Nucleophilic addition reactions of bridged triene η6-chromiumtricarbonyl complexes

Article abstract of DOI:10.1039/b207708f

The metal-mediated addition of a range of nucleophiles to several bridged η⁶-chromiumtricarbonyl complexes has been demonstrated for thefirst time. The reaction proceeds in regio- and stereoselective fashion and in fair to good yield. The new r

Full text of DOI:10.1039/b207708f

View Article Online / Journal Homepage / Table of Contents for this issue
Nucleophilic addition reactions of bridged triene
ꢀ6-chromiumtricarbonyl complexes
Rohan E. J. Beckwith,a Michael B. Gravestockb and Nigel S. Simpkins*a
1
a School of Chemistry, The University of Nottingham, University Park, Nottingham,
UK NG7 2RD. E-mail: nigel.simpkins@nottingham.ac.uk
b AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire, UK SK10 4TG
Received (in Cambridge, UK) 6th August 2002, Accepted 3rd September 2002
First published as an Advance Article on the web 11th October 2002
The metal-mediated addition of a range of nucleophiles to several bridged η6-chromiumtricarbonyl complexes
has been demonstrated for the first time. The reaction proceeds in regio- and stereoselective fashion and in fair
to good yield. The new reaction was applied to the synthesis of an advanced intermediate towards anatoxin-a.
reasonable that the activating effect of the chromium tri-
carbonyl unit present in the bridged complexes would enable
nucleophilic addition to these compounds in a similar fashion
to that seen with the arene complexes.8 Here we describe our
results, which demonstrate that this is indeed possible with a
range of nucleophiles in regio- and stereoselective fashion.9
Introduction
Over 20 years ago, seminal work by the research group
of Semmelhack established the viability of nucleophilic
substitution reactions of η6-chromiumtricarbonyl complexes.1
Particularly interesting in the context of natural product
synthesis were the classic examples of intramolecular addition
reactions leading to various kinds of annulated products, e.g.
Scheme 1.2
Results and discussion
We chose to commence our study by preparing bridged
complexes 6 and 7 from cycloheptatriene complex 510 using the
photolytic conditions described by Sheridan and co-workers,
Scheme 3.7
Scheme 1
Nucleophilic attack is facilitated by the metal, the reaction
proceeding via an intermediate anionic η5-cyclohexadienyl
complex in which the negative charge resides largely at the
chromium centre.
Scheme 3
The scope and limitations of nucleophilic addition to
chromium arenes are now firmly established, including: (i) the
types of nucleophiles that undergo addition and those that
do not. (ii) The regiochemical control possible in reactions
of substituted complexes. (iii) The type of product formed,
which may be a product complex, a metal free aromatic or
a dearomatised (diene or diene-derived) product. More details
of these possibilities can be found in a recent review.3
We became interested in exploring the nucleophilic addition
chemistry of a much less common type of organometallic
system, namely the bridged complexes generated by formal
[6 ϩ 2] cycloaddition of seven-membered η6-chromium-
tricarbonyl complexes 3, Scheme 2.4–7
Reaction of 5 in degassed hexane at room temperature using
a 125 W medium pressure mercury lamp gave 6 in good yield,
although we found the corresponding preparation of 7 more
problematic (the reported yield is 85%). Analogous reactions
involving bis-ethers or silyl ethers of 1,4-dihydroxybut-2-yne
were not successful in our hands.
The addition of nucleophiles to a solution of 6 in THF at
Ϫ78 ЊC, followed by protic work-up, resulted in the formation
of the metal-free adducts 8 and/or 9 as shown in Table 1.†
The complex 6 reacted with several different alkyllithiums,
dimethylcyanocuprate, the lithium enolates derived from ethyl
acetate or N,N-dimethylacetamide, two examples of lithiated
nitriles and a lithiated sulfone. In every case the initial addition
reaction appears to be highly regioselective for the terminus of
the complexed diene and no products arising from addition
to the internal position or to the bis-silylalkene part were
observed. This might be expected since the intermediate
organometallic benefits from allylic stabilisation, although
steric factors may also come into play. However, the position of
subsequent protonation appears to be highly dependent upon
Scheme 2
We were aware of no chemistry of the unusual η6-complexes
4, other than de-metallation to provide bridged products that
have applications in natural products synthesis.5 It seemed
† We checked that the bridged triene corresponding to 6 did not
undergo nucleophilic addition, thus establishing the crucial role of the
chromiumtricarbonyl unit.
2352
J. Chem. Soc., Perkin Trans. 1, 2002, 2352–2359
This journal is © The Royal Society of Chemistry 2002
DOI: 10.1039/b207708f

View Article Online
Table 1 Nucleophilic addition to complex 6
Nucleophile MeLi Me2Cu(CN)Li2 nBuLi PhLi LiC(OEt)᎐CH2 CH2᎐᎐C(OLi)OEt CH2᎐᎐C(OLi)NMe2 LiCH2CN LiC(CH3)2CN LiCH2SO2Ph
᎐
Product (8/9) a
a
30
b
c
d
e
f
g
50
5 : 1
h
i
Yield (%)
8 : 9
55
34
61
84
53
1 : 2
82
5 : 1
83
58
1 : 5
7 : 1 1.3 : 1
8a
8a
8a
8a
a Only isomer 8 detected by 1H NMR of crude product. Compound 8d was isolated as the corresponding methyl ketone – see text.
the nature of the group being introduced. In most cases the
presumed intermediate anionic dienyl complex undergoes
protonation distal to the entering substituent, to give exclusively
or mainly isomer 8, whereas in a few cases the alternative
isomer 9 predominates.
Although the proposed structures accorded with our
expectations, and were supported by high field NMR data,
we were also able to obtain X-ray crystal structure deter-
Scheme 4
minations of the nitrile 8g (R = CH2CN) and the sulfone 9i
Unfortunately, we were unable to detect the desired product
18 (or any alternative isomer) using MeI, allyl bromide or
propargyl‡ bromide as the electrophile, even in the presence
of additives such as DMPU, MeCN, CO or PPh3, and only the
usual product 8c was obtained.
(R = CH2SO2Ph), which confirmed our assignments and were
illustrated in our earlier communication.9
A number of analogous reactions were unsuccessful, includ-
ing those involving the varied nucleophiles 10–17 shown below.
Attempts at deuterium quenching of the intermediate anions
were successful only with d-trifluoroacetic acid (and not D2O or
MeOD), this giving complete incorporation, e.g. to give d-8a.
Interestingly d-8a was obtained as a single regioisomer
but as a 1 : 1 mixture of epimers. Thus, it appears that
the ratio of regioisomers (8 : 9) is dependent upon the nature
of the proton quench, and that the protonation does
not involve initial delivery to the metal centre, since this
would be expected to yield endo-deuterated product only.
Unfortunately we were unable to pursue these aspects in more
detail.
Nucleophilic addition to the diphenyl substituted cyclo-
adduct complex 7 was also studied briefly. Reaction with
lithiated ethyl vinyl ether proved sluggish compared with the
corresponding reaction with 6, and afforded the separable
ketones 19 and 20 in modest yield following acidic work-up,
Scheme 5.
Many of these failures appear explicable in isolation, but
are more difficult to explain when compared to the successful
examples. For instance, some of the failed reactions involve
quite bulky nucleophiles, but the successful reaction leading to
nitrile 8h appears more demanding than most. The failure of
the dithiane anion 11 is surprising given the excellent results
obtained with arene complexes and we were especially dis-
appointed by the lack of reaction with 14 and 15, given the
possibilities for chiral nucleophile driven desymmetrisation.
That lithiated dihydropyran 17 should fail to undergo addition
is perhaps the most mysterious, given the smooth reaction
observed with the acyclic variant, ethyl vinyl ether, leading to 8d
(this adduct was isolated as the corresponding methyl ketone,
following mild acid treatment).
With the success of the nucleophilic addition reactions we
were interested to see if this process could be followed in situ by
a second carbon–carbon forming reaction by inclusion of an
appropriate electrophile. This type of chemistry has been
explored extensively in the arene series, most notably by Kundig
and co-workers, and can provide a nicely stereocontrolled route
to dialkylated cyclohexadienes, and also ketones via CO
insertion.3,11 With this in mind we tested the transformation
shown in Scheme 4.
Scheme 5
‡ The IUPAC name for propargyl is prop-2-ynyl.
