-3-ol: H-NMR
CDCl ) δ 6.57–6.47 (m, 1H), 6.11 (td, J = 11.1, 1.2 Hz, 1H), 5.90–5.75 (m, 2H), 5.44 (dd, J = 18.6,
.5 Hz, 1H), 5.14–5.07 (m, 3H), 4.73 (dd, J = 15.6, 7.5 Hz, 2H), 4.66–4.63 (m, 2H), 4.30 (dd; J = 12.9,
.0 Hz, 1H), 4.03 (dd, J = 12.9, 6.5 Hz, 1H), 3.95-3.78 (m, 3H), 3.55–3.46 (m, 1H), 3.39 (s, 3H),
(
3
7
6
2
1
3
1
3
.50–2.41 (m, 1H), 2.23 (t, J = 6.6 Hz, 3H) 1.88–1.48 (m, 7H); C-NMR (CDCl ) δ 134.89, 130.25,
3
27.57, 127.22, 126.81, 117.53, 97.88, 96.32, 95.22, 75.31, 67.38, 67;09, 62.15, 55.79, 41.98, 40.97,
0.57, 25.40, 19.41.
4
. Conclusions
In summary, we have demonstrated that a catalytic amount of 18-C-6 can efficiently promote the
allylation of aldehydes. This green method features the use of small catalyst loads, avoid the
preparation of unstable allyl organometallics and the products were obtained in short reaction times
with high yield and purity at room temperature. The approach is complementary to the previously
described methods for the synthesis of homoallylic alcohols and should be synthetically useful for the
synthesis of more complex compounds.
Supplementary Materials
Supplementary materials can be accessed at: http://www.mdpi.com/1420-3049/17/12/14099/s1.
Acknowledgments
The authors gratefully acknowledge FACEPE (APQ-1402-1.06/10), CNPq (484778/2011-0), CAPES
and INCT-INAMI for financial support. P.H.M and J.C.R.F. are thankful to CNPq for their fellowships.
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2012 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article
distributed under the terms and conditions of the Creative Commons Attribution license
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(