A benzannulation strategy for the synthesis of phenols and heteroaromatic compounds based on the reaction of (trialkylsilyl)vinylketenes with lithium ynolates

Article abstract of DOI:10.1016/j.tet.2007.10.113

(Trialkylsilyl)vinylketenes react with lithium ynolates to generate 3-(oxido)dienylketenes, which undergo rapid 6π-electrocyclization. The ultimate products of this benzannulation are highly substituted resorcinol monosilyl ethers, which are formed via a [1,3] carbon to oxygen silyl?group shift. Further transformations of the benzannulation products are described providing efficient access to ortho-benzoquinones and benzofuran, benzoxepine, and benzoxocine ring systems.

Full text of DOI:10.1016/j.tet.2007.10.113

Available online at www.sciencedirect.com
Tetrahedron 64 (2008) 915e925
www.elsevier.com/locate/tet
A benzannulation strategy for the synthesis of phenols and
heteroaromatic compounds based on the reaction of
(trialkylsilyl)vinylketenes with lithium ynolates
*
Wesley F. Austin, Yongjun Zhang, Rick L. Danheiser
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Received 13 August 2007; received in revised form 17 October 2007; accepted 26 October 2007
Available online 3 December 2007
Abstract
(Trialkylsilyl)vinylketenes react with lithium ynolates to generate 3-(oxido)dienylketenes, which undergo rapid 6p-electrocyclization. The
ultimate products of this benzannulation are highly substituted resorcinol monosilyl ethers, which are formed via a [1,3] carbon to oxygen
silyl group shift. Further transformations of the benzannulation products are described providing efficient access to ortho-benzoquinones and
benzofuran, benzoxepine, and benzoxocine ring systems.
Ó 2007 Elsevier Ltd. All rights reserved.
Keywords: (Trialkylsilyl)vinylketenes; Benzannulation; Ynolates; Electrocyclic ring closure
1. Introduction
would require long, multistep routes using classical substitu-
tion methodology.
The development of efficient strategies for the synthesis of
highly substituted aromatic systems is a problem of consider-
able importance in organic chemistry. Classically, syntheses of
highly substituted benzenoid compounds have most often been
achieved by employing linear substitution strategies involving
sequential electrophilic substitution and metalationealkyl-
ation reactions. Frequently, however, a more effective ap-
proach involves the application of benzannulation methods:
convergent strategies in which the aromatic ring system is as-
sembled from two or more precursors in a single step, with all
(or most) substituents in place. Benzannulation strategies
enjoy significant advantages over conventional linear substitu-
tion strategies, especially when applied to the preparation of
highly substituted target molecules. For example, benz-
annulation routes generally avoid the regiochemical ambigui-
ties associated with aromatic substitution reactions, and
their intrinsic convergent character facilitates the efficient
assembly of highly substituted aromatic compounds that
In this paper we report full details of our studies of a benz-
annulation strategy based on the reaction of lithium ynolates
with (trialkylsilyl)vinylketenes (‘TAS-vinylketenes’).1 The uti-
lity of vinylketenes2 in organic synthesis is well-established.
Research in our laboratory has shown that [2þ2] cycloaddi-
tions of vinylketenes can serve as triggering steps in powerful
‘pericyclic cascade’ strategies for the synthesis of six- and
eight-membered carbocyclic compounds.3,4 In related studies,
we have demonstrated that (trialkylsilyl)vinylketenes are
remarkably stable ketenes, which exhibit reactivity comple-
mentary to other vinylketenes in many useful synthetic trans-
formations. Silyl substituents5 suppress the tendency of
vinylketenes to undergo dimerization and [2þ2] cycloaddi-
tion, allowing them to express their underlying reactivity as
electron-rich conjugated dienes in DielseAlder reactions6
and as reactive carbonyl compounds in [4þ1] annulations
leading to five-membered rings.7,8 Herein we report the reac-
tion of TAS-vinylketenes with lithium ynolates in a benzannu-
lation process that provides access to highly substituted
phenols and several classes of oxygen heteroaromatic com-
pounds (Scheme 1).
* Corresponding author. Tel.: þ1 617 253 1842; fax: þ1 617 252 1504.
E-mail address: danheisr@mit.edu (R.L. Danheiser).
0040-4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.10.113

916
W.F. Austin et al. / Tetrahedron 64 (2008) 915e925
OSiR3
OSiR3
produces only inert tetraalkylsilanes as byproducts. As shown
in Scheme 3, the siloxy alkyne ynolate precursors can be con-
veniently prepared in one step either from esters via the Ko-
walski reaction12 (10aed), or from readily available alkynes
by the method of Julia14 (10eek, 11). As noted previously,
TIPS ynol ethers can be purified by distillation or careful chro-
matography, and can be stored in solution at 0 ꢀC for extended
periods with minimal decomposition.
R1
O
R1
C
SiR3
R2
+
R2
R2
O
HO
OLi
R3
R3
R3
1
2
3
4
Scheme 1. Benzannulation strategy based on the reaction of lithium ynolates
with TAS-vinylketenes.
2. Results and discussion
Kowalski12
R1CO2Et
R1
OSi(i-Pr)3
10a-k
40-68%
8a-d
2.1. Synthesis of benzannulation reaction partners
a
b
c
d
e
f
R1= cyclohexyl
R1= i-Pr
Both reaction partners employed in the new benzannulation
strategy are readily available via known chemistry. TAS-vinyl-
ketenes are conveniently prepared in two steps from a0-diazo-
a,b-enones (5), which are themselves readily available from
methyl ketones using the detrifluoroacetylative diazo transfer
protocol developed in our laboratory.9 As outlined in Scheme
2, silylation10 of diazo ketones 5 furnishes a0-silyl-a0-diazo-
a,b-unsaturated ketones of type 6, which undergo photoche-
mical Wolff rearrangement6b upon irradiation to provide the
desired TAS-vinylketenes (7). As expected, these ketenes are
remarkably stable substances as compared to other vinyl-
ketenes. Triisopropyl derivatives such as 7 are recovered
unchanged after heating for several days at 80 ꢀC, and these
ketenes can be purified by conventional silica gel chromato-
graphy without detectable decomposition.
R1= CH CH OEt
2
2
R1= (E)-CH=CHPh
LiHMDS, THF;
then add
R1= CH CH CH=CH
2
2
2
LiOOt-Bu;
R1= n-Bu
i-Pr SiOTf
3
R1
H
R1= CH CH=CH
65-95%
g
h
i
2
2
R1= 1-cyclohexenyl
R1= Ph
R1= t-Bu
9e-k
j
k
R1= SiMe t-Bu
2
OSit-BuMe2
11
Scheme 3. Preparation of siloxy alkynes.
