Palladium catalysed queuing processes. Part 1: Termolecular cyclization-anion capture employing carbon monoxide as a relay switch and hydride, organotin(IV) or boron reagents

Article abstract of DOI:10.1016/S0040-4020(00)01103-0

The concept of relay switch reactants, which substantially enhance the scope of our cyclization-anion capture methodology, is introduced and exemplified by a wide variety of catalytic cyclization-carbonylation-anion capture processes employing hydride, organostannanes and NaBPh₄ as anion capture agents. Mono- and bis-cyclization processes forming 5- and 6-membered rings are described, all of which employ CO at atmospheric pressure. Cyclocarboformylation processes provide interesting analogues of hydroformylation.

Full text of DOI:10.1016/S0040-4020(00)01103-0

TETRAHEDRON
Pergamon
Tetrahedron 57 (2001) 1347±1359
Palladium catalysed queuing processes. Part 1: Termolecular
cyclization±anion capture employing carbon monoxide as a relay
switch and hydride, organotin(IV) or boron reagents
Stephen Brown,a Stephen Clarkson,b Ronald Grigg,b,p W. Anthony Thomas,b
Visuvanathar Sridharanb and D. M. Wilsonb
aAstraZeneca, PO Box A38, Hudders®eld HD2 1FF, UK
bMolecular Innovation, Diversity and Automated Synthesis (MIDAS) Centre, Leeds University, Leeds LS2 9JT, UK
Received 29 August 2000; revised 10 November 2000; accepted 16 November 2000
AbstractÐThe concept of relay switch reactants, which substantially enhance the scope of our cyclization±anion capture methodology, is
introduced and exempli®ed by a wide variety of catalytic cyclization±carbonylation±anion capture processes employing hydride, organo-
stannanes and NaBPh4 as anion capture agents. Mono- and bis-cyclization processes forming 5- and 6-membered rings are described, all of
which employ CO at atmospheric pressure. Cyclocarboformylation processes provide interesting analogues of hydroformylation. q 2001
Elsevier Science Ltd. All rights reserved.
1. Background
involves hydropalladation or chloropalladation of an
alkyne to generate a vinyl palladium(II) species. In mono-
cyclizations the organopalladium(II) species cyclizes onto
the terminating species. Exchange of halide or tri¯ate with
the anion capture agent followed by reductive elimination
generates the functionalized monocyclized product regio-
speci®cally and regenerates Pd(0).
In current studies we have been developing palladium cata-
lysed cyclization±anion capture cascades that result in the
formation of one or more rings with concomitant intro-
duction of a wide range of functionality by replacing the
b-hydride elimination step of a Heck reaction with a
group or atom transfer.1 This versatile and wide ranging
methodology is summarized in Table 1 and illustrated for
a bis-cyclization sequence with an aryl starter species in
Scheme 1.2
In Scheme 1 the starter species is an aryl halide, the relay
and terminating species are alkenes and the anion capture
agent Y is the organostannane. The ef®cient creation of a
wide range of tetrasubstituted carbon centres is a particu-
larly attractive feature of the cyclization±anion capture
methodology. A further distinctive feature is that cycli-
zations, in the absence of adverse steric constraints, invari-
ably proceed via the exo-mode. Thus Scheme 1 involves
5-exo-trig, rather than 6-endo-trig, cyclizations. Table 1
The starter species is usually employed as the appropriate
halide (Cl, Br, I), tri¯ate or carbonate (allenyl starter) and
the cascade begins with an oxidative addition reaction
between the starter species and Pd(0) to generate an organo-
palladium(II) species. An alternative initiation sequence
Table 1. Potential combinations for polycyclization anion capture processes
Starter species
Alkyl
Relay species (R)
Alkene
Terminating species (T)
Alkene
Y
Anionic [H, OAc, CN, N3,
TsNR,
Aryl
Vinyl
Allyl
Carbamyl
Alkyne
1,2-Diene
1,3-Diene
Alkyne
1,2-Diene
1,3-Diene
SO2Ph CH(CO2R)2]
Neutral (amines, MeOH/CO,
acrylates, allenes)
Organometallics RM
[MˆSn(IV),
Oxycarbonyl
B(III), Zn(II)]
Keywords: cascade reactions; palladium catalysis; cyclization; carboformylation; Stille coupling.
Corresponding author. Tel.: 144-113-233-6501; fax: 144-113-233-6501; e-mail: r.grigg@chem.leeds.ac.uk
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)01103-0

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S. Brown et al. / Tetrahedron 57 (2001) 1347±1359
Scheme 1.
and the foregoing discussion emphasize the versatility of the
general cyclization±anion capture concepts although many
details still remain to be explored. However, as initially
conceived, our cyclization±anion capture methodology
suffers from the constraint that most cascades are two
component processes, i.e. the ring `zipper' precursor and
Y. This constraint would be circumvented if polycomponent
processes could be achieved by extension of the relay phase
with incorporation of both inter- and intramolecular
segments. Thus the potential exists to intersperse the relay
species summarized in Table 1 with additional components
which would offer the potential to switch the cascade
between inter- and intramolecular processes whilst
incorporating valuable additional functionality. Such
components might intercept the cyclization±anion
capture cascade only at the relay phase, only at the
termination phase or participate in both relay and
terminating phases. We have called such components
relay switches because of their ability to extend the
relay phase and their potential to switch the cascade
between intra- and intermolecular processes. Such compo-
nents impart a major increase in the scope of the original
cyclization±anion capture scheme whilst offering tremen-
dous increases in the diversity and complexity of the
products.
can be regarded as queuing for access to the palladium, a
process followed by their incorporation into the cascade. An
important additional feature of relay switch components is
that they may be combined to provide access to poly-
component queuing processes which, in combination with
Table 1 processes and core reactions such as 1,3-cyclo-
addition,3 Diels±Alder,4 [212]-Staudinger synthesis of b-
lactams,5 etc., provide cascades of exceptional range and
diversity.
At present we have developed a range of ter-, tetra-, penta-,
hexa- and octamolecular queuing processes.1 This paper
describes the use of carbon monoxide (1 atm) in conjunction
with either diphenylmethylsilane (as hydride source)6 or
preformed organostannanes or NaBPh4.7 The accompanying
paper8 describes analogous processes employing in situ
generated vinylstannanes.
2. Results and discussion
2.1. Cyclocarboformylation
The catalytic hydroformylation of alkenes is a major indus-
trial process9 which has attracted a substantial number of
applications in ®ne chemical synthesis.10 A related process
of similar wide potential would be catalytic carboformy-
lation (Scheme 2). Cyclocarboformylation, in which RX
and the alkene are contained within a single molecule, can
potentially be accessed by a termolecular queuing process of
which Scheme 3 is a typical example.
At present the most fully developed relay switches are
carbon monoxide and allenes. The successful imple-
mentation of these components is predicated a fortiori on
the relative rates of all the possible reactions conspiring to
facilitate the desired cascade. In this context the substrates
Scheme 2.

