A protocol for the direct conversion of aldehydes into arenes - Proof of principle

Article abstract of DOI:10.1055/s-2007-991088

A functional C5-phosphonate reagent serves as the direct precursor of a phenyl group, the remaining carbon atom arising from an aldehyde. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-991088

LETTER
2823
A Protocol for the Direct Conversion of Aldehydes into Arenes – Proof of
Principle
D
irec
t
Conversion of
A
a
ldehydes
i
u
Chemistry Research Laboratory, Mansfield Rd., Oxford OX1 3TA, UK
Fax +44(1865)285002; E-mail: john.brown@chem.ox.ac.uk
Received 6 August 2007
Abstract: A functional C5-phosphonate reagent serves as the direct
precursor of a phenyl group, the remaining carbon atom arising
from an aldehyde.
HO
HO
Cl
Cl
HO
Cl
1
2
3
Key words: Horner–Emmons, E,Z,E-trienes, cyclohexadienes, Pd
coupling, semihydrogenation
Cl
Cl
Cl
Cl
4
5
There has been a revival of interest in the direct synthesis
of aromatic compounds from acyclic precursors. In addi-
tion to the application of Bergman cyclisation,1 annula-
tion,2 and alkyne trimerisation routes,3 alkene metathesis
has emerged as a useful method.4 In parallel, recent ad-
vances in organocatalytic asymmetric synthesis have pro-
vided new methods for preparation of aldehydes with a-
or b-stereogenic centres that supplement existing ones.5
This has stimulated our efforts to develop a direct conver-
sion of aldehydes into arenes in which the carbonyl car-
bon becomes the ipso-carbon of the arene. We report the
development of an approach demonstrating proof of prin-
ciple, shown in outline in Scheme 1. The aldehyde is re-
acted with the terminal carbon of a U-shaped pentadienyl
anion carrying a leaving group at the opposing terminus,
so that triene cyclisation may afford the arene in a single
step. Since the Horner–Emmons reaction may avoid com-
promising adjacent stereocentres, this provides a likely
precursor.6 The desired triene should possess an E,Z,E-
configuration, since disrotatory thermal cyclisation is far
faster here than with the Z,Z,E- or Z,Z,Z-stereoisomers.7
Figure 1
After some trials to find a satisfactory method for selec-
tive semihydrogenation of the alkyne, hydrogenation was
carried out in anhydrous degassed MeOH in the presence
of 3 mol% Rh catalyst under hydrogen pressure (1.4 atm).
As Schrock and Osborn reported in the original work,9 the
nature of the ligand can influence reactivity and selectivi-
ty. Thus, our optimum catalyst proved to be [Rh+(dp-
pb)NBD]OTf– (full conversion and excellent stereo- and
chemoselectivity). The Z-isomer 2 formed was unstable,
however, and tended to isomerise on silica gel or on stand-
ing. Hence the corresponding E-isomer was prepared by
Sonigashira coupling as before, followed by reduction
with LiAlH4 in Et2O at 0 °C giving (2E,4E)-5-chloropen-
ta-2,4-dien-1-ol (3) in quantitative yield.10 On attempted
mesylation of either E,E or Z,E allylic alcohols, the only
isolated product was the corresponding chloride 4 (64%)
or 5 (61%), most probably formed by direct SN2 displace-
ment of the mesyloxy group by chloride ion.
Exploratory chemistry was carried out with the E,E-iso-
mer 5. This was converted into the corresponding tri-
phenylphosphonium chloride 6. Under various
conditions, and with different aromatic aldehydes (4-NO2,
4-OMe, 3,4-OBn), the desired terminal E-isomer of triene
was never formed in better than 70:30 ratio with the
corresponding Z-isomer. This encouraged the synthesis of
phosphonate 7, from which a 9:1 ratio of E/Z isomers of
the terminal double bond in product 8 was readily ob-
tained under standard Horner–Emmons conditions with 4-
MeOC6H4CHO. The pure E,E-isomer was obtained by
flash chromatography. With this result in hand, the same
sequence was tested for E,Z-diene 4, with equally favour-
able results. The phosphonate ester 9, prepared in 57%
yield, reacted under the same conditions, and again gave
a 9:1 preference for the E,Z,E-isomer of product 10, sepa-
rable from its stereoisomer by flash chromatography
(Scheme 2).
