Carbonylative coupling of organozinc reagents in the presence and absence of aryl iodides: Synthesis of unsymmetrical and symmetrical ketones

Article abstract of DOI:10.1039/a606394b

The utility of the palladium(o) catalysed reaction of the iodoalanine-derived organozinc reagent 6a with functionalised aryl iodides, under a carbon monoxide atmosphere, to give protected 4-aryl-4-oxo α-amino acids 8, is illustrated by a short synthesis of L-kynurenine 4. Treatment of functionalised organozinc reagents with catalytic tetrakis(triphenylphosphine)palladium(0) under an atmosphere of carbon monoxide in the absence of any electrophile leads to the formation of symmetrical functionalised ketones 9 in good yields. This reaction is illustrated by a one-step synthesis of protected (2S,6S)-4-oxo-2,6-diaminopimelic acid 9a from commercially available compounds. It has been established that adventitious molecular oxygen plays a key role in the formation of the symmetrical ketones 9, and that rigorous exclusion of oxygen can result in substantially higher yields of ketones 8 in the cross-coupling with some aromatic iodides.

Full text of DOI:10.1039/a606394b

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Carbonylative coupling of organozinc reagents in the presence and
absence of aryl iodides: synthesis of unsymmetrical and symmetrical
ketones
Richard F. W. Jackson,*,a Debra Turner a and Michael H. Block b
a
Department of Chemistry, Bedson Building, The University of Newcastle,
Newcastle upon Tyne NE1 7RU, UK
b Zeneca Pharmaceuticals, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK
The utility of the palladium(0) catalysed reaction of the iodoalanine-derived organozinc reagent 6a with
functionalised aryl iodides, under a carbon monoxide atmosphere, to give protected 4-aryl-4-oxo á-amino
acids 8, is illustrated by a short synthesis of L-kynurenine 4. Treatment of functionalised organozinc
reagents with catalytic tetrakis(triphenylphosphine)palladium(0) under an atmosphere of carbon monoxide
in the absence of any electrophile leads to the formation of symmetrical functionalised ketones 9 in good
yields. This reaction is illustrated by a one-step synthesis of protected (2S,6S)-4-oxo-2,6-diaminopimelic
acid 9a from commercially available compounds. It has been established that adventitious molecular
oxygen plays a key role in the formation of the symmetrical ketones 9, and that rigorous exclusion of
oxygen can result in substantially higher yields of ketones 8 in the cross-coupling with some aromatic
iodides.
Over recent years, we have been exploring the applications of
iodoalanine-derived organometallic reagents in the synthesis of
non-proteinogenic amino acids in enantiomerically pure form.
For example, the organozinc reagent 1, prepared by treatment
of appropriately protected iodoalanine with activated zinc in
benzene–dimethylacetamide using sonochemical activation,
reacts under palladium catalysis with acid chlorides to give
4-oxo α-amino acids 2, and also with aryl iodides to give 3-aryl
α-amino acids 3 (Scheme 1).1 More recently, we have established
Scheme 2 P = protecting group
methyl
2-(N-tert-butoxycarbonylamino)-3-iodopropanoate.7
The most serious problem is the choice of N-protecting group
for the anthranilic acid chloride 5. Many nitrogen protecting
groups are incompatible with acid chlorides, enhance the acid-
ity of protons on nitrogen or are sufficiently bulky that they
severely retard reaction rates. An indirect approach involving
attempted coupling of o-nitrobenzoyl chloride with zinc
reagent 6a was unsuccessful.
Given these difficulties, our attention then turned to an alter-
native strategy,8 involving the palladium-catalysed carbonyl-
ative cross-coupling of organozinc reagents with aromatic
iodides as a route to unsymmetrical ketones. The viability of
this type of process has been well established using a wide
variety of organometallic reagents,9 although the use of zinc
reagents has received relatively little attention.9,10
Scheme 1
In the event, reaction of iodobenzene 7a with zinc reagent 6a
in THF under an atmosphere of carbon monoxide (1 atm,
balloon) in the presence of tetrakis(triphenylphosphine)-
palladium(0) [Pd(Ph3P)4 ] at room temperature gave the pro-
tected 4-phenyl-4-oxo α-amino acid 8a (60%) (Scheme 3),
that iodoalanine-derived zinc reagents may be prepared in THF
as solvent,2 but the reaction of these reagents with acid chlor-
ides in this solvent is compromised by the competitive cleavage
of the solvent by the acid chloride promoted by zinc.3 The only
successful coupling reactions that we have carried out in THF
between iodoalanine-derived zinc reagents and acid chlorides
have involved the use of aromatic acid chlorides.4
Synthesis of L-kynurenine
Although we had already used our approach for the synthesis
of a range of 4-oxo α-amino acids 2 with additional functional-
ity, the synthesis of -kynurenine 4,5 an intermediate in the
metabolism of -tryptophan to nicotinic acid ribonucleotide via
the kynurenine pathway,6 presented us with a challenge. The
most direct approach to -kynurenine 4 would require the coup-
ling of an anthranilic acid chloride 5 with a suitable serine-
derived zinc reagent such as 6a 2 (Scheme 2), prepared from (R)-
Scheme 3 Reagents and conditions: i, CO (1 atm, balloon), Pd(PPh3)4
(5 mol%), THF, room temp., 30 h
identical to material prepared by direct coupling of zinc reagent
6a with benzoyl chloride according to the general procedure
J. Chem. Soc., Perkin Trans. 1, 1997
865

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Table 1 Preparation of protected 4-aryl-4-oxo α-amino acids 8
Table 2 Preparation of symmetrical ketones 9
Aryl iodide
Product
Ar
Yield (%)a
Organozinc reagent
Product
R
Yield (%)a
7a
7b
7c
7d
7e
7f
7g
7h
7i
7j
7k
7l
7m
7n
7o
Iodobenzene
1-Iodonaphthalene
4-Iodotoluene
2-Iodoanisole
3-Iodoanisole
4-Iodoanisole
2-Iodoaniline
3-Iodoaniline
4-Iodoaniline
2-Fluoroiodobenzene
3-Fluoroiodobenzene
4-Fluoroiodobenzene
2-Iodonitrobenzene
3-Iodonitrobenzene
4-Iodonitrobenzene
8a
8b
8c
8d
8e
8f
8g
8h
8i
8j
8k
8l
8m
8n
8o
C6H5
1᎐C10H7
60
54
59
50
40
58
52
6b
6c
6d
6e
6f
MeO2C(CH2 )2ZnI
PhthN(CH2 )3ZnIb
EtO2C(CH2 )3ZnI
NC(CH2 )2ZnI
9b
9c
9d
9e
9f
MeO2C(CH2 )2 84
PhthN(CH2 )3
EtO2C(CH2 )3
NC(CH2 )2
53
60
43
61
4-MeC6H4
2-MeOC6H4
3-MeOC6H4
4-MeOC6H4
2-H2NC6H4
3-H2NC6H4
4-H2NC6H4
2-FC6H4
3-FC6H4
4-FC6H4
2-O2NC6H4
3-O2NC6H4
4-O2NC6H4
C6H5CH2ZnBr
C6H5CH2
a
All yields are based on the precursor to the organozinc reagent.
