Synthesis of dibenzofuran-1,4-diones using the D?tz benzannulation

Article abstract of DOI:10.1016/j.tet.2004.01.021

The chromium Fischer carbene complexes of benzofuran and benzothiophene have been prepared and can be used in D?tz benzannulations with alkynes for the regioselective and converg ent synthesis of dibenzofuran-1,4-dione heterocycles. The use of alkynylboronates led to model systems of the tricyclic ring system of popolohuanone E after oxidation. It would appear that the combination of alkynyl boronates with furan type Fischer carbene complexes leads to substantial amounts (～50%) of protodeboronated products.

Full text of DOI:10.1016/j.tet.2004.01.021

Tetrahedron 60 (2004) 2327–2335
Synthesis of dibenzofuran-1,4-diones using
¨
the Dotz benzannulation
†
*
James C. Anderson, Ross M. Denton, H. Gwen Hickin and Claire Wilson
School of Chemistry, University of Nottingham, Nottingham NG7 2RD, UK
Received 29 October 2003; revised 4 December 2003; accepted 8 January 2004
¨
Abstract—The chromium Fischer carbene complexes of benzofuran and benzothiophene have been prepared and can be used in Dotz
benzannulations with alkynes for the regioselective and converg ent synthesis of dibenzofuran-1,4-dione heterocycles. The use of
alkynylboronates led to model systems of the tricyclic ring system of popolohuanone E after oxidation. It would appear that the combination
of alkynyl boronates with furan type Fischer carbene complexes leads to substantial amounts (,50%) of protodeboronated products.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
the potential for this strategy to be divergent due to the
convergence of two different reaction partners.
The dibenzofuran-1,4-dione heterocycle is the central
structural element of popolohuanone E (Scheme 1), a
marine natural product isolated from the Pohnpei marine
sponge Dysidea sp which exhibits potent topoisomerase-II
inhibition and is cytotoxic against non-small cell lung
cancer cells.1 Access to this heterocyclic ring system has
classically relied upon the cyclisation of bisquinones using
acidic,2 photochemical,3 or oxidative4 methods. The
bisquinones were formed from the dimerisation of oxy-
genated phenyl rings, or the photochemical oxidative
dimerisation of certain quinones.5 Aside from often
mediocre to low yields and harsh reaction conditions these
classical methods restricted the structure of the final
dibenzofuran-1,4-dione due to the precursors being derived
from the homodimerisation of aromatic systems. The
convergent synthesis of dibenzofuran-1,4-diones from two
different aromatic systems has been achieved by the
phenol–chloranil reaction,6 but gave complex mixtures
with low yields of products.7 However, this last approach
has been used in a more modern and ingenious setting by
Terashima et.al. to prepare various model compounds of the
central tricyclic ring system of popolohuanone E.8 This
strategy was then used in an enantioselective synthesis of
popolohuanone E, but faltered at the removal of the 8-O-
methyl group.9 We decided to pursue a regioselective
synthesis of dibenzofuran-1,4-dione heterocycles using a
The reaction between chromium Fischer carbene complexes
10
and alkynes, first reported by Dotz in 1975, is renowned
¨
for it’s ability to construct highly substituted benzenoid
compounds from simple starting materials in one step with a
high degree of regiochemical control.11 We envisaged that
the development of this route would enable the synthesis of
diverse dibenzofuran-1,4-dione 2 systems currently inac-
cessible from existing classical methods (Scheme 2). For a
synthesis of more oxygenated heterocycles we would
require the alkynyl substituent X to be oxygen (Schemes 1
and 2). Although alkynylethers have been shown to react
with Fischer carbenes with good regioselectivities, they are
often low yielding.11e A masked oxygen function could be
introduced with the use of alkynylsilanes (X¼SiR3), but in
general these substrates show low regioselectivity.12,13 The
recent development by Harrity of alkynylboronic esters as
¨
partners in the Dotz benzannulation has shown these
substrates to provide excellent yields of regioisomerically
pure products.14 The boron substituent can be oxidised to a
hydroxyl group in the presence of basic hydrogen peroxide
to give high yields of hydroxyquinone (Scheme 2).15 We
¨
Dotz benzannulation strategy (Scheme 1). We recognised
¨
Keywords: Dibenzofuran-1,4-diones; Chromium carbenes; Dotz
benzannulation; Alkynyl boronates; Popolohuanone E.
*
Corresponding author. Tel.: þ44-115-951-4194; fax: þ44-115-951-3564;
e-mail address: j.anderson@nottingham.ac.uk
Corresponding author for X-ray crystal structures.
†
Scheme 1.
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.01.021

2328
J. C. Anderson et al. / Tetrahedron 60 (2004) 2327–2335
Scheme 3. Reagents: (i) t-BuLi; Cr(CO)6, Et2O; Me3OBF4, CH2Cl2; (ii)
0.05 M 5, 2 equiv. 6, THF, 50 8C, 18 h; 8 equiv. CAN, 0.5 M in 0.1 M
HNO3; (iii) 2 equiv. 6, 10 g SiO2 per mmol 6, 50 8C, 3 h; 8 equiv. CAN,
0.5 M in 0.1 M HNO3.
Scheme 2.
¨
Table 1. Dotz benzannulation of 5 with 6a-d
report here our results for the synthesis of dibenzofuran-1,4-
diones using the Dotz benzannulation of benzofuran
R0
R00
Yield (%)
¨
chromium Fischer carbene complex 1 with both terminal
and symmetrical alkynes and alkynylboronic esters.
Product
Conditions
7a
7b
7c
7d
7a
7b
7c
ii
ii
ii
ii
iii
iii
iii
Ph
Ph
H
H
B-pinacol
Ph
H
H
81
71
41
47
61
35
29
n-Bu
t-Bu
n-Bu
Ph
n-Bu
t-Bu
The Dotz benzannulation chemistry of 2-furyl 316 and 2-(N-
¨
methyl)indole 417 chromium Fischer carbene complexes
(Fig. 1) are known, but the corresponding reactions of
benzofuran complex 1 to the best of our knowledge has not
¨
been reported. We also report Dotz benzannulation studies
with the sulfur analogue of 1.
formation of 31% o0f the corresponding protodeboronated
product of 7d (R ¼H). Evidence suggests that the
substantial amount of protodeboronated product is formed
via protodeboronation of the acid labile alkynylboronic acid
2. Results and discussion
by the acidic phenolic proton from the initial chromium
14
arene complex formed from the Dotz reaction. The
¨
The chromium Fischer carbene complex 5 of benzofuran
was prepared in the standard way (Scheme 3).18 We found
the use of t-BuLi instead of n-BuLi avoided the formation of
small quantities of [(butyl)methoxycarbene]pentacarbonyl–
chromium impurity. Reaction with symmetrical and term-
inal acetylenes 6a-c gave different results depending on
whether solution or solid state conditions19 were employed
(Table 1). Good yields of simple dibenzofuran-1,4-diones
were obtained from reaction in THF. The moderate yield
terminal acetylene thus formed (6b) then reacts in
preference to the alkynylboronic ester (6d) with 5. It is
interesting to note that a high level of protodeboronation has
been noted by Harrity for the 2-furyl chromium Fischer
carbene complex 3.14 This, coupled with our result, points
towards this problem being characteristic of these types of
furyl complexes or intermediates derived from them.
¨
For comparison it was decided to prepare the analogous and
novel sulfur containing Fischer carbene complex 8, which
was derived from benzothiophene as before in 69% yield.