O
+
X
R
R
H
Y
X
R
Scheme 1 Proposed arene retrosynthesis
The precursor triene was prepared by a published route.8
(E)-5-Chloro-pent-4-en-2-yn-1-ol (1, Figure 1) is readily
available by Sonogashira cross-coupling between (E)-
dichloroethylene and propargyl alcohol [(PdCl2(PPh3)2,
cuprous iodide, piperidine, toluene, r.t.] in 88% yield.
This compound was kept in the freezer in order to prevent
its decomposition to a black solid.
SYNLETT 2007, No. 18, pp 2823–2826
Advanced online publication: 12.10.2007
DOI: 10.1055/s-2007-991088; Art ID: D24107ST
x
x
.x
x
.2
0
0
7
© Georg Thieme Verlag Stuttgart · New York

2824
M. Gayral, J. M. Brown
LETTER
Table 1 Cyclisation–Aromatisation in Pyridinea
Cl
(b)
Ar
Ph3P
Cl
(a)
Reactantb
Product (isolated yield, %)
Cl
6
E/Z = 50:50, various Ar
Cl
5
(c)
O
MeO
(d)
Cl
P
MeO
MeO
OMe
11 (60)
10
Cl
MeO
7
8
Cl
Cl
O
(e)
(f)
MeO
4
Cl
P
BnO
BnO
OMe
OBn
O
OBn
9
10
15 (71)
12
Me
Me
Scheme 2 Triene preparations: (a) PPh3, MeCN, 50 °C, 16 h, 79%;
(b) ArCHO, Wittig under various conditions; (c) P(OMe)3, NaI, neat,
r.t., 16 h, 46%; (d) p-MeOC6H4CHO, LiN(SiMe3)2, THF, r.t., 3 h,
50%; (e) as (c), 57%; (f) p-MeOC6H4CHO, NaN(SiMe3)2, THF, r.t., 3
h, 48%.
Cl
MeO
MeO
13
16 (68)
Cl
At this stage the relative reactivity of 8 and 10 towards
cyclisation was evaluated. On injection of the E,Z,E-iso-
mer 10 into a GC-MS inlet (15 m ZBS column, 0.25 mm
ID, 80–280 °C, 20 °C/min) the aromatised product 11 of
m/z = 184.07 (calcd 184.09) was observed. Only the par-
ent ion of the E,E,E-isomer 8 was observed in a parallel
experiment, hence cyclisation did not occur. An isolable
quantity of the product 11 (60:40 with reactant) was, how-
ever, obtained by passage of 8 through an empty 2 m pre-
parative GC column, (20 mg per pass, EtOAc solution),
with the oven held at 300 °C. Likewise the E,Z,E-isomer
10 was converted into the same mixture, but with an oven
temperature of 200 °C.
14
17 (54)
a Reaction conditions: 110 °C, 4–12 h.
b Prepared in 23–65% yield as described for 8.
appear whilst the water peak increases and shifts down-
field from 5.4 to 6.8 ppm as pyridinium chloride is
formed. The aromatisation reaction of 10 also occurs in
toluene in the presence of pyridine (1 equiv) at 100 °C
over 12 hours, product 11 being isolated in 71% yield. In
the absence of pyridine, only double-bond isomerisation
of 10 to 8 is observed.
These early results encouraged preparative-scale experi-
ments. Several further E,Z,E-trienes 12–14 were prepared
and purified as before by the Horner–Emmons route. In
the case of 13, and also the 3E,3Z)-mixture of the 4-NO2
analogue of 8,11 cyclisation–aromatisation was success-
fully demonstrated by GC-MS as described above. After
exploratory experiments, a standard technique was then
adopted.
These simple experiments demonstrate the potential of a
simple method for extending the synthetic utility of alde-
hydes. It is potentially applicable to enantiomerically pure
aldehydes, to labelled aldehydes (11C, 13C) and to more
highly substituted arenes by simple structural modifica-
tion of the C5 entity. Future work will follow these direc-
tions.
The reactant was heated in pyridine, or preferably pyri-
dine-d5 to aid monitoring by 1H NMR, for up to 12 hours
at 120 °C. At that stage cyclisation is complete, the aro-
matic product being accompanied by a small amount of
the unreactive E,E,E-isomer of the parent triene, arising
by 3Z,3E-isomerisation. The results of these experiments
are recorded in Table 1.
