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Abstract: Due to the potent biological activity exhibited by various indole derivatives, there is a continuous demand for
novel synthetic procedures in this area. In 1989, the reaction of vinyl magnesium halides with ortho-substituted
nitroarenes was discovered to lead to indoles. In the 1990s, it has attracted much attention, as it employs simple and
readily available starting materials. This reaction is now frequently reported as the “Bartoli reaction” or the “Bartoli indole
synthesis” and has rapidly become the shortest and most flexible route to 7-substituted indoles, as classical indole
syntheses generally fail in their preparation.
The flexibility of Bartoli reaction is great as it can be extended to heteroaromatic nitro derivatives and can be run on solid
support.
The necessity of an ortho-substituent on the aromatic ring is the limit of the Bartoli indole synthesis, because o,o’-
unsubstituted nitroarenes follow a completely different pathway when reacting with vinyl Grignard reagents. Bromine,
however, should be a transient group, which can enforce the sigmatropic rearrangement, as requested by the mechanism,
and is easily removed. A combination of the two methodologies can give a significant reduction of steps required for the
preparation of many complex 7-unsubstituted indoles, whose functions are tolerant to the reaction conditions, but not to
classical indole syntheses.
This review will focus both the use of the Bartoli indole synthesis as key step in many preparation of complex indoles and
the improvements of the reaction.
5 6 7 path a R=alkyl
+ RMgX + R + MgX+
NO2 R
Y
3 9 10
path b path c
8 R= R= Ar
Scheme 1. OAr
N
Ph OMgX
Also non-benzenoid aromatics, which exhibit [H]
electrophilic character per se, can undergo VNS. Usually Ph N O 15
VNS proceeds faster at the unsubstituted position than the N
HO Ph OMgBr
conventional SNAr of halogen located at reactive positions, -ArOMgX
so they survive the reaction conditions and prevent attack at 12 13
22
the substituted positions. The reaction mechanism of the PhNO
VNS is clearly a polar pathway that proceeds through the -H2O 16
reversible addition of carbanions to the nitroarene, followed
by the irreversible β-elimination of HX, oxidation or ArM gX
dehydration. Polar effects and solvation play fundamental N
roles in influencing orientation, as well as bulkiness of O Ph Ar OAr
nucleophile and the steric environment of the ring reactive 14 N N
Ph OMgX Ph MgX
positions.
Independently and complementarily, we were able to 17 18
[H]
transform once poorly known or misinterpreted procedures
H2 O H2O
upon Grignard reagents into a series of rational pathways
[15]. As VNS, also this reaction can be applied to all Ar Ar
nitroaromatics [16]. PhNH2
N N
Functionalities, reactive towards Grignard reagents such Ph H Ph OH
as esters, ketones and nitriles, are unaffected and when, 19 20 21
located at reactive positions, prevent attack at these positions
[17]. Scheme 2.
Bartoli Indole Synthesis Current Organic Chemistry, 2005, Vol. 9, No. 2 165
oxidation to alkylnitroarenes (6), [15] or dehydration to Table 1. Reaction of vinyl Grignard reagents with o-substituted
alkylnitrosoarenes (7) (path a) [15]. Allyl radicals, which are nitrobenzenes.
planar [19], exclusively link to the nitrogen atom giving XMg
tetrahedral intermediates which can then be reduced to
1) 3 eq. 1
allylhydroxylamines (12) or dehydrated to nitrones (14) NO2
R R1 R
(path b) [21]. Since the attack occurs at the nitrogen atom, X - 40 °C, THF
this reaction can be extended to every nitro compound [22]. 2) NH4Cl aq R
The same pathway is followed by a planar alkyl radical such N
as the t-butyl radical.
X H
In fact, the reaction of t-butylmagnesium chloride with
1,4-dinitrobenzene led to exclusive 1,2-attack with C-N bond R R 1
X in nitroarene Indole Yield (%)
formation [23].