Reaction with the same set of acetylenes 6a-c under solution
state conditions gave slightly lower yields of benzannulated
products 9a-c (Eq. 1), but with the same trend in yields
across the series. We assume the regioselectivity had
proceeded in line with literature precedent and by analogy
to the products from 5.
with t-butylethyne (6c) highlights the sensitivity of the Dotz
benzannulation to steric hindrance around the acetylene, no
cyclobutenone products were detected. In reactions with
terminal acetylenes 6bþc only one regioisomeric product
was observed. The regiochemistry of strutures 7b,c were
assigned (Scheme 3) based on extensive literature pre-
cedent11 and was corroborated through the single crystal
X-ray structure determination of 7c.20
Treatment of 5 with alkynylboronic ester 6d21 under
solution state conditions led to the dibenzofuran-1,4-dione
boronic ester 7d in 47% yield as a single regioisomer. The
regiochemistry was assigned based on literature precedent14
and by analogy to a similar product which was characterised
by single crystal X-ray structure determination (14, vide
supra). The mediocre yield of this reaction compared to
those with terminal acetylenes 6a and 6b is due to the
ð1Þ
¨
Having demonstrated that the Dotz benzannulation could be
used for the regioselective synthesis of certain dibenzo-
furan-1,4-diones we turned our attention to model studies
closer to the central dibenzofuran-1,4-dione core required
for the synthesis of popolohuanone E. One of the difficult
Figure 1.

J. C. Anderson et al. / Tetrahedron 60 (2004) 2327–2335
2329
bond constructions in the synthesis of this molecule and
related members of this family is the formation of the aryl-
neo-pentyl bond.9,22 In the synthesis of model acetylene 10
we encountered a similar problem in the construction of the
alkyne-neo-pentyl bond. This key bond was prepared
through homologation of an aldehyde in order to avoid
displacement reactions adjacent to the neo-pentyl centre.
Methylation of the enolate of commercially available
cyclohexane carboxaldehyde was not a trivial transform-
ation and a variety of standard reaction conditions led to low
yields, byproducts and difficulties upon scale up.23 We
reasoned that a base that was only sparingly soluble in the
reaction solvent could minimise the formation of byprod-
ucts. After a series of optimisation experiments we found
that a one pot procedure whereby the aldehyde was added to
reagent grade KOt-Bu in CH2Cl2 at 0 8C followed by methyl
iodide and warming to rt overnight led to 11 in 70–77%
yield (Scheme 4). This procedure seems to be one of very
few examples of the direct alkylation of the potassium
enolates of secondary alkyl substituted aldehydes24 and
does not require pre-drying or purification of KOt-Bu or
CH2Cl2. In order to simplify purification problems from
using excess ylid, aldehyde 11 was added to 1 equiv. of
(methoxymethyl)triphenylphosphoniumylide to give 12 in
67% yield. Hydrolysis of 12 (96%) was followed by Corey–
Fuchs alkynation, quenching with boronic ester 13,25 to give
the model alkynylboronic ester 10.
Scheme 5. Reagents: (i) 0.05 M 5, 3 equiv. 10, THF, 50 8C, 16 h; 8 equiv.
CAN, 0.5 M in 0.1 M HNO3; (ii) H2O2, Na2CO3, EtOH.
NMR revealed a ,1:1:1:1 mixture of silylated and
unsilylated, boronated/protodeboronated products. Con-
ducting a similar experiment in the presence of excess
MeI and K2CO3 led to a similar distribution of products.
These two attempts at trying to sequester the phenolic
proton before protodeboronation of 10 did not alter the ratio
of boronated to deboronated product probably because
proton transfer will be much faster than protection of the
phenolic hydroxyl group. Attempts at buffering reactions
with heterogeneous and homogeneous bases were similarly
ineffective. The boronic ester 14 was oxidised with basic
hydrogen peroxide to give hydroxy dibenzofuran-1,4-dione
16 in 88% yield.
Treatment of chromium Fischer carbene complex 5 with the
model acetylene 10 initially gave low yields of desired
product with substantial amounts of protodeboronated
product. Optimisation of reaction conditions in line with
Harrity’s original observation that good yields of quinone
products were formed using 3 equiv. of alkyne,14 led to the
isolation of dibenzofuran-1,4-dione boronic ester 14 as a
single regioisomer in 48% yield along with 42% of
protodeboronated product 15 (Scheme 5). The structure of
14 was verified by single crystal X-ray structure determi-
nation.20 The yield was similar to that observed for the
simpler system 7d. Protodeboronation is reportedly due to
the detrimental acidic proton from the phenolic reaction
intermediate.14 Wulff has isolated chromium arene (phe-
In a final study we wished to explore the reactivity of
benzofuran chromium Fischer carbene complexes that bore
oxygen substituents on the aryl ring as these would more
closely mimic the types of dibenzofuran-1,4-diones needed
for the synthesis of polopolohuanone E. Due to the lack of
commercially available benzofurans27 we opted to prepare
complex 19. Without conducting the actual synthesis of the
popolohuanone E core, this complex would probe what
effect this more influential oxy substituent would have on
the reaction. The position of this particular oxygen
substituent (along with that at C-5) allows participation in
conjugation with the empty p-orbital of the carbene centre in
addition to its -I effect. We wanted to determine the effect
this substitution would have on the benzannulation reaction.
Protection of the hydroxyl group of commercially available
17 as its TBDPS silyl ether (94%), followed by reduction
with NaBH4 and an acidic workup provided benzofuran 18
in 81% yield (Scheme 6). Formation of the chromium
Fischer carbene as before gave the complex 19 in 51% yield.
¨
nolic) intermediates from Dotz benzannulation reactions by
conducting the reaction in the presence of TBDMS-Cl.26 In
an effort to sequester the detrimental proton from the
reaction intermediate we conducted an identical benzannu-
lation of 10 with 5 in the presence of TBDMS-Cl and
i-Pr2EtN. Analysis of the crude reaction mixture by 1H
Reaction of 19 with acetylene 6b gave one regioisomeric
Scheme 4. Reagents: (i) KOt-Bu, MeI, CH2Cl2, 70–77%; (ii) Ph3-
PvCHOCH3, Et2O, 71%; (iii) CF3CO2H, CH2Cl2, 96%; (iv) PPh3, CBr4,
Zn, CH2Cl2, 77%; (v) n-BuLi, 13; HCl, 65%.
Scheme 6. Reagents: (i) t-BuPh2SiCl, imidazole, CH2Cl2, 94%; (ii) NaBH4,
EtOH; 1 M HCl, 81%; (iii) t-BuLi; Cr(CO)6, Et2O; Me3OBF4, CH2Cl2,
51%.

2330
J. C. Anderson et al. / Tetrahedron 60 (2004) 2327–2335
to substantial amounts (,50%) of protodeboronated
products. Further use of this strategy for the synthesis of
popolohuanone E is ongoing and will be reported in due
course.
4. Experimental
4.1. General
Our general experimental details have been reported.28
4.1.1. [(2-Benzofuryl)methoxycarbene]pentacarbonyl-
chromium (5). To a stirred solution of benzofuran
(901 mg, 7.60 mmol) in Et2O (20 mL) under argon at
278 8C was added t-butyl lithium (4.47 mL of a 1.70 M
solution in pentane, 7.60 mmol) dropwise over 2 min. After
45 min the light yellow solution was added via cannula to a
stirred suspension of Cr(CO)6 (1.65 g, 7.60 mmol) in Et2O
at 278 8C. The reaction was then allowed to warm to rt over
1 h. After which time the solvent was removed from the
dark red reaction mixture in vacuo affording a foamy dark
red solid to which was added CH2Cl2 (20 mL) and
Meerweins salt (1.46 g, 9.88 mmol, 1.3 equiv.) portion-
wise over 5 min. The reaction was then stirred vigorously
for a further 20 min. After which time the blood red reaction
mixture was washed with saturated NaHCO3 (2£25 mL).
The combined organics were then dried (MgSO4) and
filtered. The filter cake was washed with CH2Cl2 until white.
The solvent was then removed in vacuo leaving a dark red
solid. Purification by flash column chromatography (silica
10% EtOAc/pet. ether) gave a dark red metallic solid 5
(1.89 g 71%). Mp 110–111 8C. IR (solid) nmax 2957, 2060,
Scheme 7. Reagents: (i) 0.05 M 19, 3 equiv. 6b or 10, THF, 55 8C, 24 h;
8 equiv. CAN, 0.5 M in 0.1 M HNO3; (ii) 5 equiv. HF·Py, THF, rt, 1.5 h;
(iii) H2O2, Na2CO3, EtOH.
product 20 (Scheme 7) under solution or solid state
conditions with the highest yield of 77% being obtained
using solution state conditions. It is noteworthy that
conjugation of the ether substituent reduces the reactivity
of the carbene complex which is reflected in the longer
reaction time required for consumption of 19 when
compared to the identical reactions with 5 (,24 h versus
,16 h). The regiochemistry was assumed from previous
experiments. Deprotection of the silyl group was quantita-
tive with HF·Py complex giving 21 as a deep purple solid.