i-Pr3SiOTf, i-Pr2EtN
2.2. Benzannulation studies
O
Et2O-hexane
0 °C to rt
O
N2
N2
R3
R3
At the outset of our studies, the feasibility of the proposed
benzannulation was far from certain. As outlined in Scheme 4,
we envisaged that the reaction of lithium ynolates with TAS-
vinylketenes would lead initially to dienylketene intermediates
of type 12. Importantly, we expected that addition would
occur anti to the bulky trialkylsilyl group, thus resulting in
the stereoselective formation of the indicated (Z )-enolate. At
this point several modes of ring closure are conceivable (in
addition to intermolecular processes leading to dimeric and
oligomeric products). For example, the addition of ynolates
to aldehydes and ketones is well known and leads to the for-
mation of b-lactone enolates,11 and an analogous reaction in
this case would give rise to products of type 14. An alternative
mode of ring closure would generate the four-membered
carbocycle 15, an enolate derivative of a substituted 1,3-cyclo-
butanedione. Our expectation, however, was that intermediate
12 would most likely undergo facile 6p electrocyclic ring clo-
sure15,16 to afford the desired cyclohexadienone 13. Favoring
this mode of cyclization is the (Z )-enolate geometry of 12,
which enforces close proximity between the C-1 and C-6 car-
bon atoms at which bond formation is desired to occur. Also
important is the significant increase in charge stabilization
that should develop in the transition state leading to the 1,3-
dicarbonyl enolate system in 13. It was our expectation that
these factors would suffice to favor the desired mode of ring
75-89%
R2
6a-d
Si(i-Pr)3
R2
5a-d
R2= CH3, R3= CH3
hν (300 nm)
benzene
rt, 4 h
a
b
c
d
72-92%
R2, R3
=
(CH2)4
R2= CH3, R3= Et
R2= CH3, R3= C6H11
O
C
R3
Si(i-Pr)3
R2
7a-d
Scheme 2. Preparation of TAS-vinylketenes.
‘Ynolate anions’ serve as intermediates in a number of use-
ful synthetic transformations, and several reliable methods
have been developed for their preparation.11 For the generation
of the lithium ynolates employed in our benzannulation stu-
dies, we focused our attention on the cleavage of siloxy al-
kynes (‘silyl ynol ethers’) with methyllithium. This method,
first described by Kowalski,12 is a variant of the well known
strategy for the regiospecific generation of enolates introduced
by Stork and Hudrlik.13 For our purposes, this process offered
the attraction that it takes place under mild conditions and

W.F. Austin et al. / Tetrahedron 64 (2008) 915e925
917
OLi
OLi
R3
O
R1
6- electrocyclic
R1
SiR3
R2
C
SiR
R2
R1
O
SiR3
R2
3
closure
+
C
O
R3
R3
OLi
13
1
2
12
tautomerization
intermolecular
addition
O
reactions
LiO
SiR3
R2
OLi
R1
R1
HO
SiR3
R2
O
R1
SiR3
R2
LiO
R3
R3
14
R3
15
16
Scheme 4. Proposed benzannulation reaction pathway and potential side reactions.
closure over alternative cyclization pathways and intermole-
cular condensation reactions. The possibility that the cyclo-
hexadiene intermediate 13 might form via a concerted [4þ2]
cycloaddition of the ynolate to the ketene cannot be excluded;
however, previous research in our laboratory has demonstrated
that TAS-vinylketenes behave as electron-rich dienes in
DielseAlder cycloadditions and generally require electron-
deficient dienophiles for successful reaction.6 Consistent
with this is the observation that no reaction was observed to
take place upon heating a solution of TAS-vinylketene 7a
with siloxy alkyne 10f in toluene at reflux for 8 h.
of a 1:1 mixture of TAS-vinylketenes 7b and 17 with 1 equiv
of ynolate 18 led to the formation of two phenolic products
assigned by NMR and GCeMS analysis as 19 and 20. Neither
of the phenols 21 and 22 that would result from intermolecular
silyl group transfer could be detected in the crude product of
the reaction.
As outlined in Scheme 6, we propose that the observed silyl
group migration takes place via a 1,3 carbon/oxygen shift
involving a 6-silyl-2,4-cyclohexadienone intermediate of
type 24. 1,3-Silyl shifts in a-silyl ketones to form silyl enol
ethers are well known processes,17 and related rearrangements
involving silylcyclohexadienones have been observed in our
laboratory6b and others.18 We speculate that 24 is generated
by tautomerization of 23, which is itself derived from the ini-
tial electrocyclization product 13 via tautomerization to 16
followed by a series of (reversible) proton transfer steps.
The small difference in pKa1 and pKa2 values for the hydroxyl
groups in resorcinol (9.2 and 10.9 in water19) suggests that in-
terconversion of the monolithium salts 16 and 23 may proceed
via disproportionation to form a mixture of the corresponding
resorcinol and its dilithium derivative. Once 23 forms, tauto-
merization can produce the 6-silyl-2,4-cyclohexadienone 24,
which then aromatizes via irreversible 1,3-silyl shift.
Table 1 delineates the scope of the TAS-vinylketene-ynolate
benzannulation reaction. Optimal conditions were found to
involve the generation of the ynolate using 1 equiv of methyl-
lithium; low yields of benzannulation products were obtained
when TBAF, TBAT, or KOEt20 was employed in place of
MeLi for the reaction. Addition of the ynolate to TAS-vinylke-
tenes was observed to take place within 30e60 min at rt, and the
benzannulation products 26e36 were obtained in fair to good
yield following aqueous workup and chromatographic purifica-
tion. Direct analysis of the reaction mixture prior to workup
showed the presence of only silyl ether benzannulation prod-
ucts, suggesting that the silyl shift is not occurring during isola-
tion or purification. As noted above, direct reaction of siloxy
alkynes with TAS-vinylketenes did not take place at 25 ꢀC or
The initial investigation of the feasibility of the benzannu-
lation was conducted using TAS-vinylketene 7b and the lith-
ium ynolate derived from siloxy alkyne 10a. Cleavage of the
silyl ether took place smoothly upon exposure of the siloxy
alkyne to 1 equiv of methyllithium in THF at rt, with TLC
analysis indicating complete consumption of the silyl ynol
ether within 3.5 h. Addition of ketene 7b then resulted in
a gold-colored mixture, and TLC analysis showed the forma-
tion of a single new aromatic product, which was obtained in
67% yield following purification by silica gel chromatography.
1
Interestingly, however, H NMR data for this compound was
not consistent with that expected for the resorcinol derivative
with a hexa-substituted benzene ring that would result from
protonation of a benzannulation product of type 16. In partic-
ular, two downfield singlets were observed at 6.19 and
4.71 ppm, with only the latter exhibiting exchange with
D2O. Further analysis suggested that a migration of the trial-
kylsilyl group from carbon to oxygen had taken place, and
the benzannulation product was in fact the silyl ether 33 (Table
1, entry 1). Additional support for this structure was obtained
by NOE studies of the related annulation product 31 (Fig. 1),
which allowed unequivocal assignment of the regiochemistry
as that shown.
