Disubstituted benzenes from acyclic precursors by a [5+1] annulation

Article abstract of DOI:10.1055/s-0029-1217162

Horner-Wadsworth-Emmons reaction of stannylvinylphosphonates with aldehydes and mild thermal cyclisation provides disubstituted arylstannanes. Subsequent Stille coupling leads to regiospecific synthesis of m- and p-terphenyls. Georg Thieme Verlag Stuttgar

Full text of DOI:10.1055/s-0029-1217162

LETTER
1387
Disubstituted Benzenes from Acyclic Precursors by a [5+1] Annulation
D
isubstituted Benz
a
enes from
v
A
cyclics id S. B. Daniels, John M. Brown, Maud Gayral, Yingjian Xu, Malcolm I. Stewart*
Chemistry Research Laboratory, Mansfield Road, Oxford OX1 3TA, UK
Fax +44(1865)285002; E-mail: malcolm.stewart@chem.ox.ac.uk
Received 22 January 2009
a
HO
Cl
Abstract: Horner–Wadsworth–Emmons reaction of stannylvi-
nylphosphonates with aldehydes and mild thermal cyclisation pro-
vides disubstituted arylstannanes. Subsequent Stille coupling leads
to regiospecific synthesis of m- and p-terphenyls.
HO
+
Cl
Cl
2
, 72%
b
Key words: Horner–Wadsworth–Emmons, Palladium coupling
arylstannanes, Stille reaction, terphenyls
O
c
P
MsO
MeO
OMe
Cl
Cl
4
, 82%
3, 74%
There has been a recent revival of interest in the synthesis
Scheme 2 Reagents and conditions: a) PdCl (PPh ) , CuI, piperi-
2
3 2
of arenes from acyclic precursors, allowing their regio- dine, toluene, r.t., 16 h; b) MsCl, Et N, CH Cl , 0 °C, 15 min; c)
3
2
2
specific synthesis without the need for directing or pro- P(OMe)
, NaI, 40 °C, 16 h.
3
1
tecting groups. Current protocols include [2+2+2], or
2
3
4
[
[
4+2] cycloadditions, metathesis, as well as [3+3], or hol 2 afforded a mixture of regioisomers (5a/5b = 26:74,
5+1] annulations. A recent publication demonstrated the Scheme 3).9
5
use of phosphonate 1 as a precursor of biaryls through
Bu Sn
SnBu3
3
Horner–Wadsworth–Emmons (HWE) reaction with aro-
matic aldehydes and mild thermolysis. The limitation of
this [5+1]-annulation method is that the new aromatic ring
is monosubstituted (Scheme 1). Further work described
here demonstrates how additional functionality can be in-
corporated.
a
6
HO
+
HO
5b, major Cl
2
Cl
5
a, minor
Scheme 3 Reagents and conditions: a) PdCl (PPh ) , HSnBu ,
THF, r.t., 1 h.
2
3
2
3
O
Δ
When Pd-catalysed hydrostannation was applied to sub-
strate 4, it afforded both regioisomers, but surprisingly
with opposite regioselectivity to that observed for the cor-
responding alcohol 2 (6a/6b = 72:28, Scheme 4). It can be
speculated that the reason for this switch in regioselectiv-
ity is the availability of a potentially five-ring chelating
HWE
RCHO
P
MeO
pyridine
OMe
R
Cl
R
1
Cl
Scheme 1 Previous work reported in ref. 6
Phosphonate 4 was prepared by an adaptation of the pre- oxygen in the phosphonate 4, which is not present in alco-
vious route to the corresponding E-alkene analogue hol 2. Alternatively the Pd–C bond in the stannylation in-
6
(
Scheme 2), since alcohol 2 is readily available on multi- termediate is preferentially formed in proximity to the
gram scale by Sonogashira coupling of (E)-dichloroethyl-
7
ene with propargyl alcohol. Subsequent mesylation gave
Bu3Sn
SnBu3
Cl
propargyl mesylate 3 in 74% yield; under comparable
conditions the corresponding allyl alcohol had given only
the related chloride. Even under conditions where the
reaction was carried out at an initial 0 °C with warming to
r.t. and standing for 16 hours, a 50:50 mixture of mesylate
O
O
a
P
+
P
4
MeO
MeO
OMe
OMe
a, 67%
6
Cl
6b, 26%
O
3
and the corresponding chloride was obtained. These ob-
b
b
servations concur with the relative gas-phase stability of
allylic and propargylic cations. Arbuzov reaction with
H
8
OMe
7
(
MeO) P giving phosphonate 4 occurred in 82% yield.