17b (52)c
56
b PhthN = phthalimido.
29b
12b
34b
13b
27b
0b (21)c
preparation of analogues.12 The low yields of the three nitro-
substituted compounds, 8m–8o was rather disappointing, but
the fact that the highest yield was obtained for the meta-isomer
was some consolation, given the report of the high inhibitory
activity of (m-nitrobenzoyl)alanine against kynurenine-3-
hydroxylase.13
a
All yields are based on (R)-methyl 2-(N-tert-butoxycarbonylamino)-3-
iodopropanoate. b The major product in each of these reactions was the
symmetrical ketone 9a. c These enhanced yields of the product have
been obtained by conducting the reaction with rigorous exclusion of
oxygen.
Synthesis of symmetrical ketones
Some time ago, we had established that symmetrical ketones
were formed by palladium catalysed reaction of zinc reagents
with phenyl chloroformate and that they were also formed in
poor yield on treatment of zinc reagents with catalytic amounts
of Pd(Ph3P)2Cl2 under an atmosphere of CO in the absence of
added electrophile.14 Given the recent report on the preparation
of polyfunctional symmetrical ketones by the stoichiometric
cobalt-mediated carbonylation of functionalised organozinc
reagents,15 we have decided to attempt to optimise the process
for symmetrical ketone formation using Pd(Ph3P)4.
Our first breakthrough came when we established that an
attempted cross-coupling of the zinc reagent 6a with phenyl
trifluoromethanesulfonate using Pd(Ph3P)4 as the catalyst under
carbon monoxide led to the formation of the symmetrical
ketone 9a (60%) as the only coupled material. A subsequent
experiment established that the presence of phenyl trifluoro-
methanesulfonate was completely unnecessary and that the
same yield (60%) of coupled product 9a was obtained in its
absence. The generality of this process was established by
treatment of a range of organozinc halides under the condi-
tions described above (Scheme 5), which led to the isolation of
already reported.4 No protected phenylalanine was isolated
from this reaction, implying that direct reaction of iodobenzene
and the zinc reagent 6a did not compete under the reaction
conditions. The use of Pd(Ph3P)4 was crucial for success and
other palladium catalysts appeared to be significantly less
effective.
Given the effectiveness of this reaction, we have explored the
scope and limitations of the process using a wide variety of aryl
iodides 7 as substrates. Our results are outlined in Table 1. The
reaction is sensitive to the electronic effects of the substituents
on the aromatic ring, but does give satisfactory results in all
cases except when the substituents are strongly electron-
withdrawing or are sited in the meta position. Most strikingly,
the reaction tolerates the presence of an unprotected amino
group in both ortho and para positions of the aromatic ring. In
cases in which low yields of the desired 4-aryl-4-oxo α-amino
acids 8 were isolated, significant amounts of protected 4-oxo-
2,6-diaminopimelic acid 9a were isolated. The reasons for the
formation of the symmetrical ketone 9a are discussed later in
the paper, together with modifications to the cross-coupling
process which can permit improved yields of the desired 4-aryl-
4-oxo α-amino acids 8 to be isolated.
The easy access to the adduct 8g derived from 2-iodoaniline
enabled a short synthesis of -kynurenine 4 to be completed.
Removal of the protecting groups from the adduct 8g was
achieved by treatment with 30% HBr–HOAc to give the corre-
sponding bis(hydrobromide) salt 10, which was then converted
to the free amino acid 4 using propylene oxide (90% overall
yield from 8g) (Scheme 4).11 This completes a very short syn-
Scheme 5 Reagents and conditions: i, CO (1 atm, balloon), Pd(PPh3)4
(5 mol%), THF, room temp., 30 h
the corresponding symmetrical ketone 9 in each case (Table 2).
In all cases, the reaction was characterised by the development
of a deep red colour. It is noteworthy that the reaction pro-
ceeded satisfactorily in the case of 2-cyanoethylzinc iodide, in
contrast with the cobalt-mediated process.15 Our process also
proceeds satisfactorily in the presence of a static atmosphere of
carbon monoxide and it does not require the presence of a co-
solvent in addition to THF.
The process is, at first sight, very hard to understand. The
stoichiometric coupling of an alkylzinc halide with carbon
monoxide using palladium() can be easily rationalised, result-
ing in the formation of palladium(0) and the symmetrical
ketone product. However, in order that the process can be
catalytic in palladium(0), the presence of an oxidising agent is
necessary to bring about the conversion of palladium(0) into
palladium(). Yasui et al. have reported a related preparation
of symmetrical ketones by treatment of an organozinc reagent
with catalytic palladium(0) under a carbon monoxide atmos-
phere in the presence of allyl benzoate.9 This process is efficient
only in the presence of benzaldehyde, which serves to trap an
Scheme 4 Reagents and conditions: i, HBr (30% in AcOH), room
temp., 20 min; ii, propylene oxide, PriOH
thesis of -kynurenine 4 from commercially available materials,
and it is sufficiently flexible that it may be applicable to the
866
J. Chem. Soc., Perkin Trans. 1, 1997

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Scheme 6 Reagents and conditions: i, CO (1 atm, balloon), Pd(PPh3)4
(5 mol%), THF, room temp., 20 h
allylzinc species derived from allyl benzoate (Scheme 6). Thus
allyl benzoate acts effectively as the re-oxidant. Our results sug-
gest that an alternative pathway for symmetrical ketone for-
mation exists, in which both allyl benzoate and benzaldehyde
are unnecessary, but the question of the identity of the oxidi-
sing agent in our process remains. Of some relevance is a report
that the carbonylative dimerisation of siloxycyclopropanes
using bis(triphenylphosphine)palladium dichloride is rendered
catalytic in palladium by the use of chloroform as the solvent.16
However, this clearly cannot be the case in our system.