H H 2-Me 67a
No firm mechanistic conclusions were made for aryl
H H 2-Me 71b
derivatives. In fact, we were unable to set up the best
H H 2-Me 58b,c
conditions for isolation of the final products. Literature data
H H 2-Br 62a
reported formation of a complex mixture of anilines,
H H 2-F 42a
hydroxylamines and diarylamines [24]. In a fashion of a SET
mechanism, aryl radicals, whose shape is different from both H H 2-Cl 63a
alkyl and allyl radicals, can be supposed to attack at the H H 2-TMSO 41a
oxygen atom of the nitro group, leading to a nitroso H H 2-BnO 13d
derivative 16, which, in turn, undergoes 1,2-attack on the H H 2-Ph2CHO 57d
nitrogen atom (path c). H H 2-(9-anthracenemethoxy) 53d
Recently Knochel succeeded to prepare highly H H 2-trityloxy 62d
functionalized diarylamines from many functionalized aryl H H 2-BnO, 4-Cl 31d
Grignards and nitroarenes (Scheme 3), by reduction of the H H 2-Ph2CHO, 4-Cl 50d
unstable intermediate 17 with FeCl2/NaBH4 [25]. H H 2-BnO, 4-CF3 40d
H H 2-Ph2CHO, 4-CF3 54d
22 H H 2,4-BnO 10d
OAr
H H 2-BnO, 4-CO2Me 20d
Ar'NO2 ArMgCl Ar' N Ar'NO H H 2-CF3 56b
OMgCl H H 2,5-dibromo 69b
3 15 16
H Ph 2-Cl 47e
H Me 2-Me 35e
ArMgCl
H Me 2-Cl 38e
1) FeCl 2 (2 eq)
2) NaBH4 (1 eq) Me H 2-Me 76e
3) H2O Ar Me Me 2-Me 73b
Ar-NH-Ar' Ar' N (CH2)3 2-Me 49b
19 OMgCl (CH2)4 2-Me 47b
17 (CH2)5 2-Me 41b
Ar = p-COOEt, m-CN, p-OMe, p-I a
Ar' = p-Br, m-CN, o-OMe, p-COOEt, See ref. 27. b See ref. 33. c Using vinylmagnesium chloride instead of
thiazol-6-yl, quinol-6-yl bromide. c See ref. 34. d See ref. 29.
Table 3. Reaction of 3 equivalents of vinyl Grignard reagents Meta- and para-substituted nitroarenes as well as
with nitroarenes having unsubstituted ortho positions in THF nitronaphthalenes and nitroheterocycles without peri
at – 40 °C. hindrance give poor yields of indole and often anilines are
the main product (Table 3) [28].
R R1 Nitroarene Indole Yield (%)
In the 1990s, much attention has been paid to this indole
H H 3-chloronitrobenzene 19a synthesis, as it employs simple and readily available starting
H H 4-nitrotoluene 15b materials.
H H 4-chloronitrobenzene 17a
This reaction is now frequently reported as the “Bartoli
H Me 4-chloronitrobenzene 11b
reaction” or the “Bartoli indole synthesis” and has rapidly
H H 4-bromonitrobenzene 12a
become the shortest and most flexible way to 7-
H H 2-nitronaphthalene 17a
functionalised indoles.
H H 6-nitroquinoline Lowc
H H 8-nitroquinoline 0c
This review aims to give an overview both of the use of
H H 3-(trifluoromethyl)-nitrobenzene 0d
the Bartoli indole synthesis as key step in many preparations
H H 4-(trifluoromethyl)-nitrobenzene 0d
of complex indoles and of the improvements of the reaction.
H H 3-(trifluoromethyl)-4- 36d 2.3 Mechanism of the Reaction
methylnitrobenzene
H H 3-bromo-4-methylnitrobenzene 34 d Reaction mechanism was studied in detail to clearly
a
See ref. 27. b See ref. 29. c See ref. 28b. d See ref. 33. rationalize the observed results (Scheme 4) [29]. Firstly the
NO2 XMgO O R
N R
X R1 1
path a X R
R1
+
N
XMg R
X H
Cadogan indole
23 24 25 26
synthesis
path b R
R1
H3 O+ O
29
R
R
R1
R1 OMgBr
O O MgX
N 28 NO
X X
27 30 path c
24 24 X=H
R R
XMg O R
N R1 OMgX R1 MgX
N N NH2
X 1
R X X + X
24 H3O
29 +
34
[3,3-sigmatropic 31 28 32 33
rearrangement] +
H3O
35
R1 R1 R1 R1
stoichiometry of the reaction was investigated: a 3-fold easily be reduced by a further equivalent of Grignard to the
excess is always required to obtain satisfactory yield and, enamine salt (32), and finally hydrolyzed to aniline (33) and
together with indole (40), a carbonyl derivative (29) and an a carbonyl derivative (29). Finally, further evidence, which
alkene (38) were always recovered. The presence of 29 supports our hypothesis, is that indole and aniline yields are
clearly comes from an enolate derivative 28, which arises comparable for all the para-substituted nitroarenes, with
from a reduction of the nitro derivative. Deuterium labeling preponderance of aniline, whereas indole yields increase
experiments show only trace amounts of deuterium with steric hindrance of the substituent in ortho-substituted
incorporation on 38, demonstrating that it must be formed nitroarenes (Table 1) [29,32].
