A Cross Metathesis Based Protocol for the Effective Synthesis of Functionalised Allyl Bromides and Chlorides

Article abstract of DOI:10.1055/s-2004-815936

Functionalised allyl halides, useful starting materials for the preparation of substituted organometallic reagents can be simply obtained by a straightforward approach. Hoveyda's ruthenium carbene catalyst 3, used in catalytic amount (2 mol%), is able to

Full text of DOI:10.1055/s-2004-815936

PAPER
409
A Cross Metathesis Based Protocol for the Effective Synthesis of Function-
alised Allyl Bromides and Chlorides
Effective Synthesis of
a
F
unctionali
r
sed
A
lly
c
l
B
romides
o
and Chloride
s
Bandini, Pier Giorgio Cozzi,* Sebastiano Licciulli, Achille Umani-Ronchi*
Dipartimento di Chimica ‘G. Ciamician’, Università di Bologna, Via Selmi 2, 40126 Bologna, Italy
Fax +39(51)2099456; E-mail: piergiorgio.cozzi@ciam.unibo.it; E-mail: umanironchi@ciam.unibo.it
Received 3 December 2003
Hoveyda developed highly active and stable CM catalysts
Abstract: Functionalised allyl halides, useful starting materials for
the preparation of substituted organometallic reagents can be sim-
ply obtained by a straightforward approach. Hoveyda’s ruthenium
carbene catalyst 3, used in catalytic amount (2 mol%), is able to pro-
mote the cross metathesis of allyl bromide and chloride with a vari-
ety of different substituted olefins giving the corresponding
functionalised allyl halides in satisfactory yields. trans-Olefins are
obtained as major diastereoisomers reaching 90:10 (trans:cis) ratio
when allyl chloride is used as the metathesis partner. This reaction
represents a simple and accessible way for the preparation of valu-
able precursors for functionalised organometallic reagents. In par-
ticular, the use of functionalised allyl bromides (10b and 13) in the
enantioselective Nozaki–Hiyama reaction promoted by
[Cr(Salen)Cl] is presented.
23 and 3.4
Catalysts 2 and 3 can be employed in the presence of a va-
riety of functional groups as they have showed a function-
al group tolerance characteristic of the catalyst 1. For
instance, tri-substituted alkenes, common structural sub-
units in natural products, can be successfully prepared
with the catalyst 3.4 Moreover highly active organometal-
lic cross metathesis catalysts have been used in the syn-
thesis of small molecules containing a wide range of
functional groups including styrenes,5 sulfones,6 alkenyl
oxiranes,7 allyl silanes,8 fluorinated olefins9 and , -un-
saturated nitriles.10 Again, catalyst 3 has been used in key
step for total synthesis of natural products.11
Key words: allyl halides, cross metathesis, ruthenium catalyst,
functionalised olefins
Moreover, the unprecedented catalytic activity of com-
plexes 2 and 3 was employed in the presence of conjugat-
ed electron deficient olefins because the dimerisation rate
of , -unsaturated carbonyl compounds is negligible.12
In recent years olefin metathesis has become a valuable
synthetic tool in the field of organic chemistry. The intro-
duction of definite transition metal catalysts such as the
ruthenium benzylidene 11 and the highly oxophilic Mo
catalysts 52 (Figure 1) has considerably expanded the
scope of reaction.
During our studies focused on catalytic redox allylation
reactions of aldehydes mediated by [Cr(Salen)] complex-
es,13 we decided to explore the reactivity of functionalised
allyl halides in our protocol. To this purpose, we took into
account the cross metathesis as a suitable and direct meth-
odology for the preparation of functionalised allyl halides.
PCy3
N
N
Mes
Cl
Mes
To our surprise we found out that olefin cross metathesis
of allyl halides was scarcely studied and only few exam-
ples were reported.14 In particular, Castedo and Blanco
found that allyl benzene could react with allyl bromides in
the presence of 1,15 while Roy and co-workers have de-
scribed the coupling of allyl halides with the Grubbs’s cat-
alysts 1 and 2 in a general approach to glycosides.16
However a systematic and comprehensive study involv-
ing different olefins has never been reported to date. Here-
in we describe the application of the CM strategy to the
one-pot preparation of functionalised allyl halides em-
ploying Hoveyda’s catalyst 3 as the promoting agent.
Cl
Cl
Cy3P
Ru
Ru
Cl
PCy3
2
1
PiPr3
Ru
N
N
Mes
Cl
Mes
Cl
Cl
Ru
N
Ph
Cl
N
RO
Mo
Me
Me
O
5
4
RO
3
Figure 1 Organometallic complexes as catalysts for cross metathe-
sis (CM).
In our initial approach, the functionalised allyl bromides
were synthesised in three steps, as indicated in Scheme 1.