We eventually concluded that the mostly likely oxidant was
molecular oxygen, which is certainly capable of diffusing into
the carbon monoxide balloon which we had routinely used. In
order to investigate this hypothesis, we treated the zinc reagent
6a with catalytic Pd(Ph3P)4 under carbon monoxide using our
standard conditions, but with two additional precautions. The
reaction mixture was carefully degassed by freezing in liquid
nitrogen and pumping under vacuum and the atmosphere of
carbon monoxide was provided using a glass vessel, avoiding
completely the use of a balloon. In this reaction, the deep red
colour characteristic of the successful carbonylation reactions
did not appear and none of the symmetrical ketone 9a was
isolated (the product was simply protected alanine, derived
from protonation of the zinc reagent 6a).
To establish that palladium catalysed carbonylative couplings
with aromatic iodides did proceed under these modified con-
ditions, we carried out a coupling of the -serine-derived
organozinc reagent ent-6a with 3-iodoaniline and were able to
isolate the corresponding 4-aryl-4-oxo α-amino acid ent-8h in
much improved yield (52%, compared with 17% obtained using
a balloon). In an analogous manner, coupling of ent-6a with
4-iodonitrobenzene gave the 4-aryl-4-oxo α-amino acid ent-8o
(21%, compared with 0% using a balloon), together with the
product of direct cross-coupling 11 (31%) (Scheme 7).†
In neither case was any of the corresponding symmetrical
ketone ent-9a detected. These two results suggest that, for all
the examples in Table 1 in which the symmetrical ketone 9a was
formed, substantially improved yields of the cross-coupling
products 8 may be obtained provided oxygen is rigorously
excluded.
Scheme 7 Reagents and conditions: i, 3-iodoaniline, CO (1 atm, glass
vessel), Pd(PPh3 )4 (5 mol%), rigorously degassed THF, room temp.,
24 h; ii, 4-iodonitrobenzene, CO (1 atm, glass vessel), Pd(PPh3 )4 (5
mol%), rigorously degassed THF, room temp., 24 h
manner under the same conditions in the absence of added
electrophile. This process, which can in some cases compete
with the carbonylative cross-coupling reaction of organozinc
reagents with aryl iodides, is completely suppressed by the rig-
orous exclusion of oxygen.
Experimental
General experimental procedures and instrumentation are as
previously described.1 J values are given in Hz. [α]D Values are
given in units of 10Ϫ1 deg cm2 gϪ1. All reactions involving the use
of carbon monoxide were carried out in a fume cupboard, with an
appropriate detector to warn of any exposure. Light petroleum
refers to that fraction with boiling point 40–60 ЊC. All organic
extracts were dried over anhydrous MgSO4 and solvent was
removed using a rotary evaporator.
Reaction with aromatic iodides and carbon monoxide—general
procedure
The zinc reagent 6a (0.75 mmol) was prepared in THF accord-
ing to our previously reported method,2 and allowed to cool to
room temperature and the aromatic iodide 7 (1 mmol) and
tetrakis(triphenylphosphine)palladium(0) [Pd(Ph3P)4 ] (43 mg,
0.038 mmol) were added. The nitrogen atmosphere was then
replaced by carbon monoxide (using a balloon). The reaction
mixture was then stirred for 30 h at room temperature. The
reaction mixture was filtered, partitioned between ethyl acetate
(25 cm3 ) and water (25 cm3 ), washed with brine (25 cm3 ), dried,
filtered and concentrated to give the crude product. This was
purified by flash chromatography using light petroleum–
ethyl acetate to give the pure ketone 8.
(2S)-Methyl 2-(N-tert-butoxycarbonylamino)-4-oxo-4-phenyl-
butanoate 8a. Using iodobenzene 7a, the ketone 8a (138 mg,
60%) was isolated as pale brown needles, mp 60–63 ЊC (Found:
C, 62.5; H, 6.85; N, 4.4; Mϩ, 307.1435. C16H21O5N requires C,
62.5; H, 6.9; N, 4.6%; M, 307.1420); νmax(cap. film)/cmϪ1 3440m
(N᎐H), 1748s (C᎐O), 1717s (C᎐O), 1393m and 1368s
We believe that these results establish that molecular oxygen
is the oxidising agent in the symmetrical ketone synthesis.17
Whatever the detail of the mechanism, the carbonylative dimer-
isation of organozinc reagents in the presence of catalytic
Pd(Ph3P)4 appears to be a very simple and general method for
the synthesis of functionalised symmetrical ketones.
᎐
᎐
[C(CH3 )3 ], 1169s (C᎐O᎐C); δH (200 MHz, CDCl3 ) 1.44 [s, 9 H,
C(CH3 )3 ], 3.5–3.85 [m, 2 H, C(3)H], 3.74 (s, 3 H, OCH3 ), 4.71
[m, 1 H, C(2)H], 5.65 (d, 1 H, J 8.7, NH), 7.45–8.00 (m, 5 H, Ph);
m/z (EI) 307 (0.3%, M), 248 (30, M Ϫ CO2Me), 192 (50,
M Ϫ CO2Me Ϫ C4H8); [α]2D0 ϩ28.2 (c 1.2, dichloromethane).
The IR spectrum was obtained prior to crystallisation.
In conclusion, we have established that the palladium(0)
catalysed carbonylative coupling of organozinc reagents with
aryl iodides is a useful method for the formation of highly func-
tionalised aromatic ketones 8. We have also shown that sym-
metrical ketones 9 can be formed in a preparatively useful
(2S)-Methyl
2-(N-tert-butoxycarbonylamino)-4-oxo-4-(1Ј-
† Presumably the presence of the strongly electron-withdrawing nitro
group accelerates transmetallation between the zinc reagent and the
initial adduct derived from oxidative addition of the aryl iodide to Pd(0)
and at the same time reduces the rate of aryl migration to ligated car-
bon monoxide. These two effects would tend to increase the amount of
protected 4-nitrophenylalanine 11 at the expense of the carbonylated
product 8o.
naphthyl)butanoate 8b. Using 1-iodonaphthalene 7b, the ketone
8b (145 mg, 54%) was isolated as a brown oil (Found: Mϩ,
357.1572. C20H23NO5 requires M, 357.1576); νmax(cap. film)/
cmϪ1 3373 (N᎐H), 1747 (C᎐O), 1713 (C᎐O), 1680 (sh, C᎐O);
δH (200 MHz, CDCl3 ) 1.4 [s, 9 H, C(CH3 )3 ], 3.5–3.9 [m, 2 H,
C(3)H], 3.75 (s, 3 H, OCH3 ), 4.7 [m, 1 H, C(2)H], 5.65 (d, 1 H, J 6,
᎐
᎐
᎐
J. Chem. Soc., Perkin Trans. 1, 1997
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NH), 7.45–7.65 (m, 3 H, Ar), 7.8–8.1 (m, 3 H, Ar), 8.65–8.75 (m,
1 H, Ar); m/z (FAB) 358 (10%, MH), 302 (70, M Ϫ C4H8 ), 258
(100, M Ϫ C4H8OCO); [α]2D0 ϩ18.0 (c 0.3, dichloromethane).