during the reaction course and does not arise from To yield indole, 34 must undergo [3,3]-sigmatropic
quenching. The fate of the Grignard reagent is now clear: the rearrangement to 35, followed by immediate cyclization to
first equivalent is incorporated in the indole nucleus, a 36, where the indole nucleus is now built. The addition of a
second reduces the nitro group somewhere in the reaction third equivalent of Grignard reagent, in a acid-base reaction
pathway, and the third reacts in an acid-base fashion for removing the acidic proton bound to the nitrogen atom in
elsewhere. The second oxygen atom of the nitro group must the tautomer 37, accounts for the equivalent of alkene found
be lost as water, since it is not detected among the reaction among the reaction products.
products. Finally, carrying out the reaction in defect of The proposed mechanism is in agreement with
Grignard reagent, trace amounts of nitrosoarenes (30) were experimental evidences and reaction stoichiometry. It has not
detected. been rebutted by subsequent studies. For example, the
These evidences can be easily rationalized into our observed lower yields with vinylmagnesium chloride instead
proposed SET mechanism for the reaction of Grignard of bromide (see Table 1, entries 1-3) [33] although not
reagents and nitroarenes. The first interaction is an in-cage rationalized, are not in contrast with the proposed
electron transfer from Grignard reagent to nitroarene. Vinyl mechanism.
radicals could behave like alkyl or aryl radicals, in other
words, they can attack the ring or the oxygen atom. If the 3. IMPROVEMENTS
vinyl radical and the nitroarene radical anion collapse at the Since our discovery, Bartoli indole synthesis has
ortho position of the nitroarene ring (25) [18], the anionic attracted the attention of many organic and biological
carbon should occupy the 3-position of the indole nucleus. chemists, who have worked to improve the original reaction.
This pathway leads to a synthesis known as the Cadogan- This section collects these improvements.
Sundberg indole synthesis (Scheme 4, path a) [30]. It was,
however, ruled out by the experimental evidence that the 3.1 Synthesis of Indole-7-Carbaldehyde and 7-
anionic carbon is linked in the 2-position (see disposition of Carbomethoxyindole (Gilmore’s Modification)
alkyl chains R and R1 in Cadogan indole 26 and our indole 7-Bromoindole (42aa) provides a convenient precursor to
40). 7-formylindole and 7-carbomethoxyindole (Scheme 5).
A vinyl radical is found by theory and experiment to be It can be metalated with sodium hydride / butyllithium
bent [19]. Its shape is very similar to aryl radicals, since the and allowed to react either with DMF, as a formylating agent
bond angle (137°) is compatible with an sp2 geometry. [34], or with methylchloroformate [35].
Therefore, a 1,2-addition has to occur to give intermediates Although the two 2-step process is facile on a small
27 (Scheme 4, path b), according to aryl radical reactivity scale, it is unsuitable for scale-up, due to need for
[25]. Intermediate 27 is then reduced by organomagnesium purification of 7-bromoindole.
to nitrosoarenes (30). This reduction step accounts for
enolate 28 formation. Owing to the high interest in the synthesis of 7-
formylindole as a key intermediate for more complex
The reaction of nitrosoarene 30 with two equivalents of structures, direct Bartoli synthesis on easily available 2-
24 led to the expected indole, confirming that product 30 lies nitrobenzaldehyde was studied to give a solution to the
on the main reaction pathway [29,31]. problem [34]. A suitable protection of the aldehyde moiety is
It is reasonable to think that nitrosoarene is a better necessary, since it is the only electrophilic group which
substrate than nitroarene to undergo SET. A second 1,2- interferes with nitroarene moiety [17]. In order to improve
addition of 24 to 30 should occur to give the N,O- yields, bulky protecting groups are needed (see section 2.3).