Reaction of aldehydes 6a–c with ylide 717afforded the es-
ters 8a–c as the E diastereoisomers in good yields (87–
91%). A straightforward reduction with DIBALH in tolu-
ene gave the allylic alcohols 9a–c, which were trans-
formed into the desired allyl bromides 10a–c by treatment
with PBr3 in moderate to good yields. The overall proce-
dure was simple to perform although three steps and fol-
Of particular relevance is the olefin cross metathesis (CM)
that has emerged as a powerful synthetic shortcut for the
synthesis of functionalised acyclic structures. Later, by in-
troducing the 1,3-dimesityl-4,5-dihydroimidazol-2-
ylidene ligand into the ruthenium complexes, Grubbs and
SYNTHESIS 2004, No. 3, pp 0409–0414
x
x
.
x
x
.2
0
0
4
Advanced online publication: 26.01.2004
DOI: 10.1055/s-2004-815936; Art ID: Z17003SS.pdf
© Georg Thieme Verlag Stuttgart · New York

410
Marco Bandini et al.
PAPER
Table 1 CM Reaction Between Functionalised Olefins and Allyl
Halides Catalysed by 3a
O
R
OEt
Ph3P
OEt
RCHO
+
O
Entry Allyl halide Olefin
Product
13a
10b
13c
Yield (%)b E:Zc
6a-c
8a-c
yield 87-91%
7
1
2
12a
12a
12a
12a
12a
12a
12a
12a
12b
12b
12b
11a
11b
11c
11d
11e
11f
35
58
49
46
30
37
51
39
39
65
49
76:24
86:14
78:22
80:20
83:17
83:17
85:15
75:25
95:5
DIBALH
R
OEt
R
OH
yield 93-95%
O
9a-c
3
PBr3
R
Br
R
OH
4
13d
13e
10a-c
yield 10a 30%
10b 25%
a, R = PhCH2CH2-
b, R = BnOCH2-
c, R = Cy-
5
10c 80%
6
13f
Scheme 1 Synthesis of functionalised allyl bromides in three steps re-
7
11g
11h
11a
11b
11d
13g
13h
14a
14b
14d
actions.
8
lowing purifications were necessary in order to obtain the
desired allyl bromides in good chemical purity.
9
10
89:11
93:7
So we decided to explore the alternative strategy taking
into consideration the metathesis reaction. According to 11
this aim, Grubbs catalysts 1 and 2, Hoveyda’s catalyst 3
and the Ciba catalyst 418 were tested in the CM reaction
between allyl bromide (12a) and olefin 11a as the model
reaction (Scheme 2). After a brief survey of experimental
conditions (solvent temperature, loading of catalyst) com-
plex 3 proved to be highly active in catalysing this reac-
tion. On the other hand, no activity was observed for
catalyst 1 while 4 was able to perform the metathesis to
some extents but rapidly decomposed under the reaction
conditions employed.
a All the reactions were carried out in anhyd CH2Cl2 by using 2 mol%
of catalyst.
b Isolated yield after chromatographic purification.
The reaction appeared more stereoselective when allyl
chloride (12b) was employed. In fact, by reacting allyl
chloride and substituted alkenes in the presence of catalyst
3, the corresponding functionalised allyl chloride was iso-
lated as a mixture of diasteroisomers (89:11–95:5) in
yields ranging between 39–65% (Table 1, entries 9–12).
X
3 (2 mol %)
X
FG
The isolated allyl bromides and chlorides could be ex-
ploited in the preparation of highly functionalised organo-
metallic reagents.20 In this context, Grubbs14b and
Miyaura21 recently reported on the use of CM to obtain
functionalised allylating boron reagents. Miyaura also re-
ported that the protocol could be used with chiral allylbo-
ranes achieving the desired homoallylic alcohols in good
enantiomeric excesses (up to 82% ee).
FG
+
CH2Cl2
11a-h
12a X = Br
12b X = Cl
X = Br, 13a,10b,13c-h
X = Cl, 14a,b,d
11e: FG = NCCH2CH2CH2-
11f: FG = HOCH2-
11g: FG = BrCH2CH2-
11h: FG = C6F5-
11a: FG = TBDMSO-
11b: FG = BnO-
11c: FG = PhCO2CH2-
11d: FG = CH3COCH2-
Scheme 2 CM of allyl bromides with functionalised alkenes.
A major problem in the synthesis of organometallic re-
agent precursors via CM reaction is the poor diastereo-
selection frequently encountered in the preparation of the
stereogenic allyl halide precursors. However, chromium
organometallic reagents are peculiar in this aspect; in fact,
the high anti diastereoselection obtained in the chromium-
mediated allylation of aldehydes is generally independent
of the Z/E ratio of the stereogenic allyl halide.22
By choosing CH2Cl2 as the solvent, complex 3 (2 mol%)
allowed functionalised allyl bromides to be effectively
prepared starting from a 1:2 olefin–allyl bromide ratio
(Table 1). A large excess of olefin as well as the use of 4–
5 equivalents of 12a did not improve the yields; the homo-
coupling of allyl bromide becoming the main product.