3
SnBu3
As part of an extensive investigation, Alami and co-work-
ers reported that the Pd-catalysed hydrostannation of alco-
MeO
MeO
SnBu3
Cl
8, 26% (E/Z >99:1)
Cl
9, 36% (E/Z 77:23)
SYNLETT 2009, No. 9, pp 1387–1390
x
x.
x
x.
2
0
0
9
Advanced online publication: 13.05.2009
DOI: 10.1055/s-0029-1217162; Art ID: D02909ST
Scheme 4 Reagents and conditions: a) PdCl (PPh ) , HSnBu ,
THF, r.t., 1 h; b) NaHMDS, THF, 0 °C, 30 min; then 7, 0 °C, 15 min.
2
3
2
3
©
Georg Thieme Verlag Stuttgart · New York

1
388
D. S. B. Daniels et al.
LETTER
SnBu3
MeO
X
c
a
b
i)
6a
8
MeO
1
0
quant. (from 8)
1
2, X = C(O)Me, 91% (from 10)
3, X = F, 97% (from 10)
1
a
b
c
ii)
6b
9
MeO
SnBu3
MeO
X
1
1
1
7, X = C(O)Me, 51% (from 6b)
(
contaminated with Z,E,E triene)
1
8, X = F, 49% (from 6b)
O
c
d
b
SnBu3
SnBu3
iii) 6a
O
O
O
Cl
16, 38%
from 6a)
14
15
(
Scheme 5 (i) Terphenyls derived from 6a using a stepwise procedure. Reagents and conditions: a) NaHMDS, THF, 0 °C, 30 min; then 7,
+
–
2
0
°C, 15 min; b) Cs CO , toluene, 100 °C, 16 h; c) Pd (dba) ·CHCl , [HP(t-Bu) ] BF , CsF, R Br, NMP, 40 °C, 3 h. (ii) Terphenyls derived
2 3 2 3 3 3 4
from 6b utilising the simplified procedure. (iii) Biaryl derived from 6a utilising the simplified procedure. Reagents and conditions: d) NaH-
MDS, THF, 0 °C, 30 min; then 2-furaldehyde, 0 °C, 15 min.
6
more electronegative alkyne substituent. The regioiso- dure, yielded triene 14. Without purification beyond sili-
mers of compound 6 were readily separated by flash chro- ca gel filtration, this was subjected to thermolysis
matography, and independently characterised. Reaction (Cs CO , toluene, 100 °C, 16 h) and the residue contain-
2
3
of the ensuing phosphonate 6a with aldehyde 7 required ing 15 used directly in the Stille reaction after evacuation
the use of NaHMDS and gave triene 8 with E-specificity, of solvent. The final product 16 was isolated in 38% over-
albeit in modest yield. The Z-isomer was not detected. all yield from 6a (Scheme 5). Furthermore, the HWE
The corresponding reaction of stereoisomer 6b also gave product 9 from phosphonate 6b could be utilised in this
the desired triene 9, but now with 77:23 E/Z selectivity at way without removal of the Z,E,E-contaminant, providing
11
the new alkene. The difference in stereoselectivity be- para-linked terphenyls 17 and 18 in 51% and 49% yield,
tween the regioisomers of 6 can be explained by steric respectively, based on 6b. The formation of the C–C
suppression of the syn Z-derived product from 6a at the bonds by nucleophilic additions to the central fragment
oxaphosphetane intermediate stage.
complements Hii’s terphenyl synthesis involving succes-
sive Pd-couplings of an electrophilic dihalobenzene frag-
ment.11
With the desired triene in hand, cyclisation of 8 was at-
tempted using the previously defined conditions, heating
6
in pyridine at reflux. 4-Methoxybiphenyl was isolated in These simple reaction sequences further extend the poten-
8
9% yield, with no trace of the desired arylstannane. tial of the [5+1]-annulation route previously described.6
1
Monitoring the reaction by H NMR in toluene-d demon- Extension to a broader range of substituted aromatic and
8
strated that the reactant is readily destannylated under heterocyclic products, and the incorporation of benzylic
these conditions. When this reaction was repeated with stereogenic centres, is under way.
the stronger base Et N replacing pyridine, only compound
3
1
0 was produced, indicating that the destannylation reac-
tion is catalysed by pyridine·HCl. Armed with this infor-
mation, both trienes 8 and 9 were converted into the IR (neat): 3077, 3023, 2225, 1586, 1360, 1232, 1174, 944, 807, 716
(
E)-5-Chloropent-4-en-2-ynyl Methanesulfonate (3)
–
1 1
corresponding arenes 10, obtained pure, and impure 11 cm . H NMR (400 MHz, CDCl ): d = 6.56 (1 H, d, J = 13.5 Hz,
contaminated by unreacted Z,E,E-triene, respectively; it
proved convenient to use Cs CO as base in these reac-
tions. In order to demonstrate their synthetic utility, the
stannanes were converted into terphenyls using the condi-
tions for Stille coupling described by Fu and co-
workers. Derived products 12 and 13 were fully char- (E)-Dimethyl 5-Chloropent-4-en-2-ynylphosphonate (4)
acterised.