J. Chem. Soc., Perkin Trans. 1, 2002, 2352–2359
2353

View Article Online
At this point we were particularly interested in these types of
ketone and enone products and so we examined the chemistry
of methyl ketone 8d as outlined in Scheme 6.
tricarbonyl complexes, such as 6, 7 and 26, is possible. The
process appears quite general, but successful reaction is rather
nucleophile dependent for reasons that are not completely clear
at present. The regio- and stereochemical control possible,
make this a potentially useful access to certain types of bridged
product, as demonstrated by our synthesis of an advanced
intermediate towards anatoxin-a. A total synthesis of this
alkaloid target remains tantalising and requires only a more
effective method for removal of unwanted silicon substituents.
Scheme 6
Mild acid treatment effected alkene conjugation to give
enone 21, whereas the use of TFA resulted in additional double
desilylation to give 22. Surprisingly, desilylation of this type of
fully substituted bis-silylalkene appeared unprecedented in the
literature and so we also demonstrated the analogous conver-
sion of 8c into bicyclic alkene 23 under the same conditions.
Experimental
General Details
Melting points were recorded on a Stuart Scientific SMP3
apparatus and are uncorrected. Microanalytical data were
obtained on a Perkin-Elmer 240B elemental analyser. Infrared
spectra were recorded on a Perkin-Elmer 1600 or a Nicolet
Protégé 460 FTIR machine and are reported in cmϪ1.
NMR spectra were recorded on Bruker AM400, AV400,
DRX500, Jeol FX 270, or Varian Unity Inova 300 machines,
using CDCl3 as solvent at 298 K. Chemical shifts are given in
ppm downfield from tetramethylsilane, using either the TMS
or residual protic solvent as an internal standard. J values are
recorded in Hz and rounded to the nearest half integer value.
The following abbreviations apply- (app.) apparent, (b) broad,
(s) singlet, (d) doublet, (t) triplet, (q) quartet, (m) multiplet,
(dd) double doublet, etc. Where necessary, proton and carbon
At this stage we recognised the structural analogy between
the carbon bridged enones, such as 22, and the well-known
homotropane alkaloid anatoxin-a 24.12 Bearing in mind the
transformations described above, the potential for this method-
ology to provide a new route to anatoxin seemed clear, pro-
viding that analogous chemistry of aza-bridged complexes
could be accomplished. With this in mind we prepared the
known complexes 25 and 26,13,7 and then established that
addition of lithiated ethyl vinyl ether resulted in formation of
methyl ketone 27 in reasonable yield, Scheme 7.
As in the previous reactions using this particular nucleophile,
none of the alternative alkene regioisomer was observed.
With the complete skeleton of anatoxin-a in place com-
pletion of a formal total synthesis required only alkene isomer-
isation, selective hydrogenation and double desilylation (a
number of N-protected derivatives are known), which had
proved facile on the carbon-bridged systems.
1
assignments were assisted with H COSY, HMQC, DEPT or
NOE sequences. The chemical shifts of multiplets correspond-
ing to a single proton are quoted as a point, representing the
centre of the multiplet. Where the signals for two or more
protons overlap, a range is quoted. Diagnostic signals only are
given in some cases for minor components of isomer mixtures
where signals are obscured by those from the major isomer.
Mass spectra were obtained using a VG Micron Autospec or
VG Micromass 70E spectrometer, using electron impact (EI),
or fast atom bombardment (FAB), using m-nitrobenzyl alcohol
as the matrix.
Photolyses were conducted in Pyrex flasks (fitted with a
cooling jacket if necessary) with a water-cooled Pyrex well
containing a 125 W Hanovia medium pressure Hg lamp.
A 0.7 M CoSO4 solution was used in the coolant to absorb
wavelengths above approximately 400 nm.
Unfortunately, to date we have been unable to complete this
synthesis. Treatment of compound 27 under a wide range of
conditions, including TBAF, TFA, TsOH, HI and HF–pyridine,
did not remove the silicon substituents, although most con-
ditions did result in formation of the enone 28 (use of 2.0 M
HCl gave this compound in quantitative yield).
The use of TBAT (tetrabutylammonium triphenyldifluoro-
silicate)14 as fluoride source under forcing conditions, THF–
HMPA at 80 ЊC, appeared to remove one of the silicon
substituents, but further exposure to these vigorous conditions
lead only to destruction of the material.
All reaction mixture temperatures refer to values recorded for
an external cooling bath. Room temperature implies temper-
atures in the range 20–25 ЊC. Reaction progress was monitored
by thin layer chromatography (TLC) performed on Merck
Kieselgel 60 F254 aluminium backed plates, which were visual-
ised by a combination of ultraviolet light and potassium
permanganate. Flash column chromatography was performed
In conclusion, we have demonstrated for the first time that
metal-mediated nucleophilic addition to bridged η6-chromium-
Scheme 7
2354
J. Chem. Soc., Perkin Trans. 1, 2002, 2352–2359

View Article Online
using Merck Kieselgel 60 (230–440 mesh), in the indicated
solvent. Degassing of solvent was undertaken by bubbling
argon through the solvent.
THF (5 ml) at Ϫ78 ЊC under an atmosphere of nitrogen. The
resultant solution was stirred for 4 h at this temperature,
quenched by the addition of d-TFA (0.19 ml, 2.51 mmol) and
allowed to warm to 0 ЊC before being poured into NH4OH
(10 ml). Following extraction with diethyl ether (3 × 5 ml), the
combined organics were washed with water (10 ml), brine
(10 ml), dried (MgSO4) and concentrated in vacuo to give a
yellow oil. Flash chromatography (petroleum ether) afforded
the title compound d-8a (64 mg, 98%) as a colourless oil, vmax
Organic solvents and reagents were dried by distillation from
the following as required: THF, Et2O (sodium–benzophenone
ketyl); MeOH (magnesium); DMF (MgSO4); Me3SiCl (calcium
hydride). Petrol refers to petroleum ether (bp 40–60 ЊC), which
was distilled before use. All other solvents and reagents were
used as received from commercial suppliers unless otherwise
stated. Compounds prepared and used subsequently without
further purification were judged to be of suitable purity by
NMR analysis.
(CHCl3)/cmϪ1 2955, 2980, 1936 (C–D), 1654 and 1602 (C᎐C),
᎐
1249, 832; δH(400 MHz; CDCl3) 0.16 (9H, s, Si(CH3)3), 0.17
(9H, s, Si(CH3)3), 1.03 (3H, d, J 7.0, CH3), 1.63 (1H, d, J 12.0,
9Ј-H), 1.80 (1H, app. dt, J 12.0, 8.0, 9-H), 2.22 (0.6H, m, exo
2-H), 2.30 (0.4H, m, endo 2-H), 2.39 (1H, br s, 5-H), 2.85 (1H,
br d, J 8.0, 6-H), 3.06 (1H, ddd, J 8.0, 5.0, 3.0, 1-H), 5.13–5.19
(2H, m, 3-H and 4-H); δC(100 MHz; CDCl3) 1.3 (Si(CH3)3),
21.5 (CH3), 33.7 (CH2), 36.7 (t, J 19.0, CHD), 40.6 (CH), 50.3
(CH), 57.5 (CH), 122.9 (olefinic CH), 131.4 (olefinic CH), 156.0
(C-Si(CH3)3), 157.6 (C-Si(CH3)3); m/z (EI) 279 (Mϩ, 8%), 264
(8), 210 (60), 195 (18), 122 (80), 73 (100) (Found Mϩ, 279.1937.
C16H29DSi2 requires 279.1949).