(2Z,4E)-5-Chloropenta-2,4-dien-1-ol (2)
(E)-5-Chloro-pent-4-en-2-yn-1-ol (1, 150 mg, 1.29 mmol) and
[Rh+(dppb)NBD]OTf– (20 mg, 3% mmol) were dissolved in anhyd
and degassed MeOH (5 mL). The orange solution was put under H2
pressure in a closed vessel (1.4 atm) and the reduction was moni-
tored by computer. After 8 h stirring, the solvent was removed in
vacuo leading to a brown oil (170 mg, ca. 100% conversion). As the
obtained diene 2 is subject to isomerisation, the crude product was
used without any further purification in the next step; C5H7ClO
(118.6). IR (neat): 3608, 3020, 1522, 1430, 757, 652 cm–1. 1H NMR
(400 MHz, CDCl3): d = 6.73 (1 H, ddd, J2,1 = 13.0 Hz, J2,3 = 11.3
Hz, J2,4 = 1.1 Hz, H-2), 6.25 (1 H, d, H-1), 6.02 (1 H, ddt, J3,4 = 11.1
Hz, J3,5 = 1.0 Hz, H-3), 5.63 (1 H, m, H-4), 4.27 (2 H, dd, J4,5 = 6.8
H, H-5), 2.12 (1 H, br s, OH). 13C NMR (100 MHz, CDCl3): d =
130.6 (C-4), 128.6 (C-2), 126.7 (C-3), 122.9 (C-1), 58.6 (C-5). MS
(TOF FI+): m/z calcd for for [M+]: 118.0185; found: 118.0184. The
E,E-isomer has been prepared previously;9 we used LiAlH4 in
reduction of alkyne 1, 99% yield.
The desired aromatic products were separated by prepar-
ative TLC and fully characterised. A good example of
monitoring the course of reaction by 1H NMR is afforded
by reactant 13. The CHCH3 doublets of reactant and prod-
uct are at d = 1.41 and 1.55 ppm, respectively. After 12
hours at 120 °C, only the 1.55 ppm signal remains. The
initial spectrum shows the diene protons in the region 5.9–
6.8 ppm, and a trace of H2O in the C5D5N solvent at 5.4
ppm. Over time the diene peaks diminish and then dis-
Synlett 2007, No. 18, 2823–2826 © Thieme Stuttgart · New York

LETTER
Direct Conversion of Aldehydes into Arenes
2825
(1E,3Z)-1,5-Dichloropenta-1,3-diene (4)
Dimethyl (2Z,4E)-5-Chloropenta-2,4-dienylphosphonate (9)
Compound 9 was prepared likewise from 4 in 82% yield. IR (neat):
2956, 1576, 1464, 735, 651 cm–1. 1H NMR (400 MHz, CDCl3): d =
6.65 (1 H, ddd, J1,2 = 12.9 Hz, J2,3 = 11.5 Hz, J2,4 = 1.2 Hz, H-2),
6.28 (1 H, dd, J1,3 = 2.0 Hz, H-1), 6.11 (1 H, m, H-3), 5.46 (1 H, m,
H-4), 3.74 (3 H, s, OMe), 3.72 (3 H, s, OMe), 2.71 (2 H, ddd,
2JPH = 23.0 Hz, J4,5 = 8.2 Hz, J3,5 = 1.4 Hz, H-5). 13C NMR (100
MHz, CDCl3): d = 128.4 (d, JPC = 14.4 Hz, C-3), 128.1 (d, JPC = 4.8
Hz, C-2), 123.5 (d, JPC = 3.9 Hz, C-1), 120.0 (d, JPC = 12.0 Hz, C-
4), 52.8 (OMe), 52.7 (OMe), 25.5 (d, JPC = 140.7 Hz, C-5). 31P
NMR (161 MHz, CDCl3): d = 28.6. MS (TOF MS FI+): m/z calcd
for [M + Na+]: 233.0110; found: 233.0105.
To a solution of allylic alcohol 2 (0.41 g, 3.44 mmol) in anhyd
CH2Cl2 (10 mL) was added dropwise Et3N (0.96 mL, 6.88 mmol) at
0 °C under an argon atmosphere. After 15 min, mesyl chloride (0.40
mL, 5.16 mmol) was added dropwise at 0 °C to the brown solution.