3
5,4
H-5), 5.97 (1 H, dt, J4,5 = 13.5 Hz, J4,1 = 2.0 Hz, H-4), 4.95 (2 H, d,
1
3
J1,4 = 2.0 Hz, H-1), 3.10 (3 H, s, H-6). C NMR (101 MHz, CDCl3):
2
3
d = 133.4 (C-5), 112.2 (C-4), 84.2 (C-2), 83.4 (C-3), 57.8 (C-1),
+
+
3
2
8.9 (C-6). MS (CI ): m/z calcd for [M + NH ] C H ClO S; NH :
4 6 7 3 4
12.0148; found: 212.0155.
1
0
11
Purified by chromatography on SiO
(EtOAc–pentane, 9:1); pale
2
yellow oil. IR (neat): 2956, 2225, 1585, 1459, 1263, 1184, 1031,
These procedures lead to terphenyl synthesis (meta-relat-
ed substituents) by a three-step sequence starting with the
stannyl phosphonate 6a. In order to develop a more prac- H-4), 3.82 (6 H, d, J6,P = 11.0 Hz, H-6), 2.89 (2 H, dd, J = 22.5
tical variant of this methodology, the three steps were car- Hz, J1,4 = 2.5 Hz, H-1). C NMR (126 MHz, CDCl ): d = 130.9 (d,
ried out directly. Starting with 2-furaldehyde, the HWE
coupling, following a modification of the previous proce-
–1 1
8
18 cm . H NMR (500 MHz, CDCl ): d = 6.52 (1 H, d, J = 13.5
3 5,4
Hz, H-5), 5.91 (1 H, ddt, J4,5 = 13.5 Hz, J4,P = 5.0 Hz, J4,1 = 2.5 Hz,
1,P
1
3
3
J5,P = 6.5 Hz, C-5), 113.4 (d, J4,P = 5.0 Hz, C-4), 81.8 (d, J = 15.5
3,P
Hz, C-3), 78.0 (d, J2,P = 10.5 Hz, C-2), 53.5 (d, J6,P = 7.0 Hz, C-6),
Synlett 2009, No. 9, 1387–1390 © Thieme Stuttgart · New York

LETTER
Disubstituted Benzenes from Acyclics
1389
3
1
1
2
2
7.9 (d, J1,P = 146.5 Hz, C-1). P NMR (162 MHz, CDCl ): d =
Tributyl[(1E,3E,5E)-1-chloro-6-(4-methoxyphenyl)hexa-1,3,5-
trien-3-yl]stannane (9)
3
+
+
3.6 (s). MS (CI ): m/z calcd for [M + NH ] C H ClO P; NH :
4
7
10
3
4
26.0400; found: 226.0409.
Purified by chromatography on SiO (EtOAc–pentane, 1:9); yellow
2
oil (E/Z ratio 77:23).