5-Methyl-7,8-bis(trimethylsilyl)bicyclo[4.2.1]nona-3,7-diene 8a
and 5-methyl-7,8-bis(trimethylsilyl)bicyclo[4.2.1]nona-2,7-diene
9a by MeLi addition
MeLi (1.58 M in hexane, 0.16 ml, 0.25 mmol) was added drop-
wise to a stirred solution of complex 6 (100 mg, 0.25 mmol) in
THF (4 ml) at Ϫ78 ЊC under an atmosphere of nitrogen. The
resultant solution was warmed to 0 ЊC over 2 h, quenched by
the addition of saturated aqueous NH4Cl (1 ml) and warmed
to room temperature prior to extraction with diethyl ether
(3 × 5 ml). The combined organics were washed with water
(10 ml), brine (10 ml), dried (MgSO4) and concentrated in vacuo
to give a yellow oil. Flash chromatography (petroleum ether)
afforded an inseparable mixture of the title compounds 8a and
9a (39 mg, 55%, 7 : 1) as a colourless oil, vmax (CHCl3)/cmϪ1
5-nButyl-7,8-bis(trimethylsilyl)bicyclo[4.2.1]nona-3,7-diene 8b
nBuLi (1.49 M in hexane, 0.17 ml, 0.25 mmol) was added drop-
wise to a stirred solution of complex 6 (100 mg, 0.25 mmol) in
THF (5 ml) at Ϫ78 ЊC under an atmosphere of nitrogen. The
resultant yellow solution was stirred at this temperature for 4 h,
quenched by the addition of saturated aqueous NH4Cl (1 ml)
and warmed to room temperature prior to extraction with
diethyl ether (3 × 5 ml). The combined organics were washed
with water (5 ml), brine (5 ml), dried (MgSO4) and concentrated
in vacuo to give a yellow wax. Flash chromatography (petrol-
eum ether) afforded the title compound 8b (27 mg, 34%) as a
colourless oil, (Found: C, 72.56; H, 11.44. C19H36Si2 requires C,
2954, 2900, 1655 and 1603 (C᎐C), 876; δ (400 MHz; CDCl )
᎐
H
3
major isomer 8a: 0.16 (9H, s, Si(CH3)3), 0.17 (9H, s, Si(CH3)3),
1.03 (3H, d, J 7.0, CH3), 1.63 (1H, d, J 12.0, 9Ј-H), 1.80 (1H,
app. dt, J 12.0, 8.0, 9-H), 2.22 (1H, dm, J 18.5, exo 2-H), 2.30
(1H, dm, J 18.5, endo 2-H), 2.39 (1H, br s, 5-H), 2.85 (1H, br d,
J 8.0, 6-H), 3.06 (1H, ddd, J 8.0, 5.0, 3.0, 1-H), 5.13–5.19 (2H,
m, 3-H and 4-H), minor isomer 9a: 0.14 (9H, s, Si(CH3)3), 0.21
(9H, s, Si(CH3)3), 0.97 (3H, d, J 7.0, CH3), 1.50 (1H, app. dt,
J 11.5, 7.5, 9-H), 1.74 (1H, d, J 11.5, 9Ј-H), 2.00–2.19 (3H, m,
4-H and 5-H), 2.96 (1H, dd, J 7.5, 5.0, 6-H), 3.27 (1H, app. t,
J 7.5, 1-H), 5.47 (1H, ddd, J 11.5, 7.5, 3.5, 3-H), 5.78 (1H, ddd,
J 11.5, 7.5, 3.5, 2-H); δC(68 MHz; CDCl3) major isomer 8a: 1.2
(Si(CH3)3), 1.3 (Si(CH3)3), 21.4 (CH3), 33.7 (CH2), 37.0 (CH2),
40.5 (CH), 50.3 (CH), 57.4 (CH), 122.8 (olefinic CH), 131.3
(olefinic CH), 155.8 (C-Si(CH3)3), 157.5 (C-Si(CH3)3), minor
isomer 9a: 1.0 (Si(CH3)3), 1.5 (Si(CH3)3), 18.8 (CH3), 32.3
(CH2), 34.2 (CH2), 36.4 (CH), 52.4 (CH), 58.7 (CH), 128.6
(olefinic CH), 133.4 (olefinic CH), 151.5 (C-Si(CH3)3), 156.1
(C-Si(CH3)3; m/z (EI) 278 (Mϩ, 9%), 263 (6), 210 (41), 195 (13),
122 (63), 73 (100) (Found Mϩ, 278.1892. C16H30Si2 requires
278.1886).
72.17; H, 11.32%); vmax (CHCl3)/cmϪ1 2898, 2859, 1654 (C᎐C),
᎐
877; δH(400 MHz; CDCl3) 0.16 (9H, s, Si(CH3)3), 0.17 (9H, s,
Si(CH3)3), 0.92 (3H, t, J 7.0, CH3), 1.20–1.48 (6H, m, 3 × CH2),
1.60 (1H, d, J 12.0, 9Ј-H), 1.80 (1H, app. dt, J 12.0, 8.0, 9-H),
2.18–2.34 (3H, m, 2-H and 5-H), 2.97 (1H, br d, J 8.0, 6-H),
3.06 (1H, m, 1-H), 5.18 (1H, m, 4-H), 5.28 (1H, m, 3-H); δC(100
MHz; CDCl3) 1.2 (Si(CH3)3), 1.4 (Si(CH3)3), 14.1 (CH3), 23.1
(CH2), 30.2 (CH2), 34.2 (CH2), 35.8 (CH2), 36.8 (CH2), 45.5
(CH), 50.4 (CH), 55.0 (CH), 123.2 (olefinic CH), 130.5 (olefinic
CH), 155.9 (C-Si(CH3)3), 157.9 (C-Si(CH3)3); m/z (EI) 320 (Mϩ,
5%), 210 (53), 195 (12), 122 (81), 73 (100) (Found Mϩ, 320.2365.
C19H36Si2 requires 320.2356).
5-Phenyl-7,8-bis(trimethylsilyl)bicyclo[4.2.1]nona-3,7-diene 8c
PhLi (1.19 M in cyclohexane–diethyl ether, 1.51 ml, 1.80 mmol)
was added dropwise to a stirred solution of complex 6 (200 mg,
0.50 mmol) in THF (5 ml) at Ϫ78 ЊC under an atmosphere of
nitrogen. The resultant dark orange solution was stirred at this
temperature for 3 h, quenched by the addition of saturated
aqueous NH4Cl (1 ml) and warmed to room temperature prior
to extraction with diethyl ether (3 × 5 ml). The combined
organics were washed with water (10 ml), brine (10 ml), dried
(MgSO4) and concentrated in vacuo to give an orange oil. Flash
chromatography (nhexane) afforded the title compound 8c as a
white crystalline solid (104 mg, 61%), mp 64 ЊC (from ethanol–
water) (Found: C, 73.81; H, 9.78. C21H32Si2 requires C, 74.04;
H, 9.47%); vmax (CHCl3)/cmϪ1 3080, 3061, 3025, 3004, 2945,
2889, 2842, 1658, 1599, 1533, 1256, 827; δH(400 MHz; CDCl3)
0.18 (9H, s, Si(CH3)3), 0.29 (9H, s, Si(CH3)3), 1.56 (1H, d,
J 12.0, 9Ј-H), 1.66 (1H, app. dt, J 12.0, 7.5, 9-H), 2.39 (1H, dm,
J 16.0, 2-HH), 2.44 (1H, app. dtd, J 16.0, 4.5, 2.5, 2-HH), 3.06
(1H, app. dt, J 7.5, 4.5, 1-H), 3.14 (1H, dd, J 7.5, 2.0, 6-H), 3.74
(1H, br s, 5-H), 5.39 (1H, dm, J 12.0, 4-H), 5.54 (1H, dm, 12.0,
3-H), 7.19–7.36 (5H, m, 5 × ArCH); δC(100 MHz; CDCl3) 1.2
(Si(CH3)3), 1.6 (Si(CH3)3), 34.1 (CH2), 37.1 (CH2), 50.1 (CH),
Bridged products 8a and 9a by cuprate addition
MeLi (1.31 M in hexane, 0.38 ml, 0.50 mmol) was added
dropwise to a stirred solution of cuprous cyanide (23 mg, 0.25
mmol) in THF (1 ml) at Ϫ78 ЊC under an atmosphere of argon.
The mixture was warmed to Ϫ40 ЊC prior to dropwise cannula
addition of complex 6 (100 mg, 0.25 mmol) in THF (4 ml). The
resultant solution was stirred at this temperature for 3 h and
then quenched by the addition of saturated aqueous NH4Cl
(1 ml) and warmed to room temperature prior to extraction
with diethyl ether (2 × 5 ml). The combined organics were
washed with water (10 ml), brine (10 ml), dried (MgSO4) and
the solvent removed in vacuo to give an orange oil. Flash
chromatography (npentane) afforded an inseparable mixture of
the title compounds 8a and 9a (21 mg, 30%, 1.3 : 1) as a colour-
less oil with spectroscopic data as described above.
2-(2H)-5-Methyl-7,8-bis(trimethylsilyl)bicyclo[4.2.1]nona-3,7-
diene d-8a
MeLi (1.5M in hexane, 0.50 ml, 0.75 mmol) was added drop-
wise to a stirred solution of complex 6 (100 mg, 0.25 mmol) in
J. Chem. Soc., Perkin Trans. 1, 2002, 2352–2359
2355

View Article Online
51.8 (CH), 58.9 (CH), 126.0 (olefinic CH), 126.8 (olefinic CH),
127.7 (ArCH), 128.2 (ArCH), 128.4 (ArCH), 144.6 (ArC),
157.1 (C-Si(CH3)3), 157.5 (C-Si(CH3)3); m/z (EI) 340 (Mϩ, 8%),
210 (28), 185 (11), 122 (43), 73 (100) (Found Mϩ, 340.2032.