The dark red solution was allowed to warm to r.t. and stirred for 3
h. The dark red solution was then hydrolysed with a sat. aq NH4Cl
solution (5 mL), the layers were separated and the aqueous layer ex-
tracted with CH2Cl2 (3 × 15 mL). The organic layer was washed
with brine, dried over MgSO4, and the solvent removed in vacuo to
lead to a brown oil. The crude product was purified by chromatog-
raphy on silica gel (EtOAc–pentane, 1:9) to yield allylic chloride 4
as a pale yellow oil (0.30 g, 64%). IR (neat): 3065, 2928, 1648,
1586, 734, 651 cm–1. 1H NMR (400 MHz, CDCl3): d = 6.74 (1 H,
ddd, J1,2 = 12.9 Hz, J2,3 = 11.5 Hz, J2,4 = 1.2 Hz, H-2), 6.35 (1 H, d,
H-1), 6.10 (1 H, ddt, J3,4 = 11.3 Hz, J3,5 = 0.8 Hz, H-3), 5.66 (1 H,
m, H-4), 4.16 (2 H, dd, J4,5 = 8.1 Hz, H-5). 13C NMR (100 MHz,
CDCl3): d = 128.4 (C-3), 127.7 (C-2), 126.5 (C-4), 124.7 (C-1), 38.9
(C-5). MS (TOF FI+): m/z calcd for [M+]: 135.9847, found:
135.9848.
Typical Procedure for the HWE Reaction
The base was synthesised in situ: A solution of n-BuLi (1.6 M in
hexanes, 1.1 equiv) was added to a solution of HMDS (1.1 equiv) in
anhyd THF (2 mL) at 0 °C. After 15 min a solution of phosphonate
7 (1 equiv) in anhyd THF (3 mL) was added slowly to the pale yel-
low solution. After 30 min 4-methoxybenzaldehyde (1.2 equiv) in
anhyd THF (2 mL) was added slowly at 0 °C and allowed to warm
to r.t. After 16 h, the dark orange solution was quenched with H2O
(5 mL) and extracted with Et2O (3 × 15 mL). After washing with
brine and drying over MgSO4, the solvent was removed in vacuo.
The crude product was purified by chromatography on silica gel
(EtOAc–pentane, 1:n).
(1E,3E)-1,5-Dichloropenta-1,3-diene (5)
As 4, colourless oil (0.34 g, 72%). IR (neat): 3066, 2928, 1648,
1585, 974, 777 cm–1. 1H NMR (400 MHz, CDCl3): d = 6.46 (1 H,
dd, J1,2 = 13.1 Hz, J2,3 = 10.9 Hz, H-2), 6.28 (1 H, dd, J1,3 = 0.5 Hz,
H-1), 6.26 (1 H, ddt, J3,4 = 14.9 Hz, J3,5 = 0.8 Hz, H-3), 5.83 (1 H,
dt, J4,5 = 7.2 Hz, H-4), 4.09 (2 H, dd, H-5). 13C NMR (100 MHz,
CDCl3): d = 132.1 (C-2), 129.9 (C-3), 129.1 (C-4), 122.8 (C-1), 44.5
(C-5). MS (TOF FI+): m/z calcd for [M+]: 135.9847; found:
135.9848.
1-[(1E,3E,5E)-6-Chlorohexa-1,3,5-trienyl]-4-methoxybenzene
(8)
Pale brown solid (51%). Mp 99–101 °C (lit.13 100–102 °C).
1-[(1E,3Z,5E)-6-Chlorohexa-1,3,5-trienyl]-4-methoxybenzene
(10)
(2E,4E)-5-Chloropenta-2,4-dienyl)triphenylphosphonium
Chloride (6)
Yellow solid (25 mg, 48%), mp 79–80 °C. IR (neat): 3100, 2810,
1600, 1513, 1465, 1254, 1180, 1034, 737, 650 cm–1. 1H NMR (400
MHz, CDCl3): d = 7.39 (2 H, d, J8,9 = 8.7 Hz, H-8), 7.05 (1 H, ddd,
J5,6 = 14.4 Hz, J4,5 = 11.4 Hz, J3,5 = 0.8 Hz, H-5), 7.03 (1 H, m, H-
2), 6.88 (2 H, d, H-9), 6.57 (1 H, d, H-6), 6.25 (1 H, d, J1,2 = 13.0
Hz, H-1), 6.16 (1 H, dt, J3,4 = 10.7 Hz, H-4), 5.94 (1 H, ddd,
J2,3 = 12.3 Hz, H-3), 3.83 (3 H, s, OMe). 13C NMR (100 MHz,
CDCl3): d = 159.5 (C-10), 134.1 (C-6), 130.7 (C-4), 129.8 (C-7),
129.5 (C-2), 127.9 (C-8), 123.9 (C-3), 121.4 (C-5), 121.3 (C-1),
114.1 (C-9), 55.3 (OMe). MS (TOF CI+): m/z calcd for [M+]:
220.0655; found: 220.0652.