This is a consequence of the fact that CM of olefins is es-
sentially a competition between three different reaction
pathways: the selective cross metathesis and the dimerisa-
tions of each starting materials.12,19 Functionalised allyl
bromides were isolated as inseparable mixture of E:Z di-
astereoisomers (75:25–86:14) and a variety of functional
groups (CN, COOR, OSiR3, OBn, COR, OH) were well
tolerated. The yields were satisfactory and the functiona-
lised allyl bromides were purified by chromatography
(Table 1, entries 1–8).
We recently reported the first catalytic enantioselective
Nozaki–Hiyama (NH) addition of crotyl bromide23 and
1,3-dichloropropene24 to aromatic aldehydes in the pres-
ence of [Cr(Salen)] complexes in which the simple diaste-
reoselection can be easily modulated through the amount
of chiral ligand employed. In particular, the use of a 1:2
ratio of chromium–Salen and Mn as the stoichiometric re-
ductant allows the homoallylic alcohols to be isolated
with good syn diastereoselection and high enantioselec-
tivity. A few representative functionalised allyl bromides,
Synthesis 2004, No. 3, 409–414 © Thieme Stuttgart · New York

PAPER
Effective Synthesis of Functionalised Allyl Bromides and Chlorides
411
i) [Cr(Salen)Cl] 10 mol%
Salen (10 mol%)
OH
CHO
Mn, Me3SiCl, CH3CN
Br
+
FG
ii) H+
OR
15a R = H, yield = 28%
(syn:anti 76:24 eesyn = 81%)
15b R = Bn, yield = 40%
(syn:anti 83:17 eesyn = 81%)
13a, FG = TBDMSO-
10b, FG = BnO-
Scheme 3 Stereoselective Nozaki–Hiyama reaction catalysed by [Cr(Salen)] with functionalised allyl bromides.
obtained via the present metathesis strategy (10b, 13a),
were reacted with benzaldeyde in the presence of
(Daicel Inc.). HPLC grade i-PrOH and n-hexane were used as the
eluting solvents. Elemental analyses were carried out by using a
[Cr(Salen)Cl] (10 mol%) and 10 mol% of the free Salen EACE 1110 CHNOS analyzer. All the reactions were carried out
ligand (Scheme 3).25
under a N2 atmosphere in flame-dried glassware using standard in-
ert techniques for introducing reagents and solvents. All the com-
mercially available reagents were used without further purification
The corresponding homoallylic alcohols (15a,b) were iso-
lated after de-silylation and flash chromatographic purifi-
cation in moderate yields and good diastereoselectivity
(up to 83:17 syn) and enantioselectivity (ee up to 81%).
The absolute configuration of the isolated products were
assigned by analogy considering the general trend ob-
tained in the reaction of aldehydes promoted by
[Cr(Salen)Cl] with crotyl bromides.23–25
(CrCl3: sublimed 99%, Aldrich; Mn powder: 99.9%, -50 mesh, Al-
drich).
Cross Metathesis Reactions Catalysed by 3; General Procedure
In a two-necked flask, catalyst 3 (0.02 mmol) was dissolved in
CH2Cl2 (2 mL) and the resulting solution was stirred under N2 at r.t.
for 10 min. A separately prepared mixture of olefin (1 mmol) and
the allyl halide (2 mmol) were added to the solution of the catalyst.
The reaction mixture was stirred for 3–8 h at r.t. and the consump-
tion of the olefin was checked by TLC or GC–MS. The solvent was
evaporated under reduced pressure and the resulting black oil was
purified by flash chromatography.
Although not optimised, these preliminary results clearly
showed the functional group tolerance of our catalytic
protocol in the enantioselective addition of functionalised
allyl bromides to aldehydes.
13a
In conclusion, we have presented a new valuable method-
ology for the preparation of functionalised allyl bromides
and chlorides through CM. The desired functionalised al-
lyl halides were obtained one-pot in satisfactory yields by
using the catalyst 3 (2 mol%) and various functionalised
olefins. Although the yield of the cross metathesis of allyl
halides are only moderate and more active and selective
catalysts still need to be found,26 these results are of gen-
eral interest for the preparation of useful starting materials
for highly functionalised organometallic reagents.
Yield: 35% (E/Z, 76:24); pale yellow oil.
IR (neat): 3026 (w), 2959 (s), 2881 (m), 2860 (s), 1641 (s), 1472
(m), 1363 (w), 1160 (s), 960 (s), 730 (s), 691 (s) cm–1.
1H NMR (200 MHz, CDCl3): (E-diastereoisomer) = 0.08 (s, 6 H),
0.92 (s, 9 H), 3.98 (dd, J1 = 1.0 Hz, J2 = 6.6 Hz, 2 H), 4.19–4.22 (m,
2 H), 5.85–5.93 (m, 2 H), 13C NMR (50 MHz, CDCl3): (E-dia-
stereoisomer) = –2.9, 25.8, 26.8, 44.5, 62.8, 127.2, 134.1.