C21H32Si2 requires 340.2043). Also isolated was metal-free
starting material (20 mg, 15%, data were in accordance with the
previously reported literature).7
(1H, d, J 12.0, 9Ј-H), 1.85 (1H, m, 9-H), 2.14–2.42 (4H, m, 2-H
and CH2CO2CH2CH3), 2.82 (1H, br s, 5-H), 2.91 (1H, dd,
J 8.0, 2.5, 6-H), 3.05 (1H, m, 1-H), 4.09–4.22 (2H, m,
-CH2CO2CH2CH3), 5.18–5.27 (2H, m, 3-H and 4-H); δC(68
MHz; CDCl3) both isomers: 1.2 (Si(CH3)3), 1.4 (Si(CH3)3), 14.2
(CH3), 30.1 (CH2), 34.1 (CH2), 37.9 (CH2), 40.5 (CH2), 42.3
(CH), 50.2 (CH), 54.7 (CH), 60.3 (CO2CH2CH3), 125.1
(olefinic CH), 128.3 (olefinic CH), 156.6 (C-Si(CH3)3), 173.0
(C᎐O); m/z (FAB) 350 (Mϩ, 15%), 335 (11), 263 (3), 154 (36),
᎐
5-Acetyl-7,8-bis(trimethylsilyl)bicyclo[4.2.1]nona-3,7-diene 8d
136 (32), 122 (16), 73 (100) (Found MHϩ, 351.2145.
C19H34O2Si2 requires 351.2176).
tBuLi (1.43 M in hexane, 5.24 ml, 7.46 mmol) was added drop-
wise to a stirred solution of ethyl vinyl ether (0.85 ml, 8.93
mmol) in THF (10 ml) at Ϫ78 ЊC under an atmosphere of
nitrogen. The yellow reaction mixture was warmed to 0 ЊC and
the resultant colourless solution was recooled to Ϫ78 ЊC before
dropwise cannula addition of complex 6 (500 mg, 1.25 mmol) in
THF (10 ml). After 1 h at this temperature, HCl (0.02 M
in ethanol, 5 ml) was added and the mixture allowed to warm to
room temperature before being poured into HCl (0.02 M in
ethanol, 60 ml) and stirred for 30 min. The resultant pale
orange solution was diluted with diethyl ether (50 ml), washed
with saturated aqueous NaHCO3 and extracted with diethyl
ether (3 × 20 ml). The combined organics were washed with
water (20 ml), brine (20 ml), dried (MgSO4) and concentrated
in vacuo to give an orange oil. Flash chromatography (petroleum
ether–CH2Cl2, 7 : 3) afforded the title compound 8d (321 mg,
84%) as a colourless oil, vmax (CHCl3)/cmϪ1 2901, 2825, 1698
5-N,N-Dimethylamidomethyl-7,8-bis(trimethylsilyl)bicyclo-
[4.2.1]nona-3,7-diene 8f and 5-N,N-dimethylamidomethyl-7,8-
bis(trimethylsilyl)bicyclo[4.2.1]nona-2,7-diene 9f
nBuLi (1.52 M in hexane, 6.58 ml, 10.0 mmol) was added
dropwise to a stirred solution of diisopropylamine (1.40 ml,
10.0 mmol) in THF (10 ml) at Ϫ78 ЊC under an atmosphere
of nitrogen. The resultant solution was warmed to 0 ЊC for
15 min then recooled to Ϫ78 ЊC before addition of N,N-
dimethylacetamide (0.93 ml, 10.0 mmol). The reaction mixture
was stirred for 2 h at this temperature after which time an
aliquot (0.47 ml, 0.25 mmol) was removed and added dropwise
to a stirred solution of complex 6 (100 mg, 0.25 mmol) in THF
(3 ml) at Ϫ78 ЊC. The resultant light orange solution was stirred
for 30 min and then quenched by the addition of saturated
aqueous NH4Cl (1 ml) and warmed to room temperature prior
to extraction with diethyl ether (3 × 5 ml). The combined
organics were washed with water (10 ml), brine (10 ml), dried
(MgSO4) and the concentrated in vacuo to give a yellow oil.
Flash chromatography (diethyl ether–petroleum ether, 1 : 1)
afforded an inseparable mixture of the title compounds 8f and 9f
(72 mg, 82%, 5 : 1) as a colourless crystalline solid, mp 77–78 ЊC
(from ethanol–water); (Found: C, 65.05; H, 10.40; N, 3.89.
C19H35NOSi2 requires C, 65.27; H, 10.09; N, 4.01%); vmax
(CHCl3)/cmϪ1 3005, 2942, 2883, 2842, 2234, 1652, 1621, 1591,
1254, 828; δH(500 MHz; CDCl3) major isomer 8f: 0.14 (9H, s,
Si(CH3)3), 0.17 (9H, s, Si(CH3)3), 1.58 (1H, d, J 12.0, 9Ј-H), 1.86
(1H, app. dt, J 12.0, 8.0, 9-H), 2.22 (1H, dm, J 18.5, 2-HH), 2.28
(1H, app. dtd, J 18.5, 4.5, 2.5, 2-HH), 2.34 (1H, dd, J 14.5, 8.0,
CHHCONMe2), 2.41 (1H, dd, J 14.5, 8.0, CHHCONMe2), 2.85
(1H, br s, 5-H), 2.95 (4H, br s, N(CH3) and 6-H), 3.02 (3H, s,
N(CH3)), 3.06 (1H, m, 1-H), 5.22 (1H, ddm, J 12.5, 5.5, 4-H),
5.27 (1H, ddm, J 12.5, 5.0, 3-H), minor isomer 9f: (diagnostic
signals) 0.13 (9H, s, Si(CH3)3), 0.23 (9H, s, Si(CH3)3), 2.95 (3H,
s, N(CH3)), 3.01 (3H, s, N(CH3)), 5.46 (1H, ddd J 11.0, 8.5, 3.0,
3-H), 5.80 (1H, ddd, J 11.0, 8.0, 3.5, 2-H); δC(68 MHz; CDCl3)
major isomer 8f: 1.2 (Si(CH3)3), 34.5 (CH2), 35.5 (CH3), 36.8
(CH2), 37.7 (CH3), 38.9 (CH2), 42.3 (CH), 50.2 (CH),
54.9 (CH), 124.6 (olefinic CH), 129.0 (olefinic CH), 156.2
(C=O), 1660 (C᎐C), 1355, 877; δ (500 MHz; CDCl ) 0.16 (9H,
᎐
H
3
s, Si(CH3)3), 0.20 (9H, s, Si(CH3)3), 1.50 (1H, d, J 12.0, 9Ј-H),
1.89 (1H, app. dt, J 12.0, 8.0, 9-H), 2.22 (3H, s, CH3), 2.28 (1H,
dm, J 18.5, 2-HH), 2.36 (1H, app. dtd, J 18.5, 4.5, 2.5, 2-HH),
3.08 (1H, app. dt, J 8.0, 4.5, 1-H), 3.29 (1H, br s, 5-H), 3.41 (1H,
ddd, J 8.0, 2.5, 1.5, 6-H), 5.37 (1H, dddd, J 12.5, 6.0, 3.0,
1.5, 4-H), 5.51 (1H, dddd, J 12.5, 6.0, 2.5, 1.5, 3-H); δC(125
MHz; CDCl3) 1.2 (Si(CH3)3), 1.4 (Si(CH3)3), 29.5 (CH3), 35.6
(CH2), 36.8 (CH2), 50.6 (CH), 52.0 (CH), 60.2 (CH),
123.0 (olefinic CH), 128.7 (olefinic CH), 155.5 (C-Si(CH3)3),
158.4 (C-Si(CH ) ), 209.0 (C᎐O); m/z (FAB) 307 (MHϩ, 21%),
᎐
3
3
211 (31), 154 (21), 136 (23), 73 (100) (Found MHϩ, 307.1892.
C17H30OSi2 requires 307.1913).