MHz, CDCl3 ) 1.4 [s, 9 H, C(CH3 )3 ], 3.3–3.7 [m, 2 H, C(3)H], 3.7
(s, 3 H, OCH3 ), 4.6 [m, 1 H, C(2)H], 5.6 (d, 1 H, J 8, NH), 6.6
(m, 2 H, NH2 ), 7.4–7.8 (m, 4 H, Ph); m/z (FAB) 323 (40%, MH),
267 (35, M Ϫ C4H8 ), 223 (75, M Ϫ C4H8OCO); [α]2D0 ϩ3.0 (c
0.15, dichloromethane).
(S)-Methyl
2-(N-tert-butoxycarbonylamino)-4-oxo-4-(4Ј-
methylphenyl)butanoate 8c. Using 4-iodotoluene 7c, the ketone
8c (77 mg, 39%) was isolated as a brown oil (Found: Mϩ Ϫ
CO2CH3, 265.0937. C13H15NO5 requires M, 265.0950); νmax(cap.
film)/cmϪ1 3440 (N᎐H), 1748 (C᎐O), 1717 (C᎐O), 1682 (C᎐O);
(2S)-Methyl
2-(N-tert-butoxycarbonylamino)-4-oxo-4-(2Ј-
fluorophenyl)butanoate 8j. Using 2-fluoroiodobenzene 7j, the
ketone 8j (71.4 mg, 29%) was isolated as a yellow oil (Found:
᎐
᎐
᎐
δH (200 MHz, CDCl3 ) 1.4 [s, 9 H, C(CH3 )3 ], 2.4 (s, 3 H, CH3 ),
3.45–3.75 [m, 2 H, C(3)H], 3.75 (s, 3 H, OCH3 ), 4.65 [m, 1 H,
C(2)H], 5.6 (d, 1 H, J 8, NH), 7.25 (d, 2 H, J 7, Ph), 7.8 (d, 2 H,
J 7, Ph); m/z (FAB) 322.5 (30%, M), 266.4 (100, M Ϫ CO2CH3 ),
222.5 (95, M Ϫ C4H8OCO); [α]2D0 ϩ11.0 (c 0.3, dichloromethane).
M
ϩ Ϫ CO2Me, 266.1184. C14H17FNO3 requires M, 266.1192);
νmax(cap. film)/cmϪ1 3440 (N᎐H), 1748 (C᎐O), 1717 (C᎐O), 1682
᎐
᎐
(C᎐O); δ (200 MHz, CDCl ) 1.4 [s, 9 H, C(CH ) ], 3.4–3.8 [m,
᎐
H
3
3 3
2 H, C(3)H], 3.7 (s, 3 H, OCH3 ), 4.7 [m, 1 H, C(2)H], 5.6 (d, 1 H,
J 8.5, NH), 7.1–7.3 (m, 2 H, Ph), 7.45–7.6 (m, 1 H, Ph), 7.8–7.95
(m, 1 H, Ph); m/z (FAB) 326 (40%, MH), 270 (35, M Ϫ C4H8 ),
226 (75, M Ϫ C4H8OCO); [α]2D0 ϩ21.2 (c 0.5, dichloromethane).
(2S)-Methyl
2-(N-tert-butoxycarbonylamino)-4-oxo-4-(2Ј-
methoxyphenyl)butanoate 8d. Using 2-iodoanisole 7d, the
ketone 8d (127 mg, 50%) was isolated as a yellow oil (Found:
(2S)-Methyl
2-(N-tert-butoxycarbonylamino)-4-oxo-4-(3Ј-
M
ϩ Ϫ C5H8O2, 237.1004. C12H15NO4 requires M, 237.1001);
fluorophenyl)butanoate 8k. Using 3-fluoroiodobenzene 7k, the
ketone 8k (30 mg, 12%) was isolated as a yellow oil (Found: C,
59.5; H, 6.3; N, 3.9; Mϩ Ϫ C5H9O2, 224.0714. C16H20FNO5
requires C, 59.1; H, 6.2; N, 4.3%; C11H11FNO3 requires M,
νmax(cap. film)/cmϪ1 3440 (N᎐H), 1748 (C᎐O), 1717 (C᎐O), 1680
᎐
᎐
(C᎐O); δ (200 MHz, CDCl ) 1.4 [s, 9 H, C(CH ) ], 3.45–3.8 [m,
᎐
H
3
3 3
2 H, C(3)H], 3.75 (s, 3 H, OCH3 ), 3.95 (s, 3 H, OCH3 ), 4.6 [m,
1H, C(2)H], 5.6(br d, 1H, NH), 6.95–7.05(m, 2H, Ph), 7.45–7.55
(m, 1 H, Ph), 7.75–7.85 (m, 1 H, Ph); m/z (FAB) 338.5 (80%,
MH), 282.4 (100, M Ϫ C4H8), 238.4 (10, M Ϫ C4H8OCO);
[α]2D0 ϩ21.1 (c 0.35, dichloromethane).
224.0723); νmax(cap. film)/cmϪ1 3440 (N᎐H), 1748 (C᎐O), 1717
᎐
(C᎐O), 1683 (C᎐O); δ (200 MHz, CDCl ) 1.4 [s, 9 H,
᎐
᎐
H
3
C(CH3 )3 ], 3.4–3.7 [m, 2 H, C(3)H], 3.7 (s, 3 H, OCH3 ), 4.7 [m,
1 H, C(2)H], 5.5 (d, 1 H, J 8.7, NH), 7.2–7.8 (m, 4 H, Ph); m/z
(FAB) 326 (10%, MH), 270 (45, M Ϫ C4H8 ), 226 (100,
M Ϫ C4H8OCO); [α]2D0 ϩ19.0 (c 0.05, dichloromethane).