S. Brown et al. / Tetrahedron 57 (2001) 1347±1359
1349
Table 2. Termolecular queuing cascades with CO (1 atm) and hydride transfer from Ph2Si(Me)Ha
a
Reactions carried out in toluene (908C, 7 h) using 10 mol% Pd(Oac)2/20 mol% PPh3, Et4NCl (1 equiv), Ph2Si(Me)H (2 equiv) and CO (1 atm).
b Isolated yield.
Approximate 10% of corresponding carboxylic acid 5a also obtained.
c
d Product separated from the corresponding carboxylic acid 5c by oxime formation.
Approximately 4% of carboxylic acid 5d also formed.
Reaction carried out at 1108C for 7 h.
e
f
Molecular queuing processes employing gaseous compo-
nents such as CO and allene are clearly going to be sensitive
to the concentration (solubility) of the reactant gases in the
solvent. This in turn will be sensitive to the nature of the
solvent, the reaction temperature and the gas pressure. To
enhance the general applicability of our queuing processes
we elected to use CO at 1 atm pressure.11 For the operation
of the desired termolecular queuing process (Scheme 3) the
relative rate of hydride capture is required to be slower than
both cyclization and carbonylation.
lead to the desired product 2a. Instead the alkylpalladium(II)
intermediate 3 was captured by hydride transfer to afford 4
(70%) as the sole product. However, when diphenylmethyl-
silane (2 mol equiv.) was used as the hydride source at a
lower temperature (908C, 7 h) the desired queuing process
occurred to give a 6:1 mixture of 2a and the corresponding
carboxylic acid 5a. These were separated by ¯ash chroma-
tography (1:1 v/v petroleum ether±ethyl acetate) to give 2a
(61%).
The modi®ed conditions proved effective for a variety of
substrates (Table 2). The formation of small amounts of
the corresponding carboxylic acids was observed in
several cases (Table 2, footnotes). These by-products
Reaction (toluene/1108C/18 h) of 1a with CO (1 atm) and
sodium formate (1 equiv.) in the presence of 10 mol%
Pd(OAc)2, 20 mol% PPh3 and Et4NCl (1 equiv.) did not

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S. Brown et al. / Tetrahedron 57 (2001) 1347±1359
Scheme 3.
Scheme 4.
could arise via oxidation of the corresponding aldehyde
or by interception of the acylpalladium(II) species by
carboxylic acid 5c. The 7:1 mixture was therefore treated
with hydroxylamine and the oxime of 2c was separated
chromatographically.
adventitious
separation of the 7:1 aldehyde±carboxylic acid mixture
water.
Attempted
chromatographic
arising from 1c led to further oxidation of aldehyde 2c to
The expected slower rate of 6- versus 5-exo-trig cyclization
Scheme 5.
Scheme 6.

S. Brown et al. / Tetrahedron 57 (2001) 1347±1359
1351
Table 3. Termolecular queuing cascades with CO (1 atm) and anion transfer from Sn(IV) and B
a Reactions carried out in toluene at 1108C, for 15 h, unless otherwise noted, using a catalyst system comprising 10 mol% Pd(Oac)2, 20 mol% PPh3, Et4NCl (1
equiv).
b Reactions carried out in anisole at 1108C for 15 h employing a catalyst system comprising 10 mol% Pd(Oac)2, 20 mol% tri(2-furyl) phosphine.
Isolated yields.
c
d Xylene as solvent (see Scheme 5).
posed a threat of competition between cyclization and
direct hydride capture (Scheme 4). However, this did not
materialize and 7a and 7b were obtained in 61 and 54%
yield, respectively (Table 2).
One example of the tetramolecular cyclocarboformylation
has been studied thus far which illustrates the relay switch
principle. Thus 8 reacts (toluene, 1108C, 7 h) with the stan-
dard catalyst system to give 9 (45%). In this double

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S. Brown et al. / Tetrahedron 57 (2001) 1347±1359
Scheme 7.
carbonylation process the incorporation of the ®rst carbon
monoxide (intermolecular) is followed by a 5-exo-trig cycli-
zation (intramolecular) and then two further intermolecular
steps. The ®rst carbonylation step uprates a kinetically
unfavourable 4-exo-trig process to a favourable 5-exo-trig
process.
The key steps in the formation of 10 and 11 are migratory
insertions from intermediates such as 12 and 13 (Scheme 6).
These migratory insertions are expected to be solvent or
ligand driven. Toluene cannot function in such a role.
This role is therefore assumed by either PPh3, CO or Cl2
(from Et4NCl)12 together with, in the case of organostan-
nanes, the possible in¯uence of, the in situ generated Lewis
acid Bu3SnX.
2.2. Cascades terminating with Sn(IV) and B reagents
Solvent and temperature, as discussed above, will control
the concentration of CO in solution and in¯uence the
concentration of 12, 13 and related species. In this context
it is instructive that the corresponding tetramolecular
queuing product 15 was not observed in the solvent/
temperature study summarized in Scheme 5. Thus the rate
of 6-exo-trig acylpalladation is slower than anion capture for
intermediate 14 in toluene at 908C with 1 atm of CO.
2.2.1. 5-exo-Trig processes. A second series of termolecu-
lar queuing processes has been evaluated in which CO is
combined with preformed organostannanes or NaBPh4.
Previous studies (above) had established that CO (1 atm)
insertion occurs at a faster rate than hydride capture with
Ph2Si(Me)H. This order need not necessarily be maintained
in competition with organostannanes and NaBPh4. For
example, the outcome of the reaction of 1c with CO
(1 atm) and 2-furyltributylstannane (1.1 mol equiv.) using
the same catalyst system described above was found to be
solvent and temperature dependent (Scheme 5).
Following these studies we extended the termolecular queu-
ing processes to a variety of starter species, organostannanes
and NaBPh4 (Table 3).
Thus there is competition between the desired molecular
queuing process giving 11 and the corresponding direct
capture sequence furnishing 10. Increasing the temperature
to 1108C with xylene as the solvent, organized the molecular
queue allowing the reaction to proceed exclusively to the
desired product 11 in 88% yield. It is interesting to note that
no products lacking incorporation of carbon monoxide were
detected. The intriguing variation of selectivity for 10
versus 11 is clearly mechanism based.
All the processes in Table 3 form well-ordered queues and,
apart from 24!25, involve the formation of three new
bonds, one tetrasubstituted carbon centre and one ring.
The conversion of 24 to 25 proceeds via cyclization of the
arylpalladium(II) species onto the least hindered face of the
norbornene and results in the creation of an additional
stereocentre. Whilst the sp3±sp2 Stille type coupling reac-
tions proceed most ef®ciently in toluene or xylene, the reac-
tions involving NaBPh4 proceeded most effectively in
anisole.2,13
It is instructive to note that whilst formation of 25 from 24
occurs in excellent yield the corresponding two component
[241tributyl(2-furyl)stannane] non-carbonylative cascade
occurs in poor yield (32%).2 Thus, CO insertion is less
sterically demanding than transmetallation, and by inter-
posing CO the transmetallation is moved further away
from the steric congestion posed by the bicyclo[2.2.1]
heptane skeleton and its spirocyclic substituent.
2.2.2. 6-exo-Trig processes. Two examples of the ter-
molecular queuing cascade involving an initial 6-exo-trig