5-Ethoxycarbonylmethyl-7,8-bis(trimethylsilyl)bicyclo[4.2.1]-
nona-3,7-diene 8e and 5-ethoxycarbonylmethyl-7,8-bis-
(trimethylsilyl)bicyclo[4.2.1]nona-2,7- diene 9e
nBuLi (2.01 M in hexane, 4.97 ml, 10.0 mmol) was added
dropwise to a stirred solution of diisopropylamine (1.40 ml,
10.0 mmol) in THF (10 ml) at Ϫ78 ЊC under an atmosphere of
nitrogen. The resultant solution was warmed to 0 ЊC for 15 min
then recooled to Ϫ78 ЊC before addition of ethyl acetate (0.98
ml, 10.0 mmol). The reaction mixture was stirred for 1 h at this
temperature after which time an aliquot (0.44 ml, 0.25 mmol
was removed) and added dropwise to a stirred solution of
complex 6 (100 mg, 0.25 mmol) in THF (4 ml) at Ϫ78 ЊC. The
mixture was stirred at this tempearature for 6 h, quenched by
the addition of saturated aqueous NH4Cl (1 ml) and extracted
with diethyl ether (3 × 5 ml). The combined organics were
washed with water (5 ml), brine (5 ml), dried (MgSO4) and
concentrated in vacuo to give a yellow oil. Flash chrom-
atography (ethyl acetate–petrol, 1 : 20) afforded an inseparable
mixture of the title compounds 8e and 9e (47 mg, 53%, 1 : 2) as a
(C-Si(CH ) ), 157.0 (C-Si(CH ) ), 172.0 (C᎐O), minor isomer
᎐
3
3
3 3
9f: 1.4 (Si(CH3)3), 35.4 (CH2), 35.5 (CH3), 36.2 (CH2), 37.4
(CH3), 38.5 (CH2), 42.3 (CH), 51.9 (CH), 57.1 (CH), 128.3
(olefinic CH), 134.0 (olefinic CH), 152.0 (C-Si(CH3)3), 156.2
(C-Si(CH ) ), 172.7 (C᎐O); m/z (EI) 349 (Mϩ, 35), 334 (33), 276
᎐
3
3
(11), 159 (28), 140(63), 73 (100) (Found Mϩ, 349.2245.
C19H35NOSi2 requires 349.2257).
5-Cyanomethyl-7,8-bis(trimethylsilyl)bicyclo[4.2.1]nona-3,7-
diene 8g and 5-cyanomethyl-7,8-bis(trimethylsilyl)bicyclo[4.2.1]-
nona-2,7-diene 9g
colourless oil; vmax (CHCl3)/cmϪ1 2902, 1725 (C᎐O), 1372, 871
᎐
(Si-CH3); δH(500 MHz; CDCl3) major isomer 9e: 0.14 (9H, s,
Si(CH3)3), 0.23 (9H, s, Si(CH3)3), 1.26 (3H, t, J 6.5, CH3), 1.55
(1H, app. dt, J 12.0, 7.5, 9-H), 1.63 (1H, d, J 12.0, 9Ј-H), 2.14–
2.42 (4H, m, 4-H and CH2CO2CH2CH3), 3.02–3.09 (2H, m, 5-H
and 6-H), 3.29 (1H, app. t, J 7.5, 1-H), 4.09–4.22 (2H, m,
CH2CO2CH2CH3), 5.46 (1H, ddd, J 11.0, 8.5, 2.5, 3-H), 5.81
(1H, ddd, J 11.0, 8.0, 3.5, 2-H), minor isomer 8e: 0.16 (9H, s,
Si(CH3)3), 0.28 (9H, s, Si(CH3)3), 1.28 (3H, t, J 7.0, CH3), 1.58,
nBuLi (1.57 M in hexane, 6.37 ml, 10.0 mmol) was added
dropwise to a stirred solution of diisopropylamine (1.40 ml,
10.0 mmol) in THF (10 ml) at Ϫ78 ЊC under an atmosphere of
nitrogen. The resultant solution was warmed to 0 ЊC for 15 min
then recooled to Ϫ78 ЊC before addition of acetonitrile (0.52
ml, 10.0 mmol). The reaction mixture was stirred for 1.5 h at
this temperature after which time an aliquot (0.30 ml, 0.17
mmol) was removed and added dropwise to a stirred solution of
2356
J. Chem. Soc., Perkin Trans. 1, 2002, 2352–2359

View Article Online
complex 6 (66 mg, 0.17 mmol) in THF (4 ml) at Ϫ78 ЊC. The
resultant brown solution was quenched immediately by the
addition of saturated aqueous NH4Cl (1 ml) and warmed to
room temperature prior to extraction with diethyl ether (3 ×
5 ml). The combined organics were washed with water (10 ml),
brine (10 ml), dried (MgSO4) and concentrated in vacuo to give
a yellow oil. Flash chromatography (dichloromethane–petrol,
2 : 7) afforded an inseparable mixture of the title compounds 8g
and 9g (25 mg, 50%, 5 : 1) as a white crystalline solid, mp 106–
108 ЊC (from ethanol–water); (Found: C, 66.96; H, 9.96; N,
4.75. C17H29NSi2 requires C, 67.26; H, 9.62; N, 4.61%); δH(500
MHz; CDCl3) major isomer 8g: 0.17 (9H, s, Si(CH3)3), 0.20
(9H, s, Si(CH3)3), 1.55 (1H, d, J 12.5, 9Ј-H), 1.90 (1H, app. dt,
J 12.5, 8.0, 9-H), 2.22–2.38 (3H, m, 2-H and CHHCN), 2.42
(1H, dd, J 16.5, 6.5, CHHCN), 2.67 (1H, br s, 5-H), 3.08–3.14
(2H, m, 1-H and 6-H), 5.30 (1H, dm, J 12.5, 4-H), 5.37 (1H,
dm, J 12.5, 3-H), minor isomer 9g: 0.15 (9H, s, Si(CH3)3), 0.24
(9H, s, Si(CH3)3), 1.52 (1H, d, J 12.0, 9Ј-H), 1.62 (1H, app. dt,
J 12.0, 7.5, 9-H), 1.98 (1H, ddd, J 13.5, 8.5, 3.5, 4-HH), 2.22–
2.38 (3H, m, 4-HH, 5-H and CHHCN), 2.44 (1H, dd, J 16.5,
6.5, CHHCN), 3.19 (1H, dd, J 7.5, 5.0, 6-H), 3.34 (1H, app. t,
J 7.5, 1-H), 5.45 (1H, ddd, J 11.0, 8.5, 2.5, 3-H), 5.86 (1H, ddd,
J 11.0, 7.5, 3.0, 2-H); δC(100 MHz; CDCl3) major isomer 8g: 1.2
5-Phenylsulfonylmethyl-7,8-bis(trimethylsilyl)bicyclo[4.2.1]-
nona-3,7-diene 8i and 5-phenylsulfonylmethyl-7,8-bis(trimethyl-
silyl)bicyclo[4.2.1]nona-2,7-diene 9i
nBuLi (1.36 M in hexane, 0.18 ml, 0.25 mmol) was added
dropwise to a stirred solution of methylphenylsulfone (39 mg,
0.25 mmol) in THF (4 ml) at Ϫ78 ЊC under an atmosphere of
nitrogen. The resultant orange solution was stirred for 1 h
before dropwise cannula addition to a stirred solution of com-
plex 6 (100 mg, 0.25 mmol) in THF (2 ml) at Ϫ78 ЊC. The
mixture was stirred at this temperature for 20 min, quenched by
the addition of saturated aqueous NH4Cl (1 ml) and warmed to
room temperature. The product was extracted with ethyl acetate
(3 × 5 ml) and the combined organics were washed with water
(10 ml), brine (10 ml), dried (MgSO4) and concentrated in vacuo
to give a yellow oil. Flash chromatography (ethyl acetate–
petrol, 1 : 20) afforded an inseparable mixture of the title
compounds 8i and 9i (61 mg, 58%, 1 : 5) as a colourless crystal-
line solid, mp 84 ЊC (from ethanol–water); vmax (CHCl3)/cmϪ1
2951, 2927, 1650, 1306 and 1134 (SO2), 867; δH(500 MHz;
CDCl3) major isomer 9i: 0.12 (9H, s, Si(CH3)3), 0.13 (9H, s,
Si(CH3)3), 1.43 (1H, d, J 12.0, 9Ј-H), 1.55 (1H, app. dt, J 12.0,
7.5, 9-H), 2.13 (1H, ddd, J 16.0, 7.0, 3.0, 4-HH), 2.21 (1H, ddd,
J 16.0, 8.5, 3.0, 4-HH), 2.42 (1H, m, 5-H), 2.99 (1H, dd, J 7.5,
5.0, 6-H), 3.06 (1H, dd, J 14.5, 3.5, CHHSO2Ph), 3.21 (1H, dd,
J 14.5, 8.0, CHHSO2Ph), 3.28 (1H, app. t, J 7.5, 1-H), 5.44 (1H,
ddd, J 11.0, 8.5, 3.0, 3-H), 5.84 (1H, ddd, J 11.0, 8.0, 3.0, 2-H),
7.55–7.61 (2H, m, 2 × H meta), 7.66 (1H, app. tt, J 7.0, 1.0,
H para), 7.91–7.96 (2H, dm, J 8.0, H ortho), minor isomer 8i:
(diagnostic signals) 0.12 (9H, s, Si(CH3)3), 0.13 (9H, s,
Si(CH3)3), 1.46 (1H, d, J 12.0, 9Ј-H), 1.85 (1H, app. dt, J 12.0,
7.5, 9-H), 2.21–2.29 (2H, m, 2-H), 2.42 (1H, m, 5-H), 3.29 (1H,
dd, J 14.5, 6.5, CHHSO2Ph), 5.30 (1H, ddm, J 13.5, 6.0, 4-H),
5.36 (1H, dm, J 13.0, 3-H); δC(100 MHz; CDCl3) major isomer
9i: 0.8 (Si(CH3)3), 1.2 (Si(CH3)3), 28.9 (CH2), 35.2 (CH2), 36.6
(CH), 51.8 (CH), 57.2 (CH), 59.0 (CH2SO2Ph), 127.2 (olefinic
CH), 127.9 (olefinic CH), 129.2 (ArCH), 133.5 (ArCH), 135.0
(ArCH), 140.0 (ArC), 153.0 (C-Si(CH3)3), 154.8 (C-Si(CH3)3),
minor isomer 8i: 0.8 (Si(CH3)3), 1.1 (Si(CH3)3), 30.0 (CH2), 34.6
(CH2), 39.6 (CH), 49.8 (CH), 55.5 (CH), 61.2 (CH2SO2Ph),
126.0 (olefinic CH), 127.0 (olefinic CH), 127.9 (ArCH), 129.2
(ArCH), 133.5 (ArCH), 140.0 (ArC), 153.0 (C-Si(CH3)3), 154.8
(C-Si(CH3)3); m/z (EI) 418 (Mϩ, 10%), 210 (15), 137 (16), 122
(19), 73 (100) (Found Mϩ, 418.1816. C22H34O2SSi2 requires
418.1818).
