A new approach to dihydrobenzofurans and dihydrobenzopyrans (chromans) based on the intramolecular trapping by alcohols of benzynes generated from 7-substituted-1-aminobenzotriazoles

Article abstract of DOI:10.1016/S0040-4020(00)00021-1

1-Aminobenzotriazoles 9 having 7-hydroxyalkyl substituents are efficiently convened into the corresponding benzynes 4 when treated with N- iodosuccinimide which then undergo highly efficient intramolecular trapping by the pendant hydroxyl groups leading to dihydrobenzofurans 24-26 and dihydrobenzopyrans (chromans) 27, with incorporation of a synthetically useful iodine atom adjacent to the new ether bond, which allows subsequent and high-yielding homologations using Stille, Sonogashira and Heck couplings. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(00)00021-1

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 1013–1023
A New Approach to Dihydrobenzofurans and
Dihydrobenzopyrans (Chromans) Based on the Intramolecular
Trapping by Alcohols of Benzynes Generated from
7-Substituted-1-aminobenzotriazoles
b
c
Michael A. Birkett,a David W. Knight,b, Paul B. Little and Michael B. Mitchell
*
aChemistry Department, University Park, Nottingham NG7 2RD, UK
bChemistry Department, Cardiff University, P.O. Box 912, Cardiff CF10 3TB, UK
cSB Pharmaceuticals, The Old Powder Mills, Tonbridge, Kent TN11 9AN, UK
Received 28 October 1999; revised 10 December 1999; accepted 23 December 1999
Abstract—1-Aminobenzotriazoles 9 having 7-hydroxyalkyl substituents are efficiently converted into the corresponding benzynes 4 when
treated with N-iodosuccinimide which then undergo highly efficient intramolecular trapping by the pendant hydroxyl groups leading to
dihydrobenzofurans 24–26 and dihydrobenzopyrans (chromans) 27, with incorporation of a synthetically useful iodine atom adjacent to the
new ether bond, which allows subsequent and high-yielding homologations using Stille, Sonogashira and Heck couplings. ᭧ 2000 Elsevier
Science Ltd. All rights reserved.
Classical methods for benzyne generation are generally
related to the original method involving the elimination of
hydrogen halides from halobenzenes under strongly basic
conditions.1 Related methods include halogen–metal
exchange, typically by treatment of a 1,2-dihalobenzene
with an alkyl lithium followed by the same type of elimina-
tion of halide;1 similar but milder methodology features
fluoride-induced desilylation of an ortho-silylhalobenzene
and, again, elimination of halide.2 Alternatives which
avoid strongly basic conditions during benzyne generation
include the use of another classical benzyne precursor,
anthranilic acid, together with more exotic vicinally func-
tionalised benzenes and a variety of heteroaromatic systems,
such as benzothiadiazole-S,S-dioxide and 1-aminobenzo-
triazole.1,2 As has recently been succinctly emphasised:
‘An important drawback of the aryne routes starting with
bidentate or cyclic precursors can be the effort needed to
prepare the precursor itself, especially for substituted
arynes. However, these have the advantage that the arynic
bond can be generated without positional ambiguity.’2
Certainly, a number of relatively complex benzyne pre-
cursors have been prepared, most often from bromo-
benzenes wherein the very complexity renders both the
synthesis and subsequent benzyne generation unambiguous.
Very little has been reported on the preparation of substi-
tuted 1-aminobenzotriazoles in this context, beyond the
original seminal studies by Campbell and Rees,3 and a
few more recent, usually symmetrical examples and higher
homologues, together with a benzene fused to two amino-
triazole rings, which effectively acts as a bis-benzyne
precursor although, presumably, the process occurs in a
stepwise fashion.4
The use of 1-aminobenzotriazole 1 as a benzyne precursor
was highlighted by Campbell and Rees who demonstrated
the ease of formation of the parent benzyne 3 by oxidation
to the intermediates 2, which rapidly disintegrates pre-
sumably by the spectacular cascade shown, rather than via
an N-nitrene species, as was originally thought.3 Two of the
best methods identified for achieving this rely on direct
oxidation by lead(IV) acetate, in which case XˆOAc, or
using N-bromosuccinimide, when XˆBr; nickel peroxide
and iodobenzene diacetate were also shown to be effective
oxidants. Alternative methods include decompositions of
various lithium salts of 1-tosylamidobenzotriazole and
related species,5 along with deoxygenation of N-nitroso-
benzotriazole using ethyl diphenylphosphinite, a process
which may involve a true N-nitrene intermediate.6 The
extremely mild conditions associated with the oxidation
methods stand in stark contrast to the alternatives outlined
above which employ various strong base-induced elimina-
tions from halo- or dihalo-benzenes. It occurred to us that
these oxidative conditions might be compatible with
hydroxyl groups and perhaps enable these to act as intra-
molecular traps for the benzynes so generated, as indicated in
formula 4 (Fig. 1). In great contrast to related intramolecular
Keywords: arynes; benzofurans; intramolecular trapping; alcohols.
* Corresponding author. Tel.: ϩ44-1222-874210; fax: ϩ44-1222-874030;
e-mail: knightdw@cf.ac.uk
0040–4020/00/$ - see front matter ᭧ 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00021-1

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M. A. Birkett et al. / Tetrahedron 56 (2000) 1013–1023
Figure 1.
cyclisations using amino- and enolate nucleophiles, such
trapping by hydroxyl functions is virtually unknown and
then using only very simple types of alcohol.1,2 As arynes
are soft electrophiles, alcohols and alkoxides, the latter
inevitably formed in base-induced aryne formation, would
be expected to be less reactive partners. While inter-
molecular trapping of benzynes by phenols is well prece-
dented,1,2 related intramolecular reactions were almost
unknown7 until very recently.8
the acetone and cyclohexanone adducts of dianion 7 were
deprotected to give the free amines 11 and 12 in excellent
yields. However, the sensitive citral adduct derived from
dianion 7 failed to give more than traces of the free amine
13. Addition of anisole11 as a t-butyl cation scavenger did
not improve the situation whereas use of thioanisole, a better
carbocation scavenger,12 did lead to 40–50% isolated yields
of material which was largely the desired product 13 but
which we could never completely separate from some of the
many other products formed, presumably, by rearrangement
and dehydration, initiated by protonation of the hydroxy
group (Scheme 1).
Our starting point was the thought that it might be possible
to apply the often used principle of lateral deprotonation9 to
enable generation of the dianionic species 7 from N-Boc-1-
aminobenzotriazole 6 and hence provide a contribution to
the availability of diversely substituted 1-aminobenzo-
triazoles. If successful, one series of products [8; nˆ1,2],
derived from reactions of dianion 7 with carbonyls or
epoxides, would also present the opportunity to test the
idea of intramolecular trapping of arynes by hydroxyl
functions (Fig. 2).
Using the same method, the epoxide adducts [8; RˆEt,
(S)-Me, (R)-Ph, nˆ2] derived from dianion 7 were
converted into the free amines 14 in good yields in the
former two examples but, again, with some loss of material
due to dehydration in the case of the secondary benzylic
alcohol 14c.
Although lead(IV) acetate seems often to be regarded as the
standard oxidant for triggering benzyne generation from
1-aminobenzotriazoles,1,2 we felt that the less commonly
used N-bromosuccinimide (NBS) would be more com-
patible with the potentially oxidisable secondary alcohol
functions in the amines 10–14 and would offer the benefit
of milder conditions. Treatment of the parent 1-amino-
benzotriazole 1 with NBS in the absence of a trap had
been found by Campbell and Rees to give a 52% yield of
1,2-dibromobenzene 15; that benzyne 3 was a true inter-
mediate was indicated by the formation of the Diels–
Alder adduct 16, (Fig. 3), in an excellent isolated yield of
88%, when tetraphenylfuran was added as a trap.3
In the event, intermediate 7 turned out to be relatively
straightforward to generate and, as expected of an
sp3-centred carbanion, reacted smoothly with a wide range
of electrophiles, including aldehydes, ketones and epoxides,
to provide access to the required substrates 8.10 The starting
material 6 was readily prepared from the commercially
available nitroaniline 5 in five steps, using a slight
modification of the original Campbell and Rees method.3,10
Our first task was therefore to remove the N-Boc protecting
group from derivatives 8, for which we used the now
standard procedure of brief exposure to a 20% solution of
trifluoroacetic acid in dichloromethane at ambient tempera-
ture, followed by basification and chromatographic purifica-
tion when necessary, to give representative examples of the
free 7-hydroxyl-1-aminobenzotriazoles 9. The rather sensi-
tive benzaldehyde adduct [8; RˆPh, nˆ1] gave a relatively
modest return of the expected 1-aminobenzotriazole 10a,
due to partial dehydration, whereas the hexanal adduct [8;
Rˆn-C5H11, nˆ1] gave a respectable 75% isolated yield of
the free amine 10b. Fears that a tertiary alcohol function
would also undergo dehydration proved unfounded when
We found that when a dichloromethane solution of the
benzaldehyde-derived 1-aminobenzotriazole 10a was
slowly added to a solution of NBS in the same solvent at
ambient temperature, nitrogen evolution ensued rapidly
together with formation of an orange colouration, presum-
ably due to the generation of molecular bromine.13 A simple
work-up provided an ominously multi-component mixture
of products, according to TLC analysis. Fortunately, column
chromatography resulted in the separation of a single
Figure 2.