S. Brown et al. / Tetrahedron 57 (2001) 1347±1359
1353
Scheme 8.
cyclization have been explored; both involve NaBPh4 as the
anion transfer agent. Thus 6b reacts (anisole, 1208C, 15 h)
with NaBPh4 using the usual catalyst system (Table 3, foot-
note b) to give 26 (60%) and 27 reacts under analogous condi-
tions to give 28 (84%) (Scheme 7). The cis-ring junction
stereochemistry in the latter case was assigned from n.O.e.
data (see Experimental).
2.2.3. Bis-cyclization processes. N-(2-Iodobenzoyl)indole
29 was prepared by acylation of indole (NaH, DMF) in
76% yield. Reaction of 29 (xylene, 1108C) with CO
(1 atm) and 2-furyltributylstannane using the usual catalyst
system (Table 3, footnote a) afforded the desired product 30
in 32% yield together with direct capture product 31
(NMR).

1354
S. Brown et al. / Tetrahedron 57 (2001) 1347±1359
Scheme 9.
The desired process would appear to suffer from two
inherent problems. Firstly, the 5-exo-trig cyclization onto
the aromatic indole system is understandably slow.
Secondly the reactivity of the resulting secondary alkyl-
palladium(II) intermediate 32 is sterically compromised
by its bowl shape and the peri-H (HA). Product 31 is unusual
in that it is the only product involving cyclization onto a
double bond in an aromatic system observed to date.
apparatus and are uncorrected. Infrared spectra were
recorded on Perkin-Elmer Model 598 and 983G instruments
and refer to ®lms unless otherwise noted. Mass spectral data
were obtained from a VG AutoSpec operating at 70 eV.
Nuclear magnetic resonance spectra were recorded on
Bruker QE 300 and AM 400 machines operating at 300
and 400 MHz, respectively. Unless otherwise speci®ed,
deuterochloroform was used as solvent with tetramethyl-
silane as internal standard. Microanalyses were obtained
using a Carlo Erba MOD 11016 instrument. Thin layer
chromatography was carried out on Whatman PESIL
G/UV polyester plates coated with a 0.2 mm layer of
silica-gel and column chromatography was performed
with silica-gel 60 (Merck 9385). Anhydrous DMF was
commercially available (Aldrich), THF was sodium dried
under a nitrogen atmosphere and n-hexane was distilled
prior to use. Non-commercially available organotin(IV)
compounds were synthesized according to known
methods.15 Precursors 1a±d, 6a,b, 25 and 34b were
prepared as previously described (see Ref. 2 and earlier
papers).
Enamides 34a,b proved more effective substrates for the
bis-cyclization termolecular queuing cascades (Scheme 8)
using the catalyst system described above.
The molecular queue in the enamide systems 33a,b could
undergo carbonylation and R0SnBn3 capture at the mono-
cyclization stage 36!37. Such products are present in some
cases but always in ,20% yield. The major diastereoisomer
34 is always the one with a cis-relationship between the ring
junction R group and the R1COCH2 moiety. However, the
diastereoselectivity of these processes is lower than that
observed for the analogous cyclization±anion capture
process proceeding without carbonylation. Thus for 33a a
diastereomer ratio of 3:1 was observed, whilst 33b gave a
5:1 diastereomer ratio for formation of 39.2 The lower dia-
stereoselectivity observed in Scheme 8 may be occasioned
by the higher temperatures (1108C) for Scheme 8 versus that
(908C) for 38 (Scheme 9).2 The possible transition states for
the second cyclization in the formation of 38 have been
discussed previously.14
3.1. Cyclization precursors
3.1.1. 2-Methallyliodobenzene 8. Prepared by adaptation
of a literature method.16 Anhydrous benzene (15 ml) was
added to a freshly prepared solution of 2-propenylmagne-
sium bromide (20 mmol) in THF (100 ml). A mixture of
2-iodobenzyl chloride (5.04 g, 20 mmol), CuI (0.38 g,
2 mmol) and 2,2-bipyridyl (0.31 g, 2 mmol) in benzene
(10 ml) was prepared under N2 in a 250 ml ¯ask with stir-
ring at 08C. The propenylmagnesium bromide solution was
transferred by cannula as rapidly as possible into the stirred
2-iodobenzyl chloride mixture causing a gentle re¯ux. The
reaction was allowed to reach room temperature and stirred
for 4 h before solid NH4Cl was added followed by ether
(100 ml) and water (100 ml). The mixture was transferred
to a beaker, conc. NH3 (1.5 ml) added, the mixture stirred
for 1.5 h, the layers separated and the aqueous phase
extracted with ether (3£50 ml). The combined ether extracts
were washed successively with 2 M HCl (40 ml) and sat.
NaHCO3 solution (50 ml), dried (MgSO4) and the solvent
In summary, the relay switch concept provides signi®cant
enhancement of the original cyclization±anion capture
concept. Cyclocarboformylation can be achieved regio-
selectively and provides novel access to cyclic acetaldehyde
derivatives. Analogous cyclization±carbonylation±anion
capture processes occur with organostannanes and NaBPh4
and signpost many further developments of Table 1.
3. Experimental
Melting points were determined on a Kof¯er hot-stage