13C NMR (50 MHz, CDCl3): (Z-diastereoisomer) = 27.0.
MS: m/z (%) = 266 (1), 264 (1), 251 (1), 209 (70), 207 (90), 165
(19), 139 (100), 137 (100), 127 (78) 113 (15), 89 (28), 73 (51), 57
(48).
Anhydrous Et2O, THF and CH2Cl2 were supplied by Fluka in Sure-
1
Anal. Calcd for C10H21BrOSi: C, 45.28; H, 7.98. Found: C, 45.22;
H, 7.91.
seal® bottles and were used without any further purification. H
NMR spectra were recorded on Varian 200 (200 MHz) or Varian
300 (300 MHz) spectrometers. Chemical shifts are reported in ppm
from TMS with the solvent resonance as the internal standard
(CDCl3: = 7.27 ppm). Data are reported as follows: chemical shift,
multiplicity (s = singlet, d = duplet, t = triplet, q = quartet, br =
broad, m = multiplet), coupling constants (Hz). 13C NMR spectra
were recorded on a Varian 200 (50 MHz) or Varian 300 (75 MHz)
spectrometers with complete proton decoupling. Chemical shifts
are reported in ppm from TMS with the solvent as the internal stan-
dard (CDCl3: = 77.0 ppm). Mass spectra were recorded at an ion-
ising voltage of 70 eV. Chromatographic purification was done with
240–400 mesh silica gel. Analytical GC was performed on a
Hewlett–Packard HP 6890 gas chromatograph with a flame ionisa-
tion detector and split mode capillary injection system, using a
Crosslinked 5% PH ME Siloxane (30 m) column or a Megadex-5
chiral (25 m) column (flow rate 15 mL/min, method: 50 °C for 2
min, ramp @ 10 °C/min to 250 °C for 15 min). Analytical HPLC
was performed on a HP 1090 liquid chromatograph equipped with
a variable wavelength UV detector (deuterium lamp 190–600 nm)
and using a Daicel ChiralcelTM OD column (0.46 cm I.D. × 25 cm)
10b
Yield: 58% (E/Z, 86:14); pale yellow oil.
IR (neat): 3065 (w), 3038 (m), 2926 (m), 2853 (s), 1660 (w), 1447
(m), 1427 (w), 1361 (m), 1195 (s), 1096 (s), 963 (m), 738 (s), 691
(s) cm–1.
1H NMR (200 MHz, CDCl3): (E-diastereoisomer) = 2.35–2.50 (m,
2 H), 3.95–3.99 (m, 2 H), 4.54 (s, 2 H), 5.77–5.86 (m, 1 H), 5.95–
6.04 (m, 1 H), 7.29–7.42 (m, 5 H).
1H NMR (200 MHz, CDCl3): (Z-diastereoisomer) = 4.02–4.04 (m,
2 H).
13C NMR (50 MHz, CDCl3): (E-diastereoisomer) = 40.5, 69.2,
72.9, 127.5, 128.0, 128.3, 130.7, 132.6, 138.2.
13C NMR (50 MHz, CDCl3): (Z-diastereoisomer) = 69.6.
MS: m/z (%) = 175 (15), 145 (6), 121 (3), 107 (9), 91 (100), 65 (28),
51 (11).
Synthesis 2004, No. 3, 409–414 © Thieme Stuttgart · New York

412
Marco Bandini et al.
PAPER
Anal. Calcd for C11H13BrO: C, 54.79; H, 5.43. Found: C, 54.71; H,
5.38.
1H NMR (200 MHz, CDCl3): (E-diastereoisomer) = 2.31–2.40 (m,
2 H), 3.70 (t, J = 6.2 Hz, 2 H), 3.96 (dd, J1 = 0.8 Hz, J2 = 5.8 Hz, 2
H), 5.78–5.85 (m, 2 H).
13c
1H NMR (200 MHz, CDCl3): (Z-diastereoisomer) = 3.73 (t, J = 6.2
Hz, 2 H), 4.03 (d, J = 8.0 Hz, 2 H).
Yield: 49% (E/Z, 78:22); pale yellow oil.
IR (neat): 3065 (w), 2959 (w), 2919 (m), 2853 (w), 1712 (s), 1600
(m), 1454 (s), 1275 (s), 1109 (s), 963 (s), 904 (m), 711 (s) cm–1.
1H NMR (200 MHz, CDCl3): (E-diastereoisomer) = 2.43–2.61 (m,
2 H), 3.90–3.98 (m, 2 H), 4.34–4.41 (m, 2 H), 5.80–5.90 (m, 2 H),
7.38–7.50 (m, 2 H), 7.98–8.10 (m, 2 H), 7.50–7.58 (m, 1 H).