M. A. Birkett et al. / Tetrahedron 56 (2000) 1013–1023
1015
Scheme 1.
component in 41% yield which appeared to be a 2-phenyl-
2,3-dihydrobenzofuran, indicated particularly by the
presence of geminal diastereotopic protons at dH 3.10
(1H, dd, Jˆ13.0 and 8.3 Hz, 3-Ha) and 3.44 (1H, dd,
Jˆ13.0 and 7.5 Hz, 3-Hb) and the absence of any O–H or
N–H absorbances in the infrared spectrum of this non-polar
compound. However, it was plain from the NMR spectra of
this material that only three aromatic protons were present,
indicating that something more than simple addition of the
hydroxyl oxygen and proton to the presumed intermediate
benzyne [cf. 4] had occurred.
fully characterised, NMR and mass spectral data indicated
in both cases that major by-products were the vicinal
dibromides 18, formed presumably by direct reaction
between molecular bromine and the benzyne intermediates
(Fig. 4).
This side reaction predominated in the more stringent tests
of such intramolecular cyclisations involving the tertiary
hydroxyl groups in both the acetone- and cyclohexanone
adducts 11 and 12. In both cases, only small amounts of
the anticipated dihydrobenzofurans were formed, the
major products now being the dibromides 19. Evidently,
steric hindrance rather than a potentially beneficial
Thorpe–Ingold effect operates in these examples. Reason-
ing that molecular bromine could be responsible for this, the
reaction of the acetone adduct 11 was repeated in the
presence of 30 equiv. of 1-pentene. The idea proved correct:
a 45% isolated of the bromo-dihydrobenzofuran 20 was
obtained. However, this was a limited success as the related
That the product was actually the 7-bromo derivative 17a
was deduced from the NMR data, which was consistent with
a 1,2,3-trisubstituted benzene, along with mass spectral
analysis which clearly showed incorporation of a bromine
atom. Similarly, treatment of the hexanal-derived 1-amino-
benzotriazole 10b gave a comparable isolated yield of the
7-bromo-2-pentyldihydrobenzofuran 17b. Although not
Figure 3.
Figure 4.

1016
M. A. Birkett et al. / Tetrahedron 56 (2000) 1013–1023
Figure 5.
cyclohexanone adduct 12 delivered very largely the 1,2-
dibromo derivative 19b even in the presence of 1-pentene.
NMR and mass spectral analysis indicated the presence of
the desired dihydrobenzofuran, but only to an extent of
some 10–15%. Finally, in this series, we established that
similar cyclisations were viable for the formation of six-
membered rings. Thus, exposure of the epoxybutane adduct
14a to NBS under the usual conditions led to a 53% isolated
yield of the 8-bromo-benzopyran (chroman) 21 (Fig. 5).
Again, the corresponding uncyclised dibromide could be
detected by a combination of NMR and mass spectral
analysis, albeit in much lower yield.
benzyne pathway was being followed but that other reagents
present during the reaction, especially molecular bromine,
were seriously diminishing the efficiency of what appeared
to be a rather smooth intramolecular trapping process. We
reasoned that an iodonium source might prove more
effective; Houghton and Rees3,15 had found that oxidation
of 1-aminobenzotriazole itself with iodobenzene diacetate,
in the absence of an additional trap, led to the isolation of
1,2-diiodobenzene in 70% yield [cf. 33 below]. However,
we felt that molecular iodine, if formed, would be less reac-
tive than bromine and hence might not compete as well as
bromine with the desired intramolecular trapping reactions.
In view of the foregoing, it seems most reasonable to try
N-iodosuccinimide (NIS) in place of NBS to examine this
idea.
Despite the obvious benefits of bromine incorporation in the
successful cyclisations described above, at this stage we
briefly examined the reaction of this type of 1-amino-
benzotriazole with lead(IV) acetate, again using dichloro-
methane as solvent at ambient temperature. These
proceeded somewhat more efficiently and without inter-
ference from any unexpected processes to give the dihydro-
benzofurans 22 and 23,14 the latter in a remarkably high
yield considering the foregoing results, indicating that this
particular method is rather clean and does not result in the
generation of other species which react readily with
benzynes (Fig. 6). However, hopes that useful acetoxy func-
tions would be incorporated, along the same lines as
bromine, evidently proved groundless. It thus seems clear
that the failure of the tertiary alcohols 19 to undergo at least
reasonably clean cyclisations is associated with a rate
retardation due to steric hindrance, which allows other
species to attack the intermediate benzyne species, rather
than an intrinsic inability to cyclise.
We were delighted to find that treatment of the 1-aminobenzo-
triazole 10a derived from benzaldehyde with 2.5 equiv. of
NIS in dichloromethane resulted in the formation of essen-
tially a single product, which was isolated in 86% yield,
spectroscopic and analytical data for which showed this
to be the 7-iododihydrofuran 24a. Similarly, the amino-
benzotriazole 10b derived from hexanal gave the 2-pentyl
analogue 24b in 92% isolated yield.
Remarkably, the 1-aminobenzotriazoles 11 and 12 con-
taining tertiary hydroxyl groups also underwent smooth
cyclisation when exposed to NIS to give the 7-iododihydro-
benzofurans 25 and 26 in 95 and 82% isolated yields,
respectively, in contrast to the much poorer yields obtained
with NBS. Similarly, the homologous 1-aminobenzo-
triazoles 14 gave improved returns of the 8-iodo-dihydro-
benzopyrans 27 as indicated (Fig. 7). Along with all other
data, these iodides were identified by molecular weight
values and also especially diagnostic quaternary carbon
resonances in the ranges of 74–77 ppm in the benzofurans
and 86–88 ppm in the benzopyrans, due to the 7-C and
8-C, respectively, moved to these unusual positions for
aromatic sp2 carbons by the iodine-induced heavy atom
effect.16 Given the known availability of homochiral
monoepoxides, clearly this approach has much potential
for the synthesis of single enantiomers of 2-substituted
dihydro-benzopyrans.
We had thus established a novel approach to both dihydro-
benzofurans and -benzopyrans (chromans), with the bonus,
in terms of synthetic potential, that an additional bromine
atom is incorporated which could be useful as a handle for
further elaborations of the initial cyclisation products.
However, the uniformly moderate 40–50% isolated yields
rather mitigated against the utility of this methodology. The
formation of varying amounts of the corresponding,
uncyclised vicinal dibromides [e.g. 18 and 19], together
with the desired cyclisation products, indicated that the
Figure 6.

M. A. Birkett et al. / Tetrahedron 56 (2000) 1013–1023
1017
Figure 7.
Figure 8.
While the incorporation of a bromine atom offered possi-
bilities for further elaboration of the initial cyclisation
products described above, the iodides were expected to
show enhanced reactivities and hence represent even more
attractive intermediates. We have briefly illustrated some
of these possibilities by conducting a short, unoptimised
series of palladium-catalysed coupling reactions of the
representatives of the foregoing iodides. Thus, the 2-pentyl
derivative 24b underwent Stille coupling17 with 2-tributyl-
stannylfuran and tributylvinylstannane to give the expected
homologues 28 and 29, respectively. Both the 2,2-dimethyl-
dihydrobenzofuran 25 and the 2-ethyldihydrobenzopyran
27a underwent smooth Sonogashira coupling18 with
1-hexyne leading to the alkynyl homologues 30 and 31.
The former also underwent a successful Heck reaction19
with methyl acrylate and gave a 65% unoptimised return
of the (E)-cinnamate 32 (Fig. 8). No doubt, other related
couplings will prove possible (for example, the Suzuki
method20 with boronic acids and carbonylations may well
be successful) and it may even possible to effect halogen–
metal exchange and also useful radical trapping reactions.
1-aminobenzotriazole 1 was treated with NIS in the absence
of other trapping agents, only 1,2-diiodobenzene 33 was
isolated in 54% yield, comparable with that previously
obtained using iodobenzene diacetate (see above).3,15
Further, when furan was used as solvent in place of
dichloromethane, the Diels–Alder adduct 3421 was isolated
in 49% yield. Hence, it seems that iodine, while able to react
with benzyne, must do so at a significantly slower rate than
molecular bromine, which appears to react at a rate compar-
able with the intramolecular trapping by pendant hydroxyl
groups (Fig. 9).
Finally, we were intrigued by the possibility of trapping the
benzyne so generated by cyclic ethers with a view to gener-
ating intermediates 35 which might be expected to rearrange
as shown, resulting in annulation of the benzene ring, if such
a dipole were really to be formed. In the event, only the
diiodides 36 were isolated in moderate yields when oxetane,
tetrahydrofuran and tetrahydropyran were used as solvents,
respectively. Clearly, if dipoles 35 are true intermediates,
then either or both anion trapping by iodonium ions and ring
opening by attack of iodide are faster processes. Related
results have been obtained earlier for benzyne generated
from anthranilic acid, for example.22
The key step in which a presumed benzyne intermediate is
generated from a 1-aminobenzotriazole and NIS was very
similar in physical appearance to the related NBS reactions:
evolution of nitrogen was very rapid and, to judge from the
development of a distinct purple colouration, so was libera-
tion of molecular halogen, in this case iodine. Evidently, the
very high yields preclude the formation of significant
amounts of the 1,2-diodides, which proved a limitation in
the NBS method. Evidence that benzynes were true inter-
mediates came from two experiments. When the parent
All the evidence points to a true benzyne intermediate being
involved in the foregoing trapping reactions; however,
dipoles related to 35 appear as rather high energy inter-
mediates which seem less likely under the rather gentle
reaction conditions. In addition, a related species 37, formed
by intramolecular addition of a hydroxyl group to benzyne,
would appear very well set up to undergo simple proton
Figure 9.