Evidence that the silyl ether benzannulation products are
formed via an intramolecular silyl shift was obtained by the
crossover experiment summarized in Scheme 5. Thus, reaction

918
W.F. Austin et al. / Tetrahedron 64 (2008) 915e925
Table 1
Benzannulation via reaction of TAS-vinylketenes with lithium ynolates
OSi(i-Pr)3
R1
1 equiv MeLi,
R1
HO
THF rt 0.5-4 h
O
R2
then add
C
Si(i-Pr)3
OSiR3
R3
1.0 equiv
rt, 30-60 min
R2
10a-k, 11
R3
7a-d
Entry
1
Alkyne
Ketene
Product
Yielda (%)
Entry
Alkyne
Ketene
Product
OSi(i-Pr)3
Yielda (%)
OSi(i-Pr)3
Ph
10f
7a
62
65
55
30
46
7
8
10d
10a
10h
11
7c
37
HO
32
CH3
HO
26
CH3
CH3
OSi(i-Pr)3
OSi(i-Pr)3
i-Pr
HO
27
Cy
2
3
4
5
10b
10j
10i
10c
7a
7a
7a
7c
7b
7b
7b
7d
67e71
HO
33
CH3
CH3
OSi(i-Pr)3
OSi(i-Pr)3
OSi(i-Pr)3
t-Bu
9
43
HO
CH3
CH3
HO
34
28
OSi(i-Pr)3
Ph
10
11
44e48
44e46
HO
CH3
CH3
HO
35
29
OSi(i-Pr)3
OSi(i-Pr)3
EtO
EtO
10c
HO
36
CH3
Cy
HO
30
CH3
OSi(i-Pr)3
6
10e
7c
68e70
12
10k
7a
See text
HO
31
CH3
a
Isolated yield of products purified by column chromatography.
at elevated temperatures, and attempts to promote benzannula-
tion with Lewis or Brønsted acids (ZnI2, TiCl4, AgNTf2,
HNTf2) were unsuccessful, resulting only in complex mixtures
of products.
Awide variety of siloxy alkynes participate in the benzannu-
lation (Table 1). Primary, secondary, and tertiary alkyl substitu-
ents on the siloxy alkyne are all well tolerated, and alkenyl and
aryl derivatives react albeit in somewhat diminished yield. A
low yield of the desired benzannulation product was obtained
in the case of the allyl-substituted acetylene 10g, apparently
due to competitive metalation at the methylene carbon by
MeLi during the ynolate generation step.21 This problem is eas-
ily circumvented, however, by substituting the TBDMS ynol
ether 11 for the TIPS derivative 10g as the ynolate precursor.
Cleavage of this more reactive siloxy alkyne is complete within
minutes, and upon reaction with TAS-vinylketene 7b the de-
sired benzannulation product 35 is obtained in good yield. In
general, however, the use of triisopropylsiloxy alkynes is
13%
14%
CH3
H
CH3
8%
H
H
OSi(i-Pr)3
CH2
H3C
Si(i-Pr)2
H3C
O
CH3CH2
4%
CH3CH2
OH
4%
OH
Figure 1. NOE studies on benzannulation product 31.

W.F. Austin et al. / Tetrahedron 64 (2008) 915e925
919
OSit-BuMe2
OR1
OSi(i-Pr)3
O
C
Sit-BuMe2
R
Si(i-Pr)3
t-BuMe2Si
HO
R
CH3
HO
CH3
R2O
CH3
CH3
CH3
17
CH3
O
CH3
19
+
OLi
CH3
18
+
R = CH2CH2CH=CH2
37a R1 = H, R2 = TBDMS
37b R1 = TBDMS, R2 = H
38
OSi(i-Pr)3
C
Si(i-Pr)3
R
HO
OSi(i-Pr)3
CDCl3
61 °C, 3.5 h
7b
20
38
(0.5 equiv each)
96%
50:50
t-BuMe2SiO
CH3
CH3
39
OSit-BuMe2
Scheme 7. Results of benzannulation of TAS-vinylketene 7e with the ynolate
derived from 10k.
Not Observed
OSi(i-Pr)3
R
HO
22
R
Upon heating in chloroform or benzene, 38 underwent carbon
to oxygen 1,3-silyl shift in near quantitative yield to afford
39, the structure of which was confirmed by desilylation to pro-
duce the corresponding resorcinol.23,24 In contrast, 37 was
largely unchanged after heating in toluene at reflux for 14 h.
We believe that annulation product 38 is generated via the usual
mechanism as outlined in Scheme 6 (where R1¼tert-butyldime-
thylsilyl), while 37a and 37b can arise from tautomeric forms of
intermediates 16 and 23, respectively.
HO
21
CH3
CH3
Scheme 5. Crossover experiment.
preferred due to their increased stability toward purification and
storage. With respect to the TAS-vinylketene annulation part-
ner, the only limitation identified to date is that TAS-aryl and
TAS-heteroarylketenes do not undergo benzannulation, pro-
ducing only complex mixtures of unidentifiable products. In
these cases the 6p electrocyclic ring closure would require
disruption of aromaticity, which may retard the rate of this
cyclization step and permit the alternative processes outlined
in Scheme 4 to become competitive.
Interesting results were obtained when the tert-butyldime-
thylsilyl-substituted ynolate derived from 10k was employed
in the benzannulation. In this case a 3:2 mixture of two phenols
was produced in a combined yield of ca. 40e60%.22 Spectro-
scopic analysis identified the minor product as 38 and the major
product as either 37a or the isomeric silyl ether 37b (Scheme 7).
Unfortunately, to date we have been unable to ambiguously dis-
tinguish between these two structures for the major product.
2.3. Transformations of benzannulation products
The regiocontrolled benzannulation strategy described
herein provides access to ortho-substituted phenols that can
participate in a variety of useful synthetic transformations.
Scheme 8 outlines several straightforward functional group
manipulations. Desilylation of 26 is readily accomplished
with TBAF to afford the expected resorcinol, and oxidation
of 26 with Fremy’s salt furnishes the ortho-quinone 41 in
good yield. Of particular synthetic utility are benzannulation
products bearing unsaturated ortho substituents such as 31,
32, 34, and 35, which are useful substrates in cyclizations
leading to a variety of benzofused oxygen heterocycles.25
OLi
OLi
O
R1
R1
O
SiR3
R2
R1
C
SiR3
R2
SiR3
R2
tautomerization
+
HO
R3
R3
OLi
R3
H
1
2
13
16
proton
transfers
O
1,3 C to O
silyl
OSiR3
OH
R1
SiR3
H
R2
R1
LiO
H
R1
SiR3
R2
tautomerization
migration
R2
LiO
LiO
R3
R3
25
R3
23
24
Scheme 6. Mechanism of silyl shift in benzannulation.

920
W.F. Austin et al. / Tetrahedron 64 (2008) 915e925
OH
A variety of benzofused oxygen heterocyclic systems are
also available from the benzannulation products through the
application of ring closing metathesis.28 Scheme 11 illustrates
this strategy as applied to the synthesis of the benzoxocine 46
and benzoxepine 47.
TBAF, THF
0 °C to rt, 2.5 h
Bu
77%
HO
CH3
OSi(i-Pr)3
CH3
Bu
HO
26
40
3. Conclusions
Fremy's Salt
Na2HPO4
CH3
CH3
O
acetone-H2O
rt, 24 h
Bu
HO
41
O
We have shown that TAS-vinylketenes react with lithium
ynolates in a regiocontrolled benzannulation process that
provides efficient access to highly substituted phenols. In con-
junction with transition-metal catalyzed cyclization reactions,
this strategy can be employed for the synthesis of a variety of
benzofused oxygen heterocycles, including benzofurans, ben-
zo[b]oxocines, and benzo[b]oxepines.
66%
CH3
CH3
Scheme 8. Desilylation and oxidation of benzannulation product 26.
For example, exposure of the ortho-allyl phenol 35 to catalytic
PdCl2(MeCN)2 in the presence of LiCl and benzoquinone pro-
vides tetrahydronaphthofuran 42 in good yield (Scheme 9),26
while the vinyl-substituted benzannulation product 34 can be
converted to the tetracyclic benzofuran 43 using the general
method of Lattanzi (Scheme 10).27
4. Experimental
4.1. General
All reactions were performed in flame-dried or oven-dried
glassware under a positive pressure of argon. Reaction mix-
tures were stirred magnetically unless otherwise indicated.