(Si(CH3)3), 23.3 (CH2), 33.7 (CH2), 36.8 (CH2), 42.2 (CH), 50.1
᎐
(CH), 54.4 (CH), 119.0 (C᎐N), 126.1 (olefinic CH), 127.2
᎐
(olefinic CH), 156.0 (C-Si(CH3)3), 158.0 (C-Si(CH3)3), minor
isomer 9g: 1.1 (Si(CH3)3), 20.7 (CH2), 29.5 (CH2), 34.2 (CH2),
᎐
39.0 (CH), 51.9 (CH), 55.9 (CH), 119.5 (C᎐N), 126.6
᎐
(olefinic CH), 135.0 (olefinic CH), 156.0 (C-Si(CH3)3), 158.0
(C-Si(CH3)3); m/z (EI) 303 (Mϩ, 15%), 288 (33), 210 (63), 122
(64), 73 (100) (Found Mϩ, 303.1829. C17H29NSi2 requires
303.1839).
5-Dimethylcyanomethyl-7,8-bis(trimethylsilyl)bicyclo[4.2.1]-
nona-3,7-diene 8h
nBuLi (1.49 M in hexane, 6.70 ml, 10.0 mmol) was added
dropwise to a stirred solution of diisopropylamine (1.40 ml,
10.0 mmol) in THF (10 ml) at Ϫ78 ЊC under an atmosphere of
nitrogen. The resultant solution was warmed to 0 ЊC for 15 min
then recooled to Ϫ78 ЊC before addition of isobutyronitrile
(0.91 ml, 10.0 mmol). The reaction mixture was stirred for 1 h
at this temperature after which time an aliquot (0.48 ml,
0.25 mmol was removed) and added dropwise to a stirred
solution of complex 6 (100 mg, 0.25 mmol) in THF (5 ml) at
Ϫ78 ЊC. The mixture was stirred at this temperature for 20 min,
quenched by the addition of saturated aqueous NH4Cl (1 ml)
and warmed to room temperature. The product was extracted
with diethyl ether (3 × 5 ml) and the combined organics were
washed with water (10 ml), brine (10 ml), dried (MgSO4) and
concentrated in vacuo to give an orange oil. Flash chrom-
atography (diethyl ether–petrol, 1 : 20) afforded the title
compound 8h (69 mg, 83%) as a yellow solid, mp 80–81 ЊC (from
ethanol–water); (Found: C, 68.69; H, 10.01; N, 4.08.
C19H33NSi2 requires C, 68.81; H, 10.03; N, 4.22%); vmax
(CHCl3)/cmϪ1 2949, 2901, 2825, 2233, 1657 (C᎐C), 872; δ (500
5-Acetyl-7,8-diphenylbicyclo[4.2.1]nona-4,7-diene 19 and
5-acetyl-7,8-diphenylbicyclo[4.2.1]nona-2,7-diene 20
tBuLi (1.6 M in hexane, 1.30 ml, 2.07 mmol) was added
dropwise to a stirred solution of ethyl vinyl ether (0.21 ml,
2.17 mmol) in THF (10 ml) at Ϫ78 ЊC under an atmosphere of
nitrogen. The yellow reaction mixture was warmed to 0 ЊC and
the resultant colourless solution was recooled to Ϫ78 ЊC before
dropwise cannula addition of complex 7 (210 mg, 0.52 mmol) in
THF (4 ml). The reaction mixture was slowly warmed to 0 ЊC
over 6 h, HCl (0.1 M in ethanol, 5 ml) was added and the
mixture allowed to warm to room temperature before being
poured into HCl (0.1 M in ethanol, 60 ml) and stirred for
30 min. The resultant pale yellow solution was diluted with
diethyl ether (50 ml), washed with saturated aqueous NaHCO3
and extracted with diethyl ether (3 × 10 ml). The combined
organics were washed with water (10 ml), brine (10 ml), dried
(MgSO4) and concentrated in vacuo to give a yellow oil. Flash
chromatography (dichloromethane–petrol, 3 : 7) afforded title
ketone 20 (31 mg, 26%) as a colourless oil, vmax (CHCl3)/cmϪ1
᎐
H
MHz; CDCl3) 0.16 (9H, s, Si(CH3)3), 0.18 (9H, s, Si(CH3)3),
1.46 (3H, s, CH3), 1.47 (3H, s, CH3), 1.84 (1H, app. dt, J 12.0,
8.0, 9-H), 2.08 (1H, d, J 12.0, 9Ј-H), 2.24–2.32 (2H, m, 2-HH
and 5-H), 2.44 (1H, app. dtd, J 18.5, 4.0, 2.5, 2-HH), 3.10 (1H,
app. dt, J 8.0, 4.0, 1-H), 3.31 (1H, br d, J 8.0, 6-H), 5.41 (1H,
ddm, J 12.5, 4.5, 4-H), 5.54 (1H, ddm, J 12.5, 6.5, 3-H); δC(68
MHz; CDCl3) 1.2 (Si(CH3)3), 1.5 (Si(CH3)3), 26.4 (CH3), 27.2
(CH3), 34.2 (CH2), 36.5 (CH2), 36.9 (C-CN), 50.6 (CH), 51.6
᎐
(CH), 52.3 (CH), 124.0 (olefinic CH), 125.6 (C᎐N), 129.3
᎐
(olefinic CH), 156.8 (C-Si(CH3)3), 157.9 (C-(CH3)3); m/z (FAB)
332 (MHϩ, 7%), 136 (11), 95 (11), 73 (100) (Found MHϩ,
332.2222. C19H34Si2 requires 332.2298). Also recovered was
metal-free starting material (11 mg, 17%, data were in accord-
ance with the previously reported literature).7
2937, 1703 (C᎐O); δ (500 MHz; CDCl ) 1.47 (1H, d, J 11.5,
᎐
H 3
9Ј-H), 2.20 (3H, s, CH3), 2.52 (1H, app. dt, J 11.5, 8.0, 9-H),
2.58–2.73 (2H, m, 4-H), 3.37 (1H, app. t, J 8.0, 6-H), 3.97 (1H,
app. dt, J 8.0, 4.5, 5-H), 4.52 (1H, d, J 8.0, 1-H), 5.90 (1H, ddd,
J 11.0, 8.0, 3.0, 3-H), 6.17 (1H, ddd, J 11.0, 8.0, 3.0, 2-H),
J. Chem. Soc., Perkin Trans. 1, 2002, 2352–2359
2357

View Article Online
6.99–7.37 (10H, m, 10 × ArH); m/z (EI) 314 (Mϩ, 100%), 271
(31), 231 (21), 218 (24), 205 (32) (Found Mϩ, 314.1661. C23H22O
requires 314.1671). Further elution afforded title enone 19
(22 mg, 14%) as a colourless oil, vmax (CHCl3)/cmϪ1 2936, 1665
temperature and the solution was heated at reflux for 2 h. The
reaction mixture was cooled to room temperature before
addition of saturated aqueous NaHCO3(aq.) (1 ml) and extrac-
tion with dichloromethane (3 × 5 ml). The combined organics
were washed with water (5 ml), brine (5 ml), dried (MgSO4) and
concentrated in vacuo to give a yellow oil. Flash chrom-
atography (petroleum ether) afforded the title compound 23
(5 mg, 84%) as a colourless oil; vmax (CHCl3)/cmϪ1 2950, 2899,
1633, 868; δH(500 MHz; CDCl3) 1.69 (1H, d, J 12.5, 9Ј-H), 1.80
(1H, app. dt, J 12.5, 8.0, 9-H), 2.34 (1H, dm, J 18.5, 2-HH), 2.49
(1H, app. dtd, J 18.5, 5.0, 2.5, 2-HH), 2.84 (1H, br s, 1-H), 2.91
(1H, br d, J 8.0, 6-H), 3.66 (1H, br s, 5-H), 5.43 (1H, dm, J 12.5,
4-H), 5.56 (1H, dm, J 12.5, 3-H), 5.78 (1H, dd, J 5.5, 2.5, 7-H),
5.94 (1H, dd, J 5.5, 2.5, 8-H), 7.21 (1H, app. t, J 7.0, H para),
7.26 (2H, d, J 7.0, 2 × H ortho), 7.31 (2H, app. t, J 7.0, 2 × H
para); δC(100 MHz; CDCl3) 32.7 (CH2), 37.4 (CH2), 41.4 (CH),
50.2 (CH), 52.7 (CH), 126.1 (olefinic CH), 126.6 (olefinic CH),
127.7 (ArCH), 128.3 (ArCH), 128.4 (ArCH), 134.5 (olefinic
CH), 134.7 (olefinic CH), 144.4 (ArC); m/z (EI) 169 (Mϩ, 1%),
130 (100), 115 (14), 77 (2) (Found Mϩ, 196.1253. C15H16
requires 196.1252).