1018
M. A. Birkett et al. / Tetrahedron 56 (2000) 1013–1023
Figure 10.
transfer and not the very efficient trapping by iodine which
is observed. At present therefore, a detailed mechanistic
rationale is not clear; perhaps a hydrogen-bonded associa-
tion between the reactants, as depicted in formula 38, plays
a key role in activating the key nucleophilic attack, the
subsequent trapping by iodine and also proton transfer to
succinimide in a concerted but non-synchronous manner as
indicated. There may be a commonality between this and
two other reactions in this overall sequence. Firstly, the
initial, presumed iodination of the 1-aminobenzotriazoles
can be depicted as proceeding via a similar hydrogen-
bonded species 39. Secondly, the hydrogen halide pro-
duced during benzyne formation [cf. 2] could interact
with a second molecule of the N-halosuccinimide, again
by formation of an initial hydrogen bond, as shown in
formula 40, followed by a similar proton transfer, lead-
ing to generation of molecular halogen, either bromine
or iodine (Fig. 10).
refers to column chromatography using silica gel (SORB-
SIL᭨ C60-H [40–60 mm]) and the eluents specified. Petrol
refers to light petroleum with bp 60–80ЊC and ether refers to
diethyl ether.
Deprotection of 7-substituted 1-(t-butoxycarbonylamino)-
benzotriazoles: general procedure
To a stirred solution of the 1-[t-butyloxycarbonyl(Boc)-
amino]benzotriazole 810 (1 equiv.) in dichloromethane
(10 ml mmolϪ1) at ambient temperature was added drop-
wise, via syringe, trifluoroacetic acid to give a 20% v/v
solution. After 0.5 h, the solution was evaporated to near-
dryness and basified by the addition of excess aqueous
sodium hydroxide. The resulting mixture was extracted
with ether (3×30 ml) and the combined extracts dried and
evaporated to leave the crude 1-aminobenzotriazole, usually
as a colourless gum, which was purified if necessary by CC
[EtOAc–petrol, 1:1].
In any event, the excellent yields of the NIS step, coupled
with the good to excellent yields which can be obtained
from the initial metallation chemistry leading to the pre-
cursors 810 suggests that this approach should be useful
for the elaboration of a wide range of these types of oxygen
heterocycles and does point the way towards the elaboration
of even more highly substituted derivatives.
7-(20-Hydroxy-20-phenylethyl)-1H-benzotriazol-1-amine
10a. By the general procedure, deprotection of the benzal-
dehyde-derived N-Boc aminobenzotriazole [8; RˆPh, nˆ1]
(75 mg) gave the amine 10a (24 mg, 45%) as a colourless
gum, nmax/cmϪ1 3245, 2814, 1606, 1455, 1114, 910 and 644,
dH (250) 1.59 (1H. br s, OH), 3.47–3.56 (2H, m, 10-CH2),
4.98 (1H, dd, Jˆ8.0 and 4.6 Hz, 20-H), 5.94 (2H, s, NH2),
7.09 (1H, dd, Jˆ7.8 and 1.0 Hz, 6-H), 7.15 (1H, dd, Jˆ7.8
and 7.8 Hz, 5-H), 7.16–7.26 (5H, m, Ph) and 7.76 (1H, dd,
Jˆ7.8 and 1.0 Hz, 4-H), dC (67.5) 40.3 (10-CH2), 75.2 (20-
CH), 118.5 (CH), 122.4 (C), 124.4 (CH), 125.8 (2×CH),
127.9 (CH), 128.5 (2×CH), 129.8 (CH), 130.9, 143.8 and
145.3 (all C), m/z [FAB] 255 (MϩϩH, 100%), 237 (18) and
189 (21). HRMS Calcd for C14H15N4O: 255.1246 (MϩϩH).
Found 255.1263.
Experimental
General details
Optical rotations were measured using an Optical Activity
AA-10 polarimeter. Infrared spectra were obtained using a
Perkin–Elmer 1720 FTIR spectrometer using liquid films
on sodium chloride plates or, if solids, chloroform solutions.
1H NMR spectra were obtained using a Perkin–Elmer R32a
instrument operating at 90 MHz (90) or a Bruker WM-250
instrument operating at 250 MHz. 13C NMR spectra were
determined using a JEOL EX270 spectrometer operating at
67.8 MHz or the Bruker AM-400 instrument operating at
100 MHz. All spectra were recorded using dilute solutions
in deuteriochloroform, with tetramethylsilane as the internal
standard. Coupling constants are quoted in Hertz. Mass
spectra were obtained in the EI mode using either an AEI
MS 902 or a VG 7070E instrument operating at 70 eV.
Unless stated otherwise, all reactions were performed
under dry nitrogen in anhydrous solvents, which were
obtained by the usual methods.23 All organic solutions
from aqueous work-ups were dried by brief exposure to
anhydrous magnesium sulphate followed by filtration. CC
7-(20-Hydroxyhept-10-yl)-1H-benzotriazol-1-amine 10b.
By the general procedure, deprotection of the hexanal-
derived N-Boc aminobenzotriazole [8; Rˆn-C5H11, nˆ1]
(164 mg) gave the amine 10b (88 mg, 75%) as a colourless
gum, nmax/cmϪ1 3363, 2931, 2858, 1603, 1459, 1118 and
947, dH (250) 1.03 (3H, br t, Jˆca. 6.1 Hz, 70-Me), 1.20–
1.60 (8H, m, 4×CH2), 3.20–3.29 (2H, m, 10-CH2), 3.90–
3.94 (1H, m, 20-H), 6.21 (2H, s, NH2), 7.18–7.22 (2H, m, 5-
and 6-H) and 7.63–7.67 (1H, m, 4-H), dC (67.5) 14.0
(70-Me), 22.6, 25.4, 31.8, 37.2, 38.2 (all CH2), 72.6 (20-
CH), 117.7 (CH), 123.3 (C), 124.2, 129.2 (both CH),
131.3 and 144.3 (both C), m/z [FAB] 249 (MϩϩH,
100%), 234 (5), 148 (5) and 134 (3). HRMS Calcd for
C13H21N4O: 249.1715 (MϩϩH). Found 249.1721.

M. A. Birkett et al. / Tetrahedron 56 (2000) 1013–1023
1019
7-(20-Hydroxy-20-methylpropyl)-1H-benzotriazol-1-amine
11. By the general procedure, deprotection of the acetone-
derived N-Boc aminobenzotriazole (53 mg) gave the amine
11 (28 mg, 78%) as a colourless gum, nmax/cmϪ1 3348,
2928, 2855, 1619, 1457, 1092, 962 and 885, dH (250) 1.33
(6H, s, 2×Me), 2.76 (1H, br s, OH), 3.33 (2H, s, 10-CH2),
6.36 (2H, s, NH2), 7.17 (1H, dd, Jˆ7.3 and 1.0 Hz, 6-H),
7.26 (1H, dd, Jˆ7.3 and 7.3 Hz, 5-H) and 7.78 (1H, dd,
Jˆ7.3 and 1.0 Hz, 4-H), dC (100) 29.7 (2×Me), 43.2
(10-CH2), 71.0 (20-C), 118.2 (CH), 122.8 (C), 123.9, 130.4
(both CH), 131.3 and 143.3 (both C), m/z [FAB] 207
(MϩϩH, 100%), 191 (5) and 189 (10). HRMS Calcd for
C10H15N4O: 207.1246 (MϩϩH). Found 207.1250.
3360, 2927, 2854, 1635, 1463, 1124, 1013, 977 and 900, dH
(250) 2.04–2.24 (2H, m, 20-CH2), 3.27 (2H, t, Jˆ7.9 Hz,
10-CH2), 4.64–4.70 (1H, m, 30-H), 7.19–7.37 (7H, m) and
7.71–7.75 (1H, m, 4-H), dC (67.5) 26.5 (20-CH2), 40.6
(10-CH2), 73.4 (30-CH), 117.5, 124.4, 125.8 (all CH),
126.0 (C), 126.4, 127.6, 128.0, 128.1 (all CH), 128.4,
131.2 and 144.3 (all C), m/z [FAB] 269 (MϩϩH, 100%),
253 (15) and 251 (10). HRMS Calcd for C15H17N4O:
269.1402 (MϩϩH). Found 269.1404.
Reactions of 1-aminobenzotriazoles with N-bromosuccin-
imide: general procedure
To a stirred solution of N-bromosuccinimide (NBS;
2 equiv.) in dichloromethane (10 ml mmolϪ1) at ambient
temperature was added dropwise, via syringe, a solution
of the 1-aminobenzotriazole (1 equiv.) in dichloromethane
(1 ml mmolϪ1) which resulted in vigorous effervescence, a
mild exotherm and the development of an orange coloura-
tion. After 1 h, the solvent was evaporated and the residue
purified using CC [ether–petrol, 1:9].
7-[(1-Hydroxycyclohex-1-yl)methyl]-1H-benzotriazol-1-
amine 12. By the general procedure, deprotection of
the cyclohexanone-derived N-Boc aminobenzotriazole
(250 mg) gave the amine 12 (167 mg, 92%) as a colourless
gum, nmax/cmϪ1 3244, 2934, 2845, 1432, 964 and 910, dH
(250) 1.40–1.60 (10H, m, 5×CH2), 3.24 (2H, s, 10-CH2),
6.28 (2H, s, NH2), 7.07–7.20 (2H, m, 5- and 6-H) and
7.73 (1H, dd, Jˆ7.3 and 1.0 Hz, 4-H), dC (67.5) 22.0,
25.6, 37.7, 42.4 (all CH2), 71.6 (100-C), 117.8 (CH), 121.4
(C), 123.9, 130.3 (both CH), 130.9 and 144.3 (both C), m/z
[FAB] 247 (MϩϩH, 100%), 231 (6) and 229 (5). HRMS
Calcd for C13H19N4O: 247.1559 (MϩϩH). Found
247.1549.