(2S)-Methyl
2-(N-tert-butoxycarbonylamino)-4-oxo-4-(3Ј-
methoxyphenyl)butanoate 8e. Using 3-iodoanisole 7e, the
ketone 8e (102 mg, 40%) was isolated as a brown oil (Found:
MHϩ Ϫ C4H8, 282.0991. C13H16NO6 requires M, 282.0976); νmax
(cap. film)/cmϪ1 3440 (N᎐H), 1748 (C᎐O), 1717 (C᎐O), 1685
(2S)-Methyl
2-(N-tert-butoxycarbonylamino)-4-oxo-4-(4Ј-
fluorophenyl)butanoate 8l. Using 4-fluoroiodobenzene 7l, the
ketone 8l (83 mg, 34%) was isolated as a yellow oil (Found: Mϩ,
326.1393. C16H20FNO5 requires M, 326.1404); νmax(cap. film)/
cmϪ1 3440 (N᎐H), 1748 (C᎐O), 1717 (C᎐O), 1682 (C᎐O); δ (200
᎐
᎐
(C᎐O); δ (200 MHz, CDCl ) 1.4 [s, 9 H, C(CH ) ], 3.4–3.8 [m,
᎐
H
3
3 3
2 H, C(3)H], 3.7 (s, 3 H, OCH3 ), 3.85 (s, 3 H, OCH3 ), 4.7 [m, 1 H,
C(2)H], 5.65 (br d, 1 H, NH), 7.1–7.6 (m, 4 H, Ph); m/z (FAB)
338.4 (30%, MH), 282.4 (90, M Ϫ C4H8 ), 238.4 (100, M Ϫ
C4H8OCO); [α]2D0 ϩ6.7 (c 0.15, dichloromethane).
᎐
᎐
᎐
H
MHz, CDCl3 ) 1.4 [s, 9 H, C(CH3 )3 ], 3.4–3.8 [m, 2 H, C(3)H], 3.7
(s, 3 H, OCH3 ), 4.7 [m, 1 H, C(2)H], 5.6 (d, 1 H, J 8.5, NH), 7.0–
7.2 (m, 2 H, Ph), 7.9–8.1 (m, 2 H, Ph); m/z (FAB) 326 (90%,
MH), 270 (60, M Ϫ C4H8 ), 226 (50, M Ϫ C4H8OCO);
[α]2D0 ϩ40.8 (c 0.25, dichloromethane).
(2S)-Methyl
2-(N-tert-butoxycarbonylamino)-4-oxo-4-(4Ј-
methoxyphenyl)butanoate 8f. Using 4-iodoanisole 7f, the
ketone 8f (147 mg, 58%) was isolated as a yellow oil (Found: C,
60.8; H, 7.2; N, 3.7; Mϩ Ϫ C4H8, 281.0906. C17H23NO6 requires
C, 60.5; H, 6.9; N, 4.15%; C13H15NO6 requires M, 281.0899);
νmax(cap. film)/cmϪ1 3440 (N᎐H), 1748 (C᎐O), 1717 (C᎐O), 1688
(2S)-Methyl
2-(N-tert-butoxycarbonylamino)-4-oxo-4-(2Ј-
nitrophenyl)butanoate 8m. Using 2-iodonitrobenzene 7m, the
ketone 8m (35 mg, 13%) was isolated as a brown oil (Found: C,
54.7; H, 5.9; N, 8.0; Mϩ, 296.0639. C16H20N2O7 requires C, 54.5;
H, 5.7; N, 7.95%; M, 296.0644); νmax(cap. film)/cmϪ1 3440
᎐
᎐
(C᎐O); δ (200 MHz, CDCl ) 1.4 [s, 9 H, C(CH ) ], 3.4–3.8 [m,
᎐
H
3
3 3
2 H, C(3)H], 3.7 (s, 3 H, OCH3 ), 3.82 (s, 3 H, OCH3 ), 4.7 [m, 1 H,
C(2)H], 5.6 (br d, 1 H, NH), 7.1–7.6 (m, 4 H, Ph); m/z (FAB) 338
(49%, MH), 282 (100, M Ϫ C4H8 ), 238 (50, M Ϫ C4H8OCO);
[α]2D0 ϩ30.1 (c 0.35, dichloromethane).
(N᎐H), 1748 (C᎐O), 1717 (C᎐O), 1684 (C᎐O); δ (200 MHz,
᎐ ᎐ ᎐
H
CDCl3 ) 1.4 [s, 9 H, C(CH3 )3 ], 3.5–3.8 [m, 2 H, C(3)H], 3.8 (s,
3 H, OCH3 ), 4.7 [m, 1 H, C(2)H], 5.6 (d, 1 H, J 8, NH), 7.6–7.8
(m, 1 H, Ph), 8.2–8.5 (m, 1 H, Ph), 8.4–8.5 (m, 1 H, Ph), 8.8 (m,
1 H, Ph); m/z (FAB) 353 (80%, MH), 297 (25, M Ϫ C4H8 ), 253
(30, M Ϫ C4H8OCO).
(2S)-Methyl
2-(N-tert-butoxycarbonylamino)-4-oxo-4-(2Ј-
aminophenyl)butanoate 8g. Using 2-iodoaniline 7g, the ketone
8g (126 mg, 52%) was isolated as a yellow oil (Found: Mϩ,
322.3595. C16H22N2O5 requires M, 322.3602); νmax(cap. film)/
cmϪ1 3440 (N᎐H), 1748 (C᎐O), 1717 (C᎐O), 1687 (C᎐O); δ (200
(2S)-Methyl
2-(N-tert-butoxycarbonylamino)-4-oxo-4-(3Ј-
nitrophenyl)butanoate 8n. Using 3-iodonitrobenzene 7n, the
ketone 8n (71 mg, 27%) was isolated as a brown oil (Found: C,
54.2; H, 5.3; N, 7.9; Mϩ Ϫ C4H8, 296.0636. C16H20N2O7 requires
C, 54.5; H, 5.7; N, 7.95%; C12H12N2O7 requires M, 296.0644);
νmax(cap. film)/cmϪ1 3440 (N᎐H), 1748 (C᎐O), 1717 (C᎐O), 1682
᎐
᎐
᎐
H
MHz, CDCl3 ) 1.4 [s, 9 H, C(CH3 )3 ], 3.4–3.6 [m, 2 H, C(3)H], 3.7
(s, 3 H, OCH3 ), 4.7 [m, 1 H, C(2)H], 5.6 (d, 1 H, J 9, NH), 6.65
(m, 2 H, NH2 ), 7.2–7.7 (m, 4 H, Ph); m/z (FAB) 323 (18%,
MH), 267 (100, M Ϫ C4H8 ), 223 (70, M Ϫ C4H8OCO); [α]2D0
ϩ14.0 (c 0.5, dichloromethane).