Air- and moisture-sensitive liquids and solutions were trans-
ferred by syringe or cannula and were introduced into reaction
vessels through rubber septa. Reaction product solutions and
chromatography fractions were concentrated by rotary evapo-
ration at ca. 20 mm Hg and then at ca. 0.1 mm Hg (vacuum
pump) unless otherwise indicated. Thin layer chromatography
was performed on Merck precoated glass-backed silica gel
60 F-254 0.25 mm plates. Column chromatography was per-
formed on Silicycle silica gel 60 (230e400 mesh) or Sorbent
silica gel 60A (32e63 mm).
OSi(i-Pr)3
OSi(i-Pr)3
cat. PdCl2(MeCN)2
benzoquinone, LiCl, THF
reflux, 3.5 h
H3C
O
HO
35
Scheme 9. Palladium-catalyzed cyclization of benzannulation product 35.
60%
42
OSi(i-Pr)3
OSi(i-Pr)3
cat. VO(acac)2
TBHP, CH2Cl2; then add
CF3CO2H, reflux 21 h
O
HO
34
Scheme 10. Synthesis of benzofuran from benzannulation product 34.
55%
4.2. Materials
43
Commercial grade reagents and solvents were used without
further purification except as indicated below. Triisopropyl-
silyl trifluoromethanesulfonate, 1,1,1,3,3,3-hexamethyldisila-
zane, benzene, and diisopropylethylamine were distilled
under argon from calcium hydride. Dichloromethane, diethyl
ether, and tetrahydrofuran were purified by pressure filtration
through activated alumina. Toluene was purified by pressure
filtration through activated alumina and copper(II) oxide.
Anhydrous tert-butyl hydroperoxide in toluene was prepared
from the aqueous solution as described by Sharpless.29 Meth-
yllithium was obtained from either Aldrich Chemical Co.
(1.6 M in Et2O, 0.05 M halide content) or Alfa Aesar (1e
2 M in Et2O, ‘low halide’). In some cases decreased yields
were observed when aged methyllithium was used in the ben-
zannulation. Methyllithium and n-butyllithium were titrated
according to the WatsoneEastham method using BHT in
THF with 1,10-phenanthroline as an indicator.30 Previously
reported methods were employed for the preparation of TAS-
vinylketenes 7a,6b 7b,6b 7c,1 and 7d.1 Several known siloxy
alkynes were prepared according to the previously described
procedures either using the method of Kowalski (10a,12
NaI, K2CO3
allyl bromide
acetone, reflux, 36 h
OSi(i-Pr)3
OSi(i-Pr)3
n
n
R1
O
R1
HO
R2
44 (65%)
45 (74%)
R2
31 R1 = CH3, R2 = Et, n = 2
35 R1, R2 = -(CH2)4-, n = 1
cat. 48
CH2Cl2
reflux, 1 h
OSi(i-Pr)3
OSi(i-Pr)3
N
N
Mes
Mes
Ph
CH3
O
O
Cl
Ru
PCy3
Cl
48
47 (96%)
46 (95%)
Scheme 11. Synthesis of oxygen heterocycles via ring closing metathesis.

W.F. Austin et al. / Tetrahedron 64 (2008) 915e925
921
10b,31 10c,1 10d,12) or the method of Julia (10e,32 10f,33 10g,1
10h,1 10i,14 10j,34 and 11;1 the preparation of the new siloxy
alkyne 10k is described below.
(300 MHz, CDCl3) d 5.22 (qq, J¼7.0, 1.3 Hz, 1H), 1.80 (app
quint, J¼1.1 Hz, 3H), 1.62 (dq, J¼6.7, 1.0 Hz, 3H), 0.93
(s, 9H), 0.18 (s, 6H); 13C NMR (75 MHz, CDCl3) d 184.6,
124.1, 120.3, 27.0, 25.3, 19.3, 19.2, 14.2, ꢁ4.3.
4.3. Instrumentation
4.5. 2-tert-Butyldimethylsilyl-1-(triisopropylsiloxy)-
ethyne (10k)
Melting points were determined with a FishereJohns melt-
ing point apparatus and are uncorrected. Infrared spectra were
obtained using a PerkineElmer 2000 FT-IR spectrophotome-
A 100-mL, two-necked, round-bottomed flask equipped with
a rubber septum and argon inlet adapter was charged with a
solution of tert-butyldimethylsilylacetylene (0.86 mL, 0.65 g,
4.6 mmol) in 15 mL of THF and cooled at ꢁ78 ꢀC while
5.5 mL of LiHMDS solution (1.0 M in THF, 5.5 mmol)35 was
added rapidly dropwise over 30 s. A 50-mL, two-necked,
round-bottomed flask equipped with a rubber septum and argon
inlet adapter was charged with a solution of tert-butyl hydroper-
oxide (4.0 M in toluene, 1.4 mL, 5.6 mmol) in 10 mL of THF
and cooled at ꢁ78 ꢀC while 6.0 mL of LiHMDS solution
(1.0 M in THF, 6.0 mmol) was added rapidly dropwise over
30 s. The resulting solution was transferred into the solution
of lithium acetylide via cannula over 3 min, the dry ice-acetone
bath was replaced with an ice-water bath, and the reaction mix-
ture was stirred for 2.5 h at 0 ꢀC. The reaction mixture was then
recooled to ꢁ78 ꢀC, and TIPSOTf (1.6 mL, 1.8 g, 6.0 mmol)
was added in one portion. The resulting mixture was stirred
for 45 min at ꢁ78 ꢀC and then at 0 ꢀC for 45 min. The mixture
was recooled to ꢁ78 ꢀC, diluted with 50 mL of hexanes, and
then poured into a separatory funnel containing 40 mL of satd
aqueous NaHCO3 solution. The aqueous phase was separated
and extracted with two 25-mL portions of hexanes, and the com-
bined organic phases were washed with 75 mL of water and
75 mL of satd aqueous NaCl solution, dried over Na2SO4,
filtered, and concentrated (0.25 mm Hg, 2 h) to yield 1.549 g
of an orange oil. Bulb-to-bulb distillation (105e110 ꢀC oven
temperature, 0.25 mm Hg) provided 0.937 g (65%) of siloxy al-
kyne 10k as a colorless oil with spectral characteristics identical
to those previously reported:36 IR (neat) 2184 cmꢁ1; 1H NMR
(300 MHz, CDCl3) d 1.20e1.30 (m, 3H), 1.13 (d, J¼6.8 Hz,
18H), 0.90 (s, 9H), 0.03 (s, 6H); 13C NMR (75 MHz, CDCl3)
d 107.9, 27.8, 26.4, 17.5, 17.0, 12.1, ꢁ3.6.
1
ter. H NMR and 13C NMR spectra were measured with a
Varian Inova 500 MHz spectrometer or a Varian 300 MHz
1
spectrometer. H NMR chemical shifts are expressed in parts
per million (d) downfield from tetramethylsilane (with the
CHCl3 peak at 7.27 ppm or the residual benzene peak at
7.16 ppm used as a standard). 13C NMR spectra chemical
shifts are expressed in parts per million (d) downfield from tet-
ramethylsilane (with the central peak of CDCl3 at 77.23 ppm
or the C6D6 peak at 128.06 ppm used as a standard). High
resolution mass spectra (HRMS) were measured on a Bruker
Daltonics APEX II 3 T Fourier transform mass spectrometer
or a Bruker Daltonics APEX IV 4.7 T Fourier transform ion
cyclotron resonance mass spectrometer.