7-Bromo-2,3-dihydro-2-phenylbenzofuran 17a. By the
general procedure, treatment of the 7-(20-hydroxy-20-
phenylethyl)-1-aminobenzotriazole 10a (50 mg, 0.2 mmol)
with NBS gave the 2-phenyl-2, 3-dihydrobenzofuran 17a
(21.5 mg, 41%) as a colourless oil, nmax/cmϪ1 2980, 2914,
1624, 1480, 1119 and 970, dH (400) 3.10 (1H, dd, Jˆ13.0
and 8.3 Hz, 3-Ha), 3.44 (1H, dd, Jˆ13.0 and 7.5 Hz, 3-Hb),
4.98 (1H, dd, Jˆ8.3 and 7.5 Hz, 2-H), 7.05 (1H, dd, Jˆ7.6
and 7.6 Hz, 5-H), 7.21–7.49 (6H, m, Ph and 6-H) and 7.46
(1H, dd, Jˆ7.6 and 1.8 Hz, 4-H), dC (100) 48.0 (3-CH2),
73.3 (2-CH), 125.8 (CH), 126.1 (C), 127.9, 128.1, 128.4,
128.6, 128.9 (all CH), 130.8 (C), 131.0, 132.3 (both CH),
140.7 and 143.8 (both C), m/z [EI] 276 (Mϩ (81Br), 7%), 274
(6), 258 (48), 256 (47), 194 (12), 177 (26), 176 (28), 165
(21), 163 (21), 151 (28), 149 (25), 105 (100), 88 (33), 82
(19) and 77 (37). HRMS Calcd for C14H1179BrO: 273.9994
(Mϩ). Found 273.9992.
7-(30-Hydroxypentyl)-1H-benzotriazol-1-amine 14a. By
the general procedure, deprotection of the epoxybutane-
derived N-Boc aminobenzotriazole (100 mg) gave the
amine 14a (52 mg, 75%) as a colourless gum, nmax/cmϪ1
3360, 2930, 1647, 1470, 1118, 985, 913, 882 and 864, dH
(250) 0.91 (3H, t, Jˆ7.5 Hz, 50-Me), 1.43–1.57 (2H, m,
40-CH2), 1.73–1.96 (2H, m, 20-CH2), 3.35 (2H, t,
Jˆ7.5 Hz, 10-CH2), 3.49–3.62 (1H, m, 30-H), 6.30 (2H, s,
NH2), 7.21–7.38 (2H, m, 5- and 6-H) and 7.70–7.80 (1H, m,
4-H), dC (100) 9.8 (50-Me), 26.1, 30.1, 38.5 (all CH2), 72.0
(30-CH), 117.0, 124.4 (both CH), 126.6 (C), 127.8 (CH),
130.3 and 144.7 (both C), m/z [FAB] 221 (MϩϩH, 100%)
and 207 (25). HRMS Calcd for C11H17N4O: 221.1402
(MϩϩH). Found 221.1403.
7-Bromo-2,3-dihydro-2-pentylbenzofuran 17b. Follow-
ing the general procedure, treatment of the 7-(20-hydroxy-
heptyl)-1-aminobenzotriazole 10b (51 mg, 0.2 mmol) with
NBS gave the 2-pentyl-2,3-dihydrobenzofuran 17b (25 mg,
45%) as a colourless oil, nmax/cmϪ1 2930, 2856, 1642, 1580,
1459, 1122 and 1009, dH (250) 0.90 (3H, t, Jˆ6.8 Hz,
50-Me), 1.29–1.45 (4H, m, 2×CH2), 1.48–1.62 (4H, m,
2×CH2), 2.81 (1H, dd, Jˆ13.7 and 8.8 Hz, 3-Ha), 3.11
(1H, dd, Jˆ13.7 and 8.9 Hz, 3-Hb), 3.83–4.01 (1H, m,
2-H), 7.12 (1H, dd, Jˆ7.7 and 7.7 Hz, 5-H), 7.22 (1H, dd,
Jˆ7.7 and 1.7 Hz, 6(4)-H) and 7.52 (1H, dd, Jˆ7.7 and
1.7 Hz, 4(6)-H), dC (100) 14.1 (50-Me), 22.7, 25.4, 31.9,
37.4, 45.4 (all CH2), 71.1 (2-CH), 126.0, 127.0 (both C),
128.2, 130.4, 132.1 (all CH) and 141.4 (C), m/z [EI] 270
(Mϩ(81Br), 61%), 268 (Mϩ(79Br), 64%), 200 (63), 198 (66),
187 (97), 185 (100), 172 (51), 170 (52), 132 (87), 118 (61),
105 (25), 91 (47), 90 (31), 89 (50), 83 (91) and 77 (38).
HRMS Calcd for C13H1779BrO: 268.0463 (Mϩ). Found
268.0458.
(S)-(ϩ)-7-(30-Hydroxybutyl)-1H-benzotriazol-1-amine
14b. Deprotection of the N-Boc aminobenzotriazole
(200 mg) derived from (S)-propylene oxide by the general
procedure gave the amine 14b (94 mg, 70%) as a colourless
gum, [a]2D5 ϩ9.9 (c 1.9, CH2Cl2), nmax/cmϪ1 3367, 2928,
2854, 1635, 1457, 1121, 950 and 903, dH (250) 1.24 (3H,
d, Jˆ4.2 Hz, 40-Me), 1.74–1.89 (2H, m, 20-CH2), 3.21 (2H,
t, Jˆ7.6 Hz, 10-CH2), 3.75–3.83 (1H, m, 30-H), 5.75 (2H, br
s, NH2), 7.12–7.22 (2H, m, 5- and 6-H) and 7.61–7.75 (1H,
m, 4-H), dC (67.5) 23.3 (40-Me), 26.4 (20-CH2), 40.8
(10-CH2), 66.9 (30-CH), 117.1, 124.5 (both CH), 126.5
(C), 128.1 (CH), 130.4 and 144.1 (both C), m/z [FAB] 207
(MϩϩH, 100%), 191 (8) and 189 (11). HRMS Calcd for
C10H15N4O: 207.1246 (MϩϩH). Found 207.1241.
(R)-(ϩ)-7-(30-Hydroxy-30-phenylpropyl)-1H-benzo-
triazol-1-amine 14c. Deprotection of the N-Boc amino-
benzotriazole (129 mg) derived from (S)-styrene oxide by
the general procedure gave the amine 14c (38 mg, 40%) as a
colourless gum, [a]2D5 ϩ66.7 (c 0.65, CH2Cl2), nmax/cmϪ1
1,2-Dibromo-3-(20-hydroxy-20-methylpropyl)benzene
19a. Following the general procedure, treatment of the
1-aminobenzotriazole 11 (48 mg, 0.27 mmol) with NBS

1020
M. A. Birkett et al. / Tetrahedron 56 (2000) 1013–1023
gave the 1,2-dibromobenzene 19a (36 mg, 52%) as a pale
yellow oil [Found: C, 40.3; H, 4.4. C10H12Br2O requires C,
39.2; H, 4.0%], nmax/cmϪ1 3592, 3400–3200, 2929, 2853,
1580, 1462, 1410, 1110, 970 and 899, dH (250) 1.29 (6H, s,
2×Me), 1.51 (1H, br res, OH), 3.13 (2H, s, 10-CH2), 7.12
(1H, dd, Jˆ7.8 and 7.8 Hz, 5-H), 7.31 (1H, dd, Jˆ7.8 and
1.7 Hz, 6-H) and 7.53 (1H, dd, Jˆ7.8 and 1.7 Hz, 4-H), dC
(100) 29.7 (2×Me), 49.6 (10-CH2), 72.0 (20-C), 126.2, 126.7
(both C), 127.7, 131.0, 132.2 and 140.7 (C), (all CH), m/z
2,3-Dihydro-2-pentylbenzofuran 22. To a stirred suspen-
sion of lead(IV) acetate (487 mg, 1.1 mmol) in dichloro-
methane (10 ml) at ambient temperature was added
dropwise via syringe a solution of the 7-(20-hydroxy-
heptyl)-1-aminobenzotriazole 10b (248 mg, 1.0 mmol) in
dichloromethane (2 ml), resulting in vigorous effervescence
and a mild exotherm. After 1 h, the mixture was filtered
through celite and the solid washed with ether (2×30 ml).
The combined filtrates were evaporated and the residues
separated by CC [ether–petrol, 1:9] to give the dihydrofuran
22 (135 mg, 71%) as a colourless oil, nmax/cmϪ1 2928, 2854,
1650, 1463, 1100 and 1009, dH (250) 0.91 (3H, t, Jˆ6.8 Hz,
50-Me), 1.33–1.71 (7H, m), 1.77–1.86 (1H, m, 10-Ha), 2.84
(1H, dd, Jˆ15.5 and 7.9 Hz, 3-Ha), 3.26 (1H, dd, Jˆ15.5
and 8.9 Hz, 3-Hb), 4.74–4.79 (1H, m, 2-H), 6.75 (1H, dd,
Jˆ7.6 and 1.0 Hz, 4-H), 6.81 (1H, dd, Jˆ7.6 and 7.6 Hz,
5-H), 7.10 (1H, dd, Jˆ7.6 and 7.6 Hz, 6-H) and 7.14 (1H,
dd, Jˆ7.6 and 1.0 Hz, 7-H), dC (100) 14.1 (50-Me), 22.7
25.2, 31.6, 35.6, 36.2 (all CH2), 83.5 (2-CH), 109.3,
120.1, 125.0 (all CH), 127.1 (C), 128.0 (CH) and 159.7
(C), m/z [EI] 190 (Mϩ, 31%), 133 (54), 120 (44), 119
(51), 108 (14), 107 (100), 91 (22) and 77 (10). HRMS
Calcd for C13H18O: 190.1358 (Mϩ). Found 190.1344.
81
[EI] 295 (Mϩ-Me, (2× Br), 3%), 293 (6), 291 (3), 252 (11),
250 (23), 248 (12; MϩϪMe2CO; Found: 247.8842.
