The application of intramolecular radical cyclizations of acylsilanes in the regiospecific formation of cyclic silyl enol ethers

Article abstract of DOI:10.1021/jo010883s

Acylsilanes with terminal α-stannyl bromide or xanthate functionalities are prepared, α-Stannyl radicals generated from these acylsilanes undergo intramolecular cyclizations to give cyclic silyl enol ethers regiospecifically. The radical processes involve radical cyclization, Brook rearrangement, and β-fragmentation in sequence. A tributylstannyl group serves as the radical leaving group. The newly formed σ-bond and π-bond are located between the same two carbon atoms. This approach is limited to the formation of five-membered rings. In another route, ω-bromo-α-phenylsulfonylacylsilanes are synthesized. The radical cyclizations of these α-sulfonylacylsilanes also give cyclic silyl enol ethers. The phenylsulfonyl moiety is the radical leaving group in this system. Furthermore, the newly formed σ-bond and π-bond are located at adjacent positions sharing a single carbon atom. The latter approach is effective for both five- and six-membered ring formation.

Full text of DOI:10.1021/jo010883s

J . Org. Chem. 2001, 66, 8983-8991
8983
Th e Ap p lica tion of In tr a m olecu la r Ra d ica l Cycliza tion s of
Acylsila n es in th e Regiosp ecific F or m a tion of Cyclic Silyl En ol
Eth er s
Chih-Hao Huang, Sheng-Yueh Chang, Nung-Sen Wang, and Yeun-Min Tsai*
Department of Chemistry, National Taiwan University, Taipei, Taiwan 106, Republic of China
ymtsai@ccms.ntu.edu.tw
Received August 27, 2001
Acylsilanes with terminal R-stannyl bromide or xanthate functionalities are prepared. R-Stannyl
radicals generated from these acylsilanes undergo intramolecular cyclizations to give cyclic silyl
enol ethers regiospecifically. The radical processes involve radical cyclization, Brook rearrangement,
and â-fragmentation in sequence. A tributylstannyl group serves as the radical leaving group. The
newly formed σ-bond and π-bond are located between the same two carbon atoms. This approach
is limited to the formation of five-membered rings. In another route, ω-bromo-R-phenylsulfonyla-
cylsilanes are synthesized. The radical cyclizations of these R-sulfonylacylsilanes also give cyclic
silyl enol ethers. The phenylsulfonyl moiety is the radical leaving group in this system. Furthermore,
the newly formed σ-bond and π-bond are located at adjacent positions sharing a single carbon atom.
The latter approach is effective for both five- and six-membered ring formation.
In tr od u ction
alkoxy radicals.8 Thio- and selenoesters also undergo
similar reactions.9 The complementary acylsilane cycliza-
tions10 give cyclic alcohols in the form of silyl ethers
through irreversible radical-Brook rearrangements10-12
of â-silyl alkoxy radical intermediates. In the case of
tributyltin hydride mediated pinacol coupling developed
by Hays and Fu,13 the cyclized γ-tributylstannyloxy
alkoxy radical was trapped via an intramolecular ho-
molytic substitution at tin. A 1,3-stannyl shift from
carbon to oxygen is the driving force for the intramolecu-
lar cyclizations of R-stannyl radicals with formyl group.14
Intramolecular cyclizations of radicals with carbonyl
groups are known to be reversible processes.1 To drive
these reactions toward the cyclization side, there are two
general strategies. One is to trap the cyclized alkoxy
radical intermolecularly using excess tributyltin hydride,2
silanes,3 or organophosphorus compounds.4 The use of
large excess of triethylborane also improves the cycliza-
tion efficiency.5 This may be attributed to the trapping
of the cyclized alkoxy radical by triethylborane.5b The
other route relies on the presence of some intramolecular
processes such that the cyclized alkoxy radicals are
diverted to give other products in an irreversible way.
The most notorious application in this direction is the
ring expansion of 2-oxocyclopentylmethyl radical and
systems alike pioneered by research groups of Beckwith
and Dowd.6,7 Radical cyclizations of acylgermanes give
rise to cyclic ketones through â-scission of â-germyl
Among the intramolecular radical cyclization reactions
of carbonyl compounds, the acylsilane15 cyclization sys-
tem (Scheme 1) is unique, in which a new carbon radical
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10.1021/jo010883s CCC: $20.00 © 2001 American Chemical Society
Published on Web 12/04/2001

8984 J . Org. Chem., Vol. 66, No. 26, 2001
Huang et al.