S. Brown et al. / Tetrahedron 57 (2001) 1347±1359
1355
removed in vacuo. The residue was then puri®ed by column
chromatography eluting with petroleum ether to afford the
product (2.43 g, 47%) as a colourless oil. (Found: C, 46.35;
H, 4.15. C10H11I requires: C, 46.55; H, 4.25%); d 7.85 (d,
1H, Jˆ7 Hz, ArH), 7.35±7.20 (m, 2H, ArH), 6.91 (dt, 1H,
Jˆ5.0 and 2.0 Hz, ArH), 4.90 and 4.57 (2£s, 2£1H,
CyCH2), 3.25 (s, 2H, ArCH2) and 1.79 (s, 3H, Me); m/z
(%) 258 (M1, 86), 131 (100), 116 (43) and 91 (44).
3.2.1. 1-Benzenesulphonyl-3,3-dimethyl-2,3-dihydro-1H-
indole 4a.17 Prepared by the general procedure for 1a
(0.25 g, 0.6 mmol) but using sodium formate (1 equiv.) as
the hydride source. The reaction was carried out at 1108C
for 18 h. Puri®cation by ¯ash chromatography eluting with
1:2 v/v petroleum ether±diethyl ether afforded the product
(0.12 g, 70%) as a colourless oil. d 7.80±7.03 (m, 9H, ArH),
3.65 (s, 2H, NCH2) and 1.10 (s, 6H, 2£CH3).
3.1.2. 2-(20-Iodophenyloxy)cyclohexanone 28 (with Dr V.
Santhakumar). Sodium methoxide (68 mg, 1.25 mmol)
3.2.2. (1-Benzenesulphonyl-3-methyl-2,3-dihydro-1H-in-
dole-3-yl)-acetaldehyde 2a and (1-benzensulphonyl-3-
methyl-2,3-dihydro-1H-indole-3-yl)-acetic acid 5a.
Prepared from 1a (0.25 g, 0.6 mmol) by the general pro-
cedure. Puri®cation of the residue by ¯ash chromatography
eluting with 1:1 v/v petroleum ether±diethyl ether and
subsequent crystallization from petroleum ether±diethyl
ether afforded the product 2a (0.115 g, 61%) as pale
brown plates, mp 89±89.58C. (Found: C, 64.65; H, 5.2; N,
4.6; S, 10.25. C17H17NO3S requires: C, 64.75; H, 5.45; N,
4.6; S, 10.15%); d 9.55 (s, 1H, CHO), 7.83 (d, Jˆ7.6 Hz,
2H, ArH), 7.69 (d, Jˆ8.2 Hz, 1H, ArH), 7.56 (d, Jˆ7.7 Hz,
1H, ArH), 7.46 (m, 2H, ArH), 7.25 (m, 1H, ArH), 7.03 (m,
2H, ArH), 3.91 and 3.75 (2£d, Jˆ11.0 Hz, 2£1H, NCH2),
2.66 and 2.39 (2£d, Jˆ17.0 Hz, 2£1H, CH2CO) and 1.22 (s,
3H, CH3); m/z (%) 315 (M1, 25), 272 (53), 146 (43), 130
(100), 103 (14), 77 (90) and 51 (25); nmax (nujol) 3040 (m),
3000 (m), 2900 (m), 1730 (w), 1230 (s), 1150 (s) and 750
(s).
was added to
a solution of iodophenol (0.275 g,
1.25 mmol) in methanol (10 ml) and the mixture stirred at
room temperature for 10 min. The solvent was then
removed and the residue dissolved in ether (25 ml) and
chlorocyclohexanone (0.165 g, 1.25 mmol) in dry ether
(5 ml) added dropwise over 5 min with stirring. Stirring
was then continued at room temperature for 2 h, then
ether (50 ml) was added and the mixture washed with
water (15 ml), dried (MgSO4) and solvent removed. The
residue was puri®ed by ¯ash chromatography eluting with
1:4 v/v ether±petroleum ether to afford the product (0.21 g,
53%) as colourless needles from ether±petroleum ether, mp
92±938C. (Found: C, 45.6; H, 4.2. C12H13IO2 requires: C,
45.6; H, 4.15%); d 7.76 and 7.23 (2£m, 2£1H, ArH), 6.71
(m, 2H, ArH), 4.62 (t, 1H, OCH), and 2.37±1.68 (m, 8H,
4£CH2); m/z (%) 316 (M1, 43), 220 (99), 189 (100) and 121
(38); nmax (nujol) 1735, 1585, 1480, 1395, 1295 and
1265 cm21
.
3.2.3. Carboxylic acid 5a. Not isolated. Characterized from
the PMR spectrum of the mixture. d 7.80±7.10 (m, 9H,
ArH), 4.15 and 3.77 (2£d, Jˆ11.7 Hz, 2£1H, NCH2), 2.54
and 2.29 (2£d, Jˆ17.5 Hz, 2£1H, CH2CO2) and 1.20 (s, 3H,
Me).
3.1.3. N-(2-Iodobenzoyl)-indole 29. Indole (10 g, 0.085
mol) in DMF (50 ml) was added dropwise over 0.25 h to a
suspension of NaH (4.11 g, 0.087 mol, 50% weight in oil) at
08C in anhydrous DMF (200 ml). 2-Iodobenzoyl chloride
(22.65 g, 0.085 mol) in DMF (50 ml) was then added
dropwise over 0.5 h and the resulting mixture stirred for
2 h at room temperature, the solvent removed under
vacuo, the residue dissolved in ether (300 ml) and washed
successively with water (150 ml), brine (150 ml) and dried
(MgSO4). The ether was then removed in vacuo and the
residue crystallized from ether±petroleum ether to yield
the product (22.41 g, 76%) as colourless prisms, mp 94±
958C. (Found: C, 52.05; H, 2.9; N, 3.85. C15H10INO
requires: C, 51.9; H, 2.9; N, 4.05%); d 8.4±7.0 (m, 8H,
ArH), 6.8 (d, 1H, indole-2-H) and 6.5 (d, 1H, indole-3-H);
m/z (%) 347 (M1, 48), 231 (100), 219 (23), 203 (29) and 76
(40).
3.2.4. (1-Benzenesulphonyl-3-methoxycarbonyl-2,3-
dihydro-1H-indole-3-yl)-acetaldehyde 2b. Prepared from
1b. Puri®cation of the residue by ¯ash chromatography elut-
ing with 1:1 v/v petroleum ether±diethyl ether afforded the
product (40%) as colourless prisms, mp 103±104.58C.
(Found: C, 60.1; H, 4.7; N, 3.9; S, 8.85. C18H17NO5S
requires: C, 60.15; H, 4.75; N, 3.9; S, 8.9%); d 9.61 (s,
1H, CHO), 7.85 (d, Jˆ7.9 Hz, 2H, ArH), 7.69 (d,
Jˆ8.2 Hz, 1H, ArH), 7.59 (m, 1H, ArH), 7.48 (m, 2H,
ArH), 7.30±7.01 (m, 3H, ArH), 4.73 and 3.79 (2£d,
Jˆ11.8 Hz, 2£1H, NCH2), 3.52 (s, 3H, CH3), 3.39 and
2.51 (2£d, Jˆ18.9 Hz, CH2CHO); m/z (%) 359 (M1, 28),
315 (16), 300 (23), 258 (21), 190 (19), 159 (30), 130 (100),
116 (9), 103 (18), 77 (84) and 51 (17); nmax 2950 (m), 1670
(brs), 1300 (m), 1210 (s) and 1110 (s).
3.2. General procedure for cyclocarboformylation
Carbon monoxide was bubbled through a mixture of the
substrate (0.25 g), diphenylmethylsilane (2 equiv.), tetra-
ethylammonium chloride (1 equiv.) and a catalyst system
comprising Pd(OAc)2 (10 mol%) and PPh3 (20 mol%) in
dry toluene (15 ml) for 10 min. The reaction mixture was
then heated at 908C with stirring over 7 h under an atmos-
phere of carbon monoxide (balloon). After this time the
mixture was ®ltered and the solvent removed under reduced
pressure. The residue was taken up in diethyl ether, washed
with water (2£10 ml), dried (MgSO4) and concentrated
under reduced pressure. The residue was puri®ed by ¯ash
chromatography to afford the product.
3.2.5. (N-Benzyl-3-methyloxindol-3-yl)-acetaldoxime 2c
(oxime). Prepared from 1c but worked up without
chromatography. The residue was stirred for 15 h in 5:1
v/v methanol±water with sodium acetate (1.4 mol equiv.)
and hydroxylamine hydrochloride (1.4 mol equiv.). Metha-
nol was then removed and the aqueous mixture extracted
with DCM (2£20 ml). The organic layers were combined,
dried (MgSO4) and concentrated under reduced pressure
to afford the product (40% overall) as a pale yellow oil
which comprised a 1:1 mixture of syn- and anti-oximes.
Found (H.R.M.S.): 294.2853. C18H18N2O2 requires:
294.2814; m/z (%) (mixed isomers) 294 (M1, 43), 276