From PPh3 and halide 5 in MeCN, r.t., 79%; mp 112–114 °C. IR
(KBr): 3066, 2979, 1661, 1587, 982, 743 cm–1. 1H NMR (400 MHz,
CDCl3): d = 7.83–7.78 (6 H, m, H-8), 7.75–7.71 (3 H, m, H-9),
7.65–7.60 (6 H, m, H-7), 6.52 (1 H, m, H-3), 6.24 (1 H, dd,
J1,2 = 13.1 Hz, J2,3 = 10.9 Hz, H-2), 6.14 (1 H, dd, J1,3 = 2.4 Hz, H-
1), 5.43 (1 H, dt, J3,4 = 13.6 Hz, J4,5 = 7.1 Hz, H-4), 4.99 (2 H, dd,
JPH = 15.8 Hz, H-5). 13C NMR (100 MHz, CDCl3): d = 136.2 (d,
JPC = 13.5 Hz, C-3), 134.9 (d, JPC = 2.4 Hz, C-9), 133.9 (d, JPC = 9.6
Hz, C-7), 132.0 (d, JPC = 4.7 Hz, C-2), 130.2 (d, JPC = 12.8 Hz, C-
8), 123.5 (d, JPC = 5.6 Hz, C-1), 118.0 (d, JPC = 86.3 Hz, C-6), 117.9
(d, JPC = 11.2 Hz, C-4), 27.6 (d, JPC = 50.3 Hz, C-5). 31P NMR (161
MHz, CDCl3): d = 21.5. MS (ESI+): m/z calcd for [M+]: 363.1064;
found: 363.1067. Wittig reactions reported here were carried out us-
ing the modified method of Niwa et al.12 with (Me3Si)2NNa in THF.
{4-[(1E,3Z,5E)-6-Chlorohexa-1,3,5-trienyl]-1,2-phenylene}
Bis(oxy)bis(methylene)dibenzene (12)
Chromatography on silica gel (EtOAc–pentane, 1:6), pale yellow
solid (25%); mp 98–100 °C. IR (KBr): 3134, 1510, 1382, 1135,
1
Dimethyl (2E,4E)-5-Chloropenta-2,4-dienylphosphonate (7)
A solution of allylic chloride 5 (0.34 g, 2.48 mmol) in (Me3O)3P
(2.93 mL, 24.8 mmol) was treated with NaI (0.45 g, 2.97 mmol) and
stirred vigorously at 40 °C overnight. The cooled dark yellow solu-
tion was quenched with H2O (5 mL) and extracted with EtOAc
(3 × 15 mL). The organic layer was washed with brine, dried over
MgSO4, and the solvent was removed in vacuo. The crude product
was purified by chromatography on silica gel (EtOAc) to yield
phosphonate 7 as a pale yellow oil (0.43 g, 82%). IR (neat): 2956,
2853, 1584, 1462, 978, 733 cm–1. 1H NMR (400 MHz, CDCl3): d =
6.35 (1 H, ddd, J1,2 = 13.2 Hz, J2,3 = 11.8 Hz, J2,4 = 0.6 Hz, H-2),
6.10 (1 H, dd, J1,3 = 2.7, H-1), 6.06 (1 H, m, H-3), 5.57 (1 H, m,
J3,4 = 15.2 Hz, J4,5 = 7.6 Hz, H-4), 3.67 (3 H, s, OMe), 3.65 (3 H, s,
OMe), 2.56 (2 H, ddd, 2JPH = 22.4 Hz, J3,5 = 0.9 Hz, H-5). 13C NMR
(100 MHz, CDCl3): d = 132.6 (d, JPC = 4.8 Hz, C-2), 130.8 (d,
JPC = 14.4 Hz, C-3), 122.8 (d, JPC = 12.8 Hz, C-4), 120.7 (d,
JPC = 5.6 Hz, C-1), 52.6 (OMe), 52.5 (OMe), 30.0 (d, JPC = 140.6
Hz, C-5). 31P NMR (161 MHz, CDCl3): d = 28.5. MS (TOF FI+):
m/z calcd for [M + Na+]: 233.0110; found: 233.0105.