The use of TBAF caused degradation, possibly due to ring
opening of the furan ring by hydroxide ion, to give a deep
purple coloured solution.3a
1993, 1950, 1611, 1522, 1436, 1220 cm21 1H NMR
;
(400 MHz) d 4.93 (3H, s, OCH3), 7.25 (1H, s, ArH), 7.30
(1H, t, J¼7.2 Hz, ArH), 7.52 (1H, t, J¼7.1 Hz, ArH), 7.65
(1H, d, J¼8.1 Hz, ArH), 7.76 (1H, d, J¼7.4 Hz, ArH); 13C
NMR (100 MHz) d 66.4 (OCH3), 106.7 (CH), 112.4 (CH),
124.3 (CH), 124.6 (CH), 127.2 (Cq), 129.0 (CH), 157.4
(Cq), 162.7 (Cq), 216.7 (CO), 224.4 (CO); m/z (EIþ) 352
(13%, Mþ), 324 (31%, Mþ2CO), 296 (20%, Mþ2(CO)2),
212 (100%, Mþ2(CO)5); HRMS C15H8O572Cr calcd
351.9675, found 351.9650. Anal. calcd for C15H8O7Cr, C,
51.15; H, 2.29. Found C, 51.32; H, 2.52.
Benzannulation of model acetylene 10 with 19 gave the
typical ratio (,1:1) of boronated 22 to protodeboronated
product 23 in isolated yields of 42 and 43%, respectively.
The sequential deprotection of the phenolic hydroxyl group
followed by oxidation of the boronate ester proceeded
smoothly to give 24 in 74% yield over the two steps as a
dark purple solid.
4.1.2. 2,3-Diphenyldibenzofuran-1-4-dione (7a). Repre-
sentative solution state procedure. To a stirred solution of
Fischer carbene 5 (86 mg, 0.24 mmol) in THF (2 mL) was
added diphenylacetylene (6a, 85 mg, 0.48 mmol,
2.0 equiv.). The reaction was then heated to 50 8C for
18 h, after which time the black reaction mixture was
concentrated in vacuo. The residue was diluted with Et2O
(2 mL) and aq. CAN (3.84 mL, 1.92 mmol, 8 equiv. of a
0.5 M soltn. in 0.1 M HNO3) was added via syringe in one
portion and the reaction was exposed to the air and stirred
vigorously for 30 min. The organic layer was then separated
and the aqueous layer extracted with Et2O (2£2 mL). The
combined organics were then washed with brine (5 mL) and
dried (MgSO4) and the solvent removed in vacuo to give a
deep orange powdery solid. Purification by flash column
chromatography (silica, 30% EtOAc/pet. ether) gave 7a as a
deep orange powder (63 mg, 81%).
3. Conclusion
The chromium Fischer carbene complexes of benzofuran
and benzothiophene have been prepared and shown to be
useful for the regioselective and convergent synthesis of
dibenzofuran-1,4-dione heterocycles. The methodology
works well for simple alkynes and although further
substitution on the benzo-ring of the chromium Fischer
carbenes would appear to be tolerated, the availability of the
parent benzofurans may pose a limitation to the structural
diversity of the products which would be easily available.
With alkynyl boronate partners the synthesis of model
systems of the tricyclic ring system of popolohuanone E can
be accomplished after oxidation of the product arylboronate
esters. It would appear that the combination of alkynyl
boronates with furan type Fischer carbene complexes leads

J. C. Anderson et al. / Tetrahedron 60 (2004) 2327–2335
2331
Representative procedure for dry state conditions. To a
stirred solution of Fischer carbene 5 (70 mg, 0.20 mmol) in
Et2O (1 mL) was added silica (4.0 g). After stirring for
5 min, the solvent was removed in vacuo. The flask was then
purged with nitrogen and dipheynlacetylene (6a, 71 mg,
0.40 mmol, 2.0 equiv.) was added. The mixture was then
heated at 50 8C for 3 h. After which time the cream solid
was suspended in Et2O (2 mL) and filtered. The filtrate was
then treated with aq. CAN, worked up and purified as above
to give 7a as a deep orange powder (41 mg, 61%).
129 8C. IR (solid) nmax 2970, 1658, 1574, 1372, 1138,
1
753 cm21; H NMR (400 MHz) d 0.96 (3H, t, J¼7.3 Hz,
t
CH2CH2CH2CH3), 1.48 (9H, s, Bu), 1.44–1.57 (4H, m,
CH2CH2CH2CH3), 2.58 (2H, t, J¼7.2 Hz, CH2CH2CH2-
CH3), 7.46 (1H, t, J¼7.6 Hz, ArH), 7.53 (1H, t, J¼7.8 Hz,
ArH), 7.65 (1H, d, J¼8.4 Hz, ArH), 8.17 (1H, d, J¼8.4 Hz,
ArH); 13C NMR (100 MHz) d 14.0 (CH3), 23.3 (CH2), 24.89
(CH3), 29.9 (CH2), 32.8 (CH2), 85.2 (Cq), 112.9 (CH),
121.9 (Cq), 122.6 (Cq), 123.4 (CH), 125.9 (CH), 129.9
(CH), 152.1 (Cq), 155.3 (Cq), 155.9 (Cq), 180.6 (CO), 183.7
(CO); m/z (EIþ) 380 (75%, Mþ), 323 (71%, Mþ2CH2CH2-
CH2CH3); HRMS C22H25BO5 calcd 380.1795, found
380.1796. Anal. calcd for C22H25BO5, C, 69.49; H 6.63.
Found C, 69.36; H, 6.47.
Mp .230 8C. IR (solid) nmax 1662, 1567, 1482, 1312, 1114,
1
1096, 1060, 852 cm21; H NMR (400 MHz) d 7.08–7.10
(4H, m, phenyl), 7.22–7.26 (6H, m, phenyl), 7.50 (1H, t,
J¼7.2 Hz, ArH), 7.61 (1H, t, J¼8.4 Hz, ArH), 7.72 (1H, d,
J¼8.1 Hz, ArH), 8.21 (1H, d, J¼7.7 Hz, ArH); 13C NMR
(100 MHz) 113.0 (CH), 122.0 (Cq), 122.6 (Cq), 123.7 (CH),
126.2 (2£CH), 127.8 (CH), 127.8 (CH), 128.5 (CH), 128.5
(CH), 129.4 (CH), 130.8 (CH), 132.2 (Cq), 132.6 (Cq),
143.1 (Cq), 144.4 (Cq), 151.7 (Cq), 156.5 (Cq), 177.3 (CO),
183.4 (CO); HRMS C24H14O3 calcd 350.0943, found
350.0935. Anal. calcd for C24H14O3, C, 82.27; H, 4.03.
Found C, 82.35; H, 3.88.
4.1.6. [(2-Benzothiophene)methoxycarbene]pentacarbo-
nylchromium (8). Prepared in an identical manner to 5.
Purification by flash column chromatography (silica 10%
EtOAc/pet. ether) gave a dark red metallic solid (1.44 g
69%). Mp 114–115 8C. IR (solid) nmax 2051, 1984, 1904,
1500, 1208, 1157; 1H NMR (400 MHz) d 4.92 (3H, s,
OCH3), 7.43 (1H, t, J¼7.5 Hz, ArH), 7.49, (1H, t, J¼7.1 Hz,
ArH), 7.82 (1H, d, J¼7.9 Hz, ArH), 8.00 (1H, d, J¼8.0 Hz,
ArH), 8.71 (1H, s, ArH); 13C NMR (100 MHz) d 66.7
(CH3), 122.9 (CH), 125.2 (CH), 126.8 (CH), 129.0 (CH),
139.2 (CH), 142.0 (Cq), 153.8 (Cq), 217.0 (CuO), 223.4
(CuO); m/z (EIþ) 339 (Mþ2(CO)), 283 (Mþ2(CO)3), 227
(Mþ2(CO)5); HRMS C15H8O562CrS calcd 367.9447, found
367.9441. Anal. calcd for C15H8O6CrS, C, 48.92; H 2.19.
Found C, 49.25; H, 2.21.