1356
S. Brown et al. / Tetrahedron 57 (2001) 1347±1359
(14), 236 (75), 206 (7), 130 (12), 91 (100) and 65 (18); d
(syn-oxime) 7.35±7.17 (m, 8H, ArH and NyCH), 7.06 and
6.73 (2£d, Jˆ7.9 Hz, 2£1H, ArH), 5.01 and 4.85 (2£d,
Jˆ15.7 Hz, 2£1H, PhCH2N), 2.77 and 2.71 (2£dd,
Jˆ15.9 and 8.1 Hz, 2£1H, NyCCH2), 1.47 (s, 3H, Me); d
(anti-oxime) 8.4 (brs, 1H, OH), 7.35±7.17 (m, 7H, ArH),
7.01 (t, Jˆ8.4 Hz, 1H, ArH), 6.79 (d, Jˆ8.5 Hz, 1H, ArH),
6.51 (t, Jˆ5.3 Hz, 1H, NyCH), 4.88 and 4.95 (2£d,
Jˆ13.5 Hz, 2£1H, PhCH2N), 3.02 and 2.90 (2£dd,
Jˆ15.7 and 4.3 Hz, 2£1H, NyCCH2), 1.49 (s, 3H, Me).
3H, Me); m/z (%) 188 (M1, 4), 159 (14), 145 (100), 131
(34), 91 (42), 77 (13), 63 (17) and 51 (14).
3.3. General procedure for cyclization±carbonylation±
anion capture cascades with aryl iodides and
organostannanes
A mixture of Pd(OAc)2 (0.011 g, 0.05 mmol), PPh3
(0.026 g, 0.1 mmol), aryl iodide (0.5 mmol), organo-
stannane (0.55 mmol), Et4NCl (0.083 g, 0.5 mmol) and
xylene (5 ml) was saturated with carbon monoxide (CO
bubbled into the solution for 5 min). A balloon ®lled with
CO was then attached to the condenser and the mixture
stirred and heated at 1108C for 8 h. The mixture was then
cooled, the solvent removed in vacuo, the residue dissolved
in ether (20 ml), washed with water (10 ml), dried (MgSO4)
and the solvent removed. The residue was puri®ed by
column chromatography to afford the product.
3.2.6. (3-Methyl-2,3-dihydrobenzofuran-3-yl)-acetalde-
hyde 2d. Prepared (51%) from 1d by the general method.
The product was obtained as a pale yellow oil. Found
(H.R.M.S.): 176.0841. C11H12O2 requires: 176.0837. d
9.69 (s, 1H, CHO), 7.16±6.80 (m, 4H, ArH), 4.42 and
4.33 (2£d, Jˆ11.8 Hz, 2£1H, OCH2), 2.86 and 2.69 (2£d,
Jˆ16.9 Hz, 2£1H, CH2CHO) and 1.42 (s, 3H, Me); m/z (%)
176 (M1, 38), 161 (17), 133 (100), 119 (15), 105 (80), 91
(15), 77 (22) and 63 (8); nmax (®lm) 3000 (m), 1720 (s), 1610
3.4. General procedure for tetramolecular cascades with
sodium tetraphenylborate
(s), 1465 (m), 990 (m) and 750 (m) cm21
.
3.2.7. 2,4-Dinitrophenylhydrazone of 2d. Crystallized as
orange prisms from EtOH, mp 176±1788C. (Found: C, 57.0;
H, 4.3; N, 15.85. C17H16N4O5 requires: C, 57.3; H, 4.55; N,
15.7%); d 9.11 (s, 1H, ArH), 8.30 (d, Jˆ9.5 Hz, 1H, ArH),
7.85 (d, Jˆ9.6 Hz, 1H, ArH), 7.18±6.82 (m, 4H, ArH), 4.49
and 4.23 (2£d, Jˆ8.5 Hz, 2£1H, CH2O), 2.74 and 2.7 (2£s,
2£1H, CH2CyN) and 1.50 (s, 3H, Me); m/z (%) 356 (M1,
1), 322 (2), 281 (2), 224 (2), 190 (2) 176 (3), 133 (100), 105
(84) and 77 (30); nmax (nujol) 3140 (m), 2390 (w), 1540 (m),
A mixture of Pd(OAc)2 (0.011 g, 0.05 mmol), PPh3
(0.026 g, 0.1 mmol), aryl iodide (0.5 mmol), sodium tetra-
phenylborate (0.188 g, 0.55 mmol) and anisole (5 ml) was
saturated with carbon monoxide (CO bubbled into the solu-
tion for 5 min). A balloon ®lled with CO was then attached
to the condenser and the mixture stirred and heated at 1108C
for 15 h. The mixture was then cooled, the solvent removed
in vacuo, the residue dissolved in ether (20 ml), washed with
water (10 ml) and dried (MgSO4). The solvent was then