4.4. 2-(tert-Butyldimethylsilyl)-(E )-2-(1-methyl-1-
propenyl)ketene (17)
A 50-mL, two-necked, round-bottomed flask equipped with
a rubber septum, glass stopper, and argon inlet adapter was
charged with a solution of 1-diazo-3-methyl-3-penten-2-one9a
(0.500 g, 4.0 mmol) in 20 mL of 1:1 Et2Oehexanes and cooled
at 0 ꢀC while i-Pr2EtN (0.71 mL, 0.53 g, 4.1 mmol) was added
dropwise over 1 min. After 3 min, t-BuMe2SiOTf (0.93 mL,
1.1 g, 4.1 mmol) was added dropwise over 1 min, and the result-
ing solution was allowed to slowly warm to 10 ꢀC over 2.5 h,
and then stirred at rt for an additional 30 min. The reaction mix-
ture was filtered through Celite with the aid of 10 mL of hex-
anes, and the filtrate was concentrated to afford 1.048 g of an
orange oil. Column chromatography on 60 g of silica gel (elu-
tion with 2% EtOAce1% Et3Nehexanes) provided 0.716 g
(75%) of 1-(tert-butyldimethylsilyl)-1-diazo-3-methyl-1-(E )-
3-penten-2-one as a yellow oil: IR (neat) 2929, 2858, 2066,
1
1615 cmꢁ1; H NMR (300 MHz, CDCl3) d 6.13 (qq, J¼6.9,
4.6. Benzannulation
1.4 Hz, 1H), 1.81 (app quint, J¼1.1 Hz, 3H), 1.76 (dq, J¼6.7,
1.1 Hz, 3H), 0.94 (s, 9H), 0.23 (s, 6H); 13C NMR (125 MHz,
CDCl3) d 196.4, 136.7, 130.5, 51.6, 26.9, 19.3, 13.9, 13.3,
ꢁ6.0. A solution of this silylated diazo ketone (0.693 g,
2.91 mmol) in 30 mL of benzene was distributed evenly be-
tween two 30-cm quartz tubes fitted with rubber septa. A second
rubber septum (inverted) was secured with vinyl tape to each
tube to ensure a good seal, and the reaction mixtures were
degassed (three freezeepumpethaw cycles at ꢁ196 ꢀC,
<0.5 mm Hg) and then irradiated with 300 nm light in a Rayo-
net reactor for 3 h. The resulting solutions were combined and
concentrated at reduced pressure to afford 0.513 g of a yellow
oil. Column chromatography on 30 g of silica gel (elution
with hexanes) provided 0.393 g (64%) of ketene 17 as a yellow
Experimental procedures and characterization data for
benzannulation products 26, 27, 30, 31, 33, 34, and 36 have
been reported previously.1
4.6.1. General procedure: illustrated with preparation of 2-
(3-propenyl)-5,6,7,8-tetrahydro-3-(triisopropylsiloxy)-1-
naphthol (35)
A 25-mL, two-necked, round-bottomed flask equipped with
a rubber septum and argon inlet adapter was charged with
siloxy alkyne 10g (0.890 g, 4.53 mmol) and 6 mL of THF.
MeLi solution (1.53 M in Et2O, 3.0 mL, 4.6 mmol) was added
dropwise via syringe over 10 s, and the resulting solution was
stirred at rt for 30 min. A solution of ketene 7b (1.267 g,
4.551 mmol) in 3 mL of THF was added via cannula in one
oil: IR (neat) 2930, 2859, 2077, 1647 cmꢁ1 1H NMR
;

922
W.F. Austin et al. / Tetrahedron 64 (2008) 915e925
portion (the flask was rinsed with 1 mL of THF), and the re-
sulting solution was stirred for an additional 70 min. The reac-
tion mixture was poured into 20 mL of satd aqueous NH4Cl
solution, the aqueous phase was separated and extracted
with two 10-mL portions of Et2O, and the combined organic
phases were washed with 20 mL of water and 20 mL of satd
NaCl solution, dried over MgSO4, filtered, and concentrated
to afford 2.034 g of a yellow oil. Column chromatography
on 100 g of silica gel (25% benzeneehexanes) provided
0.788 g (48%) of phenol 35 as a yellow oil: IR (neat) 3550,
4.6.4. 6-Ethyl-5-methyl-2-[(1E )-2-phenylethenyl]-3-
(triisopropylsiloxy)phenol (32)
Reaction of siloxy alkyne 10d (0.226 g, 0.752 mmol) with
MeLi solution (1.50 M in Et2O, 0.50 mL, 0.75 mmol) and
ketene 7c (0.200 g, 0.750 mmol) in 5 mL of THF according
to the general procedure and purification by column chroma-
tography on 15 g of silica gel (gradient elution with 25e
38% benzeneehexanes) afforded 0.111 g (37%) of phenol
32 as a pale yellow oil: IR (neat) 3552, 2942, 2867, 1621,
1
1570, 1463 cmꢁ1; H NMR (500 MHz, CDCl3) d 7.50 (d, J¼
1
3077, 2942, 2866, 1618, 1578, 1495, 1426 cmꢁ1; H NMR
7.7 Hz, 2H), 7.37 (t, J¼7.7 Hz, 2H), 7.31 (d, J¼17.1 Hz, 1H),
7.25e7.29 (m, 1H), 7.03 (d, J¼17.1 Hz, 1H), 6.28 (s, 1H),
5.58 (s, 1H), 2.64 (q, J¼7.5 Hz, 2H), 2.26 (s, 3H), 1.29
(sept, J¼7.6 Hz, 3H), 1.15 (t, J¼7.6 Hz, 3H), 1.11 (d, J¼
7.4 Hz, 18H); 13C NMR (75 MHz, CDCl3) d 152.0, 151.6,
137.5, 136.4, 131.3, 128.6, 127.4, 126.1, 122.7, 121.5,
113.3, 112.5, 19.5, 19.4, 18.0, 13.7, 12.9; HRMS-EI (m/z):
Mþ calcd for C26H38O2Si, 410.2636; found, 410.2646.
(300 MHz, CDCl3) d 6.23 (s, 1H), 6.00 (ddt, J¼17.2, 10.0,
6.2 Hz, 1H), 5.20 (app dq, J¼17.3, 1.7 Hz, 1H), 5.12 (app
dq, J¼9.9, 1.7 Hz, 1H), 5.01 (s, 1H), 3.51 (app dt, J¼6.2,
1.6 Hz, 2H), 2.67 (t, J¼6.1 Hz, 2H), 2.58 (t, J¼6.1 Hz, 2H),
1.71e1.88 (m, 4H), 1.25e1.39 (m, 3H), 1.15 (d, 7.2 Hz,
18H); 13C NMR (75 MHz, CDCl3) d 153.3, 151.9, 137.0,
136.5, 116.3, 115.7, 112.5, 110.8, 31.8, 29.9, 28.6, 23.7,
22.8, 18.3, 13.3; HRMS-ESI (m/z): [MþNa]þ calcd for
C22H36O2Si, 383.2377; found, 383.2380.