(C᎐O), 1454, 1073; δ (500 MHz; CDCl ) 1.88 (1H, d, J 12.0,
᎐
H
3
9Ј-H), 2.14 (1H, app. dt, J 12.0, 7.0, 9-H), 2.41 (3H, s, CH3),
2.68 (1H, dd, J 15.5, 7.0, 2-HH), 2.81 (1H, m, 2-HH), 3.24 (1H,
m, 3-H), 3.34 (1H, app. dt, J 14.0, 7.0, 3-HH), 4.34 (1H, d, J 7.0,
6-H), 4.78 (1H, app. t, J 7.0, 1-H), 6.79–6.84 (2H, m, 4-H and
ArH), 7.05–7.19 (4H, m, 4 × ArH), 7.28–7.35 (3H, m, 3 ×
ArH), 7.69 (2H, d, J 6.9, 2 × ArH); δC(100 MHz; CDCl3) 26.0
(CH3), 39.0 (CH2), 39.6 (CH2), 41.0 (CH), 55.3 (CH), 57.9
(CH2), 92.8 (C-Ph), 98.8 (C-Ph), 126.6 (ArCH), 127.2 (ArCH),
127.3 (ArCH), 128.8 (ArCH), 129.1 (ArCH), 139.2 (ArC),
140.5 (ArC), 146.5 (C-4), 148.5 (C-5), 199.0 (C᎐O); m/z (EI) 314
᎐
(Mϩ, 30%), 271 (10), 223 (32), 105 (100), 77 (27) (Found Mϩ,
314.1660. C23H22O requires 314.1671).
5-Acetyl-7,8-bis(trimethylsilyl)bicyclo[4.2.1]nona-4,7-diene 21
Ketone 8d (40 mg, 0.13 mmol) was treated with HCl (1.0 M in
ethanol, 8 ml) and stirred at room temperature for 3 d. The
mixture was diluted with diethyl ether (5 ml), neutralised with
aqueous NaHCO3 (20 ml) and extracted with diethyl ether
(3 × 5 ml). The combined organic extracts were washed with
water (10 ml), dried (MgSO4) and concentrated in vacuo to give
a pale yellow oil. Flash chromatography (dichloromethane–
petrol, 3 : 7) afforded the title enone 21 (33 mg, 84%) as a colour-
less oil; vmax (CHCl3)/cmϪ1 2928, 2858, 1660 (C᎐O), 1623 (C᎐C),
5-Acetyl-7,8-bis(trimethylsilyl)-9-ethoxycarbonyl-9-azabicyclo-
[4.2.1]nona-3,7-diene 27
tBuLi (1.5 M in hexane, 4.02 ml, 6.03 mmol) was added
dropwise to a stirred solution of ethyl vinyl ether (0.69 ml,
7.25 mmol) in THF (10 ml) at Ϫ78 ЊC under an atmosphere of
nitrogen. The yellow reaction mixture was warmed to 0 ЊC and
the resultant colourless solution recooled to Ϫ78 ЊC before
dropwise cannula addition of complex 26 (481 mg, 1.02 mmol)
in THF (12 ml). The brown reaction mixture was stirred for 1 h
at this temperature prior to addition of HCl (0.02 M in ethanol,
5 ml) and the resultant red solution was allowed to warm to
room temperature before being poured into HCl (0.02 M in
ethanol, 60 ml) and stirred for 30 min. The resultant yellow
solution was diluted with diethyl ether (50 ml), poured into
saturated aqueous NaHCO3 (5 ml) and extracted with diethyl
ether (3 × 20 ml). The combined organics were washed with
water (20 ml), brine (20 ml), dried (MgSO4) and concentrated
in vacuo to give an orange oil. Flash chromatography
(dichloromethane–petrol, 3 : 7) afforded the title compound 27
(250 mg, 52%) as a colourless oil, (Found: C, 59.81; H, 8.71; N,
3.69. C19H33NOSi2 requires C, 60.11; H, 8.76; N, 3.69%); vmax
(CHCl3)/cmϪ1 3428, 2958, 1704, 1357; δH(400 MHz; CDCl3, 333
K) 0.21 (9H, s, Si(CH3)3), 0.27 (9H, s, Si(CH3)3), 1.24 (3H, t,
J 7.0, OCH2CH3), 2.23 (3H, br s, CH3), 2.35 (1H, dd, J 18.5,
6.5, 2-HH), 2.85 (1H, br d, J 18.5, 2-HH), 3.29 (1H, br s, 5-H),
4.03–4.18 (2H, m, OCH2CH3), 4.99 (1H, br s, 1-H), 5.25 (1H, br
s, 6-H), 5.28 (1H, dddt, J 12.5, 6.0, 3.0, 1.0, 4-H), 5.56 (1H, app.
ddt, J 12.5, 6.5, 1.0, 3-H); δC(100 MHz; CDCl3, 2 rotamers)
major rotamer: 0.8 Si(CH3)3), 14.4 (OCH2CH3), 29.6 (CH3),
36.1 (C-2), 61.1 (OCH2CH3), 61.7 (C-5), 67.9 (C-1), 69.2 (C-6),
122.7 (C-4), 128.0 (C-3), 152.4 (NCO2CH2CH3), 152.7
᎐
᎐
877 (Si-CH3); δH(500 MHz; CDCl3) 0.07 (9H, s, Si(CH3)3), 0.22
(9H, s, Si(CH3)3), 1.21 (1H, d, J 11.5, 9Ј-H), 1.62 (1H, dddd,
J 14.0, 12.5, 3.5, 2.0, 2-HH), 1.81 (1H, dm, J 14.0, 2-HH), 1.90
(1H, app. dtd, J 11.5, 7.5, 1.5, 9-H), 2.17 (1H, app. ddt, J 16.5,
9.0, 3.5, 3-HH), 2.26 (1H, m, 3-HH), 2.29 (3H, s, CH3), 3.18
(1H, ddd, J 7.5, 5.5, 1.5, 1-H), 4.24 (1H, dd, J 7.5, 1.5, 6-H),
6.87 (1H, ddd, J 9.0, 3.5, 1.0, 4-H); δC(100 MHz; CDCl3) 0.9
(Si(CH3)3), 1.3 (Si(CH3)3), 25.4 (CH2), 25.6 (CH3), 33.6 (CH2),
42.2 (CH2), 48.3 (CH), 52.2 (CH), 144.1 (C-4), 148.3 (C-5),
152.6 (C-Si(CH ) ), 156.8 (C-Si(CH ) ), 198.5 (C᎐O); m/z (EI)
᎐
3
3
3 3
306 (Mϩ, 20%), 291 (30), 233 (11), 147 (13), 109 (16), 73 (100)
(Found Mϩ, 306.1850. C17H30OSi2 requires 306.1835).