᎐
᎐
(C᎐O); δ (200 MHz, CDCl ) 1.4 [s, 9 H, C(CH ) ], 3.5–3.8 [m,
᎐
H
3
3 3
2 H, C(3)H], 3.8 (s, 3 H, OCH3 ), 4.7 [m, 1 H, C(2)H], 5.6 (m, 1 H,
NH), 7.6–7.8 (m, 1 H, Ph), 8.2–8.5 (m, 1 H, Ph), 8.4–8.5 (m, 1 H,
Ph), 8.8 (m, 1 H, Ph); m/z (FAB) 353 (80%, MH), 297 (25,
M Ϫ C4H8 ), 253 (30, M Ϫ C4H8OCO); [α]2D0 ϩ13.3 (c 0.3,
dichloromethane).
(2S)-Methyl
2-(N-tert-butoxycarbonylamino)-4-oxo-4-(3Ј-
aminophenyl)butanoate 8h. Using 3-iodoaniline 7h, the ketone
8h (42 mg, 17%) was isolated as an amber oil (Found: Mϩ,
322.1534. C16H22N2O5 requires M, 322.1528); νmax(cap. film)/
cmϪ1 3440 (N᎐H), 1745 (C᎐O), 1708 (C᎐O); δ (200 MHz,
᎐
᎐
H
CDCl3 ) 1.4 [s, 9 H, C(CH3 )3 ], 3.4–3.6 [m, 2 H, C(3)H], 3.7 (s,
3 H, OCH3 ), 4.7 [m, 1 H, C(2)H], 5.6 (d, 1 H, J 9, NH), 6.65 (m,
2 H, NH2 ), 7.2–7.7 (m, 4 H, Ph); m/z (FAB) 323 (18%, MH),
267 (100, M Ϫ C4H8 ), 223 (70, M Ϫ C4H8OCO); [α]2D0 ϩ27.9
(c 0.2, dichloromethane).
Synthesis of L-kynurenine 411
Compound 8g (36.2 mg, 0.11 mmol) was stirred in 30% HBr in
acetic acid (1 cm3 ) for 20 min at room temperature. Diethyl
ether (12 cm3 ) was then added to precipitate the bis(hydro-
bromide salt) as a colourless solid. The diethyl ether layer was
decanted and the procedure repeated several times to remove as
much HBr as possible. The last traces of diethyl ether were
removed in vacuo, and the colourless solid was thoroughly dried.
This material was dissolved in propan-2-ol (5 cm3 ) and treated
with propylene oxide (46.5 µl, 0.7 mmol). -Kynurenine 4 (21
(2S)-Methyl
2-(N-tert-butoxycarbonylamino)-4-oxo-4-(4Ј-
aminophenyl)butanoate 8i. Using 4-iodoaniline 7i, the ketone 8i
(135 mg, 58%) was isolated as a brown oil (Found: Mϩ Ϫ C4H8,
265.0823. C12H13N2O5 requires M, 265.0824); νmax(cap. film)/
cmϪ1 3440 (N᎐H), 1748 (C᎐O), 1717 (C᎐O), 1687 (C᎐O); δ (200
᎐
᎐
᎐
H
868
J. Chem. Soc., Perkin Trans. 1, 1997

View Article Online
mg, 0.1 mmol, 90%) precipitated as a light yellow powder, mp
162–163 ЊC (lit.,5 155–160 ЊC) (Found: C, 57.6; H, 6.2; N,
13.0; Mϩ 208.0850. C12H12N2O3 requires C, 57.7; H, 5.8; N,
13.5%; M, 208.0848); νmax(KBr disc)/cmϪ1 3471 (C᎐H), 3049
CO2CH2); m/z (EI) 258 (2%, M), 213 (10, M Ϫ OEt), 185 (49,
M Ϫ CO2Et).
1,5-Dicyanopentan-3-one 9e. Using the zinc reagent 6e, the
ketone 9e (38 mg, 43%) was isolated as a clear oil (lit.,18 mp
37 ЊC) (Found: C, 61.8; H, 5.9; N, 20.6; Mϩ, 136.0630. C7H8N2O
requires C, 61.75; H, 5.9; N, 20.6%; M, 136.0637); νmax(KBr
(N᎐H3ϩ ), 2994 (C᎐H), 2704 (N᎐H3ϩ ), 1661 (C᎐O), 1614
᎐
(C᎐O), 1578 (C᎐O); δ (200 MHz, CD OD) 3.63–3.77 [dd, 1
᎐
᎐
H
3
H, J 9.1 and 18.5, C(3)H], 3.86–3.97 [dd, 1 H, J 2.9 and 18.5,
C(3)H], 4.16–4.22 [dd, 1 H, J 2.9 and 9.1, C(2)H], 6.74–6.83
(dt, 1 H, J 1.0 and 8.0, Ph), 6.91–6.96 (dd, 1 H, J 1.0 and
8.0, Ph), 7.41–7.49 (dt, 1 H, J 1.5 and 8.0, Ph), 7.91–7.96 (dd,
1 H, J 1.5 and 8.0, Ph); m/z (FAB) 209 (64%, MH), 192.6
(70, MH Ϫ NH3 ); [α]2D0 Ϫ106.6 (c 0.5, methanol).
disc)/cmϪ1 2250 (CN), 1716s (C᎐O) (lit.,18 2250, 1710); δH (200
᎐
MHz, CDCl3 ) 2.61–2.68 [t, 4 H, J 6.5, C(2)H and C(6)H], 2.84–
2.91 [t, 4 H, J 6.5, C(3)H and C(5)H]; m/z (EI) 136 (20.6%, M),
80 [44, M Ϫ (CH2 )2CN].