disubstituted (34) and the N,N-disubstituted (31) Unsubstituted cyclic acetals are not sterically demanding
hydroxylamino derivatives with a second SET step. The enough, while 4-phenyl-2-(2-nitrophenyl)-1,3-dioxolane is
former attack resembles the early one, the latter follows the difficult to form and problematic to deprotect. The best
aryl pathway [24,25]. We think that, conversely from aryl results were obtained with dibutyl acetal. The 3-step
derivatives, where the C-N bond formation is always procedure can be performed without need for purification of
favored, the bulkiness of the ortho-substituent influences this the intermediates and provides 7-formylindole in 68%
attack. Bulky substituents crowd the nitrogen atom overall yield on a 70g-scale.
addressing the Grignard reagent on the oxygen atom,
favoring 34 which leads to indole. This hypothesis is 3.2 Synthesis of 7-Alkylindoles
supported by the observation that, in a SET mechanism, a 7-Alkylindoles are important as intermediates for natural
collapse of a radical species is much more sensitive to steric products synthesis. Both the Heck and Suzuki reactions are
hindrance that polar reactions [18]. Little or no substituents the most commonly performed alkylation reactions on 7-
allow addition to the nitrogen atom leading to 31, as aryl bromoindole (42aa), pre-formed by Bartoli indole synthesis
derivatives prevalently do [18,24,25]. Intermediate 31 can (see section 4).
168 Current Organic Chemistry, 2005, Vol. 9, No. 2 Dalpozzo and Bartoli
NO2
Br 1) NaH/BuLi
THF, -40 °C 2) ClCOOMe
MgBr +
N N
H H
Br MeOOC
24a 41a 42aa
45
1) NaH/BuLi
2) DMF
34% overall yield
CHO H
43 44
ROH overall yield
1,2-ethandiol 23%
1-phenyl-1,2-ethandiol 35%
methanol 44%
n-butanol 68%
n-pentanol 39%
Scheme 5.
Li Li
49ae H H 41
50 aa, ca-ia
3
TsN3 or DPPA
-70 to -40 °C
49ba 5-Mea 43
X X
Red-Al
-40 to 0 °C
49ca 4-Mea 49 N N
NH2 Li N3 Li
a
It should be noted that a 4-substituent in the benzene ring assumes the 5-
52aa, ca-ia 51aa, ca-ia
position in the indole nucleus and vice versa, owing to the nomenclature
rules of the two compounds.
Scheme 8.
N N N N
NO2 N 24a, THF,
O H 35 -78°C to -20 °C
O
NO2 N
F
18%
F H
56 55
Scheme 9.
N N 33
NO2 N
35 XMg
N N
NO2 N 1) 2 eq.
Cl Cl H NO R
Cl N N - 40 °C, THF
2) NH4Cl aq R
18
N X N
NO2 X
H
H
N Cl N
R X Solvent Indole Yield (%)
50
NO2 N Me 7-Cl THF 32a
OBn H Me 7-Me Et2O 56a
N N Ph 7-Me Bu2O 48b
TMS 7-Me Bu2O 46b
N 25 TMS 7-Br Bu2O 42b
NO2
OMe OBn H TMS 7-Cl Bu2O 50b
TMS 7-Et Bu2O 39b
N N
TMS 5,7-dichloro Bu2O 42b
42aa/KOH/DMF/ 1
R
r.t./ 24 h (87%) X
Br X NO2 24a-c,e,
N R
-40°C, THF
45f N
Br Br
Br H
41a,c 42
64
R1
Bu3SnH/AIBN X
toluene, reflux, 12 h Bu3SnH (1.2 eq)
AIBN, toluene R
N
+ 67 H
Scheme 12.
N
N
Table 8. Examples of Bartoli reaction followed by radical
reduction.
N 94% N
Br H H
Scheme 13. 72 73
Bartoli Indole Synthesis Current Organic Chemistry, 2005, Vol. 9, No. 2 173
The ortho-substituent can now enforce selectivity in The first reported example was the total synthesis of
attack to the nitrosoarene intermediate according to the (+/-)-cis-trikentrin-A (76), a cytotoxic indole alkaloid
pathway depicted in Scheme 4, but can be easily removed by isolated from the marine sponge Trikentrion flabelliforme
radical reduction. The combination of these two [47].
methodologies allows the synthesis of many indoles, where 5-Ethyl-1,3-dimethyl-7-nitro-1H-indene (74) and 2-
the Bartoli approach is advantageous, but ortho-substitution bromo-5-ethylnitrobenzene (77) were the substrates for
undesirable. Some examples are summarized in Table 8. indole synthesis (Scheme 14). The latter failed to give the
This method may reduce the number of steps required for target molecule, owing to a rearrangement during a
the synthesis of some complex indoles and also offers the subsequent Friedel-Crafts construction of the cyclopentane
advantage that many functionalities are tolerant to both the ring fused to indole.