Dimethyl (2E,4E)-5-Chloro-2-(tributylstannyl)penta-2,4-dienyl-
phosphonate (6a)
Data provided for E-isomer: IR (CH Cl ): 2957, 2926, 1652, 1605,
2
2
–1
1
1
508, 1458, 1253, 1174, 1035, 817 cm . H NMR (500 MHz,
Purified by chromatography on SiO (Et O–pentane, 3:1); pale yel-
2
2
CDCl ): d = 7.40 (2 H, d, J = 8.5 Hz, H-8), 7.33 (1 H, dd,
3
8,9
low oil. IR (neat): 2955, 2925, 1602, 1464, 1252, 1061, 1036, 833
J2,1 = 13.0 Hz, J2,4 = 1.5 Hz, H-2), 7.13 (1 H, dd, J5,6 = 15.5 Hz,
J5,4 = 11.0 Hz, H-5), 6.88 (2 H, d, J9,8 = 8.5 Hz, H-9), 6.54 (1 H, d,
J6,5 = 15.5 Hz, H-6), 6.35 (1 H, d, J4,5 = 11.0 Hz, H-4 also dd,
J4,Sn = 59.5 Hz, J4,5 = 11.0 Hz, H-4), 6.08 (1 H, d, J1,2 = 13.0 Hz, H-
–
1 1
cm . H NMR (500 MHz, CDCl ): d = 6.79 (1 H, ddd, J = 13.0
3
4,5
Hz, J4 = 11.0 Hz, J = 1.5 Hz, H-4), 6.28 (1 H, d, J = 13.0 Hz,
,3
4,P
5,4
H-5), 6.24 (1 H, dd, J3,4 = 11.0 Hz, J3,P = 6.0 Hz, H-3 also ddd,
J3,Sn = 57.0 Hz, J3,4 = 11.0 Hz, J3,P = 6.0 Hz, H-3), 3.73 (6 H, d,
J6,P = 11.0 Hz, H-6), 2.94 (2 H, dd, J1,P = 23.5 Hz, J1,3 = 1.0 Hz, H-
1
), 3.83 (3 H, s, H-11), 1.45–1.55 (6 H, m, H-13), 1.32 (6 H, sext,
13
H-14), 0.90–1.04 (6 H, m, H-12), 0.90 (9 H, t, H-15). C NMR (126
1
), 1.40–1.60 (6 H, m, H-8), 1.32 (6 H, sext, H-9), 0.90–1.04 (6 H,
MHz, CDCl ): d = 159.6 (C-10), 141.4 (C-4), 138.9 (C-3), 135.3 (C-
1
3
3
m, H-7), 0.90 (9 H, t, H-10). C NMR (126 MHz, CDCl ): d =
3
2
1
1
–
), 133.7 (C-5), 130.0 (C-7), 127.9 (C-8), 121.7 (C-6), 120.0 (C-1),
1
(
4
38.4 (d, J2,P = 13.0 Hz, C-2), 137.7 (d, J3,P = 13.5 Hz, C-3) also
dd, J3,Sn = 29.5 Hz, J3,P = 13.5 Hz, C-3), 128.5 (d, J4,P = 5.5 Hz, C-
also dd, J4,Sn = 56.5 Hz, J4,P = 5.5 Hz, C-4), 123.1 (d, J5,P = 4.5 Hz,
14.1 (C-9), 55.3 (C-11), 29.1 (C-13), 27.3 (C-14), 13.7 (C-15),
119
0.1 (C-12). Sn NMR (93 MHz, CDCl ): d = –31.9 (s, E-isomer),
3
48.0 (s, Z-isomer).
C-5), 52.6 (d, J6,P = 7.0 Hz, C-6), 31.0 (d, J1,P = 137.5 Hz, C-1 also
dd, J1,P = 137.5 Hz, J1,Sn = 34.5 Hz), 28.9 (C-8 also d, J8,Sn = 19.5
Hz, C-8), 27.3 (C-9 also d, J9,Sn = 59.5 Hz, C-9), 13.7 (C-10), 10.1
Tributyl(4¢-methoxybiphenyl-3-yl)stannane (10)
1
Colourless oil. H NMR (250 MHz, CDCl ): d = 7.64 (1 H, s, H-7
3
(
C-7 also d, J
= 342.0 Hz, C-7 and (d, J7,117Sn = 327.0 Hz, C-
7,119Sn
also d, J7,Sn = 40.5 Hz, H-7), 7.54 (2 H, d, J4,3 = 9.0 Hz, H-4), 7.49
3
1
7
). P NMR (202 MHz, CDCl ): d = 29.5 (s also d, J = 25.5 Hz).
3 P,Sn
(
1 H, m, H-8), 7.42 (1 H, m, H10), 7.39 (1 H, m, H-9), 7.01 (2 H, d,
J3,4 = 9.0 Hz, H-3), 3.87 (3 H, s, H-1), 1.58 (6 H, m, H-13), 1.37 (6
H, m, H-14), 1.10 (6 H, m, H-12 also m, J = 51.0 Hz, H-12),
1
19
Sn NMR (93 MHz, CDCl ): d = –30.0 (d, J = 25.5 Hz). MS
3
Sn,P
+
+
(
ESI ): m/z calcd for [M + Na] C H ClO PSn; Na: 523.1158,
19 38 3
1
2,Sn
found 523.1161.