4.6.5. 5-(tert-Butyldimethylsiloxy)-3,4-dimethyl-2-(triiso-
propylsilyl)phenol (37a) or 5-(tert-butyldimethyl-
siloxy)-2,3-dimethyl-4-(triisopropylsilyl)-
4.6.2. 5,6-Dimethyl-2-tert-butyl-3-(triisopropyl-
siloxy)phenol (28)
phenol (37b) and 2-(tert-butyldimethyl-
silyl)-5,6-dimethyl-3-(triisopropyl-
siloxy)phenol (38)
Reaction of siloxy alkyne 10j (0.198 g, 0.778 mmol) with
MeLi solution (1.63 M in Et2O, 0.49 mL, 0.80 mmol) and
ketene 7a (0.200 g, 0.792 mmol) in 5 mL of THF according
to the general procedure and purification by column chroma-
tography on 20 g of silica gel (elution with 2% EtOAcehex-
anes) provided 0.180 g of a yellow oil. Further purification
on a column of 20 g silica gel (elution with 25% benzenee
hexanes) afforded 0.151 g (55%) of phenol 28 as a pale yellow
Reaction of siloxy alkyne 10k (0.250 g, 0.800 mmol) with
MeLi solution (1.63 M in Et2O, 0.50 mL, 0.82 mmol) and ke-
tene 7a (0.205 g, 0.812 mmol) in 5 mL of THF according to
the general procedure provided 0.501 g of orange oil. NMR
analysis of this material indicated the presence of two aro-
matic products 37 and 38 in a ratio of 66:34 and an estimated
combined yield of 40e60%. Pure samples of each compound
could not be obtained without significant losses due to the
presence of impurities with similar chromatographic proper-
ties and the fact that both compounds underwent partial de-
composition upon attempted purification by chromatography
under a variety of conditions. A pure sample of 38 was
obtained by the following procedure. Column chromatography
on 20 g of silica gel deactivated with acetone and triethyl-
amine (elution with 5% EtOAce1% Et3Nehexanes) provided
0.120 g of a yellow oil, which was applied to the top of a
column of 5 g of acetone-deactivated silica gel and eluted
with 0e1% EtOAcehexanes to yield 0.047 g (14%) of phenol
38 as a white powder, mp 92e95 ꢀC: IR (CH2Cl2) 3603, 3053,
oil: IR (neat) 3622, 2947, 2868, 1610, 1567, 1484 cmꢁ1; H
1
NMR (500 MHz, CDCl3) d 6.22 (s, 1H), 5.13 (s, 1H), 2.17
(s, 3H), 2.07 (s, 3H), 1.57 (s, 9H), 1.37 (sept, J¼7.5 Hz,
3H), 1.15 (d, J¼7.5 Hz, 18H); 13C NMR (75 MHz, CDCl3)
d 154.2, 153.8, 134.8, 121.5, 115.6, 114.3, 36.7, 32.5, 20.8,
18.6, 13.9, 11.9; HRMS-ESI (m/z): [MþH]þ calcd for
C21H38O2Si, 351.2714; found, 351.2719.
4.6.3. 5,6-Dimethyl-2-phenyl-3-(triisopropylsiloxy)-
phenol (29)
Reaction of siloxy alkyne 10i (0.200 g, 0.729 mmol) with
MeLi solution (1.63 M in Et2O, 0.46 mL, 0.75 mmol) and
ketene 7a (0.1850 g, 0.733 mmol) in 5 mL of THF according
to the general procedure and purification by column chroma-
tography on 15 g of silica gel (elution with 20% benzeneehex-
anes) afforded 0.080 g (30%) of phenol 29 as a pale yellow oil:
IR (neat) 3552, 2942, 2867, 1621, 1570, 1463 cmꢁ1; 1H NMR
(300 MHz, CDCl3) d 7.42e7.49 (m, 2H), 7.32e7.39 (m, 3H),
6.36 (s, 1H), 4.97 (s, 1H), 2.26 (s, 3H), 2.15 (s, 3H), 1.01e1.14
(m, 3H), 0.92 (d, J¼7.5 Hz, 18H); 13C NMR (75 MHz,
CDCl3) d 151.5, 151.0, 137.4, 134.0, 131.4, 131.4, 129.2,
129.2, 128.0, 117.4, 115.1, 112.4, 20.6, 18.1, 13.0, 11.7;
HRMS-ESI (m/z): [MþH]þ calcd for C23H34O2Si, 371.2401;
found, 371.2412.
2948, 2948, 2868, 1601, 1469 cmꢁ1 1H NMR (500 MHz,
;
CDCl3) d 6.25 (s, 1H), 4.96 (s, 1H), 2.21 (s, 3H), 2.06
(s, 3H), 1.42 (sept, J¼7.6 Hz, 3H), 1.15 (d, J¼7.6 Hz, 18H),
0.95 (s, 9H), 0.40 (s, 6H); 13C NMR (75 MHz, CDCl3)
d 160.3, 160.1, 139.5, 113.7, 112.6, 108.5, 27.5, 20.9, 18.8,
18.6, 14.0, 11.5, ꢁ0.9; HRMS-ESI (m/z): [MþH]þ calcd for
C23H44O2Si2, 409.2953; found, 409.2957. A pure sample of
37 could not be obtained, but a sample of sufficient purity
for identification of NMR characteristics was obtained by
the following procedure. The crude product of another run
of the benzannulation was first partially purified by column
chromatography on 20 g of silica gel deactivated with
acetone and triethylamine (elution with 5% EtOAce1%

W.F. Austin et al. / Tetrahedron 64 (2008) 915e925
923
Et3Nehexanes) to afford 0.133 g of a red oil. This material
was dissolved in 10 mL of Et2O, washed with five 5-mL por-
tions of satd aqueous NH4Cl solution, dried over MgSO4,
filtered, and concentrated to afford 0.069 g of a sample of
the major benzannulation product assigned as either 37a or
was added dropwise over 3 min. The resulting solution was
stirred at rt for 24 h and then extracted with three 30-mL por-
tions of EtOAc. The combined organic phases were dried over
MgSO4, filtered, and concentrated to afford 0.163 g of an or-
ange oil. This material was diluted with hexanes and concen-
trated onto 0.450 g of silica gel, which was transferred to the
top of a column of 15 g silica gel. Elution with 0e10%
EtOAcehexanes provided 0.146 of an orange oil. Further con-
centration (0.2e0.3 Torr, rt, 1 h) followed by column chroma-
tography on 10 g of silica gel (elution with 5% EtOAce
hexanes) yielded 0.073 g (66%) of quinone 41 as fluorescent
orange needles, mp 63e68 ꢀC: IR (KBr) 3392, 2956, 2928,
1
37b (ca. 80% purity) as a yellow oil: H NMR (500 MHz,
CDCl3) d 6.20 (s, 1H), 4.87e5.00 (br s, 1H), 2.31 (s, 3H),
2.08 (s, 3H), 1.66 (sept, J¼7.5 Hz, 3H), 1.09 (d, J¼7.5 Hz),
1.00 (s, 9H), 0.27 (s, 6H); 13C NMR (125 MHz, CDCl3)
d 160.1, 154.8, 146.8, 117.7, 115.7, 104.3, 27.6, 23.1, 20.4,
19.3, 14.5, 12.1, ꢁ2.7.