1H NMR (200 MHz, CDCl3): (Z-diastereoisomer) = 4.01–4.08 (m,
2 H), 4.21–4.30 (m, 2 H).
13C NMR (50 MHz, CDCl3): (E-diastereoisomer) = 32.8, 35.3,
61.6, 129.0, 132.1.
13C NMR (50 MHz, CDCl3): (Z-diastereoisomer) = 128.0, 131.3.
MS: m/z (%) = 166 (2), 164 (2), 146 (10), 133 (6), 119 (5), 107 (5),
95 (5), 85 (43), 67 (48), 54 (100).
Anal. Calcd for C5H9BrO: C, 36.39; H, 5.50. Found: C, 36.35; H,
5.45.
13C NMR (50 MHz, CDCl3): (E-diastereoisomer) = 31.6, 32.6,
63.6, 128.3, 129.1, 129.5, 130.1, 131.2, 132.9, 166.4.
13g
MS: m/z (%) = 189 (19), 148 (3), 146 (3), 123 (4), 105 (88), 77 (59),
Yield: 51% (E/Z, 85:15); pale yellow oil.
67 (100), 51 (30).
IR (neat): 2952 (w), 2952 (m), 2853 (w), 1732 (s), 1659 (w), 1434
(s), 1367 (m), 1255 (s), 1202 (s), 1162 (s), 963 (m), 857 (w) cm–1.
1H NMR (200 MHz, CDCl3): (E-diastereoisomer) = 1.88–2.03 (m,
2 H), 2.16–2.30 (m, 2 H), 3.38–3.47 (m, 2 H), 3.94–3.96 (m, 2 H),
5.43–5.46 (m, 1 H), 5.73–5.79 (m, 1 H).
1H NMR (200 MHz, CDCl3): (Z-diastereoisomer) = 4.02 (d, J =
8.0 Hz, 2 H).
13C NMR (50 MHz, CDCl3): (E-diastereoisomer) = 30.4, 31.6,
32.3, 32.5, 127.8, 134.0.
13C NMR (50 MHz, CDCl3): [Z-diastereoisomer (diagnostic sig-
nals)] = 30.8, 33.3, 129.7.
Anal. Calcd for C12H13BrO2: C, 44.00; H, 5.80. Found: C, 43.95; H,
5.75.
13d
Yield: 46% (E/Z, 80:20); pale yellow oil.
IR (neat): 2999 (w), 2972 (m), 2912 (m), 2846 (w), 1712 (s), 1659
(w), 1427 (m), 1368 (s), 1202 (s), 1162 (s), 970 (s), 725 (w) cm–1.
1H NMR (200 MHz, CDCl3): (E-diastereoisomer) = 2.16 (s, 3 H),
2.33–2.39 (m, 2 H), 2.51–2.59 (m, 2 H), 3.93 (d, J = 6.6 Hz, 2 H),
5.68–5.81 (m, 2 H).
1H NMR (200 MHz, CDCl3): (Z-diastereoisomer) = 4.02 (d, J =
8.2 Hz, 2 H), 2.17 (s, 3 H).
13C NMR (50 MHz, CDCl3): (E-diastereoisomer) = 25.9, 29.8,
32.9, 42.3, 127.0, 134.2, 207.
13C NMR (50 MHz, CDCl3): (Z-diastereoisomer) = 26.7, 126.1,
MS: m/z (%) = 163 (27), 161 (33), 150 (36), 95 (35), 81 (100), 67
(47), 59 (35), 53 (36), 51(36).
Anal. Calcd for C6H10Br2: C, 29.78; H, 4.17. Found: C, 29.71; H,
4.13.
133.5.
13h
MS: m/z (%) = 135 (3), 133(3), 111 (100), 93 (34), 81 (6), 67 (42),
Yield: 39% (E:Z, 75:25); pale yellow oil.
53 (44).
IR (neat): 3038 (w), 2939 (w), 2853 (w), 1719 (m), 1660 (m), 1520
(s), 1507 (s), 1301 (m), 1268 (m), 1202 (m), 1116 (s), 996 (s), 957
(s), 725 (w) cm–1.
Anal. Calcd for C7H11BrO: C, 56.94; H, 5.18. Found: C, 56.88; H,
5.14.
1H NMR (200 MHz, CDCl3): (E-diastereoisomer) = 3.39–3.48 (m,
2 H), 3.90–3.93 (m, 2 H), 5.76–5.86 (m, 2 H).
1H NMR (200 MHz, CDCl3): (Z-diastereoisomer) = 3.39–3.40 (m,
2 H), 3.96–3.98 (m, 2 H), 5.55–5.64 (m, 2 H).
13C NMR (50 MHz, CDCl3): (E-diastereoisomer) = 30.8, 33.2,
112.6 (m), 117.3, 130.8, 135.9 (m), 139.2 (m), 143.1 (m), 146.6 (m).