Bartoli synthesis and the radical-generating conditions, The key intermediate 80 for the synthesis of two
without the need for their protection as demonstrated by the pyrrolophenanthridinone alkaloids extracted from
synthesis of three indole alkaloids (67, 71, 73) from Amaryllidaceae (oxoassoanine, 81 and hippadine 82,
European Tricholoma species (Scheme 13) [45]. Scheme 15) was accomplished by a Suzuki coupling on 42aa
[48].
4. USE IN SYNTHESIS OF NATURAL PRODUCTS
Since its appearance in the literature, the Bartoli indole
B(OH) 2
synthesis has provided a useful way to key intermediates for 42aa, Pd(PPh3) 4,toluene
the synthesis of complex indoles. Two examples are already EtOH, NaHCO3aq N
reported in the previous section [39,45]. This section is reflux, 4 d
H
dedicated to other examples of synthetic applications.
OR
4.1 7-Haloindoles OR
RO
7-Haloindoles are certainly the most important building
79 OR
block prepared via vinyl Grignard addition to nitroarenes,
owing to the high versatility of the halogenated function to 80
further transformations. As reported above, both Heck and
Suzuki couplings are very often used to attach a suitable side
chain to the 7-position of the indole.
N
O
24a, THF,
-50 °C, 25 min N
MeO
N OMe
14% O
NO2 H 81
74 oxoassoanine O
75
82
O
H2/Pd-C, M eOH hippadine
rt, 22 h Scheme 15.
80%
Hippadine was also prepared via a four-step synthesis;
using a copper(I) promoted aryl to aryl coupling from 42aa
as a precursor (Scheme 16) [49]. Interestingly, 42aa was
prepared in a 53% yield at -70 °C, starting from
vinylmagnesium chloride, in sharp contrast with Dobbs’
N
assertions that decreasing the temperature and using chloride
H instead of bromide lowers yields [33,50].
The synthesis of the eastern subunit of chloropeptine
76
(Scheme 17), a glycopeptide antibiotic produced by
r ac-cis -trikentrin-A
Streptomices species, was also accomplished starting from
42aa. Two strategies are reported. The first prepares, in 1%
X yield, the macrocyclic derivative 86 [51]. The second builds
the biaryl derivative, ethyl 2-acetamido-3-[7-(5-formyl-2,3-
dimethoxyphenyl)-1H-indol-3-yl]propanoate (87) in a 30%
24a, THF, yield [51].
-40 °C, 25 min
Synthesis of 87 requires the preparation of 7-
47% bromotryptophan. It can be achieved from 42aa, by coupling
N
NO2 either with dehydroserine in the presence of PdCl2-NaOAc
Br Br H [52] or with serine in Ac2O-AcOH [53]. A third route to 7-
77 78
bromotriptophan was suggested in the synthesis of
Scheme 14. macrocyclic peptide analogues of proteasome inhibitor
174 Current Organic Chemistry, 2005, Vol. 9, No. 2 Dalpozzo and Bartoli
O Br
(83)
O Br 2 BuLi, THF, -78 °C BaMnO4,
2 CuI, P(OEt) 3, 3 h N
KOH, DMSO, CH2Cl2
24a, THF, Br to rt, 21 h
rt, 2 h N rt, 12 h
41a -70 °C, 3h 42aa 82
53% 72% Br 49% 79%
O
84 85
O O
O
Scheme 16.
42aa O
ref. 51 ref. 52
NHAc POCl 3
42aa + EtCONMe2
N
COOEt
Br H
88
N ArB(OH) 2,
HN Pd(PPh3) 4
H
O H MeO Na 2CO3
N
N O
MeO CHO
H O
86 87
Ar = Ph, 2-MeOPh,
3-MeOPh, 3-CF 3Ph, N
Ar H
89
Scheme 18.
HN
OH chlorophenol and the indole ring is built by Bartoli indole
RO synthesis (Scheme 19).
Cl
OH Cl
O H O OH DEAD, PPh3 O
OH
RHN N Cl
N R N Cl
O H O H O
NO2 NO2
Cl Cl
Cl Cl
90 91
OH
Cl H
eastern subunit of chloropeptin
24a
N
Scheme 17.