1,3-Diphenylpropan-2-one 9f. Using the zinc reagent 6f, the
ketone 9f (48 mg, 61%) was isolated as a clear oil (Found: Mϩ,
210.1035. C15H14O requires M 210.1045); νmax(cap. film)/cmϪ1
3062 (C᎐H), 2918 (C᎐H), 1716s (C᎐O); δ (200 MHz, CDCl )
3.71 (s, 4 H, CH2 ), 7.01–7.67 (m, 10 H, Ph); m/z (EI) 210 (7%,
᎐
H
3
Preparation of aliphatic zinc reagents
Zinc dust (325 mesh, 300 mg, 4.5 mmol) was added to a nitro-
gen purged flask. THF (0.34 cm3 ) and 1,2-dibromoethane (19.4
cm3, 0.225 mmol) were added and the flask was heated at 60 ЊC
for 15 min using a hot water bath. The reaction mixture was
allowed to cool to room temperature and trimethylsilyl chloride
(6.0µl, 0.046mmol)wasadded. Theresultant mixturewasstirred
vigorously for 30 min under nitrogen. The iodide (0.75 mmol)
in THF (0.34 cm3 ) was added to the flask which was heated at
35 ЊC until no starting material remained (as judged by TLC,
10:1, toluene–ethyl acetate).
M).
Reaction with aromatic iodides and carbon monoxide—improved
procedure
The zinc reagent ent-6a (0.75 mmol) was prepared in the usual
manner, allowed to cool to room temperature and the aromatic
iodide (1 mmol) and Pd(Ph3P)4 (43 mg, 0.038 mmol) were
added. The reaction was frozen using liquid nitrogen and
then put under vacuum for 5 min after which the flask was
filled with nitrogen and the reaction mixture allowed to thaw.
This process was repeated six times. After the final freezing,
carbon monoxide was used to fill the flask whilst the mixture
was thawing. The reaction mixture was then stirred for 30 h at
room temperature. The reaction mixture was filtered, par-
titioned between ethyl acetate (25 cm3 ) and water (25 cm3 ),
washed with brine (25 cm3 ), dried, filtered and concentrated to
give the crude product. This was purified by flash chroma-
tography using light petroleum–ethyl acetate to give the
product(s).
Synthesis of symmetrical ketones—general procedure
The zinc reagent was allowed to cool to room temperature and
Pd(Ph3P)4 (43 mg, 0.038 mmol) was added. The nitrogen
atmosphere was then replaced with carbon monoxide (a bal-
loon). The reaction mixture was then stirred for 30 h at room
temperature. The reaction mixture was filtered, partitioned
between ethyl acetate (25 cm3 ) and water (25 cm3 ), washed with
brine (25 cm3 ), dried, filtered and concentrated to give the
crude product. This was purified by flash chromatography
using light petroleum–ethyl acetate to give the pure ketone.
(2S)-Methyl
2-(N-tert-butoxycarbonylamino)-4-oxo-4-(3Ј-
aminophenyl)butanoate ent-8h. Using 3-iodoaniline as the sub-
strate, the product ent-8h (126 mg, 52%) was isolated as a brown
oil. Data identical with 8h, apart from [α]2D0 Ϫ28.5 (c 0.3,
dichloromethane).
Reaction with 4-iodonitrobenzene. The first eluted product
was (2S)-methyl 2-(N-tert-butoxycarbonylamino)-3-(4Ј-nitro-
phenyl)propanoate 11 (75 mg, 31%) isolated as brown needles,
mp 94–95 ЊC (lit.,19 92–94 ЊC) (Found: Mϩ Ϫ CO2Me, 265.1194;
C13H17O4N2 requires M, 265.1188); νmax(cap. film)/cmϪ1 3393m
(2S,6S)-Dimethyl
4-oxo-2,6-bis(N-tert-butoxycarbonyl-
amino)heptanedioate 9a. Using the zinc reagent 6a, the ketone
9a (66 mg, 60%) was isolated as a pale yellow powder, mp
89–92 ЊC (Found: C, 52.3; H, 7.4; N, 6.1;
M
ϩ Ϫ NH-
CO2C4H8, 317.1453. C19H32N2O9 requires C, 52.7; H, 7.45;
N, 6.5%; C14H23NO5 requires M, 317.1475); νmax(KBr disc)/
cmϪ1 3440 (N᎐H), 1748 (C᎐O), 1717 (C᎐O); δ (200 MHz,
᎐
᎐
H
CDCl3 ) 1.4 [s, 18 H, C(CH3 )3 ], 2.8–3.2 [m, 4 H, C(3)H], 3.8 (s, 6
H, OCH3 ), 4.5 [m, 2 H, C(2)H], 5.6 (d, 2 H, J 8, NH); m/z (FAB)
317 (5%, M Ϫ NHCO2C4H8 ); [α]1D7 ϩ34.3 (c 0.7, dichloro-
methane).
(N᎐H), 1730s (C᎐O), 1393m and 1368s [C(CH ) ], 1346s
᎐
3
3
(C᎐NO2 ), 1169s (C᎐O᎐C); δH (200 MHz, CDCl3 ) 1.42 [s, 9 H,
C(CH3 )3 ], 3.18 [dd, 1 H, J 6.2 and 13.7, C(3)H], 3.22 [dd, 1 H, J
5.7 and 13.7, C(3)H], 3.74 (s, 3 H, OCH3 ), 4.64 [m, 1 H, C(2)H],
5.04 (d, 1 H, J 7.5, NH), 7.29–7.34 [d, 2 H, J 7.3, C(2Ј)H and
C(6Ј)H], 8.14–8.19 [d, 2 H, J 7.3, C(5Ј)H and C(3Ј)H]; m/z (EI)
265 (0.6%, M Ϫ CO2Me), 223 (5, M Ϫ CO2C4H8 ), 137 (80,
M Ϫ C7H6NO2 ); [α]2D0 ϩ53.4 (c 1.055, dichloromethane). The
second eluted product was (2S)-methyl 2-(N-tert-butoxy-
carbonylamino)-4-oxo-4-(4Ј-nitrophenyl)butanoate (ent-8o) (55
mg, 21%) isolated as a brown oil (Found: C, 54.7; H, 5.9; N, 8.0;
Dimethyl 4-oxoheptanedioate 9b. Using the zinc reagent 6b,
the ketone 9b (64 mg, 84%) was isolated as a white solid, mp 52–
54 ЊC (lit.,18 55 ЊC) (Found: Mϩ, 171.0668. C9H14O5 requires M,
171.0667); νmax(KBr disc)/cmϪ1 3011m (C᎐H), 2914m (C᎐H),
1744s (C᎐O), 1716s (C᎐O), 1706s (C᎐O); δ (200 MHz, CDCl )
᎐
᎐
᎐
H
3
2.58–2.65 [t, 4 H, J 5.9, C(2)H and C(6)H], 2.65–2.79 [t, 4 H, J
5.9, C(3)H and C(5)H], 3.68 (s, 6 H, OMe); m/z (EI) 202 (5.2%,
M), 171 (9.5, M Ϫ OMe), 143 (25, M Ϫ CO2Me).