1
4.7. Transformations of annulation products
2859, 1650, 1633, 1620, 1365; H NMR (300 MHz, CDCl3)
d 6.94 (s, 1H), 2.39e2.46 (m, 2H), 2.04 (t, J¼1.1 Hz, 3H),
2.03 (t, J¼1.1 Hz, 3H), 1.26e1.49 (m, 4H), 0.90 (t, J¼
7.1 Hz, 3H); 13C NMR (75 MHz, CDCl3) d 187.6, 184.0,
150.8, 143.8, 136.3, 121.8, 30.7, 23.01, 22.95, 14.1, 13.1,
11.8; HRMS-ESI (m/z): [MþH]þ calcd for C12H16O3,
209.1172; found, 209.1171.
4.7.1. 4,5-Dimethyl-3-tert-butyldimethylsiloxy-1-
triisopropylsiloxy-benzene (39)
A 5-mm NMR tube was charged with a solution of phenol
38 (0.026 g, 0.064 mmol) in 0.70 mL of CDCl3. The reaction
mixture was heated at reflux for 3.5 h then allowed to cool and
concentrated to yield 0.025 g (96%) of 39 as a pale yellow oil:
IR (neat) 2945, 2866, 1603, 1473, 1333 cmꢁ1
;
1H NMR
4.7.4. 5-Triisopropylsiloxy-1,2,3,4,7,8,9,10-
(CDCl3, 500 MHz) d 6.35 (d, J¼2.4 Hz, 1H), 6.22 (d, J¼
2.4 Hz, 1H), 2.18 (s, 3H), 2.04 (s, 3H), 1.22 (m, 3H), 1.10
(d, J¼7.3 Hz, 18H), 1.01 (s, 9H), 0.19 (s, 6H); 13C NMR
d 154.6, 154.3, 139.0, 120.5, 115.3, 108.9, 26.5, 21.2, 19.0,
18.7, 13.4, 12.6, ꢁ3.6; HRMS-ESI (m/z): [MþH]þ calcd for
C23H44O2Si2, 409.2953; found, 409.2959.
octahydrobenzo[d]naphtho[1,2-b]furan (43)
A 10-mL round-bottomed flask equipped with a rubber sep-
tum and argon inlet needle was charged with a solution of
phenol 34 (0.125 g, 0.311 mmol) in 2 mL of CH2Cl2 and
VO(acac)2 (0.006 g, 0.02 mmol). The mixture was stirred for
5 min, and then anhydrous TBHP solution (4.0 M in toluene,
0.100 mL, 0.400 mmol) was added. The rubber septum was re-
placed with a cold finger reflux condenser and the mixture was
heated at reflux for 4.5 h. Additional VO(acac)2 (0.006 g,
0.02 mmol) and TBHP solution (4.0 M in toluene, 0.100 mL,
0.400 mmol) were added, and heating was continued for 2 h.
TFA (0.060 mL, 92 mg, 0.81 mmol) was next added and the
reaction mixture was heated at reflux for an additional 21 h
and then allowed to cool to rt. Concentration afforded
0.260 g of a viscous blue-green oil, which was diluted with
CH2Cl2 and concentrated onto 0.600 g of silica gel, which
was transferred to the top of a column of 20 g of silica gel
and eluted with 5% benzeneehexanes to provide 0.068 g
(55%) of 43 as a yellow oil: IR (neat) 2940, 1618, 1592,
4.7.2. 2-Butyl-5,6-dimethylresorcinol (40)
A 10-mL, two-necked, round-bottomed flask equipped with
a rubber septum and argon inlet adapter was charged with a so-
lution of phenol 26 (0.200 g, 0.570 mmol) in 2 mL of THF and
stirred at 0 ꢀC while TBAF solution (1.0 M in THF, 0.85 mL,
0.85 mmol) was added. The reaction mixture was allowed to
slowly warm to rt over 2.5 h, and then partitioned between
5 mL Et2O and 5 mL water. The aqueous phase was extracted
with 5 mL of Et2O, and the combined organic phases were
washed with 5 mL of satd NaCl solution, dried over MgSO4,
filtered, and concentrated to yield 0.303 g of an orange-brown
oil. Column chromatography on 15 g of silica gel (elution with
10% EtOAcehexanes) afforded 0.086 g (77%) of the resor-
cinol 40 as a white powder, mp 126e129 ꢀC: IR (neat)
1
1507, 1463, 1448 cmꢁ1; H NMR (300 MHz, CDCl3) d 6.30
(s, 1H), 2.80e2.87 (m, 4H), 2.74e2.78 (m, 2H), 2.68e2.72
(m, 2H), 1.77e1.92 (m, 8H), 1.34 (sept, J¼7.8 Hz, 3H),
1.14 (d, J¼7.5 Hz, 18H); 13C NMR (75 MHz, CDCl3)
d 154.9, 151.9, 148.1, 132.8, 118.2, 114.1, 113.2, 112.2,
30.2, 24.2 (2C), 23.8, 23.54, 23.48, 23.2, 23.1, 18.9, 14.0;
HRMS-ESI (m/z): [MþH]þ calcd for C25H38O2Si, 399.2714;
found, 399.2716.
3426, 3054, 2987, 1631, 1422 cmꢁ1 1H NMR (300 MHz,
;
CDCl3) d 6.25 (s, 1H), 4.67 (s, 1H), 4.43 (s, 1H), 2.59 (t, J¼
7.6 Hz, 2H), 2.19 (s, 3H), 2.08 (s, 3H), 1.33e1.57 (m, 4H),
0.93 (t, J¼7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3) d 152.6,
151.8, 135.5, 114.2, 112.5, 109.3, 31.8, 23.5, 23.1, 20.3,
14.3, 11.6; HRMS-ESI (m/z): [MþH]þ calcd for C12H18O2,
195.1385; found, 195.1386.