Sch em e 1
ketones and aldehydes. Another is to prepare them from
enones. The latter approach may be the better choice
when regiochemically pure silyl enol ethers are required.
Both methodologies are performed under basic condi-
tions. Alternatively, silyl enol ethers can be prepared
from acylsilanes.18,19 In this regard, a useful method
involves the coupling of an acylsilane with a carbanion
bearing R-leaving group (eq 1) was developed by Reich
et al.19 The initial adduct undergoes a Brook rearrange-
ment, and the resulting silyloxy substituted carbanion
fragments to give the silyl enol ether regiospecifically.
The leaving group can also be placed at the R-position of
the acylsilane as shown in eq 2.19 Conceptually, the two
3 is generated after the radical-Brook rearrangement of
â-silyl alkoxy radical 2. By introducing additional struc-
tural features, one may utilize the newly generated
carbon radical in useful ways. One possibility involves a
preexisting radical leaving group X at the â-position of
the carbon radical as in radical 4. A â-scission will occur
to generate a silyl enol ether in a regiospecific fashion.
In principle, there are two possible approaches to obtain
radical 4. Route a starts from the generation of radical 6
with the radical leaving group attached at the carbon
carrying the initial radical. In this direction, we found
that the tributylstannyl group served well as the desired
radical leaving group.16 An alternative approach (route
b) is to put the radical leaving group at the R-position of
the carbonyl group. We found that this route can be
realized by the use of phenylsulfonyl group.17 In this
paper, we describe our full investigation of the use of
these two approaches in the regiospecific formation of
silyl enol ethers.18,19
routes described in Scheme 1 belong to a neutral radical
version of Reich’s polar acylsilane chemistry.
Resu lts a n d Discu ssion
In tr a m olecu la r Cycliza tion s of r-Sta n n yl Br o-
m id e w ith Acylsila n es. To explore the route a approach
(Scheme 1), we selected a tributylstannyl group as the
radical leaving group. There are two reasons for this
selection. First, the tributylstannyl group when situated
at the â-position of a radical as exemplified in the well-
known radical chemistry of allyltributylstannane readily
undergoes â-scission.20 In addition, the tributyltin radical
generated through â-scission can be recycled in the
radical chain reactions. Second, R-stannyl bromides are
a known class of compounds that can be synthesized
through established methods.21
As shown in Scheme 2, alkylation of 2-silyldithianes
822 with the unprotected 4-chlorobutanol in the presence
of excess LDA gave alcohols 9 in excellent yields. Alcohols
9 were oxidized with PCC in dichloromethane to give
aldehydes 10 in mild yields. Aldehydes 10 were coupled
with tributyltin lithium, and the resulting R-stannyl
alcohols were converted to bromides 11 with carbon
tetrabromide and triphenylphosphine.23 As a result of the
presence of nucleophilic sulfur atoms in bromides 11,
these compounds are not stable. Therefore, it is better
to hydrolyze these bromides immediately with ceric
Silyl enol ethers are important synthetic intermediates.
There are two widely used methodologies for their
synthesis.18 One is to generate silyl enol ethers from
(16) For a preliminary report, see: Tsai, Y.-M.; Chang, S.-Y. J .
Chem. Soc., Chem. Commun. 1995, 981-982.
(17) For some examples of homolytic cleavage of sulfonyl groups,
see: (a) Motherwell, W. B.; Crich, D. Free Radical Chain Reactions in
Organic Synthesis; Academic Press: New York, 1992; Chapter 4, p 131.
(b) Ueno, Y.; Aoki, S.; Okawara, M. J . Am. Chem. Soc. 1979, 101, 5414-
5415. (c) Harvey, I. W.; Whitham, G. H. J . Chem. Soc., Perkin Trans.
1 1993, 185-190. (d) Harvey, I. W.; Whitham, G. H. J . Chem. Soc.,
Perkin Trans. 1 1993, 191-196. (e) Quiclet-Sire, B.; Zard, S. Z. J . Am.