removed and the residue puri®ed by column chromato-
graphy.
1520 (m), 1280 (s), 1210 (s) and 840 (m) cm21
.
3.2.8. (4-Methylchroman-4-yl)-acetaldehyde 7a. Prepared
(61%) from 6a as a colourless oil. (Found: C, 75.85; H, 7.25.
C12H14O2 requires: C, 75.75; H, 7.4%); d 9.62 (t, Jˆ2.8 Hz,
1H, CHO), 7.11 (m, 2H, ArH), 6.87 (m, 2H, ArH), 4.24 (m,
2H, CH2O), 2.78 and 2.69 (2£dd, Jˆ15.4 and 2.5 Hz, 2£1H,
CH2yO), 2.11 (ddd, Jˆ17.4, 6.2 and 3.2 Hz, 1H,
CH2CH2O), and 1.46 (s, 3H, Me); m/z (%) 190 (M1, 55),
147 (100), 131 (21), 119 (13), 115 (19), 91 (72), 77 (20) and
65 (11); nmax (®lm) 2650 (m), 1670 (s), 1560 (m), 1535 (m),
3.4.1. 2-(1-Benzenesulphonyl-3-methyl-2,3-dihydro-1H-
indole-3-yl)-1-(pyridin-20-yl)-ethanone 16. Column chro-
matography eluting with 3:7 v/v ether±petroleum ether
afforded the product (71%) as colourless prisms, mp 65±
678C from ether±petroleum ether. (Found: C, 63.6; H, 4.4;
N, 6.75. C22H20N2O3S´H2O requires: C, 63.9; H, 4.8; N,
6.8%); d 8.6 (brs, 1H, py-H), 8.0±7.0 (m, 12H, ArH,
py-H), 4.13 and 3.9 (2£d, 2H, Jˆ11 Hz, NCH2), 3.8 and
3.0 (2£d, 2£1H, Jˆ17.7 Hz, CH2CO) and 1.2 (s, 3H, Me);
m/z (%) 392 (M1, 5), 271 (63), 144 (32), 130 (97), 121
(100), 78 (50) and 51 (19).
1440 (s), 1400 (s) and 710 (s) cm21
.
3.2.9. (N-Benzyl-4-methyl-1-oxo-1,2,3,4-tetrahydroiso-
quinolin-4-yl)-acetaldehyde 7b. Column chromatography
eluting with 4:1 v/v ether±petroleum ether afforded the
product (54%) as a pale yellow oil. Found (H.R.M.S.) (elec-
trospray): 316.1323. C19H19NO21Na requires: 316.1313. d
9.32 (t, 1H, Jˆ2.4 Hz, CHO), 8.2±7.2 (m, 9H, ArH), 4.84
and 4.66 (2£d, 2£1H, Jˆ13.35 Hz, NCH2Ph), 3.42 and 3.6
(2£d, 2£1H, Jˆ12.8 Hz, NCH2), 2.5 (m, 2H, CH2CO) and
1.4 (s, 3H, Me); m/z (%) 293 (M1, 17), 265 (38), 145 (60),
120 (24), 91 (100) and 77 (10).
3.4.2. 2-(1-Benzenesulphonyl-3-methyl-2,3-dihydro-1H-
indol-3-yl)-1-phenyl-ethanone 17. Column chromato-
graphy eluting with 1:9 v/v ether±petroleum ether afforded
the product (82%) as colourless prisms, mp 98±1008C.
(Found: C, 70.3; H, 5.55; N, 3.4. C23H21NO3S requires: C,
70.58; H, 5.35; N, 3.6%); d 8.0±7.0 (m, 14H, ArH), 4.1 and
3.9 (2£d, 2H, Jˆ10.8 Hz, NCH2), 3.3 and 2.8 (2£d, 2H,
Jˆ17.5 Hz, CH2CO) and 1.25 (s, 3H, Me); m/z (%) 391
(M1, 3), 271 (100), 130 (93), 105 (47) and 73 (64).
3.2.10. (2-Methyl-1-oxo-indan-2-yl)-acetaldehyde 9. Work
up by ¯ash chromatography eluting with 3:1 v/v petroleum
ether±ether to afford the product (45%) as a colourless oil.
(Found: C, 76.35; H, 6.2. C12H12O2 requires: C, 76.6; H,
6.45%); d 9.71 (s, 1H, CHO), 7.79 (d, Jˆ7.6 Hz, 1H,
ArH), 7.62 (t, Jˆ7.2 Hz, 1H, ArH), 7.59±737 (m, 2H,
ArH), 3.18 and 2.99 (2£d, Jˆ17.1 Hz, 2£1H, CH2), 2.92
and 2.83 (2£d, Jˆ18.3 Hz, 2£1H, CH2CHO) and 1.25 (s,
3.4.3. N-Benzyl-3-(2-furan-2-yl-2-oxo-ethyl)-3-methyl-
1,3-dihydroindol-2-one 18. Column chromatography elut-
ing with 2:3 v/v ether±petroleum ether afforded the product
(87%) as colourless prisms, mp 104±1058C. (Found: C,
76.5; H, 5.65; N, 4.1. C22H19NO3 requires: C, 76.5; H,
5.5; N, 4.05%); d 7.6±7.11 (m, 9H, ArH11£furyl-H),
6.93 (d, 1H, Jˆ6 Hz, ArH), 6.71 and 6.49 (2£d, 2£1H,