4.1.3. 2-Butyldibenzofuran-1,4-dione (7b). Purification by
flash column chromatography (silica, 20% EtOAc/pet.
ether) gave 7b as a yellow solid, 66 mg, 71% by solution
state and 45 mg, 35% by solid state. Mp 89–90 8C. IR
1
(solid) nmax 2960, 1660, 1602, 1572, 1318 cm21; H NMR
(400 MHz) d 0.97 (2H, t, J¼7.3 Hz, CH2CH2CH2CH2),
1.44 (2H, ap sex, J¼7.3 Hz, CH2CH2CH2CH2), 1.57 (2H, ap
quin J¼7.5 Hz, CH2CH2CH2CH2), 2.57 (2H, td, J¼7.7,
1.3 Hz, CH2CH2CH2CH2), 6.58 (1H, t, J¼1.3 Hz, ArH),
7.31 (1H, t, J¼7.8, 7.6 Hz, ArH), 7.55 (1H, t, J¼8.4, 7.6 Hz,
ArH), 7.67 (1H, d, J¼8.4 Hz, ArH), 8.18 (1H, d, J¼8.4 Hz,
ArH); 13C NMR (100 MHz) d 13.9 (CH3), 22.5 (CH2), 28.8
(CH2), 30.6 (CH2), 112.9 (CH2), 122.4 (Cq), 122.5 (Cq),
123.4 (CH), 126.0 (CH), 129.2 (CH), 131.4 (CH), 151.2
(Cq), 156.0 (Cq), 177.7 (CO), 183.8 (CO); m/z (EIþ) 254
(62%, Mþ), 212 (100%, Mþ2C3H6), 184 (27%,
Mþ2C4H6O); HRMS C16H14O3 calcd 254.0943, found
254.0931.
4.1.7. 2,3-Diphenyldibenzothiophene-1-4-dione (9a). Pre-
pared using solution state method. Purification by flash
column chromatography (silica 30% EtOAc/pet. ether) gave
9a as a deep orange powder (77 mg, 61%). Mp .230 8C. IR
1
(solid) nmax 1654, 1601, 1463, 1382, 1090, 944 cm21; H
NMR (400 MHz) d 7.18 (4H, m, phenyl), 7.23 (6H, m,
phenyl), 7.65 (2H, m, ArH), 8.04 (1H, d, J¼7.0 Hz, ArH),
8.85 (1H, d, J¼6.5 Hz, ArH); 13C NMR (125 MHz) d
123.07 (CH), 126.97 (CH), 127.29 (CH), 127.77 (CH),
128.21 (CH), 128.42 (CH), 132.66 (Cq), 133.05 (Cq),
133.62 (Cq), 136.18 (Cq), 142.04 (Cq, 144.30 (Cq), 145.55
(Cq), 181.55 (CuO), 182.27 (CuO); m/z (EIþ) 366
(100%, Mþ); HRMS C24H14O2S calcd 366.0711, found
366.0717.
4.1.4. 2-t-Butyldibenzofuran-1-4-dione (7c). Purification
by flash column chromatography (silica, 20% EtOAc/pet.
ether) gave 7c as a yellow solid, 26 mg, 41% by solution
state and 31 mg, 29% by solid state. Mp sublimed at 182 8C.
IR (solid) nmax 2971, 1660, 1750, 1124, 753 cm21; 1H NMR
(400 MHz) d 1.40 (9H, s, C(CH3)3), 6.57 (1H, s, C3-H), 7.28
(1H, ddd, J¼8.0, 7.0, 1.0 Hz, ArH), 7.55 (1H, ddd, J¼8.4,
7.2, 1.3 Hz, ArH), 7.67 (1H, d, J¼7.7 Hz, ArH), 8.20 (1H, d,
J¼8.0 Hz, ArH). 13C NMR (100 MHz) d 29.8 (CH3), 35.8
(Cq), 112.9 (CH), 122.9 (Cq), 123.5 (Cq), 126.0 (CH), 129.2
(CH), 130.8 (CH), 151.2 (Cq), 156.2 (Cq), 157.3 (Cq), 178.0
(CvO), 184.0 (CvO); m/z (EIþ) 254 (100%, Mþ), 198
(17%, Mþ2(CH3)3); HRMS C16H14O3 calcd 254.0943,
found 254.0951.
4.1.8. 2-Butyldibenzothiophene-1,4-dione (9b). Prepared
using solution state method. Purification by flash column
chromatography (silica 20% EtOAc/pet. ether) gave 9b as
orange needles (63 mg, 52%). Mp 86–87 8C. IR (solid) nmax
1
2959, 1613, 1463, 1332, 1293, 1082, 890 cm21; H NMR
(400 MHz) d 0.98 (3H, t, J¼7.2 Hz, CH2CH2CH2CH3),
1.45 (2H, sex, J¼7.2 Hz, CH2CH2CH2CH3), 1.69 (2H, quin,
J¼7.1 Hz, CH2CH2CH2CH3), 2.57 (2H, td, J¼7.0 Hz, 1.2,
CH2CH2CH2CH3), 6.85 (1H, t, J¼1.3 Hz, ArH), 7.52–7.55
(2H, m, ArH), 7.92 (1H, d, J¼7.2 Hz, ArH), 8.75 (1H, d,
J¼7.1 Hz, ArH); 13C NMR (100 MHz) d 13.9 (CH3), 22.6
(CH2), 29.0 (CH2), 30.5 (CH2), 123.1 (CH), 125.5 (CH),
127.4 (CH), 128.0 (CH), 132.8 (CH), 133.9 (Cq), 135.1
(Cq), 141.5 (Cq), 145.5 (Cq), 152.1 (Cq), 182.0 (CuO),
182.5 (CuO); m/z (EIþ) 270 (100%, Mþ), 241 (21%,
Mþ2CH2CH3), 228 (96%, Mþ2CH2CH2CH3); HRMS
C16H13O2S calcd 270.0714, found 270.0709.
4.1.5. 2-Butyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaboro-
lan-2-yl)dibenzofuran-1-4-dione (7d). Purification by
flash column chromatography (silica, 10% EtOAc/pet.
ether) gave 7d as dark yellow needles (32 mg, 47%) and
7b a yellow solid (14 mg, 31%). Data for 7d. Mp 127–

2332
J. C. Anderson et al. / Tetrahedron 60 (2004) 2327–2335
4.1.9. 2-t-Butyldibenzothiophene-1,4-dione (9c). Prepared
using solution state method. Purification by flash column
chromatography (silica 10% EtOAc/pet. ether) gave 9c as a
dark yellow needles (20 mg, 29%). Mp 172–174 8C. IR
(solid) nmax 2965, 2358, 1726, 1654, 1521, 1459, 1094,
749 cm21; H NMR (400 MHz) d 1.41 (9H, s, Bu), 6.75
(1H, s, ArH), 7.52–7.57 (2H, m, ArH), 7.92 (1H, d,
J¼8.0 Hz, ArH), 8.81 (1H, d, J¼7.8 Hz, ArH); 13C NMR
(100 MHz) d 29.8 (CH3), 35.9 (Cq), 123.1 (CH), 126.8
(CH), 127.1 (CH), 128.0 (CH), 132.1 (CH), 135.1 (Cq)136.4
(Cq), 141.7 (Cq), 144.3 (Cq), 158.4 (Cq), 182.5 (Cq), 182.8
(Cq); m/z (EIþ) 270 (100%, Mþ), 213 (21% Mþ2tBu);
HRMS C16H14O2S calcd 270.0714, found 270.0703.
J¼12.9 Hz, CHCHO), 6.22(1H, d, J¼12.9 Hz, CHCHO);
13C NMR (125 MHz) d 22.4 (CH2), 26.4 (CH2), 28.5 (CH3),
33.5 (Cq), 39.0 (CH2), 56.0 (OCH3), 114.2 (CH), 145.6
(CH); m/z (EIþ) 154 (2%, Mþ), 96 (98%, CH7CH12); HRMS
C10H18O calcd 154.1358, found 154.1359.