Chem. Soc. 1996, 118, 1209-1210. (f) Le Guyader, F.; Quiclet-Sire,
B.; Seguin, S.; Zard, S. Z. J . Am. Chem. Soc. 1997, 119, 7410-7411.
(g) Quiclet-Sire, B.; Seguin, S.; Zard, S. Z. Angew. Chem., Int. Ed. Engl.
1998, 37, 2864-2866. (h) Bertrand, F.; Quiclet-Sire, B.; Zard, S. Z.
Angew. Chem., Int. Ed. 1999, 38, 1943-1946. (i) Chatgilialoglu, C.;
Ballestri, M.; Vecchi, D.; Curran, D. P. Tetrahedron Lett. 1996, 37,
6383-6386. (j) Chatgilialoglu, C.; Alberti, A.; Ballestri, M.; Maccian-
telli, D.; Curran, D. P. Tetrahedron Lett. 1996, 37, 6391-6394. (k)
Xiang, J . S.; Fuchs, P. L. Tetrahedron Lett. 1996, 37, 5269-5272. (l)
Van Dort, P. C.; Fuch, P. L. J . Org. Chem. 1997, 62, 7137-7141. (m)
Van Dort, P. C.; Fuch, P. L. J . Org. Chem. 1997, 62, 7142-7147. (n)
Godfrey, C. R. A.; Hegarty, P.; Motherwell, W. B.; Uddin, M. K.
Tetrahedron Lett. 1998, 39, 723-726. (o) Clive, D. L. J .; Kang, S.
Tetrahedron Lett. 2000, 41, 1315-1319.
(20) (a) Keck, G. E.; Enholm, E. J .; Yates, J . B.; Wiley, M. R.
Tetrahedron 1985, 41, 4079-4094. (b) Clive, D. L. J .; Paul, C. C.; Wang,
Z. J . Org. Chem. 1997, 62, 7028-7032 and references therein.
(21) Pereyre, M.; Quintard, J .-P.; Rahm, A. Tin in Organic Synthesis;
Butterworth: London, 1987; p 174.
(22) (a) Brook, A. G.; Duff, J . M.; J ones, P. F.; Davis, N. R. J . Am.
Chem. Soc. 1967, 89, 431-434. (b) Corey, E. J .; Seebach, D.; Freedman,
R. J . Am. Chem. Soc. 1967, 89, 434-436.
(23) Torisawa, Y.; Shibasaki, M.; Ikegami, S. Tetrahedron Lett. 1981,
22, 2397-2400.
(18) (a) Brownbridge, P. Synthesis 1983, 1-28. (b) Brownbridge, P.
Synthesis 1983, 85-104. (c) Colvin, E. Silicon in Organic Synthesis;
Butterworth: London, 1981; Chapter 17, p 198. (d) Colvin, E. Silicon
Reagents in Organic Synthesis; Academic Press: New York, 1988;
Chapter 15, p 99.
(19) Reich, H. J .; Holtan, R. C.; Bolm, C. J . Am. Chem. Soc. 1990,
112, 5609-5617 and references therein.

Regiospecific Formation of Cyclic Silyl Enol Ethers
J . Org. Chem., Vol. 66, No. 26, 2001 8985
Sch em e 2a
Sch em e 3
â-silyl alkoxy radicals 21. Radicals 21 were converted to
R-silyloxy radicals 22 through a radical-Brook rearrange-
ment. As a result of the presence of a â-stannyl group,
radicals 22 underwent a facile â-scission to give silyl enol
ethers 18 with concomitant formation of tributyltin
radical. Since tributyltin radical was regenerated in the
reaction, a catalytic amount of tributyltin hydride (0.15
equiv) was sufficient. The cyclization of acyl-tert-bu-
tyldimethylsilane 12c gave low yield (36%) of hydrazone
19 indicating a sluggish cyclization of 12c. This may be
due to the presence of a bulky tert-butyldimethylsilyl
(TBDMS) group on the carbonyl carbon of the R-stannyl
radical 20c. The steric interaction between the TBDMS
and tributylstannyl groups presumably decreased the
rate of cyclization significantly. The cyclization of the
homologous acylsilane 17 did not occur when a catalytic
amount of tributyltin hydride (0.15 equiv) was used.