C7H679Br2 requires M, 247.8837), 130 (9), 89 (14) and 59
(100). HRMS Calcd for C9H979Br2O: 290.9021 (MϩϪMe).
Found 290.8984.
7-Bromo-2,3-dihydro-2,2-dimethylbenzofuran 20. Follow-
ing the general procedure, except that 1-pentene (420 mg,
6 mmol) was added prior to the aminobenzotriazole 11
(50 mg, 0.2 mmol), reaction between the latter and NBS
gave the dimethyl-2,3-dihydrobenzofuran 20 (25 mg, 45%)
as a colourless oil, nmax/cmϪ1 2930, 2855, 1603, 1582, 1462,
1372, 1329, 1294, 1144, 1122, 1101, 971 and 904, dH (250)
1.45 (6H, s, 2×Me), 3.03 (2H, s, 3-CH2), 6.70 (1H, dd,
Jˆ7.7 and 7.7 Hz, 5-H), 7.06 (1H, dd, Jˆ7.7 and 1.3 Hz,
6-H) and 7.27 (1H, dd, Jˆ7.7 and 1.3 Hz, 4-H), dC (67.5)
28.3 (2×Me), 43.8 (3-CH2), 87.8 (2-C), 102.8, 112.7 (both
C), 121.3, 124.1 (both CH), 128.6 (C) and 131.1 (CH), m/z
[EI] 228 (Mϩ(81Br), 100%), 226 (98), 213 (9), 211 (10), 147
(67), 120 (15) and 104 (20). HRMS Calcd for C10H1179BrO:
225.9994 (Mϩ). Found 225.9991.
2,3-Dihydro-2,2-dimethylbenzofuran 23. By the fore-
going method, oxidation of the 1-aminobenzotriazole 11
(21 mg, 0.12 mmol), derived from acetone, using lead(IV)
acetate gave the dihydrobenzofuran 2314 (11 mg, 75%) as a
colourless oil, nmax/cmϪ1 2928, 2854, 1590, 1459, 1100 and
1009, dH (250) 1.48 (6H, s, 2×Me), 3.01 (2H, s, 3-CH2),
6.98 (1H, dd, Jˆ7.6 and 1.0 Hz, 4-H), 7.07 (1H, dd, Jˆ7.6
and 7.6 Hz, 5-H) and 7.33–7.40 (2H, m, 6- and 7-H), m/z
[EI] 148 (Mϩ, 4%), 147 (16), 133 (10), 120 (60), 107 (25),
105 (18), 97 (23), 95 (22), 93 (30), 83 (40), 77 (21) and 69
(100). HRMS Calcd for C10H12O: 148.0888 (Mϩ). Found
148.0863.
1,2-Dibromo-3-[(1-hydroxycyclohex-1-yl)methyl]benzene
19b. By the foregoing procedure, with the addition of
30 equiv. of 1-pentene, reaction between the cyclohexyl-
methyl-l-aminobenzotriazole 12 (35 mg) gave the 1,2-
dibromobenzene 19b (25 mg, 51%), nmax/cmϪ1 3591,
2933, 2854, 1579, 1450, 1410, 1127, 1096, 979, 956, 905
and 806, dH (250) 1.35–1.65 (10H, 5×CH2), 3.07 (2H, s,
10-CH2), 7.08 (1H, dd, Jˆ7.7 and 7.7 Hz, 5-H), 7.27 (1H,
dd, Jˆ7.7 and 1.6 Hz, 6-H) and 7.49 (1H, dd, Jˆ7.7 and
1.6 Hz, 4-H), dC (100) 21.8 (2×CH2), 25.6 (CH2), 37.4
(2×CH2), 49.6 (10-CH2), 72.5 (100-C), 126.6 (C), 127.6
(CH), 128.0 (C), 131.0, 132.0 (both CH) and 139.3 (C),
Reactions of 1-aminobenzotriazoles with N-iodosuccin-
imide: general procedure
To a solution of N-iodosuccinimide (NIS; 2.5 equiv.) in
dichloromethane (10 ml mmolϪ1) stirred in the dark at
ambient temperature was added dropwise, via syringe,
a solution of the 1-aminobenzotriazole (1 equiv.) in
dichloromethane (1 ml mmolϪ1) which resulted in vigorous
effervescence, a mild exotherm and the development of a
purple colouration. After 1 h, the mixture was washed with
saturated aqueous sodium thiosulphate (10 ml mmolϪ1),
water (10 ml mmolϪ1) and brine (10 ml mmolϪ1), then
dried, filtered and evaporated. The residue was purified
using CC [ether–petrol, 1:9].
81
m/z [FAB] 333 (MϩϪH2O, (2× Br), 14%), 331 (30), 329
(13), 267 (20), 250 (30), 249 (42) and 248 (25). HRMS
Calcd for C13H1579,81Br2: 331.0725 (MϩϪH2O). Found
331.0719.
8-Bromo-3,4-dihydro-2-ethyl-2H-1-benzopyran 21. By
the general procedure, reaction between the 30-hydroxy-
pentyl-1-aminobenzotriazole 14a (45 mg, 0.2 mmol) and
NBS gave the 8-bromo-benzopyran 21 (26 mg, 53%),
nmax/cmϪ1 2929, 1602, 1458, 1409, 1097, 981 and 908, dH
(250) 0.97 (3H, t, Jˆ7.5 Hz, 20-Me), 1.46–1.83 (4H, m, 10-
and 3-CH2), 2.84–3.02 (2H, m, 4-CH2), 3.55–3.64 (1H, m,
2-H), 7.09 (1H, dd, Jˆ7.7 and 7.7 Hz, 6-H), 7.20 (1H, dd,
Jˆ7.7 and 1.7 Hz, 7-H) and 7.48 (1H, dd, Jˆ7.7 and 1.7 Hz,
5-H), dC (100) 10.0 (20-Me), 30.4, 34.4, 38.9 (all CH2), 72.3
(2-CH), 126.1, 126.7 (both C), 128.4, 129.0, 131.6 (all CH)
and 144.6 (C), m/z [EI] 242 (Mϩ, (81Br), 11%), 240 (15), 211
(72), 209 (67), 185 (24), 183 (25), 171 (15), 169 (15), 167
(25), 102 (15) and 77 (15). HRMS Calcd for C11H1379BrO:
240.0149 (Mϩ). Found 240.0142.
2,3-Dihydro-7-iodo-2-phenylbenzofuran 24a. Following
the general procedure, treatment of the 1-aminobenzo-
triazole 10a (96 mg, 0.39 mmol) with NIS gave the
7-iodo-2,3-dihydrobenzofuran 24a (107 mg, 86%) as a
colourless oil, nmax/cmϪ1 2928, 2854, 1600, 1580, 1491,
1120, 973, 909 and 871, dH (250) 3.31 (1H, dd, Jˆ15.8
and 9.5 Hz, 3-Ha), 3.40 (1H, dd, Jˆ15.7 and 8.0 Hz,
3-Hb), 5.85 (1H, dd, Jˆ9.5 and 8.0 Hz, 2-H), 6.65 (1H,
dd, Jˆ7.7 and 7.7 Hz, 5-H), 7.12 (1H, dd, Jˆ7.7 and
1.1 Hz, 6-H), 7.32–7.44 (5H, m, Ph) and 7.52 (1H, dd,
Jˆ7.7 and 1.1 Hz, 4-H), dC (67.5) 39.8 (3-CH2), 74.1

M. A. Birkett et al. / Tetrahedron 56 (2000) 1013–1023
1021
(7-C), 83.2 (2-CH), 122.5, 124.7 (both CH), 125.6 (2×CH),
127.8 (C), 128.1 (CH), 128.7 (2×CH), 137.0 (CH), 142.9
and 144.1 (both C), m/z [EI] 322 (Mϩ, 100%), 244 (5), 194
(20), 165 (27), 152 (11), 89 (10) and 77 (5). HRMS Calcd
for C14H11IO: 321.9857 (Mϩ). Found 321.9844.
27.1, 28.3 (all CH2), 78.5 (2-CH), 85.7 (8-C), 121.4 (CH),
123.1 (C), 129.6, 136.9 (both CH) and 153.1 (C), m/z [EI]
288 (Mϩ, 69%), 259 (8), 233 (100), 132 (28), 105 (19) and
77 (14). HRMS Calcd for C11H13IO: 288.0013 (Mϩ). Found
288.0011.
2,3-Dihydro-7-iodo-2-pentylbenzofuran 24b. By the
general procedure, reaction between NIS and the 1-amino-
benzotriazole 10b (30 mg, 0.12 mmol) gave the 7-iodo-2,3-
dihydrobenzofuran 24b (35 mg, 92%) as a colourless oil,
nmax/cmϪ1 2981, 2858, 1599, 1579, 1457, 1117, 984, 897
and 869, dH (250) 0.94 (3H, t, Jˆ6.6 Hz, 50-Me), 1.10–1.70
(7H, m), 1.81–1.90 (1H, m, 10-Ha), 2.97 (1H, dd, Jˆ15.5
and 7.6 Hz, 3-Ha), 3.40 (1H, dd, Jˆ15.5 and 8.8 Hz, 3-Hb),
4.75–4.90 (1H, m, 2-H), 6.58 (1H, dd, Jˆ7.8 and 7.8 Hz,
5-H), 7.10 (1H, d, Jˆ7.8 Hz, 6-H) and 7.45 (1H, d,
Jˆ7.8 Hz, 4-H), dC (100) 14.0 (50-Me), 22.5, 24.6, 31.7,
35.8, 36.6 (all CH2), 73.6 (7-C), 83.3 (2-CH), 121.9, 124.8
(both CH), 127.8 (C), 136.6 (CH) and 148.0 (C), m/z [EI]
316 (Mϩ, 89%), 246 (50), 233 (100), 132 (58), 118 (44), 105
(28) and 77 (18). HRMS Calcd for C13H17IO: 316.0326
(Mϩ). Found 316.0302.