1
t
4.1.12. 4,4,5,5-Tetramethyl-2-[3-(1-methylcyclohexyl)-
prop-1-ynyl]-[1,3,2]-dioxaborolane (10). To a solution of
12 (2.81 g, 18.0 mmol) in CH2Cl2 (90 mL) at 0 8C was
added TFA (5.54 mL, 72 mmol, 4 equiv.). After 1 h the
reaction was brought to rt and stirred for a further 30 min.
Saturated aq. NaHCO3 (50 mL) was then added and stirring
continued until effervescence ceased. The aqueous layer
was then separated and extracted with CH2Cl2 (50 mL). The
combined organics were then washed with brine (40 mL)
and dried (MgSO4). The solvent was removed in vacuo to
give a pale yellow liquid, which was purified by flash
column chromatography (silica 10% EtOAc/pet. ether) to
afford the homologated aldehyde as a colourless liquid
(2.35, 92%). Spectroscopic data was identical to the
literature.29
4.1.10. 1-Methylcyclohexanecarboxaldehyde (11). To a
well stirred solution of cyclohexylcarboxaldehyde (15.0 g,
133 mmol) in CH2Cl2 (665 mL) at 0 8C was added KOtBu
(19.4 g, 172 mmol, 1.30 equiv.) in one portion followed by
MeI (25.0 mL, 399 mmol, 3.0 equiv.) in one portion. After
30 min the cloudy reaction mixture was brought to rt and
stirred for a further 1.5 h. The reaction mixture was then
poured into brine (500 mL) and the layers were separated.
The organic layer was then dried (MgSO4) and the solvent
removed in vacuo affording a light yellow oil. Purification
by a silica plug eluting with petrol gave a colourless oil
(13.9 g, 81%). IR (CHCl3) nmax 2905, 2852, 1714 cm21; 1H
NMR (400 MHz) d 1.00 (3H, s, CH3), 1.23–1.33 (2H, m,
Cy), 1.33–1.45 (2H, m, Cy), 1.45–1.54 (2H, m, Cy), 1.54–
1.63 (2H, m, Cy), 1.80–1.88 (2H, m, Cy), 9.44 (1H, s,
CHO)); 13C NMR (67.8 MHz) d 21.7 (CH3), 22.4 (CH2),
25.5 (CH2), 32.4 (CH2), 46.2 (Cq), 206.7 (CHO); m/z (EIþ)
126 (5%, Mþ), 97 (80%, Mþ2CHO); HRMS C8H14O calcd
126.1045, found 126.1050.
To a stirred suspension of Ph3P (10.5 g, 40.0 mmol,
2.0 equiv.) and Zn dust (2.61 g, 40.0 mmol, 2.0 equiv.) in
CH2Cl2 (90 mL) at 0 8C was added CBr4 (13.3 g,
40.0 mmol, 2.0 equiv.). The reaction was warmed to rt
and stirred for a further 15 h. The homologated aldehyde
from above (2.83 g, 20.0 mmol, 1.0 equiv.) was added to the
purple solution via cannula as a solution in CH2Cl2
(5 mLþ3 mL wash). After 1 h the reaction was concen-
trated in vacuo to give a dark purple foam which was
suspended in CH2Cl2 (5 mL) and extracted with petrol
(5£15 mL). The resulting cream solution was concentrated
in vacuo and purified immediately by flash column
chromatography (neutral alumina, pet. ether) and the vicinal
vinyl dibromide was obtained as a colourless liquid (4.49 g,
78%), which was stored under nitrogen, protected from light
and in a freezer to avoid decomposition. IR (CHCl3) nmax
2925, 2847, 1613, 1449 cm21; 1H NMR (400 MHz) d 0.91
(3H, s, CH3), 1.20–1.38 (5H, m, Cy), 1.38–1.52 (5H, m,
Cy), 2.04 (2H, d, J¼7.6 Hz, CH2CHCBr2), 6.43 (1H, t,
J¼7.6 Hz, CH2CHCBr2); 13C NMR (100 MHz) d 22.1
(CH2), 25.1 (CH3) 26.2 (CH2), 34.0 (Cq), 37.6 (CH2), 45.1
(CH2CHBr2), 89.0 (CH2CHCBr2); m/z (EIþ) 295 (3%, Mþ),
4.1.11. 1-(2-Methoxyvinyl)-1-methylcyclohexane (12). To
a well stirred suspension of methoxymethylphosphonium
chloride (15.7 g, 38.7 mmol) in Et2O (175 mL) at 0 8C was
added KOtBu (4.33 g, 38.7 mmol, 1.30 equiv.) in one
portion. The reaction was then stirred at 0 8C for 45 min.
After which time 11 (4.47 g, 35.2 mmol, 1.0 equiv.) was
added as a solution in Et2O (10 mLþ5 mL wash) via
cannula to the deep red coloured reaction mixture. After 1 h
the now chalky coloured reaction mixture was poured into
brine (200 mL) and the organic layer was separated and
washed again with brine (100 mL). The organic layer was
then dried (MgSO4) and concentrated in vacuo. Purification
by flash column chromatography (silica, 5% EtOAc/pet.
ether) afforded a colourless oil (3.56 g, 71%, 3:2, Z:E by 1H
NMR). The mixture of geometric isomers was not separated
and used directly in the next reaction.
215 (5%, C4H851Br2), 213 (10%, C4H759Br81Br), 211 (5%,
79
15
C4H759Br2), 97 (100%, C7H13); HRMS C10H Br81Br calcd
294.9520, found 294.9520. Anal. calcd for C10H16Br2, C,
40.57; H, 5.45. Found C, 40.68; H, 5.37.
To a stirred solution of the vicinal vinyl dibromide from
above (1.09 g, 3.61 mmol) in Et2O (15 mL) at 278 8C was
added n-butyl lithium (3.11 mL of a 2.35 M solution in
hexanes, 7.32 mmol, 2.0 equiv.) dropwise over 2 min under
an atmosphere of argon. After 1 h the resultant light yellow
solution was added to a solution of boronic ester 1324
(504 mg, 3.66 mmol 1 equiv.) in Et2O (2 mL) at 278 8C via
cannula over 5 min. The reaction was stirred for 3 h at
278 8C. After which time anhydrous HCl (8.06 mL of a
2.35 M solution in Et2O, 40.3 mmol, 1 equiv.) was added to
the reaction mixture which contained a voluminous white
precipitate and the reaction mixture was warmed to rt over
1 h. The reaction was then concentrated in vacuo. The
resultant pale orange liquid was filtered through a celite pad.
A small sample was partially separated on silica (hexane)
and gave in order of elution, Z-isomer. IR (CHCl3) nmax
2903, 2851, 1652, 1456, 1103 cm21; 1H NMR (400 MHz) d
0.98 (3H, s, CH3), 1.21–1.82 (10H, m, Cy), 3.53 (3H, s,
OCH3), 4.13 (1H, d, J¼7.1 Hz, CHCHO), 5.77 (1H, d,
J¼7.1 Hz, CHCHO); 13C NMR (67.8 MHz) d 23.0 (CH2),
26.3 (CH2), 28.6 (CH3), 35.2 (Cq), 38.9 (CH2), 59.5
(OCH3), 114.9 (CHCHO), 145.2 (CHCHO).