When 1.2 equiv of tributyltin hydride was used, we only
isolated 83% of straight reduction product 23 (Scheme
3). Previously, we found that 1,6-radical cyclizations of
acylsilanes are sensitive toward steric effect.10 Presum-
ably, with a bulky R-tributylstannyl radical the cycliza-
tion of acylsilane 17 becomes very slow.
To demonstrate the regiospecific nature of this silyl
enol ether preparation method, we studied the radical
cyclization of acylsilane 29 (Scheme 4). We started from
the alkylation of dithiane 8b with bromide 24. The
resulting acetal 25 (82% yield) was hydrolyzed in aqueous
acetic acid to give aldehyde 26 in 74% yield. Originally
we tried to prepare bromide 28 according to the meth-
odology described in Scheme 2. However, because of the
instability of bromide 28, we obtained this bromide in
very low yield. We then decided to prepare the xanthate
27 because the xanthate moiety may tolerate the pres-
ence of the two sulfur atoms in the same molecule.27
Indeed, when aldehyde 26 was treated with tributyltin
lithium followed by trapping the alkoxide intermediate
with carbon disulfide and methyl iodide in sequence, we
a
Reagents and conditions: (i) Cl(CH2)4OH (2 equiv), LDA (3.6
equiv), THF, -78 °C; (ii) PCC, CH2Cl2, 0 °C to room temperature;
(iii) Bu3SnH, LDA, THF, -78 °C; (iv) CBr4, PPh3, CH2Cl2; (v) CAN,
CH3CN, H2O; (vi) BuLi, 8b; (vii) TsOH, THF, H2O.
ammonium nitrate (CAN) in wet acetonitrile24 to gener-
ate acylsilanes 12.
For the preparation of the homologous acylsilane 17
(Scheme 2), a slightly different approach was employed.
The dithiane 8b25 was first alkylated with bromide 1326
to obtain acetal 14 (81%). The acetal unit was hydrolyzed
in wet THF in the presence of p-toluenesulfonic acid to
give aldehyde 15 in 90% yield. Acylsilane 17 was then
prepared from aldehyde 15 through similar methods as
described above.
When acylsilanes 12 were treated with catalytic amount
of tributyltin hydride (0.15 equiv) and AIBN (0.05 equiv)
in refluxing benzene, we obtained silyl enol ethers 18
(Scheme 3). However, to avoid possible hydrolysis of silyl
enol ethers 18 during purification, the products were
directly converted to the 2,4-dinitrophenylhydrazone of
cyclopentanone (19) in 89% and 84% yields for the
cyclizations of acylsilanes 12a and 12b, respectively.
These results indicate that we have obtained silyl enol
ethers 18 in good yields. The cyclization reactions oc-
curred through the generation of R-stannyl radicals 20
that cyclized with the acylsilane functionality to give
(24) (a) Ho, T.-L.; Ho, H. C.; Wong, C. M. J . Chem. Soc., Chem.
Commun. 1972, 791-791. (b) Ho, H. C.; Ho, T.-L.; Wong, C. M. Can.
J . Chem. 1972, 50, 2718-2721.
(25) Chang, S.-Y.; J iaang, W.-T.; Cherng, C.-D.; Tang, K.-H.; Huang,
C.-H.; Tsai, Y.-M. J . Org. Chem. 1997, 62, 9089-9098.
(26) (a) Baker, J . K.; Little, T. L. J . Med. Chem. 1985, 28, 46-50.
(b) Kulkarni, S. U.; Patil, V. D. Heterocycles 1982, 18, 163-167.
(27) For a recent review about xanthates, see: Zard, S. Z. Angew.
Chem., Int. Ed. Engl. 1997, 36, 673-685.

8986 J . Org. Chem., Vol. 66, No. 26, 2001
Huang et al.
Sch em e 4a
Sch em e 5
a
Reagents and conditions: (i) 8b, BuLi, THF, 0 °C; (ii) AcOH,
H2O; (iii) Bu3SnH, LDA, THF, -78 °C; CS2, -78 °C; MeI, -78 °C;
(iv) (CF3COO)2IPh, CH3CN, H2O; (v) Bu3SnH (0.15 equiv), AIBN
(0.05 equiv), PhH, 80 °C; (vi) PhSeBr, CH2Cl2, -78 °C.
were able to synthesize xanthate 27 in quantitative yield.