13
0
1
.92 (9 H, t, J15,14 = 7.5 Hz, H-15). C NMR (63 MHz, CDCl ): d =
59.0 (C-2), 142.5 (C-11 also d, J11,119Sn = 382.0 Hz, C-11 and d,
3
Dimethyl (2E,4E)-5-Chloro-3-(tributylstannyl)penta-2,4-dienyl-
phosphonate (6b)
J11,117Sn = 336.0 Hz, C-11), 140.2 (C-6 also d, J6,Sn = 40.0 Hz, C-6),
34.8 (C-10 also d, J10,Sn = 30.0 Hz, C-10), 134.7 (C-7 also d,
1
Purified by chromatography on SiO (Et O–pentane, 3:1); pale yel-
2
2
J7,Sn = 31.5 Hz, C-7), 134.3 (C-5), 128.3 (C-4), 128.1 (C-9 also d,
J9,Sn = 42.0 Hz, C-9), 126.6 (C-8 also d, J8,Sn = 10.0 Hz, C-8), 114.2
low oil. IR (neat): 2955, 2927, 1561, 1464, 1257, 1061, 1036, 828
–
1 1
cm . H NMR (500 MHz, CDCl ): d = 6.90 (1 H, dt, J = 13.5 Hz,
3
4,5
(
1
C-3), 55.4 (C-1), 29.1 (C-13 also d, J8,Sn = 20.0 Hz, C-13), 27.4 (C-
4 also d, J9,Sn = 56.5 Hz, C-14), 13.7 (C-15), 9.6 (C-12 also d,
J
= 1.5 Hz, H-4), 6.10 (1 H, dd, J = 13.5 Hz, J = 1.5 Hz, H-5),
4
,2
5,4 5,2
5
.63 (1 H, m, H-2 also m, J2,Sn = 58.5 Hz, H-2), 3.74 (6 H, d,
119
J12,119Sn = 339.5 Hz, C-12 and d, J7,117Sn = 324.5 Hz, C-12). Sn
J6,P = 11.0 Hz, H-6), 2.83 (2 H, dd, J1,P = 22.5 Hz, J1,2 = 8.0 Hz, H-
NMR (93 MHz, CDCl ): d = –41.1 (s).
3
1
1
0
also ddd, J1,P = 22.5 Hz, J1,2 = 8.0 Hz, J1,Sn = 7.5 Hz, H-1), 1.40–
.55 (6 H, m, H-8), 1.32 (6 H, sext, H-9), 0.90–1.04 (6 H, m, H-7),
Tributyl[(1E,3E,5E)-1-chloro-6-(furan-2-yl)hexa-1,3,5-trien-3-
yl]stannane (14)
.90 (9 H, t, H-10). 1 C NMR (126 MHz, CDCl ): d = 142.5 (d,
3
3
J3,P = 14.0 Hz, C-3), 134.0 (d, J4,P = 3.5 Hz, C-4 also dd, J = 27.5
4,Sn
Purified by chromatography on SiO (Et O–pentane, 1:9); yellow
2
2
Hz, J4,P = 3.5 Hz, C-4), 129.9 (d, J2,P = 11.0 Hz, C-2 also dd,
J2,Sn = 29.5 Hz, J2,P = 11.0 Hz, C-2), 121.0 (d, J5,P = 4.0 Hz, C-5),
oil (E/Z ratio 80:20).
Data provided for E-isomer. IR (CHCl ): 2928, 2872, 1582, 1464,
5
2
1
2.7 (d, J6,P = 7.0 Hz, C-6), 28.8 (C-8 also d, J8,Sn = 20.0 Hz, C-8),
7.2 (C-9 also d, J9,Sn = 58.0 Hz, C-9), 27.1 (d, J1,P = 138.0 Hz, C-
3
–
1 1
1
377, 1216, 1152, 1073, 1014, 908, 733 cm . H NMR (500 MHz,
CDCl ): d = 7.41 (1 H, d, J = 15.5 Hz, H-5 also dd, J5,Sn = 78.5
), 13.6 (C-10), 10.1 (C-7 also d, J
= 338.5 Hz, C-7 and d,
3
5,6
7
,119Sn
3
1
Hz, J = 15.5 Hz, H-5), 7.40 (1 H, s, H-10), 7.12 (1 H, dd,
J7,117Sn = 323.5 Hz, C-7). P NMR (202 MHz, CDCl ): d = 30.0 (s
5,6
3
1
19
J2,1 = 13.0 Hz, J2,3 = 11.5 Hz, H-2), 6.42 (1 H, m, H-9), 6.31 (1 H,
m, H-8), 6.27 (1 H, d, J1,2 = 13.0 Hz, H-1), 6.24 (1 H, d, J6,5 = 15.5
Hz, H-6), 6.15 (1 H, d, J3,2 = 11.5 Hz, H-3 also dd, J3,Sn = 58.5 Hz,
J5,6 = 15.5 Hz, H-3), 1.51 (6 H, m, H-12), 1.33 (6 H, sext, H-13),
also d, JP,Sn = 26.0 Hz). Sn NMR (93 MHz, CDCl ): d = –31.7 (d,
3
+
+
Na]+
JSn,P = 26.0 Hz). MS (ESI ): m/z calcd for [M
C H ClO PSn; Na: 523.1158; found: 523.1160.