E-isomer. IR (CHCl3) nmax 2914, 2854, 1650, 1455,
1104 cm21 1H NMR (400 MHz) d 0.97 (3H, s, CH3),
;
1.10–1.52 (10H, m, Cy), 3.51 (3H, s, OCH3), 4.78 (1H, d,

J. C. Anderson et al. / Tetrahedron 60 (2004) 2327–2335
2333
The filtrate was then concentrated in vacuo to give a
colourless liquid which was distilled at reduced pressure
(142–143 8C at 0.1 mm/Hg) to give a colourless liquid
which immediately solidified to give 10 as a colourless solid
(591 mg, 68%). Mp 58 8C. IR (CHCl3) nmax 2980, 2854,
2204, 1449, 1382, 1343 cm21; 1H NMR (500 MHz) d 0.98
(3H, s, CH3), 1.23–1.58 (10H, m, Cy), 1.28 (12H, s,
((CH3)2CC(CH3)2), 2.19 (2H, s, CH2CC); 13C NMR
(125 MHz) d 22.1 (CH2), 24.6 (CH3), 24.9 (CH3), 26.2
(CH2), 32.7 (CH2), 33.4 (Cq), 37.1 (CH2), 83.2 (CuC), 84.1
(Cq), 103.0 (CuC); m/z (EIþ) 262 (3%, Mþ), 166 (17%,
Mþ2C7H12), 151 (33%, Mþ2C8H15); HRMS C16H27BO2
calcd 262.2104, found 262.2111.
nmax 3422, 3156, 2927, 2855, 2253, 1794, 1672, 1650, 1571,
1461, 1381, 1348, 1319, 1265, 1094, 895 cm21; H NMR
(500 MHz) d 0.93 (3H, s, CyCH3), 1.26–1.57 (10H, m, Cy),
2.53 (2H, s, CH2), 7.47 (1H, t, J¼8.2 Hz, ArH), 7.57 (1H, t,
J¼8.5 Hz, ArH), 7.64 (1H, d, J¼8.5 Hz, ArH), 8.20 (1H, d,
ArH); 13C NMR (500 MHz) d 22.3 (CH2, CH3), 26.4 (CH2),
33.52 (Cq), 35.5 (CH2), 38.50 (CH2), 112.9 (CH), 119.8
(Cq), 124.1 (CH), 124.5 (Cq), 126.2 (CH), 149.0 (Cq), 152.7
(Cq), 157.3 (Cq), 172.7 (CvO), 184.1 (CvO); m/z (EIþ)
324 (25%, Mþ), 228 (73%, C13H8O4), 97 (100%, C7H13);
HRMS C20H20O4 calcd 324.1362, found 324.1346.
1
4.1.15. 6-t-Butyldiphenylsilyloxybenzofuran (18). To a
stirred solution of alcohol 17 (624 mg, 4.14 mmol) in
CH2Cl2 (20 mL) was added t-butyldiphenylsilylchloride
(1.14 g, 4.14 mmol) and imidazole (281 mg, 4.14 mmol).
The reaction was then left to stir for 18 h at rt. After which
time the reaction was poured into brine (30 mL) and the
aqueous layer was extracted with CH2Cl2 (20 mL). The
combined organics were dried (MgSO4) and the solvent
removed in vacuo. Purification by column chromatography
(silica, 10% EtOAc/pet. ether) gave silyl protected 17 as a
white solid (1.52 g, 94%). Mp 100 8C. IR (CHCl3) nmax
2933, 2860, 1763, 1612, 1449, 1324, 1149, 1106, 1006,
956 cm21; 1H NMR (400 MHz) d 1.12 (9H, s, (CH3)3), 4.53
(2H, s, CH2), 6.40 (1H, d, J¼2.0 Hz, ArH), 6.55 (1H, dd,
J¼8.3, 1.8 Hz, ArH), 7.9–7.47 (7H, m, phenyl, ArH), 7.7 (4H,
m, phenyl); 13C NMR (100 MHz) d 26.38 (CH3), 60.48 (Cq),
75.38 (CH2), 103.74 (CH), 114.99 (Cq), 115.91 (CH), 124.97
(CH), 128.95 (CH), 130.43 (CH), 131.64 (Cq), 135.42 (CH),
164.65 (Cq), 175.86 (Cq), 197.88 (CvO); m/z (EIþ) HRMS
C24H24O3Si calcd 388.1495, found 388.1477. Anal. calcd for
C24H24O3Si, C, 74.19; H, 6.23. Found C, 74.49; H, 6.08.
4.1.13. 2-(1-Methylcyclohexylmethyl)-3-(4,4,5,5-tetra-
methyl-[1,3,2]-dioxaborolan-2-yl)dibenzofuran-1,4-
dione (14) and 2-(1-methylcyclohexylmethyl)dibenzo-
furan-1,4-dione (15). To a stirred solution of Fischer
carbene 5 (35 mg, 0.10 mmol, azeotroped from PhMe) in
THF (1.9 mL) was added acetylene 10 (80 mg, 0.30 mmol,
3 equiv., azeotroped from PhMe) and the reaction per-
formed in an identical manner to 7a to give a crude yellow
solid. Purification by flash column chromatography (silica,
10% EtOAc/pet. ether) afforded, in order of elution: 15 as
yellow needles (13 mg, 42%). Mp 191–192 8C. IR (CHCl3)
n
max 2928, 2851, 1665, 1570, 1446, 1374, 1313, 1142 cm21
;
1H NMR (400 MHz) d 0.91 (3H, s, CH3), 1.15–1.62 (10H,
m, Cy), 2.52 (2H, s, CH2Cy), 6.58 (1H, s, Ar), 7.47 (1H, m,
Ar), 7.55 (1H, m, Ar), 7.66 (1H, d, J¼8.4 Hz, Ar), 8.19 (1H,
d, J¼7.6 Hz, Ar); 13C NMR (125 MHz) d 22.1 (CH2), 24.7
(CH3), 26.3 (CH2), 35.2 (CH2), 38.0 (CH2), 40.0 (Cq), 112.9
(CH), 122.3 (Cq), 122.7 (Cq), 123.5 (CH), 126.0 (CH),
129.2 (CH), 134.1 (CH), 148.4 (Cq), 151.8 (Cq), 156.1 (Cq),
177.4 (CO), 184.0 (CO); m/z (EIþ) 308 (14%, Mþ), 212
(100%, Mþ2C7H12), 97 (52%, C7H13); HRMS C20H20O3
calcd 308.1412, found 308.1402.
To a stirred solution of silyl protected 17 from above
(980 mg, 2.52 mmol) in EtOH (12 mL) was added NaBH4
(48 mg, 1.26 mmol, 0.5 equiv.) portionwise over 5 min. The
reaction was then stirred at rt for 1 h. After which time 1 M
HCl (10 mL) was added. The product was extracted with Et2O
(2£10 mL) and the organics washed with brine (15 mL). The
combined organics were then dried (MgSO4) and the solvent
removed in vacuo. Purification by column chromatography
(silica, 20% EtOAc/pet. ether) gave the benzofuran 18
(759 mg, 81%) as a colourless viscous oil. IR (CHCl3) nmax
Compound 14 as yellow needles (22 mg, 48%). Mp 191–
192 8C. IR (solid) nmax 2931, 1657, 1602, 1348, 1141 cm21
;
1H NMR (500 MHz) d 0.97 (3H, s, CyCH3), 1.39–1.41 (6H,
m, Cy), 1.50 (12H, s, (CH3)2CC(CH3)3), 1.60–1.69 (4H, m,
Cy), 2.69 (2H, s, CH2), 7.54 (1H, t, J¼7.7 Hz, ArH), 7.60
(1H, t, J¼7.6 Hz, ArH), 7.72 (1H, d, J¼8.4 Hz, ArH), 8.26
(1H, d, J¼7.7 Hz, ArH); 13C NMR (125 MHz) d 22.3
(CH2), 24.9 (CH3), 25.1 (CH3), 26.4 (CH2), 85.1 (Cq), 113.0
(CH), 122.0 (Cq), 122.7 (Cq), 123.5 (CH), 125.8 (CH),
128.9 (CH), 152.0 (Cq), 153.7 (Cq), 156.0 (Cq), 180.3
(CvO), 184.4 (CvO); m/z (EIþ) 434 (5%, Mþ), 338
2933, 2894, 1619, 1589, 1291, 1154, 1106, 1103, 966 cm21
;
1H NMR (400 MHz) d 1.18 (9H, s, (CH3)3), 6.67 (1H, d,
J¼2.2 Hz, ArH), 6.88 (1H, dd, J¼8.5, 2.2 Hz, ArH), 7.01 (1H,
s, ArH), 7.42–7.81 (7H, m, phenyl, ArH), 7.85 (4H, m,
phenyl); 13C NMR (400 MHz) d 19.59 (Cq), 26.64 (CH3),
102.71 (CH), 106.34 (CH), 116.23 (CH), 120.76 (CH), 121.76
(CH), 127.88 (CH), 127.88 (CH), 130.01 (CH), 132.93 (Cq),
135.63 (CH), 144.18 (CH), 153 (Cq), 155.58 (Cq); m/z (EIþ)
372 (51%, Mþ), 315 (100%, Mþ2tBu); HRMS C24H24O2Si
calcd 372.1554, found 372.1546.