13C NMR (50 MHz, CDCl3): (Z-diastereoisomer) = 118.2.
13e
Yield: 30% (E/Z, 83:17); pale yellow oil.
IR (neat): 3032 (w), 2932 (s), 2859 (m), 2249 (m), 1653 (w), 1460
(m), 1421 (m), 1202 (s), 963 (s), 910 (w), 738 (m) cm–1.
1H NMR (200 MHz, CDCl3): (E-diastereoisomer) = 1.56–1.68 (m,
4 H), 2.12–2.15 (m, 2 H), 2.36 (t, J = 7.0 Hz, 2 H), 3.93–3.96 (m, 2
H), 5.71–5.76 (m, 2 H),.
1H NMR (200 MHz, CDCl3): (Z-diastereoisomer) = 2.33–2.41 (m,
2 H), 3.98–4.03 (m, 2 H).
MS: m/z (%) = 302 (1), 300 (1), 221 (65), 201 (12), 181 (100), 151
(23), 143 (8), 117 (8), 105 (34), 77 (20), 54 (26).
13C NMR (50 MHz, CDCl3): (E-diastereoisomer) = 17.1, 24.7,
27.7, 31.1, 33.0, 119.5, 127.3, 134.8.
Anal. Calcd for C10H6BrF5: C, 39.90; H, 2.01. Found: C, 39.85; H,
1.99.
13C NMR (50 MHz, CDCl3): (Z-diastereoisomer) = 132.8, 135.2.
14a
MS: m/z (%) = 203 (1), 201 (1), 175 (1), 135 (3), 122 (73), 105 (10),
Yield: 39% (E:Z, 95:5); pale yellow oil.
94 (16), 81 (100), 67 (31), 53 (62).
IR (neat): 3025 (w), 2959 (s), 2926 (s), 2880 (m), 2859 (s), 1665
(w), 1467 (m), 1129 (s), 1049 (m), 957 (m), 837 (s), 771 (s), 678 (m)
cm–1.
Anal. Calcd for C8H12BrN: C, 47.55; H, 5.99; N, 6.93. Found: C,
47.50; H, 5.94, N, 6.92.
1H NMR (200 MHz, CDCl3): (E-diastereoisomer) = 0.09 (s, 6 H),
0.92 (s, 9 H), 4.06–4.11 (m, 2 H), 4.18–4.22 (m, 2 H), 5.84–5.90 (m,
2 H).
13f
Yield: 37% (E/Z, 83:17); pale yellow oil.
IR (neat): 3314 (br), 3025 (m), 2944 (s), 2878 (s), 1709 (m), 1661
(w), 1434 (m), 1369 (w), 1205 (s), 1044 (s), 967 (s), 750 (w), 725
(w) cm–1.
1H NMR (200 MHz, CDCl3) (Z-diastereoisomer) = 4.28–4.33 (m,
2 H).
Synthesis 2004, No. 3, 409–414 © Thieme Stuttgart · New York

PAPER
Effective Synthesis of Functionalised Allyl Bromides and Chlorides
413
13C NMR (50 MHz, CDCl3): (E-diastereoisomer) = –5.2, 25.9,
ic phases were combined and evaporated under reduced pressure.
29.7, 44.7, 62.6, 125.3, 134.1.
The resulting brown oil was dissolved in THF (2 mL) and 2 N HCl
(2 mL) was added. The reaction mixture was stirred at r.t. until com-
plete desilylation (checked by TLC, 2–4 h). THF was evaporated
under reduced pressure and the aq phase was extracted with Et2O (2
× 4 mL). The organic layers were dried over Na2SO4 and evaporat-
ed under reduced pressure to give an oil which was further purified
by chromatography.
MS: m/z (%) = 220 (1), 205 (1), 185 (3), 163 (45), 149 (2), 127 (54),
113 (5), 93 (100), 73 (20), 57 (7).
Anal. Calcd for C10H21ClOSi: C, 54.39; H, 9.59. Found: C, 54.31;
H, 9.50.
14b
Yield: 65% (E:Z, 89:11); pale yellow oil.
15a
Yield: 28% (syn:anti 76.24, dr was evaluated by GC analysis on the
crude silylated product); pale yellow oil; Rf 0.3 (cyclohexane–
EtOAc, 7:3).
IR (neat): 3086 (w), 3058 (w), 3038 (m), 2926 (m), 2853 (s), 1666
(w), 1460 (m), 1354 (m), 1255 (m), 1102 (s), 970 (s), 731 (s), 698
(s) cm–1.
1H NMR (300 MHz, CDCl3): (syn diastereoisomer) = 2.57–2.77
(m, 1 H), 3.77–3.92 (m, 2 H), 4.72 (d, J = 7.6 Hz, 1 H), 4.95 (dd,
J1 = 2.2 Hz, J2 = 10.8 Hz, 1 H), 5.02 (dd, J1 = 0.8 Hz, J2 = 2.6 Hz, 1
H), 5.56 (ddd, J1 = 8.2 Hz, J2 = 10.8 Hz, J3 = 17.0 Hz, 1 H), 7.13–
7.30 (m, 5 H).