4.8. Allylation of phenolic benzannulation products
4.7.3. 3-Butyl-4-hydroxy-5,6-dimethyl-ortho-quinone (41)
A 100-mL, two-necked, round-bottomed flask equipped
with a rubber septum and 50-mL addition funnel fitted with
an argon inlet adapter was charged with a solution of phenol
26 (0.187 g, 0.533 mmol) in 30 mL of acetone and stirred at
rt while a solution of Na2HPO4 (0.56 g, 3.9 mmol) and potas-
sium nitrosodisulfonate (0.575 g, 2.1 mmol) in 20 mL of water
4.8.1. General procedure: 2-propenyl 2-(2-propenyl)-3-
triisopropylsiloxy-5,6,7,8-tetrahydronaphthyl ether (45)
A 10-mL round-bottomed flask equipped with a rubber sep-
tum and argon inlet needle was charged with K2CO3 (0.100 g,
0.723 mmol) and NaI (0.021 g, 0.14 mmol) and flame dried
under vacuum. The flask was back-filled with argon, allowed

924
W.F. Austin et al. / Tetrahedron 64 (2008) 915e925
to cool to rt, and a solution of naphthol 35 (0.083 g, 0.23 mol) in
2 mL of acetone was added. Allyl bromide (0.100 mL, 0.140 g,
1.16 mmol) was added, the septum was replaced with a cold fin-
ger condenser, and the reaction mixture was heated at reflux for
18 h. Additional allyl bromide (0.100 mL, 0.140 g, 1.16 mmol)
was then added, and heating was continued for an additional
18 h. The resulting mixture was allowed to cool to rt and parti-
tioned between 5 mL of Et2O and 5 mL of water. The aqueous
phase was extracted with two 5-mL portions of Et2O, and the
combined organic phases were dried over MgSO4, filtered,
and concentrated to yield 0.171 g of a yellow oil, which was di-
luted with hexanes and concentrated onto 0.300 g of silica gel,
which was transferred to the top of a column of 10 g of silica
gel. Elution with 5e10% benzeneehexanes furnished 0.068 g
(74%) of allyl ether 45 as a yellow oil: IR (neat) 3078, 2942,
of CH2Cl2. The septum was replaced with a cold finger con-
denser fitted with an argon inlet and the reaction mixture was
heated at reflux for 1 h and then allowed to cool to rt and concen-
trated to yield 0.080 g of a brown oil. Column chromatography
on 5 g of silica gel (elution with 1% EtOAcehexanes) afforded
0.050 g (96%) of 47 as a yellow oil: IR (neat) 2944, 2867, 1609,
1572, 1481 cmꢁ1; 1H NMR (300 MHz, CDCl3) d 6.34 (s, 1H),
5.77e5.88 (m, 1H), 5.40 (dm, J¼11.3 Hz, 1H), 4.52 (app quint,
J¼2.4 Hz, 2H), 3.51 (dd, J¼5.3, 2.0 Hz, 2H), 2.62e2.69
(m, 4H), 1.70e1.80 (m, 4H), 1.21e1.34 (m, 3H), 1.11 (d, J¼
7.0 Hz, 18H), 13C NMR (75 MHz, CDCl3) d 157.3, 150.4,
136.2, 127.7, 126.6, 124.5, 122.4, 114.9, 69.9, 29.8, 23.4,
23.3, 23.2, 23.1, 18.3, 13.3; HRMS-ESI (m/z): [MþH]þ calcd
for C23H36O2Si, 373.2557; found, 373.2567.
2867, 1637, 1605, 1573, 1477, 1425 cmꢁ1
;
1H NMR
4.9.2. 10-Ethyl-9-methyl-3-triisopropylsiloxy-5,6-dihydro-
2H-benzo[b]oxocine (46)
(300 MHz, CDCl3) d 6.35 (s, 1H), 6.11 (ddt, J¼17.1, 10.5,
5.3 Hz, 1H), 6.00 (ddt, J¼17.1, 10.0, 6.0 Hz, 1H), 5.43 (app
dq, J¼17.2, 1.7 Hz, 1H), 5.24 (app dq, J¼10.5, 1.5 Hz, 1H),
4.99 (app dq, J¼17.1, 1.8 Hz, 1H), 4.94 (app dq, J¼10.1,
1.7 Hz, 1H), 4.38 (dt, J¼5.3, 1.6 Hz, 2H), 3.41 (dt, J¼6.0,
1.6 Hz, 2H), 2.64e2.71 (m, 4H), 1.72e1.78 (m, 4H), 1.24e
1.36 (m, 3H), 1.11 (d, J¼7.1 Hz, 18H); 13C NMR (75 MHz,
CDCl3) d 156.3, 152.6, 137.9, 136.4, 134.6, 130.3, 123.1,
121.1, 116.8, 114.4, 73.4, 29.8, 29.2, 23.7, 23.4, 23.3, 18.4,
13.3; HRMS-ESI (m/z): [MþH]þ calcd for C25H40O2Si,
401.2870; found, 401.2861.
Reaction of allyl ether 44 (0.044 g, 0.11 mmol) with ruthe-
nium catalyst 48 (0.005 g, 0.006 mmol) in 25 mL of CH2Cl2
according to the general procedure and purification by column
chromatography on 5 g of silica gel (elution with 1% EtOAce
hexanes) afforded 0.039 g (95%) of 46 as a yellow oil: IR
(neat) 2944, 2867, 1603, 1569, 1465 cmꢁ1
;
1H NMR
(300 MHz, CDCl3) d 6.41 (s, 1H), 5.81 (dtt, J¼11.4, 6.7,
1.5 Hz, 1H), 5.40 (dtt, J¼11.3, 4.5, 1.2 Hz, 1H), 4.68 (dd, J¼
4.6, 1.3 Hz, 2H), 2.97 (d, J¼6.3 Hz, 1H), 2.94 (d, J¼4.8 Hz,
1H), 2.60e2.69 (m, 2H), 2.59 (q, J¼7.5 Hz, 2H), 2.23
(s, 3H), 1.21e1.35 (m, 3H), 1.11 (d, J¼7.0 Hz, 18H), 1.12
(t, J¼7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3) d 155.8,
152.0, 134.7, 133.5, 128.2, 125.3, 122.4, 116.0, 71.9, 28.0,
25.7, 19.9, 19.6, 18.4, 14.9, 13.3; HRMS-ESI (m/z):
[MþH]þ calcd for C23H38O2Si, 375.2714; found, 375.2713.
4.8.2. 2-Propenyl 2-(3-butenyl)-6-ethyl-5-methyl-3-
triisopropylsiloxy-phenyl ether (44)
Reaction of phenol 31 (0.083 g, 0.23 mol) with K2CO3
(0.100 g, 0.723 mmol), NaI (0.021 g, 0.14 mmol), and allyl
bromide (0.200 mL total, 0.280 g, 2.32 mmol) in 2 mL of
acetone according to the general procedure and purification
by column chromatography on 10 g of silica gel (elution
with 0e10% benzeneehexanes) provided 0.060 g (65%) of al-
lyl ether 44 as a yellow oil: IR (neat) 3077, 2945, 2867, 1640,
Acknowledgements
We thank the National Institutes of Health (GM 28273),
Merck Research Laboratories, and Boehringer Ingelheim
Pharmaceuticals for generous financial support. Y.Z. was sup-
ported by a Po Ting Ip Postdoctoral Fellowship and W.F.A.
was supported in part by a fellowship from the Kenneth M.
Gordon Fund.
1
1603, 1569, 1479 cmꢁ1; H NMR (300 MHz, CDCl3) d 6.41
(s, 1H), 6.11 (ddt, J¼17.2, 10.4, 5.2 Hz, 1H), 5.91 (ddt, J¼
17.1, 10.2, 6.6 Hz, 1H), 5.46 (app dq, J¼17.1, 1.7 Hz, 1H),
5.26 (app dq, J¼10.4, 1.5 Hz, 1H), 5.04 (app dq, J¼17.1,
1.7 Hz, 1H), 4.96 (dm, J¼10.1 Hz, 1H), 4.30 (dt, J¼5.2,
1.6 Hz, 2H), 2.63e2.71 (m, 2H), 2.58 (q, J¼7.5 Hz, 2H),
2.25e2.34 (m, 2H), 2.23 (s, 3H), 1.22e1.36 (m, 3H), 1.08e
1.14 (m, 21H); 13C NMR (75 MHz, CDCl3) d 156.6, 152.7,
139.4, 134.8, 134.6, 128.5, 123.3, 116.7, 116.4, 114.3, 75.3,
34.4, 24.9, 20.1, 19.6, 18.4, 15.0, 13.4; HRMS-ESI (m/z):
[MþH]þ calcd for C25H42O2Si, 403.3027; found, 403.3017.
References and notes
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2,5,8,9,10,11-hexahydronaphtho[1,2-b]oxepine (47)
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