(100%, Mþ2C7H12), 97 (52%, C7H13); HRMS C26H BO5
11
31
calcd 434.2264, found 434.2281.
4.1.14. 3-Hydroxy-2-(1-methylcyclohexylmethyl)diben-
zofuran-1,4-dione (16). To a stirred solution of quinone
14 (28 mg, 0.06 mmol) in EtOH (2.4 mL) was added excess
H2O2 (2.4 mL of a 30% aq. soltn.) followed by solid
Na2CO3 (6 mg, 0.06 mmol). The reaction mixture was
allowed to stir at rt for 30 min. After this time H2O (10 mL)
was added to the dark blue reaction. The product was
extracted with CH2Cl2 (2£3 mL) the combined organics
were then washed with brine (5 mL) and dried (MgSO4) and
the solvent removed in vacuo. Purification by flash
chromatography (silica 20% EtOAc/hex) afforded 16 as a
dark red solid (17 mg, 88%). Mp 162–164 8C. IR (CHCl3)
4.1.16. [(2-(6-t-Butyldiphenylsilyloxybenzofuryl))-
methoxycarbene]pentacarbonylchromium (19). Prepared
in an identical manner to 5. Purification by flash column
chromatography (silica 7% EtOAc/pet. ether) followed by
recrystallisation from petrol gave 19 as dark red plates
(615 mg, 55%). Mp .230 8C. IR (CHCl3) nmax 2055, 1988,
1
1620, 1493, 1257, 1204, 1166, 1121, 990 cm21; H NMR
(400 MHz) d 1.13 (9H, s, (CH3)3), 4.84 (3H, s, OCH3), 6.77

2334
J. C. Anderson et al. / Tetrahedron 60 (2004) 2327–2335
(1H, dd, J¼8.7, 2.1 Hz, ArH), 6.94 (1H, br s, ArH), 7.27
(1H, d, J¼5.7 Hz, ArH), 7.38–7.54 (7H, m, phenyl, ArH),
7.75 (4H, d, J¼7.3 Hz, phenyl); 13C NMR (100 MHz) d
19.91 (Cq), 26.85 (CH3), 66.49 (CH3), 103.17 (CH), 111.10
(Cq), 119.17 (CH), 121.68 (Cq), 130.60 (CH), 132.50 (CH),
135.87 (CH), 158.26 (Cq), 158.68 (Cq), 163.13 (Cq), 217.26
(CuO), 224.57 (CuO); m/z meaningful data could not be
obtained. Anal. calcd for C31H28OSiCr, C, 60.48; H, 4.32.
Found C, 60.86; H, 4.37.
(74 mg, 0.12 mmol, azeotroped from PhMe) in THF (2 mL)
was added acetylene 10 (95 mg, 0.36 mmol, 3 equiv.,
azeotroped from PhMe) and the reaction performed in an
identical manner to 7a, but heated for 24 h, to give a dark
orange oil. Purification by flash column chromatography
(silica, 30% EtOAc/pet. ether) gave, in order of elution, 23
(22 mg, 43%) as a dark orange viscous oil. IR (CHCl3) nmax
1
2927, 2873, 1662, 1621, 1562, 1199, 987, 822 cm21; H
NMR (400 MHz) d 0.87 (3H, s, CH3 cHexyl), 1.14 (9H, s,
t
CH3, Bu), 1.29–1.56 (10H, m, cHexyl), 2.47, (2H, CH2
4.1.17. 2-Butyl-7-(t-Butyldiphenylsilyloxy)dibenzofuran-
1,4-dione (20). To a stirred solution of Fischer carbene 19
(100 mg, 0.16 mmol) in THF (3 mL) was added acetylene
6b (0.035 mL, 0.37 mmol, 2.0 equiv.) and the reaction
performed in an identical manner to 7a, but heated for 24 h,
to give an orange solid. Purification by flash column
chromatography (silica, 10% EtOAc/pet. ether) gave 20 as a
yellow solid (64 mg, 55%). Mp .230 8C; nmax (CHCl3)
cHexyl), 6.47 (1H, s, ArH), 6.90 (1H, d, J¼2.1 Hz, ArH),
7.01 (1H, dd, J¼8.0, 2,2 Hz, ArH), 7.26.7.45 (6H, m, ArH),
7.72 (4H, m, ArH), 7.89 (1H, d, J¼8.7 Hz, ArH); 13C NMR
(100 MHz) d 19.6 (Cq), 22.1 (CH2), 24.6 (CH3), 26.2 (CH2),
26.5 (CH3), 35.1 (Cq), 38.0 (CH2), 39.9 (CH2), 103.5 (Cq),
116.4 (Cq), 120.2 (CH), 122.5 (Cq), 123.5 (CH), 128.1
(CH), 130.4 (CH), 132.0 (CH), 134.0 (CH), 135.6 (CH),
147.7 (Cq), 151.2 (Cq), 157.2 (Cq), 157.5 (Cq), 176.9 (Cq),
184.2 (Cq); m/z (EIþ) 562 (19%, Mþ), 505 (100%,
Mþ2tBu); HRMS C36H38O4Si calcd 562.2540, found
562.2535.
1
2399, 1662, 1602, 1521, 1424, 1232, 1016, 927 cm21; H
NMR (400 MHz) d 0.95 (3H, t, J¼7.2 Hz, CH2CH2CH2-
CH3), 1.14 (9H, s, (CH3)3); 1.42 (2H, sext, J¼7.3 Hz,
CH2CH2CH2CH3), 1.50 (2H, quin. J¼7.3 Hz, CH2CH2-
CH2CH3), 2.50 (1H, td, J¼7.1, 1.1 Hz, CH2CH2CH2CH3),
6.47 (1H, t, J¼1.1 Hz, ArH), 7.01 (1H, dd, J¼8.9, 2.1 Hz,
ArH), 7.37–7.45 (6H, m, phenyl), 7.71 (4H, d, J¼7.2 Hz,
phenyl), 7.88 (1H, d, J¼8.7 Hz, ArH); 13C NMR (400 MHz)
d 13.9 (CH3), 19.6 (Cq), 22.51 (CH2), 26.5 (CH3), 28.8
(CH2), 30.6 (CH2), 103.5 (CH), 116.3 (Cq), 120.3 (CH),
122.6 (Cq), 123.4 (CH), 128.1 (CH), 130.4 (CH), 131.3
(CH), 132.0 (Cq), 135.5 (CH), 150.4 (Cq), 151.4 (Cq), 157.2
(Cq), 157.5 (Cq), 177.2 (CvO), 184.1 (CvO); m/z (EIþ)
HRMS C32H32O4Si calcd 508.2070, found 508.2071.
Compound 22 (35 mg, 42%) as a dark orange viscous oil. IR
(CHCl3) nmax 3019, 2399, 1709, 1600, 1519, 1420, 1362,
1219, 1016 cm21; 1H NMR (400 MHz) d 0.92 (3H, s, CH3
t
cHexyl), 1.12 (9H, s, CH3, Bu), 1.40 (12H, s, CH3
boronate), 1.26–1.57 (10H, m, cHexyl), 2.56, (2H, CH2
cHexyl), 6.91 (1H, d, J¼2.1 Hz, ArH), 6.97 (1H, dd, J¼8.6,
2.1 Hz, ArH), 7.36.7.40 (6H, m, ArH), 7.70–7.81 (4H, m,
ArH), 7.85 (1H, d, J¼8.7 Hz, ArH); 13C NMR (100 MHz) d
19.6 (Cq), 22.3 (CH2), 24.1 (CH3), 25.0 (CH3), 26.3 (CH2),
26.5 (CH3), 35.6 (Cq), 38.0 (CH2), 42.8 (CH2), 85.1 (Cq),
103.5 (CH), 116.4 (Cq), 119.9 (CH), 122.2 (Cq), 123.4
(CH), 128.1 (CH), 130.3 (CH), 132.1 (Cq), 135.5 (CH),
151.5 (Cq), 153.0 (Cq), 157.1 (Cq), 157.3 (Cq), 179.8 (CO),
184.5 (CO); m/z (EIþ) 690 (12%, MH2þ); HRMS
C42H51BO6Si calcd 690.3548, found 690.3562.