H
O
N O O
O CHO (CH2OH)2,
TsOH, benzene,
Dean-Stark, 1 h
24a, THF
-40 °C, 1.5 h
HO OH 24%
OMe
O
Fig. (2). Structure of rebeccamycin. Both indole nuclei highlightned O
CHO 10% HCl, THF
in figure are constructed by Bartoli indole synthesis [58].
rt, 0.5 h
precursor for N^N-chelating ligands for titanium(IV)[58] and 79%
nickel(II)[59] complexes (Figure 3). They are subsequently MeO N MeO N
employed as catalysts for ethylene polymerization. Titanium
complexes can polymerize ethylene in a living fashion to OBn H OBn H
form linear polyethylenes with, in same cases, extremely 96 95
narrow molecular weight distributions [58]. On the other
hand, the nickel complex is completely inactive in ethylene Scheme 20.
polymerization [59].
Ph2 CHBr,
Na2 CO3, DMF NO2
NO2 87% O Ph
N N
OH
Ph
Ni Ph
TiCl2 N
N 97 98
PPh3
R 2 R
OBn Br
HO
NO2 24a, THF
H -40 °C
N
Cl 33% N
Br OBn H
102
103
O N
many steps
H
O NH2
HO
HN
NH
Fig. (4). Structure of AJ-9677. The building block prepared
according to Bartoli indole synthesis is highlightened.
N NH
starting from 1-benzyloxy-4-bromo-2-nitrobenzene via
Gilmore’s procedure (Scheme 22) [64]. N
HO H O
4.3 Miscellaneous N
Br
Classes of indolocarbazole derivatives (analogues of H Dragmacidin D
rebeccamycin, Figure 2), which are potent inhibitors of Scheme 22.
cyclin D1/CDK4, a protein involved in the cell division
cycle, have been recently synthesized [65]. The western remains unaffected (Scheme 24). The product 112 inhibits
subunit was synthesized by Gilmore’s modification and, both varicella-zoster virus and cytomegalovirus and its
among the eastern units, the 7-(2-hydroxyethyl) substituted activity is comparable with acyclovir [66].
indole was prepared by the Bartoli reaction (Scheme 23).
On methyl 12-bromo-13-nitrodeisopropyl dehydroa- CONCLUSIONS
bietate 111 has been constructed an indole ring by Bartoli The reaction of vinyl Grignard reagents with nitroarenes,
indole synthesis in very good yields and the ester function owing to the peculiarity of the vinyl radical when it attacks
O
COOMe
OH TBDMSCl, OTBDMS
NO2 imidazole NO2 24a, THF (COCl) 2, Et2O
CH2Cl2 -45 °C N NaOMe, MeOH N
H H
96% 56% 57%
O H
N
see scheme 5 4 steps 107, KOtBu
43 44 DMF O
72% H
N N
H N
H2NOC HO H
108
109
hν, DDQ,
dioxane
95%
H
O
N
O
H
N
N
HO H
110
Scheme 23.
Bartoli Indole Synthesis Current Organic Chemistry, 2005, Vol. 9, No. 2 177
[43] Russel, G. A.; Geels, E. J. Am. Chem. Soc., 1965, 87, 122-123. [50] Actually, lower yields decreasing temperature badly joins with an
[44] Knepper K.; Brase, S. Org. Lett., 2003, 5, 2829-2832. SET mechanism, where lower temperatures should increase in-cage
[45] Dobbs, A. P. J. Org. Chem., 2001, 66, 638-641. reactions and therefore addition over redox processes. Dobbs did
[46] Dobbs, A. P. Jones, K.; Veal, K. T. Tetrahedron Lett., 1997, 38, not describe reaction product distribution. Other products arising
5379-5382. from in-cage mechanism, such as anilines or diarylamines should
[47] Wiedenau, P.; Monse, B.; Blechert, S. Tetrahedron, 1995, 51, be the by-products, which lowers yields. Nevertheless, Dobbs’
1167-1176. results are in contrast with Harrowven’s.
[48] Banwell, M. G.; Bisset, B. D.; Busato, S.; Crowden, C. J.; [51] Roussi, G.; Zamora, E. G. Heterocycles, 1999, 51, 2041-2063.
Hockless, D. C. R.; Holman, J.W.; Read, R. W.; Wu, A.W. J. [52] Gurjar, M.K.; Tripathy, N. K. Tetrahedron Lett., 1997, 38, 2163-
Chem. Soc., Chem. Comm., 1995, 2551-2553. 2166.
[49] Harrowven, D. C.; Lai, D.; Lucas, M. C. Synthesis, 1999, 1300-
1302.