S. Brown et al. / Tetrahedron 57 (2001) 1347±1359
1357
Jˆ3 and 2 Hz, furyl-H), 5.08 and 4.96 (2£d, AB, 2£1H,
Jˆ9 Hz, NCH2Ph), 3.63 and 3.55 (2£d, AB, 2£1H,
Jˆ11 Hz, CH2CO) and 1.57 (s, 3H, Me); m/z (%) 345
(M1, 71), 235 (99), 95 (53) and 91 (100); nmax (nujol)
Jˆ7 Hz, ArH), 7.63 (d, 1H, Jˆ9 Hz, ArH), 7.48 (t, 1H,
Jˆ7 Hz, ArH), 7.39±6.89 (m, 6H, ArH1indole-3-H), 6.07
(s, 2H, NCH2O), 4.75 and 4.55 (2£d, AB, 2£1H, Jˆ9 Hz,
ArOCH2), 3.61 (m, 2H, OCH2), 3.5 and 3.3 (2£d, AB,
2£1H, Jˆ16 Hz, CH2CO), 1.58 (s, 3H, Me), 0.95 (m, 2H,
CH2Si), and 0.0 (s, 9H, SiMe3); m/z (%) 421 (M1, 7), 406
(6), 171 (68), 133 (100), 105 (77) and 73 (91); nmax (®lm)
3010, 2905, 1700, 1645 and 1350 cm21
.
3.4.4. 1-Benzyl-3-methyl-3-[2-oxo-2-(1-(2-trimethylsilanyl-
ethoxymethyl)-1H-indol-2-yl)-ethyl]-indolin-2-one 19.
Column chromatography eluting with 3:7 v/v ether±
petroleum ether afforded the product (61%) as a colourless
oil. (Found: C, 73.35; H, 7.1; N, 5.35. C32H36N2O3Si
requires: C, 73.3; H, 6.85; N, 5.35%); d 7.7 (d, 1H,
Jˆ8 Hz, ArH), 7.51±7.11 (m, 10H, ArH1indole 3-H),
7.08 (t, 1H, Jˆ7 Hz, ArH), 6.93 (t, 1H, 8 Hz, ArH), 6.69
(d, 1H, Jˆ8 Hz, ArH), 5.87 and 5.79 (2£d, AB, 2£1H,
Jˆ11 Hz, NCH2O), 5.07 and 4.95 (2£d, AB, 21£1H,
Jˆ15 Hz, NCH2Ph), 3.80 and 3.70 (2£d, AB, 2£1H,
Jˆ17 Hz, CH2CO), 3.24 (t, 2H, Jˆ8 Hz, OCH2), 1.50 (s,
3H, Me), 0.69 (t, 2H Jˆ8 Hz, CH2Si) and 20.19 (s, 9H,
SiMe3); m/z (%) 524 (M1, 24), 423 (62), 309 (41), 260
(57), 236 (97), 91 (100) and 73 (83); nmax (®lm) 3040,
2940, 2874, 1650 and 1480 cm21
.
3.4.9. 2-(3-Methyl-2,3-dihydrobenzofuran-3-yl)-1-phen-
yl-ethanone 23. Column chromatography eluting with 3:7
v/v ether±petroleum ether afforded the product (80%) as
colourless needles from ether±petroleum ether, mp 78±
808C. (Found: C, 81.0; H, 6.55. C17H16O2 requires: C,
80.95; H, 6.35%); d 7.9±6.8 (m, 9H, ArH), 4.56 (s, 2H,
OCH2), 3.6 and 3.2 (2£d, 2£1H, Jˆ17.5 Hz, OCH2) and
1.4 (s, 3H, Me); m/z (%) 252 (M1, 2), 237 (5), 132 (43),
105 (93), 77 (100) and 51 (41).
3.4.10. 3-(2-Furanylcarbonyl)-20-phenylmethyl-spiro[bi-
cyclo[2.2.1]heptane-2,10-[1H]isoindole]-30(20H)-one 25.
Chromatography eluting with 2:3 v/v ether±petroleum
ether afforded the product (82%) as colourless prisms, mp
202±2048C. (Found: C, 78.7; H, 6.05; N, 3.4. C26H23NO3
requires: C, 78.6; H, 5.8; N, 3.55%); d 7.57 (d, 1H, Jˆ7 Hz,
ArH), 7.46 (d, 1H, Jˆ8 Hz, ArH), 7.39±7.21 (m, 8H, ArH,
1£furyl-H), 6.53 (d, 1H, Jˆ3 Hz, furyl-H), 6.13 (m, 1H,
furyl-H), 5.29 and 4.69 (2£d, AB, 2£1H, Jˆ16 Hz,
NCH2Ph), 3.62 (d, 1H, Jˆ3 Hz, CHCO furyl), 2.97 (d,
1H, Jˆ5.0 Hz, CHCHCO furyl), 2.4 (d, 1H, Jˆ3 Hz,
CHCNBn), 2.70 and 1.61 (m, 2£1H, CH2) and 1.9±1.43
(m, 4H, CH2CH2); n.O.e data.
2925, 1695, 1650, 1595 and 1345 cm21
.
3.4.5. 1-Furan-2-yl-2-(3-methyl-2,3-dihydrobenzofuran-
3-yl)-ethanone 11. Column chromatography eluting with
1:4 v/v ether±petroleum ether afforded the product
(0.107 g, 88%) as a colourless oil. (Found: C, 74.25; H,
5.65. C15H14O3 requires: C, 74.4; H, 5.8); d 7.55 (s, 1H,
furyl-H), 7.17±6.80 (m, 5H, ArH11£furyl-H), 6.51 (dd,
1H, Jˆ2 Hz, furyl-H), 4.6 and 4.43 (2£d, AB, 2£1H,
Jˆ9 Hz, OCH2), 3.39 and 3.05 (2£d, AB, 2£1H,
Jˆ16 Hz, CH2CO) and 1.47 (s, 3H, Me); m/z (%) 242
(M1, 13), 227 (15), 132 (100), 110 (71), 105 (62) and 95
(46); nmax (®lm) 2940, 2855, 1645, 1480 cm21
.
3.4.6. 2-(3-Methyl-2,3-dihydrobenzofuran-3-yl)-1-pyridin-
2-yl-ethanone 20. Column chromatography eluting with 3:7
v/v ether±petroleum ether afforded the product (83%) as a
pale yellow oil. (Found: C, 73.0; H, 5.5; N, 5.65.
C16H15NO2´0.5H2O requires: C, 73.3; H, 5.35; N, 5.7%); d
8.59 (br s, 1H, py-H), 7.9±6.7 (m, 7H, ArH), 4.51 (br s, 2H,
OCH2), 3.97 and 3.37 (2£d, 2£1H, Jˆ17.4 Hz, CH2CO) and
1.28 (s, 3H, Me); m/z (%) 253 (M1, 11), 133 (25), 121 (100),
93 (35) and 78 (51).
3.4.11. N-Benzyl-4-methyl-1-oxo-1,2,3,4-tetrahydroiso-
quinolin-4-yl-1-phenyl-ethanone 26. Column chromato-
graphy eluting with 3:7 v/v ether±petroleum ether
followed by crystallization from ether±petroleum ether
afforded the product (60%) as colourless prisms, mp 68±
708C. (Found: C, 81.05; H, 6.3; N, 3.5. C25H23NO2 requires:
C, 81.3; H, 6.25; N, 3.8%); d 8.1±7.06 (m, 14 H, ArH), 4.74
and 4.71 (2£d, 2H, Jˆ14.5 Hz, NCH2Ph), 3.75 and 3.71
(2£d, 2£1H, Jˆ12.7 Hz, NCH2), 3.17 and 2.97 (2£d,
2£1H, Jˆ16.5 Hz, CH2CO) and 1.49 (s, 3H, Me); m/z (%)
369 (M1, 12), 286 (15), 249 (100) 105 (74), 91 (95) and 84
(55).
3.4.7. (E)-1-(3-Methyl-2,3-dihydrobenzofuran-3-yl)-4-
phenyl-but-3-en-2-one 21. Column chromatography elut-
ing with 3:7 v/v ether±petroleum ether afforded the product
(61%) as a colourless oil. (Found: C, 81.75; H, 6.35.
C19H18O2 requires: C, 82.0; H, 6.5%); d 7.35±6.8 (m,
10H, ArH1yCHPh), 6.58 (d, 1H, Jˆ15 Hz, COCHy),
4.74 and 4.58 (2£d, AB, 2£1H, Jˆ8 Hz, OCH2), 3.51 and
3.28 (2£d, AB, 2£1H, Jˆ15 Hz, CH2CO) and 1.61 (s, 3H,
Me); m/z (%) 278 (M1, 5), 263 (7), 146 (56), 132 (100) and
105 (72); nmax (®lm) 2995, 2900, 1630, 1480 and
1450 cm21
.
3.4.8. 2-(3-Methyl-2,3-dihydrobenzofuran-3-yl)-1-[1-(2-
trimethylsilanylethoxymethyl)-1H-indol-2-yl]-ethanone
22. Column chromatography eluting with 1:4 v/v ether±
petroleum ether afforded the product (52%) as a colourless
oil. (Found: C, 71.05; H, 7.55; N, 3.35. C25H31NO3Si
requires: C, 71.25; H, 7.35, N, 3.35%); d 7.75 (d, 1H,
3.4.12. 1-Phenyl-2-(6,7,8,9-tetrahydro-5aH-dibenzofuran-
9a-yl)-ethanone 28. Column chromatography eluting with
1:1 v/v ether±petroleum ether afforded the product (84%) as
a pale yellow oil. Found (H.R.M.S.) (electrospray):
315.1370. C20H20O21Na requires: 315.1361. d 7.84±6.8
(m, 9H, ArH), 4.85 (t, 1H, Jˆ5.5 Hz, CHO), 3.35 and