(S)-(Ϫ)-3,4-Dihydro-8-iodo-2-methyl-2H-1-benzopyran
27b. By the general procedure, reaction between NIS and
the aminobenzotriazole 14b (102 mg, 0.49 mmol), derived
from (S)-propylene oxide, gave the (S)-2-methylpyran 27b
(103 mg, 76%) as a colourless oil, [a]2D5 Ϫ44.1 (c 0.32,
CH2Cl2), nmax/cmϪ1 2935, 2848, 1595, 1562, 1461, 1121,
1103, 1076, 949, 940, 906 and 848, dH (250) 1.46 (3H, d,
Jˆ6.3 Hz, 10-Me), 1.74 (1H, dddd, Jˆ13.6, 11.1, 9.9 and
5.7 Hz, 3-Ha), 2.03 (1H, dddd, Jˆ13.6, 6.1, 3.5 and 2.3 Hz,
3-Hb), 2.72 (1H, ddd, Jˆ16.5, 5.7 and 3.5 Hz, 4-Ha), 2.85
(1H, ddd, Jˆ16.5, 11.1 and 6.1 Hz, 4-Hb), 4.24 (1H, dqd,
Jˆ9.8, 6.3 and 2.3 Hz, 2-H), 6.58 (1H, dd, Jˆ7.6 and
7.6 Hz, 5-H), 7.02 (1H, dd, Jˆ7.6 and 1.0 Hz, 6-H) and
7.58 (1H, dd, Jˆ7.6 and 1.0 Hz, 4-H), dC (67.5) 21.1
(10-Me), 25.0 (3-CH2), 29.1 (4-CH2), 73.5 (2-CH), 88.3
(8-C), 121.5 (CH), 122.1 (C), 129.7, 137.0 (both CH) and
143.4 (C), m/z [EI] 274 (Mϩ, 100%), 233 (56), 232 (16), 132
(27), 131 (40), 118 (10), 105 (19), 83 (14) and 77 (13).
HRMS Calcd for C10H11IO: 273.9857 (Mϩ). Found
273.9861.
2,3-Dihydro-2,2-dimethyl-7-iodobenzofuran 25. By the
general procedure, reaction between NIS and the 1-amino-
benzotriazole 11 (100 mg, 0.49 mmol) gave the 7-iodo-2,3-
dihydrobenzofuran 25 (126 mg, 95%) as a colourless oil,
nmax/cmϪ1 2929, 2854, 1599, 1577, 1459, 1142, 1099,
970, 890 and 871, dH (250) 1.44 (6H, s, 2×Me), 3.04 (2H,
s, 3-CH2), 6.49 (1H, dd, Jˆ7.5 and 7.5 Hz, 5-H), 7.00 (1H,
dd, Jˆ7.5 and 1.0 Hz, 6-H) and 7.38 (1H, dd, J 4-H), dC
(67.5) 28.2 (2×Me), 44.1 (3-CH2), 74.1 (7-C), 88.1 (2-C),
121.7, 124.9 (both CH), 125.7 (C), 136.7 (CH) and 144.1
(C), m/z [EI] 274 (Mϩ, 100%), 259 (16), 147 (10), 132 (72),
131 (32), 119 (23), 91 (15), 89 (17) and 77 (17). HRMS
Calcd for C10H11IO: 273.9857 (Mϩ). Found 273.9830.
(R)-(ϩ)-3,4-Dihydro-8-iodo-2-phenyl-2H-1-benzopyran
27c. By the general procedure, reaction between NIS and
the aminobenzotriazole 14c (33 mg, 0.12 mmol), derived
from (S)-styrene oxide, gave the (S)-2-phenylpyran 27c
(32 mg, 77%) as a colourless oil, [a]2D5 ϩ25.6 (c 0.36,
CH2Cl2), nmax/cmϪ1 2926, 2854, 1595, 1564, 1494, 1450,
1128, 1092, 997 and 904, dH (250) 1.95–2.20 (1H, m, 3-Ha),
2.26–2.40 (1H, m, 3-Hb), 2.75 (1H, ddd, Jˆ16.3, 4.4 and
4.4 Hz, 4-Ha), 3.00 (1H, ddd, Jˆ16.3, 10.8 and 5.7 Hz,
4-Hb), 5.24 (1H, dd, Jˆ9.5 and 2.5 Hz, 2-H), 6.64 (1H,
dd, Jˆ7.6 and 7.6 Hz, 6-H), 7.05 (1H, d, Jˆ7.6 Hz, 7-H),
7.24–7.58 (5H, m, Ph) and 7.64 (1H, d, Jˆ7.6 Hz, 5-H), dC
(67.5) 25.6 (3-CH2), 29.1 (4-CH2), 77.8 (2-CH), 88.2 (8-C),
122.7 (C), 125.5 (2×CH), 126.5 (CH), 128.5 (2×CH), 129.3,
136.4 (both CH), 142.7 and 143.7 (both C), m/z [EI] 336
(Mϩ, 100%), 245 (10), 244 (10), 232 (20), 209 (29), 118
(31), 105 (84), 104 (49), 91 (38) and 77 (48). HRMS Calcd
for C15H13IO: 336.0013 (Mϩ). Found 336.0016.
7-Iodo-spiro[benzofuran-2(3H)]-10-cyclohexane 26. By
the general procedure, reaction between NIS and the
cyclohexanone-derived aminobenzotriazole 12 (35 mg,
0.14 mmol) gave the spiro derivative 26 (37 mg, 82%) as
a colourless oil, nmax/cmϪ1 2940, 2856, 1598, 1577, 1457,
1126, 1110, 946, 916 and 860, dH (250) 1.27–1.91 (10H,
m), 3.08 2H, s, 3-CH2), 6.59 (1H, dd, Jˆ7.7 and 7.7 Hz,
5-H), 7.07 (1H, dd, Jˆ7.7 and 1.1 Hz, 6-H) and 7.44 (1H,
dd, Jˆ7.7 and 1.1 Hz, 4-H), dC (67.5) 22.9, 23.0, 25.1, 36.9,
37.0, 42.2 (all CH2), 76.5 (7-C), 88.3 (2-C), 121.5, 125.0
(both CH), 126.8 (C), 136.6 (CH) and 138.2 (C), m/z [EI]
314 (Mϩ, 75%), 246 (10), 234 (16), 233 (66), 105 (18), 81
(100), 80 (34) and 77 (18). HRMS Calcd for C13H15IO:
314.0169 (Mϩ). Found 314.0161.
2,3-Dihydro-7-(2-furyl)-2pentylbenzofuran 28. To a solu-
tion of the 7-iodo-dihydrobenzofuran 24b (115 mg,
0.35 mmol), in dry tetrahydrofuran (10 ml) was added
dichloro-bis-triphenylphosphinepalladium(0) (8 mg) and
(2-furyl)tributylstannane (140 mg, 0.40 mmol). The result-
ing solution was refluxed for 14 h then cooled and evapo-
rated. The residue was dissolved in ether (50 ml) and filtered
through alumina. The solid was washed with ether
(2×50 ml) and the combined filtrates evaporated. CC of
the residue [petrol–EtOAc, 99:1] separated the furyl-
dihydrobenzofuran 28 (54 mg, 48%) as a colourless oil,
nmax/cmϪ1 2931, 2858, 1598, 1464, 1156, 1014, 987, 908,
886 and 870, dH (250) 0.95 (3H, t, Jˆ6.9 Hz, 50Me), 1.36–
1.78 (7H, m), 1.82–1.96 (1H, m, 10-Hb), 2.88 (1H, dd,
Jˆ15.3 and 7.8 Hz, 3-Ha), 3.32 (1H, dd, Jˆ15.3 and
8.9 Hz, 3-Hb), 4.84–4.96 (1H, m, 2-H), 6.50 (1H, dd,
Jˆ3.2 and 1.8 Hz, furyl 4-H), 6.88 (1H, dd, Jˆ7.5 and
3,4-Dihydro-2-ethyl-8-iodo-2H-1-benzopyran 27a. By
the general procedure, reaction between NIS and the
1-aminobenzotriazole 14a (83 mg, 0.38 mmol), derived
from 1,2-epoxybutane, gave the pyran 27a (65 mg, 63%)
as a colourless oil, nmax/cmϪ1 2939, 2848, 1594, 1562,
1459, 1119, 979, 944, 904, 863 and 837, dH (250) 1.14
(3H, t, Jˆ7.4 Hz, 20-Me), 1.58–1.88 (3H, m, 10-CH2 and
3-Ha), 1.96–2.06 (1H, m, 3-Hb), 2.68–2.93 (2H, m, 4-CH2),
3.96–4.06 (1H, m, 2-H), 6.58 (1H, dd, Jˆ7.7 and 7.7 Hz,
6-H), 7.02 (1H, dd, Jˆ7.7 and 0.6 Hz, 7-H) and 7.57 (1H,
dd, Jˆ7.7 and 0.6 Hz, 5-H), dC (67.5) 9.9 (20-Me), 25.0,

1022
M. A. Birkett et al. / Tetrahedron 56 (2000) 1013–1023
7.5 Hz, 5-H), 6.90 (1H, d, Jˆ3.2 Hz, furyl 3-H), 7.06 (1H,
dd, Jˆ7.5 and 0.5 Hz, 4-H), 7.45 (1H, d, Jˆ1.8 Hz, furyl
5-H) and 7.58 (1H, dd, Jˆ7.5 and 0.5 Hz, 6-H), dC (67.5)
15.0 (50-Me), 23.5, 26.3, 32.1, 36.4, 37.2 (all CH2), 84.9
(2-CH), 109.5, 112.6 (both CH), 115.2 (C), 121.2, 123.9,
124.3 (all CH), 128.5 (C), 142.0 (CH), 152.2 and 156.1
(both C), m/z [EI] 256 (Mϩ, 100%), 199 (32), 186 (15),
173 (87), 172 (30), 157 (11), 144 (13), 128 (10) and 115
(15). HRMS Calcd for C17H20O2: 256.1463 (Mϩ). Found
256.1455.