Hydrolysis of the dithiane moiety in xanthate 27 was
carried out with iodobenzenebis(trifluoroacetate)28 in wet
acetonitrile to afford acylsilane 29 (70%). This new route
turned out to be a much better way to provide suitable
substrates to generate R-stannyl radicals. Treatment of
acylsilane 29 with a catalytic amount of tributyltin
hydride and AIBN in refluxing benzene led to the
formation of silyl enol ether 30. Simply concentrating the
reaction mixture and redesolving the residue in dichlo-
romethane, followed by the addition of phenylselenenyl
bromide at -78 °C, gave the selenide 31 in 77% yield as
a mixture of cis/ trans isomers.29 In this way, we dem-
onstrated that silyl enol ether 30 was formed in a
regiospecific way. In principle, silyl enol ethers such as
30 can be prepared from 3-substituted cyclopentanones
through deprotonation. However, it is difficult to control
the regiochemistry of the enolate. Although the use of a
bulky base may give the regioisomer such as 30,30 the
other isomer cannot be eliminated completely. Our
method provides a useful approach in addition to other
methods.18,19
R a d ica l Cycliza t ion s of r-Su lfon yla cylsila n es.
Although the R-stannyl radical cyclization of acylsilanes
is successful for five-membered ring formation, this
strategy cannot be applied to six-membered ring forma-
tion. The route b approach shown in Scheme 1 may
provide an alternative way to accomplish the same goal.
In the route b approach, the radical leaving group X is
designed at the R-position of the carbonyl. The initial
radical 7 does not carry a large substituent at the carbon
bearing the radical. Therefore, it will not introduce bad
steric interaction between the initial radical and the
acylsilane moiety during cyclization as in the case of
R-stannyl radical cyclizations.
The selection of the radical leaving group X is crucial
for the success of this strategy. We found that the
selenide 3331,32 (Scheme 5), prepared from acylsilane 32,
reacted with 2 equiv of tributyltin hydride and gave only
straight reduction product 34 in 62% yield. We believe
that this result indicates that tributyltin hydride has
selectively removed the iodo group to generate the
terminal radical 35. If the phenylselenenyl group were
removed first, this would give iodide 38. We knew that
the iodide 38 will further react with tributyltin hydride
to give cyclized product 39.25 Since we did not observe
the formation of silyl ether 39, it indicates that the iodo
group has been removed first. Although the terminal
radical 35 was formed, a 1,5-hydrogen atom transfer
presumably occurred to give R-carbonyl radical 36. Acyl-
methyldiphenylsilane without an R-phenylselenenyl group
undergoes 1,6-radical cyclization quite efficiently with
little problem associated with the 1,5-hydrogen transfer
process.33 The presence of the phenylselenenyl group
probably enhanced the R-radical formation by weakening
the R-C-H bond.34 Hydrogen abstraction of radical 36
from tin hydride gave R-phenylselenenylacylsilane 37
which was further reduced to give acylsilane 34.
With the above understanding in mind, we picked a
phenylsulfonyl group as the radical leaving group. There
are several reasons for this choice. First, the phenylsul-
(31) Cossy, J .; Furet, N. Tetrahedron Lett. 1993, 34, 7755-7756.
(32) For the use of selenides as radical leaving groups, see: (a)
Feldman, K. S.; Kraebel, C. M. J . Org. Chem. 1992, 57, 4574-4576.
(b) Feldman, K. S. Synlett 1995, 217-225.
(28) Stork, G.; Zhao, K. Tetrahedron Lett. 1989, 30, 287-290.
(29) The isomeric ratio was determined to be 8.8/1 by 1H NMR
integration. However, we did not determine the stereochemistry of the
two isomers.
(30) For an example of regioselective deprotonation of 3-substituted
cyclopentanone, see: Angle, S. R.; Fevig, J . M.; Knight, S. D.; Marquis,
R. W., J r.; Overman, L. E. J . Am. Chem. Soc. 1993, 115, 3966-3976.
(33) Tsai, Y.-M.; Tang, K.-H.; J iaang, W.-T. Tetrahedron Lett. 1993,
34, 1303-1306.
(34) Bordwell, F. G.; Zhang, X.-M.; Alnajjar, M. S. J . Am. Chem.
Soc. 1992, 114, 7623-7629.