4.1.18. 2-Butyl-7-hydroxydibenzofuran-1,4-dione (21).
To a stirred solution of silyl ether 20 (13 mg, 0.025 mmol)
in THF (0.1 mL) was added HF·py (1.7 mL of a ,70% soltn.
of HF in pyridine, 0.025 mmol). The reaction was stirred at
rt for 1.5 h after which time satd. aq. NaHCO3 (2 mL) was
added. The organic layer was separated and the aqueous
layer extracted with Et2O (3£1 mL). The combined
organics were then washed with brine (3 mL) and dried
(MgSO4). Purification by flash column chromatography
(silica, 30% EtOAc/pet. ether) afforded a dark purple solid
(6.5 mg, 97%). Mp 170–171 8C. IR (CHCl3) nmax 3685, 3156,
4.1.20. 7-Hydroxy-2-(1-methylcyclohexylmethyl)-3-
(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)dibenzo-
furan-1,4-dione (24). To a stirred solution of quinone 22
(18 mg, 0.026 mmol) in THF (0.2 mL) was added HF.py
(1.48 mL of a ,70% soltn of HF in pyridine, 0.052 mmol,
2.0 equiv.) the reaction was then stirred for 1 h at rt after
which time satd. aq. NaHCO3 (1 mL) was added and stirring
continued until effervescence ceased. The organic layer was
then separated and the aqueous layer extracted with Et2O
(2£1 mL) the combined organic layers dried (MgSO4) and
the solvents removed in vacuo to give the alcohol as a dark
red oil, which was used directly without purification in the
next step.
1
3012, 1974, 1661, 1571, 1097, 945, 897 cm21; H NMR
(400 MHz) d 0.97 (3H, t, J¼7.3 Hz, CH2CH2CH2CH3), 1.44
(2H, sex, J¼7.0 Hz, CH2CH2CH2CH3), 1.54, (2H, quin.
J¼7.3 Hz, CH2CH2CH2CH3), 2.54 (2H, td, J¼7.6, 1.0 Hz,
CH2CH2CH2CH3), 6.53, (1H, t, J¼1.4 Hz, ArH), 7.02 (1H,
dd, J¼8.6, 2.1 Hz, ArH), 7.13 (1H, d, J¼2.4 Hz, ArH), 8.01
(1H, d, J¼8.8 Hz); 13C NMR (100 MHz) d 13.9 (CH3), 22.5
(CH3), 28.8 (CH3), 30.6 (CH3), 99.2 (CH), 115.0 (Cq), 116.1
(CH), 122.8 (Cq), 124.1 (CH), 131.4 (CH), 150.5 (Cq), 151.3
(Cq), 157.6 (Cq), 157.7 (Cq), 177.4 (CO), 184.1 (CO); m/z
(EIþ) 270 (100%, Mþ), 228 (83%, Mþ2CH2CH2CH3), 213
(28%, Mþ2CH2CH2CH2CH3); HRMS C16H14O4 calcd
270.0892, found 270.0895.
To a stirred solution of the crude alcohol (11 mg) in EtOH
(0.1 mL) was added aq. H2O2 (0.2 mL, excess, of a 20
volumes aq. soltn.) followed by solid Na2CO3 (2 mg,
0.02 mmol, 1 equiv.) and the reaction was stirred at rt for
1.5 h, after which time water (1 mL) followed by Et2O
(1 mL) were added and the purple organic layer separated.
The aqueous layer was then extracted a further three times
with Et2O (1 mL). The combined organics where then dried
(MgSO4) and the solvent removed in vacuo to give a dark
purple solid which was purified by flash column chroma-
tography (silica, 30% EtOAc/pet. ether) to give 24 (6 mg,
4.1.19. 7-(t-Butyldiphenylsilyloxy)-2-(1-methylcyclohex-
ylmethyl)-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-
yl)dibenzofuran-1,4-dione (22) and 7-(t-butyldiphenylsi-
lyloxy)-2-(1-methylcyclohexylmethyl)dibenzofuran-1,4-
dione (23). To a stirred solution of Fischer carbene 19

J. C. Anderson et al. / Tetrahedron 60 (2004) 2327–2335
2335
in this strategy, but encountered many problems with the
¨
synthesis of model alkyne substrates. Their subsequent Dotz
74%) as a purple solid. Mp 176–179 8C. IR (CHCl3) nmax
3697, 3420, 2901, 1667, 1649, 1620, 1570, 1448, 1340,
1117, 1045, 972 cm21; 1H NMR (400 MHz) d 0.90 (3H, s,
CH3), 1.21–1.44 (10H, m, chexyl), 5.89 (1H, br s, OH), 7.00
(1H, dd, J¼7.0, 2.2 Hz, ArH), 7.06 (1H, d, J¼1.9 Hz, ArH),
7.11 (1H, s, OH), 8.04 (1H, d, J¼8.4 Hz); 13C NMR
(125 MHz) CD3OD d 22.0 (CH2), 24.1 (CH3), 26.9 (CH2),
34.4 (Cq), 35.7 (CH2). 38.2 (CH2), 97.1 (CH), 113.9 (Cq),
115.4 (Cq), 115.7 (CH), 117.1 (Cq), 123.0 (CH), 123.7 (Cq),
148.2 (Cq), 158.9 (Cq), 160.0 (Cq), 172.7 (Cq), 184.5 (Cq);
m/z (EIþ) 340 (2%, Mþ), 244 (100%, Mþ2C7H13); HRMS
C20H20O5 calcd 340.13107, found 340.12940.
benzannulations were low yielding and showed poor regio-
chemistry. Hickin, H. G. PhD Thesis, University of Nottingham,
2002.
14. Davies, M. W.; Johnson, C. N.; Harrity, J. P. A. J. Org. Chem.
2001, 66, 3525.
15. Davies, M. W.; Johnson, C. N.; Harrity, J. P. A. Chem.
Commun. 1999, 2107.
¨
16. (a) Dotz, K. H.; Dietz, R. Chem. Ber. 1978, 111, 2517. (b)
Yamashita, A.; Scahill, T. A. Tetrahedron Lett. 1982, 23,
3765. (c) Yamashita, A. J. Am. Chem., Soc. 1985, 107, 5823.
(d) McCallum, J. S.; Kunng, F. A.; Gilbertson, S. R.; Wulff,
W. D. Organometallics 1988, 7, 2346.
Acknowledgements
17. Bauta, W. E.; Wulff, W. D.; Pavkovic, S. F.; Zaluzec, E. J.
J. Org. Chem. 1989, 54, 3249.
We would like to thank the EPSRC, Syngenta (HGH) and
Pfizer (RMD) for financial support, Mr. T. Hollingworth and
Mr. D. Hooper for providing mass spectra and Mr. T. J.
Spencer for micro analytical data.
18. For an overview of the synthesis of Fischer carbene complexes
see: Fischer, E. O.; Kreiter, C. G.; Kollmeier, H. J.; Muller, J.;
Fischer, R. D. J. Organomet. Chem. 1971, 28, 237.
19. Harrity, J. P. A.; Kerr, W. J.; Middlemiss, D. Tetrahedron
1993, 49, 5565.
20. Crystallographic data (excluding structure factors) for 7c, 14
have been deposited with the Cambridge Crystallographic
Data Centre as supplementary publication numbers CCDC
221371 and 221372 respectively. Copies of data can be
obtained, free of charge, on application to CCDC, 12 Union
Road, Cambridge CB2 1EZ, UK (fax:þ44-1223-336033 or
e-mail: deposit@ccdc.cam.ac.uk).
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