5-H), 6.96 (1H, dd, Jˆ7.5 and 1.0 Hz, 6-H) and 7.28 (1H,
dd, Jˆ7.5 and 1.0 Hz, 4-H), dC (67.5) 9.8, 13.7 (both Me),
19.5, 21.9, 24.8, 26.8, 28.3, 30.9 (all CH2), 77.7 (2-CH),
93.2, 112.4 (10- and 2-C), 119.3 (CH), 121.5 (C), 128.9,
131.6 (both CH) and 153.3 (C), m/z [EI] 242 (Mϩ, 100%),
213 (16), 212 (16), 199 (18), 187 (93), 171 (18), 157 (20),
145 (38), 144 (23), 115 (29) and 113 (25). HRMS Calcd for
C17H22O: 242.1671 (Mϩ). Found 242.1659.
Methyl (E)-3-(2,3-dihydro-2,2-dimethyl-7-benzofuranyl)-
2-propenoate 32. To a solution of palladium(II) acetate
(1 mg) and triphenylphosphine (4 mg) in dimethylforma-
mide (5 ml) was added the 7-iododihydrobenzofuran 27a
(45 mg, 0.16 mmol), anhydrous sodium acetate (15 mg,
0.18 mmol) and methyl acrylate (18 mg, 0.18 mmol). The
resulting solution was stirred and heated at 120ЊC for 20 h
then cooled, diluted with water (5 ml) and extracted with
petrol (3×10 ml). The combined extracts were washed with
water (2×3 ml) then dried and evaporated. CC [petrol–
EtOAc, 99:1] of the residue separated the unsaturated
ester 32 (25 mg, 65%) as a pale yellow oil, nmax/cmϪ1
2951, 1704, 1630, 1606, 1450, 1322, 1294, 1174, 1137,
988 and 879, dH (250) 1.52 (6H, s, 2×20-Me), 3.02 (2H, s,
30-CH2), 3.81 (3H, s, OMe), 6.71 (1H, d, Jˆ16.2 Hz, 2-H),
6.83 (1H, 1H, dd, Jˆ7.6 and 7.6 Hz, 50-H), 7.14 (1H, dd,
Jˆ7.6 and 1.0 Hz, 60-H), 7.19 (1H, dd, Jˆ7.6 and 1.0 Hz,
40-H) and 7.70 (1H, d, Jˆ16.2 Hz, 3-H), dC (67.5) 28.5
(2×20-Me), 42.5 (30-CH2), 51.6 (OMe), 88.0 (20-C), 117.3
(C), 118.9, 120.2, 126.8 (all CH), 128.2 (C), 128.9 (CH),
130.4 (C), 141.2 (CH) and 168.3 (CO), m/z [EI] 232 (Mϩ,
100%), 200 (23), 199 (13), 185 (9), 113 (10), 97 (8) and 85
(12). HRMS Calcd For C14H16O3: 232.1099 (Mϩ). Found
232.1085.
2,3-Dihydro-7-ethenyl-2-pentylbenzofuran 29. By the
foregoing method, reaction between the 7-iodo-dihydro-
benzofuran 24b (87 mg, 0.33 mmol) and tributylvinyl-
stannane (120 mg, 0.38 mmol) gave the 7-ethenyl
derivative 29 (60 mg, 87%) as a colourless oil, nmax/cmϪ1
2932, 2858, 1624, 1598, 1570, 1453, 995, 912 and 863, dH
(250) 0.93 (3H, t, Jˆ6.9 Hz, 50-Me), 1.34–1.92 (8H, m),
2.83 (1H, dd, Jˆ15.4 and 8.8 Hz, 3-Ha), 3.25 (1H, dd,
Jˆ15.4 and 8.8 Hz, 3-Hb), 4.76–4.88 (1H, m, 2-H), 5.28
(1H, dd, Jˆ11.3 and 1.6 Hz, :CHc), 5.92 (1H, dd, Jˆ17.6
and 1.6 Hz, :CHt), 6.74 (1H, dd, Jˆ17.6 and 11.3 Hz, :CH),
6.78 (1H, dd, Jˆ7.5 and 7.5 Hz, 5-H), 7.04 (1H, dd, Jˆ7.5
and 0.5 Hz, 6-H) and 7.13 (1H, dd, Jˆ7.5 and 0.5 Hz, 4-H),
dC (100) 14.0 (50-Me), 22.6, 25.2, 31.7, 35.3, 36.2 (all CH2),
83.6 (2-CH), 115.3 (:CH2), 120.0 (CH), 120.2 (C), 123.9,
126.1 (both CH), 127.5 (C), 132.2 (CH) and 157.3 (C), m/z
[EI] 216 (Mϩ, 77%), 159 (41), 145 (24), 133 (100), 131 (60),
117 (22), 115 (23), 91 (9) and 77 (7). HRMS Calcd for
C15H20O: 216.1514 (Mϩ). Found 216.1503.
2,3-Dihydro-2,2-dimethyl-7-(hexyn-1-yl)benzofuran 30.
To a solution of the 2,2-dimethyl-7-iododihydorbenzofuran
25 (45 mg, 0.14 mmol) in diethylamine (3 ml) was added
copper(I) iodide (7 mg, 4 mol%), dichloro-bis-triphenyl-
phosphinepalladium(0) (15 mg, 1 mol%) and 1-hexyne
(14 mg, 0.17 mmol). The resulting mixture was stirred and
gently refluxed for 16 h then cooled and evaporated. CC
[petrol] separated the 7-hexynly-dihydrobenzofuran 30
(26 mg, 80%) as a pale yellow oil, nmax/cmϪ1 2932, 2858,
2216, 1592, 1443, 1167, 1137, 969 and 881, dH (250) 0.91
(3H, t, Jˆ7.1 Hz, 60-Me), 1.46–1.66 (4H, m, 40- and
50-CH2), 1.50 (6H, s, 2×2-Me), 2.45 (2H, t, Jˆ7.0 Hz,
30-CH2), 2.99 (2H, s, 3-CH2), 6.72 (1H, dd, Jˆ7.6 and
7.6 Hz, 5-H), 7.30 (1H, dd, Jˆ7.6 and 1.0 Hz, 6-H) and
7.14 (1H, dd, Jˆ7.6 and 1.0 Hz, 4-H), dC (67.5) 13.7
(60-Me), 19.5, 22.0 (40- and 50-CH2), 28.2 (2×2-Me), 30.9,
42.9 (3- and 30-CH2), 87.1 (2-C), 93.8, 106.0 (10- and 20-C),
119.6, 124.5 (both CH), 127.1 (C), 131.6 (CH) and 158.1
(C), m/z [EI] 228 (Mϩ, 100%), 213 (28), 199 (13), 185 (64),
171 (24), 157 (13), 145 (19), 128 (11) and 115 (17). HRMS
Calcd for C16H20O:228.1514 (Mϩ). Found 228.1527.
1,2-Diiodobenzene 33. By the general procedure for
benzyne formation using NIS, reaction between 1-amino-
benzotriazole 1 (150 mg, 1.2 mmol) and NIS (630 mg,
2.8 mmol) gave the diiodide 333,15 (199 mg, 54%) as a
light-sensitive oil which displayed spectral data identical
to an authentic sample (Aldrich).
1,4-Dihydro-1,4-epoxynaphthalene 34. By the general
procedure for benzyne generation using NIS, but with
freshly distilled furan as the solvent in place of dichloro-
methane, reaction between 1-aminobenzotriazole
1
(100 mg, 0.68 mmol) and NIS (380 mg, 1.69 mmol) gave
the 1,4-epoxynaphthalene 34 (48 mg, 49%) as an off-white
solid, mp 52–53ЊC [lit.21 mp 53–55ЊC]. An authentic
sample (Aldrich) showed mp 54–55ЊC (mixed mp
52–53ЊC) together with identical spectroscopic and
chromatographic characteristics.
1-Iodo-2-(30-iodopropyloxy)benzene 36a. By the general
procedure for benzyne generation using NIS, but with
freshly distilled oxetane as the solvent in place of dichloro-
methane, reaction between 1-aminobenzotriazole 1 (50 mg,
0.37 mmol) and NIS (210 mg, 0.93 mmol) gave the diiodide
36a (43 mg, 30%) as a yellow gum, nmax/cmϪ1 3002, 2930,
2877, 1582, 1478, 1464, 1440, 1179, 1162, 1120, 1054,
1018, 914 and 651, dH (250) 2.20–2.31 (2H, m, 20-CH2),
3.42 (2H, t, Jˆ6.7 Hz, 30-CH2), 4.10 (2H, t, Jˆ5.6 Hz,
10-CH2), 6.74 (1H, dd, Jˆ7.6 and 7.6 Hz, 5-H), 6.85 (1H,
dd, Jˆ7.6 and 1.1 Hz, 6-H), 7.31 (1H, dd, Jˆ7.6 and 7.6 Hz,
3,4-Dihydro-2-ethyl-8-(hexyn-1-yl)-2H-1-benzopyran
31. By the foregoing method, Sonogashira coupling
between the 7-iodo-dihydrobenzofuran 27a (101 mg,
0.35 mmol) and 1-hexyne (38 mg, 0.47 mmol) gave the
8-hexynylbenzopyran 31 (70 mg, 84%) as a pale yellow
oil, nmax/cmϪ1 2900, 2860, 2226, 1590, 1464, 1140, 908
and 880, dH (250) 0.95 (3H, t, Jˆ7.5 Hz, 60-Me), 1.10
(3H, t, Jˆ7.1 Hz, 2-CH2CH3), 1.45–2.06 (8H, m), 2.48
(2H, t, Jˆ6.7 Hz, 30-CH2), 2.67–2.90 (2H, m, 4-CH2),
3.92–4.03 (1H, m, 2-H), 6.72 (1H, dd, Jˆ7.5 and 7.5 Hz,

M. A. Birkett et al. / Tetrahedron 56 (2000) 1013–1023
1023
1979; Vol. 1, p. 477; Rienecke, M. G. Tetrahedron 1982, 38, 427;
Moody, C. J.; Whitham, G. H. Reactive Intermediates; Oxford
University Press: Oxford, 1992 and references cited therein.