Regiospecific Formation of Cyclic Silyl Enol Ethers
J . Org. Chem., Vol. 66, No. 26, 2001 8987
Sch em e 6
Sch em e 7
of 42. Gas chromatographic analysis of the crude cycliza-
tion mixture showed the presence of cyclohexanone.
Addition of a methanol solution of 2,4-dinitrophenylhy-
drazine (2,4-DNP) and sulfuric acid to the reaction
mixture resulted in the isolation of the 2,4-dinitrophe-
nylhydrazone 43 in 81% yield. These results indicate that
silyl enol ether 42 was initially formed. However, as a
result of the presence of phenylsulfinic acid (44) as the
byproduct, silyl enol ether 42 likely reacted further with
sulfinic acid 44 to produce cyclohexanone as the final
product.
To stop the cyclization reaction at the silyl enol ether
stage, one needs to remove the nuisance acid 44 in situ.
When we used 6 equiv of freshly ground sodium bicar-
bonate powder in the cyclization condition, silyl enol ether
42 was isolated in 41% yield through silica gel column
chromatography. Further increment of sodium bicarbon-
ate powder to 10 equiv resulted in 88% isolation yield of
silyl enol ether 42. Because we did not isolate any
reduction product or cyclization product such as 39
(Scheme 5), we believe that the bromide in sulfone 41
was removed selectively by tributyltin radical in the
presence of the â-ketosulfonyl group.
There is another way that one can eliminate the
formation of sulfinic acid 44. As shown in Scheme 7,
acylsilane 32 was treated with allyltributyltin (1.2 equiv)
in the presence of catalytic amount of tributyltin hydride
(0.1 equiv) and AIBN (0.1 equiv) to yield silyl enol ether
42 (79%) and allyl phenyl sulfone38 (81%). This process
involves the formation of radical 45 first. Cyclization of
45 followed by radical-Brook rearrangement of the re-
sulting alkoxy radical gave R-silyloxy radical 46. â-Elim-
ination of phenylsulfinyl radical produced silyl enol ether
42. The phenylsulfinyl radical was trapped by allyltribu-
tyltin and converted to allyl phenyl sulfone. Tributyltin
radical was formed at the same time and reacted further
with acylsilane 32 to continue a new cycle. Without the
formation of phenylsulfinic acid (44), silyl enol ether 42
was obtained successfully.
fonyl group is a well-known radical leaving group exem-
plified in the radical chemistry of allyl sulfones and vinyl
sulfones.17 Furthermore, radicals adjacent to the strongly
electron-withdrawing sulfonyl group will be destabi-
lized.34,35 We hope that this feature will inhibit the
undesired 1,5-hydrogen atom transfer process mentioned
above. Moreover, we hope that the presence of an
electron-withdrawing group at the R-position will en-
hance the positive character of the carbonyl carbon.
Alkyl-substituted radicals are generally considered as
nucleophilic radicals. Therefore, the cyclization rate may
be increased. Although there are reports about reductive
cleavage of â-ketosulfones by tributyltin hydride,36 the
reactions appear to have a short radical chain length,36a
an indication of a slow process. Therefore, it is possible
to find proper substrates to selectively generate the
desired radicals without the interference of the â-keto-
sulfone functionality.
We found that the R-phenylthioacylsilane 40 (Scheme
6) could be prepared in 88% yield from the reaction of
bromoacylsilane 32 with N-phenylthiosuccinimide in
acetonitrile catalyzed by p-toluenesulfonic acid (0.05
equiv).37 Oxidation of sulfide 40 was performed using
m-chloroperbenzoic acid (MCPBA) to afford sulfone 41
in 85% yield. Radical cyclization of sulfone 41 employing
tributyltin hydride was expected to give silyl enol ether
42. However, by examining the crude cyclization mixture
This methodology can be employed in five-membered
ring formation. As shown in Scheme 8, R-sulfonylacylsi-
lanes 49 and 53 were prepared in high yields from
acylsilanes 4725 and 51,25 respectively, according to the
methods described above. Radical cyclization of acylsilane
49 with tributyltin hydride (1.2 equiv) in the presence of
large excess of sodium bicarbonate powder (15 equiv)
resulted in the formation of silyl enol ether 50. This silyl
enol ether appeared to be quite sensitive toward silica
1
with H NMR, we were not able to observe the presence
(35) Bordwell, F. G.; Zhang, X.-M. Acc. Chem. Res. 1993, 26, 510-
517.