5-Acetylbicyclo[4.2.1]nona-4,7-diene 22
Trifluoroacetic acid (0.50 ml, 6.54 mmol) was added dropwise
to ketone 8d (200 mg, 0.65 mmol) in dichloromethane (12 ml) at
room temperature and the solution was heated at reflux for
14 h. The reaction mixture was cooled to room temperature
before addition of saturated aqueous NaHCO3 (5 ml) and
extraction with dichloromethane (3 × 5 ml). The combined
organics were washed with water (10 ml), brine (10 ml), dried
(MgSO4) and concentrated in vacuo to give a yellow oil. Flash
chromatography (dichloromethane–petroleum ether, 2 : 3)
afforded the title compound 22 (106 mg, 100%) as a colourless
oil; vmax (CHCl3)/cmϪ1 3688, 2931, 1712 (C᎐O), 1601 (C᎐C);
᎐
᎐
(C-Si(CH ) ) 154.7 (C-Si(CH ) ), 207.5 (C᎐O), minor rotamer:
᎐
3
3
3 3
δH(500 MHz; CDCl3) 1.27 (1H, d, J 11.5, 9Ј-H), 1.73 (1H, m, 2-
HH), 1.86 (1H, m, 2-HH), 2.12 (1H, app. dt, J 11.5, 8.0, 9-H),
2.25–2.42 (2H, m, 3-H), 2.29 (3H, s, CH3), 2.86 (1H, app. dt,
J 8.0, 2.5, 1-H), 4.05 (1H, dd, J 8.0, 2.5, 6-H), 5.54 (1H, dd,
J 5.5, 2.5, 7-H), 5.94 (1H, dd, J 5.5, 2.5, 8-H), 6.88 (1H, dd,
J 8.0, 3.0, 4-H); δC(100 MHz; CDCl3) 25.6 (CH3), 26.2 (CH2),
34.5 (CH2), 40.2 (CH), 41.9 (CH2), 43.1 (CH), 129.4 (olefinic
CH), 133.0 (olefinic CH), 144.2 (olefinic CH), 147.3 (olefinic
1.0 Si(CH3)3), 14.8 (OCH2CH3), 28.9 (CH3), 36.3 (C-2), 61.1
(OCH2CH3), 61.7 (C-5), 67.4 (C-1), 69.2 (C-6), 123.1 (C-4),
128.3 (C-3), 152.6 (NCO2CH2CH3), 153.2 (C-Si(CH3)3) 154.2
(C-Si(CH ) ), 206.9 (C᎐O); m/z (FAB) 380 (MHϩ, 35%), 307
᎐
3
3
(13), 284 (55), 268 (24), 154 (57), 136 (50), 73 (100) (Found
MHϩ, 380.2068. C19H34NO3Si2 requires 380.2077).
5-Acetyl-7,8-bis(trimethylsilyl)-9-ethoxycarbonyl-9-azabicyclo-
[4.2.1]nona-4,7-diene 28
C), 198.9 (C᎐O); m/z (EI) 162 (Mϩ, 64%), 147 (25), 119 (43),
᎐
96 (98), 87 (100) (Found Mϩ, 162.1051. C11H14O requires
162.1045).
Ketone 27 (7 mg, 0.02 mmol) was treated with HCl (2.0 M in
ethanol, 5 ml) and stirred at room temperature for 3 d. The
mixture was diluted with ethyl acetate (10 ml), neutralised with
aqueous 2 M NaOH (5 ml) and extracted with ethyl acetate
(3 × 5 ml). The combined organic extracts were washed with
water (5 ml), brine (5 ml), dried (MgSO4) and concentrated
5-Phenylbicyclo[4.2.1]nona-3,7-diene 23
Trifluoroacetic acid (0.04 ml, 0.44 mmol) was added dropwise
to 8c (10 mg, 0.03 mmol) in dichloromethane (5 ml) at room
2358
J. Chem. Soc., Perkin Trans. 1, 2002, 2352–2359

View Article Online
Chemistry II, eds. E. W. Abel, F. G. A. Stone, G. Wilkinson,
in vacuo to give a yellow oil. Purification by passing through a
plug of silica (diethyl ether–petrol, 3 : 7) afforded the title com-
pound 28 (7 mg, 100%) as a colourless oil, vmax (CHCl3)/cmϪ1
2954, 1685, 1669; δH(400 MHz; CDCl3, 2 rotamers, 333 K) 0.15
(9H, s, Si(CH3)3), 0.29 (9H, s, Si(CH3)3), 1.10–1.40 (3H, m,
OCH2CH3), 1.82–1.93 (1H, dm, J 14.5, 2-HH), 2.21–2.50 (3H,
m, 2-HH and 3-H), 2.32 (3H, s, CH3), 3.97–4.23 (2H, m,
OCH2CH3), 4.95 (1H, br s, 1-H), 5.92 (1H, d, J 1.5, 6-H), 6.88
(1H, br d, J 8.5, 4-H); δC(100 MHz; CDCl3) 0.8 Si(CH3)3), 1.3
Si(CH3)3), 14.7 (OCH2CH3), 24.6 (CH2), 25.6 (CH3), 32.3
(CH2), 60.7 (OCH2CH3), 63.3 (CH), 68.8 (CH), 145.2 (C-4),
146.6 (C-5), 149.9 (C-Si(CH3)3), 152.2 (C-Si(CH3)3), 152.4
L. S. Hegedus, Elsevier Science Ltd., 1995, vol. 12, 979.
2 M. F. Semmelhack, J. J. Harrison and Y. Thebtaranonth, J. Org.
Chem., 1979, 44, 3275.
3 A. R. Pape, K. P. Kaliappan and E. P. Kundig, Chem. Rev., 2000,
100, 2917.
4 For a review of metal-mediated cycloadditions, see M. Lautens,
W. Klute and W. Tam, Chem. Rev., 1996, 96, 49.
5 J. H. Rigby, Tetrahedron, 1999, 55, 4521.
6 I. Fischler, F-W. Grevels, J. Leitich and S. Ozkar, Chem. Ber., 1991,
124, 2857.
7 K. Chaffee, P. Huo, J. B. Sheridan, A. Barbieri, A. Aistan,
R. A. Lalancette, R. L. Ostrander and A. L. Rheingold, J. Am.
Chem. Soc., 1995, 117, 1900.
8 Nucleophilic addition to cycloheptatriene complexes is known, see
(a) W. Chen, J. B. Sheridan, M. L. Cote and R. A. Lalancette,
Organometallics, 1996, 15, 2700; (b) C. Wang and J. B. Sheridan,
Organometallics, 1994, 13, 3639; (c) M.-C. P. Yeh and C-N Chuang,
J. Chem. Soc., Chem. Commun., 1994, 703.
(NCO CH CH ), 196.2 (C᎐O), m/z (EI) 379 (Mϩ, 32%), 364
᎐
2
2
3
(16), 306 (42), 73 (100) (Found Mϩ, 379.2015. C19H33NO3Si2
requires 379.1999).
9 R. E. J. Beckwith, A. J. Blake, M. B. Gravestock, N. S. Simpkins and
C. Wilson, Chem. Commun., 2000, 1097.
Acknowledgements
10 C. A. L. Mahaffy and P. L. Pauson, Inorg. Synth., 1979, 19,
We would like to thank the Engineering and Physical Sciences
Research Council (EPSRC) and AstraZeneca for support of
R.E.J.B.
154.
11 E. P. Kundig, J. A. F. Cunnigham, P. Paglia, D. P. Simmons and
G. Bernardinelli, Helv. Chim. Acta, 1990, 73, 386.
12 For
6025.
a review, see H. L. Mansell, Tetrahedron, 1996, 52,
References
13 C. G. Kreiter and S. Ozkar, Naturforsch, 1977, 32b, 408.
14 A. S. Pilcher and P. DeShong, J. Org. Chem., 1996, 61,
6901.
1 For a review of nucleophilic addition to η6-chromiumtricarbonyl
complexes, see M. F. Semmelhack in Comprehensive Organometallic
J. Chem. Soc., Perkin Trans. 1, 2002, 2352–2359
2359