2. Kessar, S. V. In Comprehensive Organic Synthesis, Trost, B. M.,
Fleming, I., Eds.; Pergammon: Oxford, 1991; Vol. 4, p 483.
3. Campbell, C. D.; Rees, C. W.; J. Chem. Soc (C) 1969, 742, 748
and 752; See also Fleet, G. W. J.; Fleming, I. J. Chem. Soc (C),
1969, 1758.
4. For preparations of other substituted aminobenzotriazoles, see,
for example, Hart, H.; Ok, D. J. Org. Chem. 1986, 51, 979; Hart,
H.; Lai, C-Y.; Nurukogu, G. C.; Shamoniken, S. Tetrahedron
1987, 43, 5203; Rigby, J. H.; Holsworth, D. D.; James, K. J. Org.
Chem. 1989, 59, 4019. For applications to the generation of
2,3-dihydronaphthalene and dehydrophenanthrene, see Hales,
R. H.; Bradshaw, J. S.; Pratt, D. R. J. Org. Chem. 1971, 36, 314;
Hales, R. H.; Bradshaw, J. S. J. Org. Chem. 1971, 36, 318; See also
Rees, C. W.; Storr, R. C.; J. Chem. Soc. (C) 1969, 760.
5. Keating, M.; Peck, M. E.; Rees, C. W.; Storr, R. C. J. Chem.
Soc., Perkin Trans. 1 1972, 1315; Graveling, F. Ph.D. thesis,
University of Leicester, 1969.
4-H) and 7.78 (1H, dd, Jˆ7.6 and 1.1 Hz, 3-H), dC (67.5)
4.4 (30-CH2), 32.8 (20-CH2), 68.3 (10-CH2), 84.2 (1-C),
112.2, 122.8, 129.5, 139.4 (all CH) and 153.1 (2-C), m/z
[EI] 388 (Mϩ, 76%), 220 (72), 203 (17), 191 (10), 169
(100), 134 (17), 106 (21), 92 (23) and 76 (21). HRMS
Calcd for C9H10I2O: 387.8825 (Mϩ). Found 387.8778.
1-Iodo-2-(40-iodobutyloxy)benzene 36b. By the general
procedure for benzyne generation using NIS, but with tetra-
hydrofuran as the solvent in place of dichloromethane, reac-
tion between 1-aminobenzotriazole 1 (100 mg, 0.74 mmol)
and NIS (420 mg, 1.86 mmol) gave the diiodide 36b
(104 mg, 35%) as a yellow oil, nmax/cmϪ1 3001, 2945,
2875, 1582, 1455, 1440, 1162, 1121, 1051, 1018, 942, 908
and 650, dH (250) 1.89–2.20 (4H, m, 20- and 30-CH2), 3.30
(2H, t, Jˆ6.3 Hz, 40-CH2), 4.02 (2H, t, Jˆ6.3 Hz, 10-CH2),
6.68 (1H, dd, Jˆ7.7 and 7.7 Hz, 5-H), 6.80 (1H, dd Jˆ7.7
and 1.0 Hz, 6-H), 7.29 (1H, dd, Jˆ7.7 and 7.7 Hz, 4-H) and
7.78 (1H, dd, Jˆ7.7 and 1.0 Hz, 3-H), dC (67.5) 8.0
(40-CH2), 30.3, 30.6 (20- and 30-CH2), 68.3 (10-CH2), 88.2
(1-C), 112.5, 122.8, 129.5, 139.4 (all CH) and 152.1 (2-C),
m/z [EI] 402 (Mϩ, 8%), 220 (49), 203 (10), 183 (100), 155
(10), 106 (7), 93 (10), 92 (10) and 76 (11) [Found: Mϩ,
401.8937. C10H12I2O requires M, 401.8981]. HRMS Calcd
for C10H12I2O: 401.8981 (Mϩ). Found 401.8937.
6. Cadogan, J. I. G.; Thomson, J. B. J. Chem. Soc., Chem.
Commun. 1969, 770.
7. Buente, J. M.; Castedo, L.; Rodriguez de Lera, L.; Saa, J. M.;
Suau, R.; Vidal, M. C. Tetrahedron Lett. 1993, 24, 2298.
8. Knight, D. W.; Little, P. B. Synlett 1998, 1141.
9. For a review of lateral metallation directed by N-Boc groups,
see Clark, R. D.; Jahangir, A. Org. React. 1995, 47, 1.
10. Birkett, M. A.; Giles, R. G.; Knight, D. W.; Mitchell, M. B.
J. Chem. Soc., Perkin Trans. 1 1998, 2301.
11. Masui, Y.; Chino, N.; Sawakibura, S. Bull. Chem. Soc. Jpn.
1980, 53, 464 (and references therein).
12. Lundt, B. F.; Johansen, N. L.; Volund, A.; Markussen, J. Int. J.
Pept. Protein Res. 1978, 12, 258.
13. For preliminary reports on sections of this work, see Birkett,
M. B.; Knight, D. W.; Mitchell, M. B. Tetrahedron Lett. 1993, 34,
6939; Synlett 1994, 253.
1-Iodo-2-(50-iodopentyloxy)benzene 36c. By the general
procedure for benzyne generation using NIS, but with tetra-
hydropyran as the solvent in place of dichloromethane, reac-
tion between 1-aminobenzotriazole 1 (50 mg, 0.37 mmol)
and NIS (210 mg, 0.93 mmol) gave the diiodide 36c
(34 mg, 24%) as a yellow oil, nmax/cmϪ1 3002, 2944,
2876, 1644, 1582, 1479, 1465, 1439, 1162, 1122, 1051,
1018, 980, 908, 865 and 650, dH (250) 2.14–2.51 (6H, m,
20-, 30- and 40-CH2), 3.74 (2H, t, Jˆ7.0 Hz, 50-CH2), 4.52
(2H, t, Jˆ6.1 Hz, 10-CH2), 6.72 (1H, dd, Jˆ7.7 and 7.7 Hz,
6-H), 6.83 (1H, dd, Jˆ7.7 and 7.7 Hz, 5-H), 7.31 (1H, dd,
Jˆ7.7 and 7.7 Hz, 4-H) and 7.77 (1H, dd, Jˆ7.7 and 1.0 Hz,
3-H), dC (67.5) 6.8 (50-CH2), 27.8, 28.0, 33.1 (20-, 30- and
40-CH2), 68.6 (10-CH2), 85.1 (1-C), 112.0, 122.4, 129.4,
139.4 (all CH) and 153.1 (2-C), m/z [EI] 416 (Mϩ, 26%),
220 (100), 197 (65), 162 (12), 151 (33), 113 (27), 106 (8), 92
(10), 76 (9) and 69 (69). HRMS Calcd for C11H14I2O:
415.9134 (Mϩ). Found 415.9117.
14. Kim, K. M.; Kim, H. R.; Ryu, E. J. C. Heterocycles 1993, 36,
497.
15. Houghton, P. G.; Rees, C. W. J. Chem. Res. (S) 1980, 303.
16. Gunther, H. NMR Spectroscopy, 2nd. ed.; George Thieme:
¨
Stuttgart, 1992 (English translation).
17. McKean, D. R.; Parrinello, G.; Renaldo, A. F.; Stille, J. K.
J. Org. Chem. 1987, 52, 422; Stille, J. K. Angew. Chem., Int. Ed.
Engl. 1986, 25, 508; Mitchell, T. N. Synthesis 1992, 803.
18. Sonogashira, K. In Comprehensive Organic Synthesis, Trost,
B. M., Fleming, I. Eds.; Pergamon: Oxford, 1991; Vol. 3, p 521.
19. Heck, R. F. Org. React. 1982, 27, 345; Comprehensive
Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon:
Oxford, 1991; Vol. 4, p. 833; de Meijere, A.; Meyer, F. E.
Angew. Chem., Int. Ed. Engl. 1994, 33, 2379.
20. Suzuki, A. Acc. Chem. Res. 1982, 15, 178; Pure Appl. Chem.
1991, 63, 419.
21. Wittig, G.; Pohmer, L. Angew. Chem. 1956, 67, 348; Chem.
Ber. 1956, 89, 1334.
Acknowledgements
We are most grateful to Dr Robert G. Giles (SB, Tonbridge)
for helpful advice, to the EPSRC Mass Spectrometry
Centre, University of Wales, Swansea, for the provision of
some of the HRMS data and to SB Pharmaceuticals and the
EPSRC for financial support through the CASE Scheme.
22. Wolthuis, E.; Bouma, B.; Mudderman, J.; Sytsma, L. Tetrahedron
Lett. 1970, 407; Pal, R. S.; Bohadia, M. M. Pol. J. Chem. 1978, 52,
1473.
23. Armarego, W. L. F.; Perrin, D. D. Purification of Laboratory
Chemicals; Butterworth Heinemann: Oxford, 1996.
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