1090, 735, 650 cm–1. H NMR (400 MHz, CDCl3): d = 7.51–7.32
(10 H, m, OCH2C6H5), 7.07 (1 H, m, H-2), 7.01 (1 H, ddd,
J5,6 = 15.4 Hz, J4,5 = 11.9 Hz, J3,5 = 0.8 Hz, H-5), 6.96–6.87 (3 H, m,
H-8, H-11, and H-12), 6.50 (1 H, d, H-6), 6.26 (1 H, d, J1,2 = 12.9
Hz, H-1), 6.14 (1 H, dt, J3,4 = 11.1 Hz, H-4), 5.94 (1 H, dt, H-3),
5.20 (4 H, d, Jgem = 2.5 Hz, OCH2Ph). 13C NMR (100 MHz, CDCl3):
d = 149.1 (C-9), 149.0 (C-10), 137.2 (C-14), 137.0 (C-14¢), 134.0
(C-6), 130.7 (C-4), 130.5 (C-5), 129.4 (C-7), 128.6 and 126.5 (C-15
and C-15¢), 127.9 and 127.8 (C-17 and C-17¢), 127.3 and 127.2 (C-
16 and C-16¢), 124.2 (C-3), 121.9 (C-1), 121.5 (C-8), 120.7 (C-12),
114.7 (C-11), 112.7 (C-2), 71.5 and 71.2 (C-13 and C-13¢). MS
(TOF ESI+): m/z calcd for [M + Na+]: 425.1284; found: 425.1279.
2-[(3E,5Z,7E)-8-Chloroocta-3,5,7-trien-2-yl]-6-methoxy Naph-
thalene (13)
Chromatography on silica gel (EtOAc–pentane, 5:95), pale yellow
solid (65%); mp 71–73 °C. IR (KBr): 3054, 1654, 1422, 1265, 1029,
929, 740 cm–1. H NMR (400 MHz, CDCl3): d = 7.70 (1 H, d,
1
J11,12 = 8.3 Hz, H-11), 7.69 (1 H, m, H-16), 7.59 (1 H, m, H-9), 7.34
Synlett 2007, No. 18, 2823–2826 © Thieme Stuttgart · New York

2826
M. Gayral, J. M. Brown
LETTER
(1 H, dd, J16,17 = 8.2 Hz, J17,9 = 1.8 Hz, H-17), 7.16–7.11 (2 H, m,
H-12 and H-14), 6.90 (1 H, tt, J5,6 = 13.1 Hz, J6,7 = 1.3 Hz, H-6),
6.49 (1 H, m, H-2), 6.21 (1 H, d, J1,2 = 12.9 Hz, H-1), 6.06–5.99 (2
H, m, H-3 and H-5), 5.86 (1 H, m, H-4), 3.93 (3 H, s, H-19), 3.70 (1
H, dq, J7,18 = 6.8 Hz, H-7), 1.49 (3 H, d, H-18). 13C NMR (100 MHz,
CDCl3): d = 155.9 (C-13), 141.8 (C-8), 140.3 (C-15), 134.6 (C-6),
130.7 (C-4), 130.5 (C-5), 129.4 (C-10), 129.1 (C-11), 127.0 (C-17),
126.6 (C-9), 125.0, 123.7 and 123.5 (C-1, C-2, and C-3), 121.3 (C-
16), 118.8 (C-12), 105.7 (C-14), 55.3 (C-19), 42.6 (C-7), 14.2 (C-
18). MS (TOF ESI+): m/z calcd for [M + Na+]: 321.1022; found:
321.1017.
(S)-[4-(Prop-1-en-2-yl)cyclohex-1-enyl]benzene (17)
Preparative plate chromatography (EtOAc–pentane, 5:95), pale yel-
low oil (54%). IR (KBr): 3054, 1625, 1422, 896 cm–1. 1H NMR (400
MHz, CDCl3): d = 7.40 (2 H, m, H-2 and H-4), 7.34–7.30 (2 H, m,
H-1 and H-5), 7.23 (1 H, tt, J1,3 and 3,5 = 1.4 Hz, J2,3 and 3,4 = 7.1 Hz, H-
3), 6.15 (1 H, m, H-8), 4.78–4.77 (2 H, m, H-14), 2.55–2.49 (2 H,
m, H-12), 2.40–1.96 (4 H, m, H-9 and H-11), 1.80 (3 H, s, H-15),
1.64 (1 H, m, H-10). 13C NMR (100 MHz, CDCl3): d = 149.8 (C-
13), 142.2 (C-6), 136.3 (C-7), 128.2 (C-2 and C-4), 126.6 (C-8),
124.9 (C-1 and C-5), 124.1 (C-3), 108.7 (C-14), 40.8 (C-10), 31.3
(C-9), 28.0 (C-12), 27.9 (C-11), 20.9 (C-15). MS (TOF CI+): m/z
calcd for [M+]: 198.1409; found: 198.1404.