1
9
38
3
1
3
1
.02 (6 H, m, H-11), 0.90 (9 H, t, H-14). C NMR (126 MHz,
Tributyl[(1E,3E,5E)-6-chloro-1-(4-methoxyphenyl)hexa-1,3,5-
trien-3-yl]stannane (8)
CDCl ): d = 153.3 (C-7), 145.1 (C-4), 142.2 (C-10), 135.3 (C-3),
3
1
1
29.4 (C-2), 128.0 (C-5), 122.3 (C-1), 121.2 (C-6), 111.8 (C-9),
08.6 (C-8), 29.0 (C-12 also d, J12,Sn = 19.0 Hz, C-12), 26.8 (C-13
Purified by flash chromatography on SiO (EtOAc–pentane, 1:9);
2
yellow oil (E/Z ratio >99:1). IR (CHCl ): 3019, 2400, 1967, 1605,
3
–
1
1
also d, J13,Sn = 57.0 Hz, C-13), 13.6 (C-14), 10.2 (C-11 also d,
1
7
7
509, 1420, 1218, 930, 762 cm . H NMR (500 MHz, CDCl ): d =
3
1
19
J11,117Sn = 321.5 Hz, C-11 and d, J11,119Sn = 336.5 Hz, C-11). Sn
.39 (1 H, d, J1 = 15.5 Hz, H-1), 7.38 (2 H, d, J = 9.0 Hz, H-8),
,2
8,9
NMR (93 MHz, CDCl ): d = –31.9 (s, E-isomer), –48.7 (s, Z-
.13 (1 H, dd, J5,6 = 13.0 Hz, J5,4 = 11.5 Hz, H-5), 6.89 (2 H, d,
3
isomer).
J9,8 = 9.0 Hz, H-9), 6.41 (1 H, d, J2,1 = 15.5 Hz, H-2), 6.26 (1 H, dd,
J6,5 = 13.0 Hz, J6,4 = 0.5 Hz, H-6), 6.13 (1 H, d, J4,5 = 11.5 Hz, H-4
also 1H, dd, J4,Sn = 59.5 Hz, J4,5 = 11.5 Hz, H-4), 3.84 (3 H, s, H-
General Procedure for the Condensed HWE and One-Step
Cyclisation–Stille Coupling
To a solution of the phosphonate (1 equiv) in anhyd THF (50 mL
per 250 mg of phosphonate) at 0 °C under an argon atmosphere was
added NaHMDS (1 M in THF, 1.1 equiv). After 30 min stirring the
aldehyde (1.5 equiv) was added dropwise to the solution. After a
further 15 min stirring the reaction was quenched with sat. aq
1
1), 1.45–1.55 (6 H, m, H-13), 1.32 (6 H, sext, H-14), 0.90–1.04 (6
1
3
H, m, H-12), 0.90 (9 H, t, H-15). C NMR (126 MHz, CDCl ): d =
3
1
1
5
59.8 (C-10), 146.5 (C-3), 134.7 (C-4), 134.1 (C-1), 130.8 (C-7),
29.9 (C-5), 128.2 (C-8), 127.8 (C-2), 122.3 (C-6), 114.6 (C-9),
5.8 (C-11), 29.5 (C-13 also d, J13,Sn = 20.0 Hz, C-13), 27.8 (C-14
also d, J14,Sn = 57.5 Hz, C-14), 14.1 (C-15), 10.8 (C-12 also d,
1
19
NH Cl (10 mL) and extracted with EtOAc; with the desired triene
J12,119Sn = 336.0 Hz, C-12 and d, J12,117Sn = 321.0 Hz, C-12). Sn
4
isolated by filtration of the crude residue through a short plug of
NMR (93 MHz, CDCl ): d = –32.1 (s).