1358
S. Brown et al. / Tetrahedron 57 (2001) 1347±1359
3.25 (2£d, 2H, Jˆ16.3 Hz, CH2COPh) and 2.0±1.2 (m, 8H,
(CH2)4); m/z (%) 292 (M1, 5), 249 (16), 172 (100), 144 (28),
105 (25), 91 (16) and 77 (18).
3.4.19. Minor isomer 35b. d 7.75±7.32 (m, 5H, Ar-H and
1£furyl-H), 6.89 (dd, 1H, Jˆ0.5, 3.0 Hz, furyl-H), 6.52 (t,
1H, Jˆ2.0 Hz, furyl-H), 4.12 and 3.15 (2£d, AB, 2£1H,
Jˆ13.0 Hz, NCH2), 2.71±2.62 (2£d, AB, 2£1H,
Jˆ16.0 Hz, CH2CO), 2.02 and 1.94 (2£d, AB, 2£1H,
Jˆ14.0 Hz, CH2C(Me)) and 1.54 and 1.39 (2£s, 2£3H,
Me).
3.4.13. 11-(2-Furan-2-yl-2-oxo-ethyl)-10b, 11-dihydro-
isoindolo[2,1-a]-indol-6-one 30. Column chromatography
eluting with 2:3 v/v ether±petroleum ether afforded the
product (32%) as colourless needles, mp 142±1448C.
Found (H.R.M.S.): 315.0900. C20H13NO3 requires:
315.0895. d 7.86±7.22 (m, 7H, ArH), 7.52 (d, 1H,
Jˆ1.0 Hz, furyl-H), 7.09 (t, 1H, Jˆ7.0 Hz, ArH), 6.87 (d,
1H, Jˆ3.0 Hz, furyl-H), 6.43 (dd, 1H, Jˆ1.0, 3.0 Hz, furyl-
H), 5.84 (d, 1H, Jˆ8.0 Hz, NCH) and 5.17 (d, 1H,
Jˆ8.0 Hz, CHCO); m/z (%) 315 (M1, 31), 220 (100), 165
(33) and 95 (15); nmax (nujol) 3010, 1690, 1650 and
3.4.20. Compound 34c/35c. Column chromatography elut-
ing with 2:3 v/v ether±petroleum ether afforded the product
(64%) as a colourless viscous oil which comprised a 3.5:1
mixture of diastereomers. Found (H.R.M.S., mixed
isomers): 488.2512. C29H36N2O3Si requires: 488.2495. m/z
(%) (mixed isomers) 488 (M1, 10), 415 (9), 370 (100), 212
(32), 200 (79), 184 (65), 171 (96), 159 (55) and 73 (63); nmax
(®lm) 2955, 1680, 1650, 1365 cm21
.
1430 cm21
.
The 1H NMR spectra of the major and minor isomers were
assigned from the mixture.
3.4.14. Compound 34a/35a. Column chromatography elut-
ing with 1:1 v/v ether±petroleum ether afforded the product
(55%) as a colourless viscous oil which comprised a 1.5:1
mixture of diastereomers. Found (H.R.M.S.): 371.1526.
C24H21NO3 requires: 371.1521; m/z (%) 272 (M111, 46),
261 (100), 220 (46) and 165 (24); nmax (®lm) 2915, 2845,
3.4.21. Major isomer 34c. d 7.79 and 7.70 (2£d, 2£1H,
Jˆ7.0 Hz, ArH), 7.58±7.14 (m, 7H, ArH and indole 3-H),
6.03 (s, 2H, OCH2N), 4.1 and 3.39 (2£d, AB, 2£1H,
Jˆ12.0 Hz, NCH2), 3.53 (t, 2H, Jˆ8.0 Hz, OCH2), 3.21
and 3.19 (2£d, AB, 2£1H, Jˆ15.0 Hz, CH2CO), 2.25 and
1.97 (2£d, AB, 2£1H, Jˆ14.0 Hz, CH2C(Me)), 1.57 and
0.91 (2£s, 2£3H, Me), 0.88 (m, 2H, CH2Si), and 20.89
(s, 9H, SiMe3).
1670, 1650, 1450 and 1360 cm21
.
The 1H NMR spectra of the major and minor isomers were
obtained from the mixture.
3.4.15. Major isomer 34a. d 7.78 (d, 1H, Jˆ7.0 Hz, ArH),
7.54±7.20 (m, 9H, ArH11£furyl-H), 6.99 (d, 1H,
Jˆ3.0 Hz, furyl-H), 6.47 (dd, 1H, Jˆ1.0 and 2.0 Hz,
furyl-H), 4.1 and 3.28 (2£d, AB, 2£1H, Jˆ12.0 Hz,
NCH2), 3.07 and 2.04 (2£d, AB, 2£1H, Jˆ13.0 Hz,
CH2C(Me)), 2.81 and 2.70 (2£d, AB, 2£1H, Jˆ16.0 Hz,
CH2CO) and 1.16 (s, 3H, Me).
3.4.22. Minor isomer 35c. d 7.83 (d, 1H, Jˆ7.0 Hz, ArH),
7.54±7.14 (m, 7H, ArH), 6.78 (s, 1H, indole 3-H), 5.94 and
5.92 (2£d, AB, 2£1H, Jˆ9.0 Hz, NCH2O), 4.19 and 3.2
(2£d, AB, 2£1H, Jˆ13.0 Hz, NCH2), 3.4 (t, 2H,
Jˆ9.0 Hz, OCH2), 2.83 (s, 2H, CH2CO), 2.15 and 1.94
(2£d, AB, 2£1H, Jˆ14.0 Hz, CH2C(Me)), 1.59 and 1.44
(2£s, 2£3H, Me), 0.82 (t, 2H, Jˆ8.0 Hz, CH2Si) and
20.13 (s, 9H, SiMe3).
3.4.16. Minor isomer 35a. d 7.77 (d, 1H, Jˆ7.0 Hz, ArH),
7.56±7.25 (m, 9H, ArH11£furyl-H), 7.07 (d, 1H,
Jˆ3.0 Hz, furyl-H), 6.47 (dd, 1H, Jˆ1.0 and 2.0 Hz,
furyl-H), 4.17 and 3.18 (2£d, AB, 2£1H, Jˆ12.0 Hz,
NCH2), 2.99 and 2.89 (2£d, AB, 2£1H, Jˆ16.0 Hz,
CH2CO) 2.85 and 2.1 (2£d, AB, 2£1H, Jˆ13.0 Hz,
CH2C(Me)) and 1.01 (s, 3H, Me).
Acknowledgements
We thank Leeds University, AstraZeneca, Organon and the
EPSRC for support.
3.4.17. Compound 34b/35b. Column chromatography elut-
ing with 3:2 v/v ether±petroleum ether afforded the product
(61%) as a colourless viscous oil which comprised a 3.5:1
mixture of diastereomers. (Found (mixed isomers): C,
73.65; H, 5.85; N, 4.3. C19H19NO3 requires: C, 73.8; H,
6.15; N, 4.55%); m/z (%) (FAB, mixed isomers) 310
(M111, 100), 200 (22), 146 (12) and 95 (13); nmax (®lm)
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