(S)-1-[(1E,3Z,5E)-6-Chlorohexa-1,3,5-trienyl]-4-(prop-1-en-2-
yl)cyclohex-1-ene (14)
Acknowledgment
Chromatography on silica gel (pentane), yellow oil (23%). IR
1
(KBr): 3054, 2987, 1422, 909, 737 cm–1. H NMR (400 MHz,
We thank the Descartes Prize Fund of the European Commission
and Avecia for postgraduate support of M.G.
CDCl3): d = 6.95 (1 H, ddd, J2,4 = 1.0 Hz, J2,3 = 11.7 Hz, J1,2 = 13.9
Hz, H-2), 6.50 (1 H, dd, J4,5 = 11.4 Hz, J5,6 = 15.2 Hz, H-5), 6.30 (1
H, d, H-1), 6.22 (1 H, d, H-6), 6.07 (1 H, td, J3,4 = 11.5 Hz, H-4),
5.91–5.86 (2 H, m, H-3 and H-8), 4.76–4.73 (2 H, m, H-14), 2.42–
2.31 (2 H, m, H-12), 2.28–2.17 (4 H, m, H-9 and H-11), 1.77 (3 H,
s, H-15), 1.53 (1 H, m, H-10). 13C NMR (100 MHz, CDCl3): d =
149.5 (C-13), 137.9 (C-6), 137.9 (C-7), 135.6 (C-8), 131.2 (C-4),
131.0 (C-2), 129.5 (C-5), 123.6 (C-3), 120.2 (C-1), 108.9 (C-14),
41.0 (C-10), 31.6 (C-9), 29.7 (C-12), 27.3 (C-11), 20.8 (C-15). MS
(TOF MS FI+): m/z calcd for [M+]: 234.1175; found: 234.1177.
References and Notes
(1) (a) Smith, D. W. Jr.; Shah, H. V.; Perera, K. P. U.; Perpall,
M. W.; Babb, D. A.; Martin, S. J. Adv. Funct. Mater. 2007,
17, 1237. (b) Taduri, B. P.; Ran, Y.-F.; Huang, C.-W.; Liu,
R.-S. Org. Lett. 2006, 8, 883. (c) Pickard, F. C. I. V.;
Shepherd, R. L.; Gillis, A. E.; Dunn, M. E.; Feldgus, S.;
Kirschner, K. N.; Shields, G. C.; Manoharan, M.; Alabugin,
I. V. J. Phys. Chem. A 2006, 110, 2517. (d) Zeidan, T. A.;
Kovalenko, S. V.; Manoharan, M.; Alabugin, I. V. J. Org.
Chem. 2006, 71, 962. (e) Lewis, K. D.; Matzger, A. J. J. Am.
Chem. Soc. 2005, 127, 9968. (f) O’Connor, J. M.; Friese, S.
J.; Tichenor, M. J. Am. Chem. Soc. 2002, 124, 3506.
(g) Bowles, D. M.; Palmer, G. J.; Landis, C. A.; Scott, J. L.;
Anthony, J. E. Tetrahedron 2001, 57, 3753.
General Procedure for Cyclisation–Aromatisation in Pyridine
Triene (20 mg) was dissolved in pyridine-d5 (1 mL) and the result-
ing pale brown solution heated at 120 °C. The reaction was moni-
tored by 1H NMR and after 12 h, the brown solution was quenched
with an aq HCl solution (1 M, 1 mL) and extracted with EtOAc
(3 × 5 mL). The organic layer was washed with brine, dried over
MgSO4, and the solvent removed in vacuo. Preparative plate chro-
matography yielded the biphenyl.
(2) (a) Bull, J. A.; Hutchings, M. G.; Quayle, P. Angew. Chem.
Int. Ed. 2007, 46, 1869. (b) Bhar, S. S.; Ramana, M. M. V.
Tetrahedron Lett. 2006, 47, 7805.
4-Methoxybiphenyl (11)
(3) (a) Agenet, N.; Buisine, O.; Slowinski, F.; Gandon, V.;
Aubert, C.; Malacria, M. Org. React. 2007, 68, 1. (b) Hopf,
H. In Modern Arene Chemistry; Wiley-VCH: Weinheim,
2002, 169–195. (c) Yamamoto, Y. Curr. Org. Chem. 2005,
9, 503.
(4) (a) Yoshida, A.; Horiuchi, S.; Iwadate, N.; Kawagoe, F.;
Imamoto, T. Synlett 2007, 1561. (b) Yoshida, K.; Kawagoe,
F.; Iwadate, N.; Takahashi, H.; Imamoto, T. Chem. Asian J.
2006, 1, 611. (c) Donohoe, T. J.; Orr, A. J.; Bingham, M.
Angew. Chem. Int. Ed. 2006, 45, 2664.