3
SiO (pentane), with concentration of the crude reaction mixture in
2
Synlett 2009, No. 9, 1387–1390 © Thieme Stuttgart · New York

1
390
D. S. B. Daniels et al.
LETTER
–
1
–
vacuo. Thermolysis was performed in toluene (15 mL per 250 mg
of triene) with Cs CO (2 equiv) at 100 °C for 16 h. The toluene was
1182, 1040, 813 cm . UV/vis (MeOH): l = 286.3 (e = 31000 M
–1 1
max
1
cm ). H NMR (500 MHz, CDCl ): d = 7.66–7.56 (8 H, m, H-4, 7,
8, 12), 7.15 (2 H, t, J
d, J3,4 = 8.5 Hz, H-3), 3.88 (3 H, s, H-1). C NMR (126 MHz,
CDCl ): d = 162.4 (d, J = 246.5 Hz, C-13), 159.3 (C-2), 139.8
(C-6), 138.5 (C-9), 136.9 (d, J10,F = 3.0 Hz, C-10), 133.2 (C-5),
128.5 (d, J12,F = 8.0 Hz, C-12), 127.3 and 127.1 (C-7, C-8), 128.0
(C-4), 115.6 (d, J11,F = 22.0 Hz, C-11), 114.4 (C-3), 55.4 (C-1). F
NMR (376 MHz, CDCl ): d = –115.8 (s). MS (CI ): m/z calcd for
[M] C H OF: 278.1107; found: 278.1108.
2
3
3
removed in vacuo, with presence of the cyclised product confirmed
= 8.5 Hz, J = 8.5 Hz, H-11), 7.01 (2 H,
1
1,12 11,F
1
13
by crude H NMR. Anhydrous NMP was added to the solid residue
without further purification, and the resulting suspension used di-
rectly in the Stille coupling. Solid Pd (dba) ·CHCl (6 mol%),
3
13,F
2
3
3
+
–
[
(
HP(t-Bu) ] BF (12 mol%), the aryl bromide (1.5 equiv) and CsF
3 4
1
9
2.2 equiv) were added to a 10 mL vial under argon. To this mixture
+
was added the crude aryl stannane mixture (1 equiv). The reaction
was heated to 40 °C and stirred vigorously for 1–3 h, until starting
material had been consumed by TLC. The reaction mixture was di-
luted with Et O and washed with NH OH (sat. aq). The layers were
3
+
1
9
15
2
4
Acknowledgment
separated, the organic layer dried (MgSO ), and the solvent re-
4
moved in vacuo. The crude products were purified as stated below.
We wish to thank Dr Barbara Odell for assistance with the NMR
studies and St. Hugh’s College, Oxford for the scholarship award to
D.D.
4
-Methoxy-4¢¢-fluoro-1,1¢:3¢,1¢¢-terphenyl (13)
Purified by flash chromatography on SiO (Et O–pentane, 1:9);
2
2
white solid [19 mg, 97% (from isolated 10)]; mp 131–132 °C. IR
(
7
CH Cl ): 2934, 2840, 1607, 1513, 1291, 1253, 1181, 1035, 838,
2
2
–
References
1
–1
–1
88 cm . UV/vis (MeOH): l = 253.3 nm (e = 39444 M cm ).
max
1
H NMR (400 MHz, CDCl ): d = 7.72 (1 H, m, H-7), 7.60 (2 H, m,
(1) (a) Doherty, S.; Knight, J. G.; Smyth, C. H.; Harrington,
R. W.; Clegg, W. Org. Lett. 2007, 9, 4925. (b) Suda, T.;
Noguchi, K.; Hirano, M.; Tanaka, K. Chem. Eur. J. 2008, 14,
6593.
(2) (a) Ashburn, B. O.; Carter, R. G.; Zakharov, L. N. J. Org.
Chem. 2008, 73, 7305. (b) For a review, see: Harrity, J. P.
A. Tetrahedron 2007, 64, 767. (c) Shibata, T.; Fujiwara, R.;
Takano, D. Synlett 2007, 2766; and references cited therein.
(3) (a) Yoshida, K.; Narui, R.; Imamoto, T. Chem. Eur. J. 2008,
14, 9706. (b) Yoshida, K.; Takahashi, H.; Imamoto, T.
Chem. Eur. J. 2008, 14, 8246.