1H NMR (300 MHz, CDCl3): (anti diastereoisomer) = 2.31–2.69
(m, 1 H), 3.56–3.62 (m, 2 H), 4.79–4.89 (m, 1 H), 5.07–5.24 (m, 2
H), 5.82 (ddd, J1 = 8.8 Hz, J2 = 10.6 Hz, J3 = 17.0 Hz, 1 H).
1H NMR (200 MHz, CDCl3): (E-diastereoisomer) = 2.35–2.48 (m,
2 H), 4.05 (d, J = 6.6 Hz, 2 H), 4.53 (s, 2 H), 5.67–5.87 (m, 2 H),
7.29–7.40 (m, 5 H).
1H NMR (200 MHz, CDCl3): (Z-diastereoisomer) = 4.12 (d, J =
6.6 Hz, 2 H) 4.58 (s, 2 H).
13C NMR (50 MHz, CDCl3): (E-diastereoisomer) = 45.2, 69.2,
72.9, 127.5, 127.6, 128.0, 128.3, 132.2, 138.1.
13C NMR (50 MHz, CDCl3): (Z-diastereoisomer) = 72.0, 127.0,
131.2.
13C NMR (50 MHz, CDCl3): (syn diastereoisomer) = 29.7, 52.2,
64.9, 118.2, 126.6, 127.8, 128.3, 135.3, 142.5.
MS: m/z (%) = 210 (1), 175 (17), 126 (3), 107 (3), 91 (100), 77 (3),
65 (7).
13C NMR (50 MHz, CDCl3): (anti diastereoisomer) = 53.5, 62.8,
119.6, 126.3, 128.1, 133.2.
Anal. Calcd for C11H13ClO: C, 67.18; H, 6.66. Found: C, 67.05; H,
6.60.
MS (silylated alcohol): m/z (%) = 259 (10), 219(10), 189 (25), 163
(15), 147 (100), 115 (8), 107 (15), 75 (37).
The enantiomeric excess was determined by HPLC analysis
(Chiralcel OF, isocratic, n-hexane–IPA, 75:25, flow 0.35 mL/min);
anti: [(1R,2S) 15.8 min.; (1S,2R) 16.7 min.]; syn: [(1S,2S) 17.1 min,
(1R,2R) 20.6 min]; eeanti = 16%, eesyn = 81%.
14d
Yield: 49% (E:Z, 93:7); pale yellow oil.
IR (neat): 3000 (w), 2952 (m), 2919 (m), 2860 (w), 1712 (s), 1659
(w), 1427 (m), 1361 (m), 1255 (m), 1162 (m), 963 (m), 930 (w), 740
(w), 671 (m) cm–1.
1H NMR (200 MHz, CDCl3): (E-diastereoisomer) = 2.16 (s, 3 H),
2.27–2.42 (m, 2 H), 2.51–2.58 (m, 2 H), 4.01 (d, J = 6.6 Hz, 2 H),
5.70–5.86 (m, 2 H).
15b
Yield = 40% (syn:anti 83:17, dr was evaluated by GC analysis on
the silylated crude product); pale yellow oil; Rf 0.3 (cyclohexane–
Et2O, 8:2).
1H NMR (200 MHz, CDCl3): (Z-diastereoisomer) = 2.17 (s, 3 H),
4.12 (d, J = 7.2 Hz, 2 H).
13C NMR (50 MHz, CDCl3): (E-diastereoisomer) = 26.0, 30.0,
42.5, 45.1, 126.8, 133.9, 207.5.
13C NMR (50 MHz, CDCl3): (Z-diastereoisomer) = 126.2, 133.2.
1H NMR (300 MHz, CDCl3): (syn diastereoisomer) = 2.63–2.80
(m, 1 H), 3.49–3.60 (m, 2 H), 3.75 (d, J = 4.5 Hz, 1 H), 4.56 (s, 2
H), 4.83 (dd, J1 = 3.6 Hz, J2 = 6.6 Hz, 1 H), 5.02 (d, J = 10.2 Hz, 1
H), 5.06 (d, J = 1.5 Hz, 1 H); 5.68 (ddd, J1 = 8.1 Hz, J2 = 10.2 Hz,
J3 = 17.3 Hz, 1 H), 7.20–7.43 (m, 10 H).
1H NMR (300 MHz, CDCl3): (anti diastereoisomer) = 2.94 (br s,
1 H), 3.43–3.90 (m, 1 H), 4.51 (s, 2 H), 4.88–4.94 (m, 1 H), 5.14–
5.22 (m, 1 H), 5.19 (dd, J1 = 1.8 Hz, J2 = 10.5 Hz, 1 H); 5.87 (ddd,
J1 = 1.6 Hz, J2 = 8.7 Hz, J3 = 10.5 Hz, 1 H).