Preparative plate chromatography (EtOAc–pentane, 1:9); yield 10
mg, 60%; mp 90–91 °C (lit.14 90–91 °C).
3,4-Bis(benzyloxy)biphenyl (15)
Preparative plate chromatography (EtOAc–pentane, 1:4), yellow
1
solid (71%). IR (KBr): 3134, 1514, 1378, 1133, 1090 cm–1. H
NMR (400 MHz, CDCl3): d = 7.50–7.47 (6 H, m, H-1, H-5, H-15
and H-15¢), 7.42–7.37 (6 H, m, H-2, H-4, H-16, and H-16¢), 7.34–
7.31 (3 H, m, H-3, H-17, and H-17¢), 7.21 (1 H, d, J8,12 = 2.1 Hz, H-
8), 7.13 (1 H, dd, J11,12 = 8.2 Hz, H-12), 7.01 (1 H, d, H-11), 5.24 (2
H, s, H-13), 5.22 (2 H, s, H-13¢). 13C NMR (100 MHz, C5D5N):
142.8 (C-7), 139.8 and 139.7 (C-9 and C-10), 136.7 (C-6), 130.9 (C-
14 and C-14¢), 130.5 (C-2, C-4, 2 C-16, and 2 C-16¢), 129.9 (C-17
and C-17¢), 129.8 (C-1 and C-5), 129.7 and 129.6 (C-15 and C-15¢),
128.8 (C-3), 116.1 (C-12), 107.3 (C-11), 100.0 (C-8), 73.1 and 72.9
(C-13 and C-13¢). MS (TOF ESI+): m/z calcd for [M + Na+]:
389.1517; found: 389.1512.
(5) For example: Marigo, M.; Jorgensen, K. A. Chem. Commun.
2006, 2001; and references cited therein.
(6) Davis, F. A.; Kasu, P. V. N.; Sundarababu, G.; Qi, H. Y. J.
Org. Chem. 1997, 62, 7546.
(7) (a) Marvell, E. N.; Caple, G.; Schatz, B.; Pippin, W.
Tetrahedron 1973, 29, 3781. (b) Marvell, E. N. Tetrahedron
1973, 29, 3791. (c) Marvell, E. N.; Caple, G.; Schatz, B.
Tetrahedron Lett. 1965, 385.
(8) Chemin, D.; Linstrumelle, G. Tetrahedron 1994, 50, 5335.
(9) Schrock, R. R.; Osborn, J. A. J. Am. Chem. Soc. 1976, 98,
2143.
(10) Mladenova, M.; Alami, M.; Linstrumelle, G. Synth.
Commun. 1996, 26, 2831.
(11) This E/Z mixture arose from both the Wittig and Horner–
Emmons olefination procedures.
(12) Niwa, H.; Watanabe, M.; Inagaki, H.; Yamada, K.
Tetrahedron 1994, 50, 7385.
2-Methoxy-6-(1-phenylethyl)naphthalene (16)
Preparative plate chromatography (EtOAc–pentane, 5:95), white
solid (68%). IR (KBr): 3049, 1652, 1423, 1244, 1029, 742 cm–1. 1H
NMR (400 MHz, CDCl3): d = 7.71–7.64 (3 H, m, H-9, H-11, and H-
16), 7.32–7.26 (5 H, m, H-1 to H-5), 7.20 (1 H, m, H-17), 7.15–7.10
(2 H, m, H-12 and H-14), 4.30 (1 H, q, J7,18 = 7.5 Hz, H-7), 3.92 (3
H, s, H-19), 1.73 (3 H, d, H-18). 13C NMR (100 MHz, CDCl3): d =
157.4 (C-13), 146.5 (C-6), 141.5 (C-8), 134.1 (C-15), 129.2 (C-10),
129.0 (C-11), 128.4 (C-2 and C-4), 127.8 (C-1 and C-5), 127.3 (C-
16), 126.8 (C-17), 126.1 (C-9), 125.2 (C-3), 118.7 (C-12), 105.6 (C-
14), 55.3 (C-19), 44.6 (C-7), 21.9 (C-18). MS (TOF CI+): m/z calcd
for [M+]: 262.1358; found: 262.0696.
(13) Crousse, B.; Mladenova, M.; Ducept, P.; Alami, M.;
Linstrumelle, G. Tetrahedron 1999, 55, 4353.
(14) Denmark, S. E.; Ober, M. H. Org. Lett. 2003, 5, 1357.
Synlett 2007, No. 18, 2823–2826 © Thieme Stuttgart · New York

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