3
H-14), 7.59 (2 H, d, J = 9.0 Hz, H-4), 7.54 (1 H, m, H-8 or H-10),
4
,3
7
.49 (1 H, m, H-9), 7.49 (1 H, m, H-8 or H-10), 7.15 (2 H, dd,
J13,14 = 8.5 Hz, J13,F = 8.5 Hz, H-13), 7.01 (2 H, d, J = 9.0 Hz, H-
3
3,4
1
3
), 3.88 (3 H, s, H-1). C NMR (125.8 MHz, CDCl ): d = 162.5 (d,
3
J15,F = 246.5 Hz, C-15), 159.3 (C-2), 141.4 (C-6), 140.7 (C-11),
37.4 (d, J12,F = 3.5 Hz, C-12), 133.5 (C-5), 129.2 (C-9), 128.8 (d,
J14,F = 8.0 Hz, C-14), 128.2 (C-4), 125.7 (C-8 or C-10), 125.6 (C-7),
1
1
5
25.4 (C-8 or C-10), 115.6 (d, J = 21.5 Hz, C-13), 114.2 (C-3),
13,F
19
5.3 (C-1). F NMR (376.5 MHz, CDCl ): d = –116.6 (s). MS
3
+
+
(
CI ): m/z calcd for [M] C H OF: 278.1107; found: 278.1096.
19 15
(
4) (a) Hefner, J.; Langer, P. Tetrahedron Lett. 2008, 49, 4470.
(b) Fatusin, O.; Shkoor, M.; Riahi, A.; Reinke, H.; Langer,
P. Synlett 2009, 201.
1
-[3¢-(Furan-2-yl)biphenyl-4-yl]ethanone (16)
Purified by flash chromatography on SiO (Et O–pentane, 1:4); yel-
2
2
low oil (50 mg, 38% from 6a). IR (CH Cl ): 3115, 1681, 1604,
1
(5) Bi, X. H.; Dong, D. W.; Liu, Q.; Pan, W.; Zhao, L.; Li, B.
J. Am. Chem. Soc. 2005, 127, 4578.
(6) Gayral, M.; Brown, J. M. Synlett 2007, 2823.
(7) Chemin, D. G.; Linstrumelle, G. Tetrahedron 1994, 50,
5335.
(8) Mole, S. J.; Zhou, X.; Liu, R. J. Phys. Chem. 1996, 100,
14665.
(9) Hamze, A.; Provot, O.; Brion, J. D.; Alami, M. J. Org.
Chem. 2007, 72, 3868.
(10) (a) Littke, A. F.; Schwarz, L.; Fu, G. C. J. Am. Chem. Soc.
2002, 124, 6343. (b) Netherton, M. R.; Fu, G. C. Org. Lett.
2001, 3, 4295.
(11) Hii, K. K.; Antelo Miguez, J. M.; Adrio, L. A.; Sousa-
Pedrares, A.; Vila, J. M. J. Org. Chem. 2007, 72, 7771.
2
2
–
1
358, 1269, 1009, 957, 842, 792, 739 cm . UV/vis (MeOH):
–
1
–1
1
lmax = 282.7 nm (e = 35000 M cm ). H NMR (500 MHz,
CDCl ): d = 8.07 (2 H, d, J = 8.5 Hz, H-13), 7.94 (1 H, m, H-6),
3
13,12
7
.74 (2 H, d, J1 = 8.5 Hz, H-12), 7.65 (1 H, dt, J7,8 = 7.5 Hz,
2,13
J7,9 = 1.5 Hz, H-7), 7.52 (1 H, m, H-9), 7.52 (1 H, d, J1,2 = 2.0 Hz,
H-1), 7.50 (1 H, m, H-8), 6.75 (1 H, d, J3,2 = 3.5 Hz, H-3), 6.52 (1
1
3
H, dd, J2,3 = 3.5 Hz, J2,1 = 2.0 Hz, H-2), 2.68 (3 H, s, H-16). C NMR
126 MHz, CDCl ): d = 197.7 (C-15), 153.6 (C-4), 145.5 (C-11),
(
3
1
1
1
42.3 (C-1), 140.4 (C-10), 136.0 (C-14), 131.5 (C-5), 129.3 (C-8),
28.9 (C-13), 127.3 (C-12), 126.2 (C-9), 123.6 (C-7), 122.6 (C-6),
+
11.8 (C-2), 106.5 (C-3), 26.7 (C-16). MS (CI ): m/z calcd for [M +
+
H] C H O ; H: 263.1072; found: 263.1073.
1
8
14
2
4
-Methoxy-4¢¢-fluoro-1,1¢:4¢,1¢¢-terphenyl (18)
Purified by precipitation from toluene. Off-white solid (54 mg, 49%
from 6b); mp 234–235 °C. IR (neat): 3035, 1654, 1605, 1490, 1243,
Synlett 2009, No. 9, 1387–1390 © Thieme Stuttgart · New York

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