MS: m/z (%) = 146 (1), 129 (1), 111 (100), 97 (6), 93 (21), 88 (4),
75 (8), 67 (48), 53 (31).
Anal. Calcd for C7H11ClO: C, 57.34; H, 7.56. Found: C, 57.28; H,
7.50.
13C NMR (50 MHz, CDCl3): (syn diastereoisomer) = 50.4, 72.3,
73.6, 76.4, 117.5, 126.6, 127.1, 127.6, 127.8, 128.4, 128.9, 135.6,
137.5, 142.5.
Addition of Functionalised Allyl Bromides to Benzaldehyde
Mediated by [Cr(Salen)] Complex; General Procedure
13C NMR (50 MHz, CDCl3): (anti diastereoisomer) = 51.4, 71.6,
CrCl3 (0.016 g, 0.1 mmol) was suspended in anhyd CH3CN to
which Mn powder (0.16 g, 3 mmol) was added. The mixture was
kept at r.t. without stirring for 5–8 min. After that, the mixture was
vigorously stirred until a green-white precipitate was formed (10–
15 min.). Then Salen (0.11 g, 0.2 mmol) and anhyd Et3N (0.028 mL,
0.2 mmol) were added. The resulting heterogeneous mixture was
stirred at r.t. for 1 h, then the functionalised allyl bromide (13a or
10b, 1.5 mmol) was added. The colour of the mixture turned ma-
roon-red and the resulting suspension was stirred for 1 h at r.t. After
that time benzaldehyde (1 mmol) and Me3SiCl (1.5 mmol) were
added to the reaction mixture. The mixture was stirred until com-
plete consumption of the aldehyde (checked by GC, 48 h). The re-
action mixture was quenched with a sat. solution of NaHCO3 (5 mL)
and filtered over celite®. The organic phase was separated and the
aq phase was extracted with Et2O (2 × 4 mL). The combined organ-
73.4, 74.7, 118.5, 126.4, 127.7, 128.0, 128.4, 135.2, 137.9, 142.1.
MS (silylated alcohol): m/z (%) = 325 (1), 195 (1), 179 (100), 163
(2), 149 (2), 129 (3), 91 (22), 73 (28).
The enantiomeric excess was determined by 1H NMR analysis with
Eu(Hfc)3. (1R,2R) : 8.17 (d, J = 7.8 Hz, 1 H); (1S,2S) : 8.13 (d,
J = 7.8 Hz, 1 H): eesyn = 81%.
Acknowledgement
This work was supported by MIUR (Rome), FIRB funds: ‘Progetta-
zione, preparazione e valutazione biologica e farmacologica di nuo-
ve molecole organiche quali potenziali farmaci innovativi’,
National project ‘Stereoselezione in sintesi organica: metodologie
Synthesis 2004, No. 3, 409–414 © Thieme Stuttgart · New York

414
Marco Bandini et al.
PAPER
and applicazioni’, and the University of Bologna (Funds for selec-
ted research topics). We are indebted to Professor A. H. Hoveyda
for the generous gift of the catalyst 3.
Int. Ed. 2001, 40, 3441; and references therein.
(b) Goldberg, S. D.; Grubbs, R. H. Angew. Chem. Int. Ed.
2002, 41, 807.
(15) Blanco, O. M.; Castedo, L. Synlett 1999, 557.
(16) Liu, B.; Das, S. K.; Roy, R. Org. Lett. 2002, 4, 2723.
(17) Elemes, Y.; Foote, C. S. J. Am. Chem. Soc. 1992, 114, 6044.
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65.
(19) The use of trans-1,3-dibromo or trans-1,3-dichloropropene
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reaction. For this strategy see: Blackwell, H. E.; O’Leary, D.
J.; Chatterjee, A. K.; Washenfelder, R. A.; Bussmann, D. A.;
Grubbs, R. H. J. Am. Chem. Soc. 2000, 122, 5871.
(20) Selected examples: (a) [Sn]:Marshall, J. A. In
Organometallic in Synthesis: A Manual; Schlosser, M., Ed.;
Wiley: Chichester, 2002, 353. (b) [Ti]: Reetz, M. T. In
Organometallic in Synthesis: A Manual; Schlosser, M., Ed.;
Wiley: Chichester, 2002, 817. (c) [Zn]: Nakamura, E. In
Organometallic in Synthesis: A Manual; Schlosser, M., Ed.;
Wiley: Chichester, 2002, 353. (d) [Cu]: Lipshutz, B. H. In
Organometallic in Synthesis: A Manual; Schlosser, M., Ed.;
Wiley: Chichester, 2002, 665.
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Synthesis 2004, No. 3, 409–414 © Thieme Stuttgart · New York