1,7-Diphthalimidoheptan-4-one 9c. Using the zinc reagent 6c,
the ketone 9c (47 mg, 53%) was isolated as a white solid, mp
142–146 ЊC (Found: Mϩ, 404.1376. C23H20O5N2 requires M,
404.1372); νmax(KBr disc)/cmϪ1 1721s (C᎐O), 1707s (C᎐O);
M
ϩ Ϫ C2H3O2, 293.1140. C16H20N2O7 requires C, 54.5; H, 5.7;
N, 7.95%. C14H17O5N2 requires M, 293.1137); νmax(cap. film)/
cmϪ1 3385 (N᎐H), 1747 (C᎐O), 1684 (C᎐O); δ (200 MHz,
᎐
᎐
H
CDCl3 ) 1.41 [s, 9 H, C(CH3 )3 ], 3.5–3.8 [m, 2 H, C(3)H], 3.73 (s,
3 H, OCH3 ), 4.7 [m, 1 H, C(2)H], 5.6 (d, 1 H, J 8, NH), 8.0–8.1
(d, 2 H, J 9, Ph), 8.2–8.3 (d, 2 H, J 9, Ph); m/z (EI) 296 (19,
M Ϫ C4H8 ), 252 (20, M Ϫ C4H8OCO); [α]2D0 ϩ26.3 (c 0.15,
dichloromethane).
᎐
᎐
δH (200 MHz, CDCl3 ) 1.83–2.18 [m, 4 H, C(2)H and C(6)H],
2.47 [t, 4 H, J 7.1, C(3)H and C(5)H], 3.69 [t, 4 H, J 6.7, C(1)H
and C(7)H], 7.67–7.89 (m, 8 H, Ph); m/z (EI) 405 (0.4%, MH),
257 [4.0, M Ϫ NH(CO)2Ph].
Diethyl 5-oxononanedioate 9d.9 Using the zinc reagent 6d,
the ketone 9d (58.4 mg, 60%) was isolated as a clear oil (Found:
C, 60.5; H, 8.6; Mϩ, 258.1462. C13H22O5 requires C, 60.4; H,
Acknowledgements
8.5%; M, 258.1467); νmax(cap. film)/cmϪ1 1734s (C᎐O), 1716s
We thank the EPSRC for a CASE award (D. T.), Sarah Filling-
ham for experimental assistance and Zeneca Pharmaceuticals
for support. R. F. W. J. also thanks the Nuffield Foundation for
a One Year Science Research Fellowship.
᎐
(C᎐O); δ (200 MHz, CDCl ) 1.26 (t, 6 H, J 7.0, Me), 1.88 [quin-
᎐
H
3
tet, 4 H, J 7.0, C(3)H and C(7)H], 2.35 [t, 4 H, J 7, C(4)H and
C(6)H], 2.48 [t, 4 H, J 7, C(2)H and C(8)H], 4.14 (q, 4 H, J 7.0,
J. Chem. Soc., Perkin Trans. 1, 1997
869

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11 These conditions are derived from those reported by Salituro and
References
McDonald for an analogous deprotection (ref. 5 above).
12 See R. Pellicciari, M. A. Gallo-Mezo, B. Natalini and A. M. Amer,
Tetrahedron Lett., 1992, 33, 3003.
1 R. F. W. Jackson, K. James, M. J. Wythes and A. Wood, J. Org.
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2 M. J. Dunn, R. F. W. Jackson, J. Pietruszka and D. Turner, J. Org.
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3 S. Bhar and B. C. Ranu, J. Org. Chem., 1995, 60, 745.
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15 A. Devasagarayaj and P. Knochel, Tetrahedron Lett., 1995, 36, 8411.
16 S. Aoki and E. Nakamura, Tetrahedron, 1991, 47, 3935.
17 For a discussion of the mechanism of self-coupling of arylboronic
acids to give biaryls under palladium catalysis, which also invokes
oxidation by molecular oxygen, see M. Moreno-Mañas, M. Pérez
and R. Pleixats, J. Org. Chem., 1996, 61, 2346 and references cited
therein. For related observations on the homocoupling of
arylstannanes, see V. Farina, B. Krishnan, D. R. Marshall and
G. P. Roth, J. Org. Chem., 1993, 58, 5434.
5 For
a recent synthesis and references to earlier work, see
F. G. Salituro and I. A. McDonald, J. Org. Chem., 1988, 53, 6138.
6 N. P. Botting, Chem. Soc. Rev., 1995, 24, 401.
7 J. A. Bajgrowicz, A. El Hallaoui, R. Jacquier, C. Pigiere and
P. Viallefont, Tetrahedron, 1985, 41, 1833. The compound is now
available from the Aldrich Chemical Company.
8 For a preliminary communication on part of the work discussed in
this paper, see: R. F. W. Jackson, D. Turner and M. H. Block,
J. Chem. Soc. Chem. Commun., 1995, 2207.
9 For the preparation of unsymmetrical and symmetrical ketones by
carbonylation of zinc organometallics, see K. Yasui, K. Fugami,
S. Tanaka and Y. Tamaru, J. Org. Chem., 1995, 60, 1365. For the
carbonylation of other organometallic reagents, see references cited
therein.
18 J. E. Baldwin, R. M. Adlington, A. U. Jain, J. N. Kolhe and
M. W. D. Perry, Tetrahedron, 1986, 42, 4247.
19 S. Tokutake, S. Imanishi and M. Sisido, Mol. Cryst. Liq. Cryst.,
1989, 170, 245.
10 For an important preliminary report which describes the in situ
carbonylative coupling of aryl iodides with alkyl iodides mediated
by zinc and palladium(0), see Y. Tamaru, H. Ochiai, Y. Yamada and
Z.-I. Yoshida, Tetrahedron Lett., 1983, 24, 3869.
Paper 6/06394B
Received 17th September 1996
Accepted 30th October 1996
870
J. Chem. Soc., Perkin Trans. 1, 1997