(36) (a) Smith, A. B., III; Hale, K. J .; McCauley, J . P., J r. Tetrahe-
dron Lett. 1989, 30, 5579-5582. (b) Giovannini, R.; Petrini, M. Synlett
1995, 973-974. (c) Parsons, A. F.; Pettifer, R. M. Tetrahedron Lett.
1996, 37, 1667-1670. (d) Wnuk, S. F.; Rios, J . M.; Khan, J .; Hsu, Y.-
L. J . Org. Chem. 2000, 65, 4169-4174.
(37) Huang, C.-H.; Liao, K.-S.; De, S. K.; Tsai, Y.-M. Tetrahedron
Lett. 2000, 41, 3911-3914.
(38) Russell, G. A.; Herold, L. L. J . Org. Chem. 1985, 50, 1037-
1040.

8988 J . Org. Chem., Vol. 66, No. 26, 2001
Huang et al.
Sch em e 8
Sch em e 9a
gel column chromatography. We were able to isolate 50
in 52% yield. Gas chromatographic analysis using decane
as internal standard showed that silyl enol ether 50 was
actually formed in 99% yield.
Radical cyclization of acylsilane 53 under similar
condition produced silyl enol ether 54. Gas chromato-
graphic analysis using tetradecane as internal standard
indicated that 54 was formed in 92% yield. For the
purpose of analysis, an authentic sample of silyl enol
ether 54 was prepared by sequential reactions of 2-me-
thylcyclopentanone with LDA and methyldiphenylsilyl
chloride.39 A mixture of 54 and its regioisomer (GC ratio
of 9/1 in favor of 54) was obtained and separable by gas
chromatography (10% SE-30 on Chromosorb W). Gas
chromatographic analysis also showed that the silyl enol
ether synthesized from radical cyclization is a single
isomer corresponding to the kinetic isomer 54 obtained
from 2-methylcyclopentanone.
a
Reagents and conditions: (i) 8b, BuLi, THF, 0 °C; (ii) AcOH,
Dem on str a tion of Regiosp ecific Syn th esis of Iso-
m er ic Silyl En ol Eth er s th r ou gh a Com m on Sta r t-
in g Ma ter ia l. With the development of two methods of
silyl enol ether synthesis from radical cyclizations of
acylsilanes, one can begin with a single starting material
and control the regiochemistry of silyl enol ether forma-
tion by proper choice of the method. As shown in Scheme
9, alkylations of dithiane 8b with bromide 5540 gave
acetal 56 in 83% yield. Hydrolysis of the acetal afforded
aldehyde 57 (72%). Conversion of aldehyde 57 to xanthate
58 (66%) was performed using methods described above.
On the other hand, reduction of aldehyde 57 with sodium
borohydride in ethanol gave alcohol 59 (88%). This
alcohol was converted to bromoacylsilane 60 using carbon
tetrabromide and triphenylphosphine41 followed by hy-
drolysis of the dithiane moiety with CAN in wet aceto-
nitrile.24 R-Sulfonylacylsilane 62 was prepared from
acylsilane 60 through R-sulfenylation37 and oxidation
processes.
H2O; (iii) Bu3SnH, LDA, THF, -78 °C; CS2, -78 °C; MeI, -78 °C;
(iv) (CF3COO)2IPh, CH3CN, H2O; (v) NaBH4, EtOH/CH2Cl2, 0 °C;
(vi) CBr4, PPh3, CH2Cl2, 0 °C; (vii) red HgO, BF3‚OEt2, H2O, THF,
rt; (viii) N-phenylthiosuccinimide, TsOH, CH3CN, rt; (ix) MCPBA
(2.2 equiv), NaHCO3, CH2Cl2, 0 °C; (x) Bu3SnH (0.15 equiv), AIBN
(0.05 equiv), PhH, 80 °C; (xi) PhSeBr, CH2Cl2, -78 °C; (xii)
Bu3SnH (1.2 equiv), AIBN (0.1 equiv), NaHCO3 powder (15 equiv),
PhH, 80 °C.
In comparison, R-sulfonylacylsilane 62 was treated
with 1.2 equiv of tributyltin hydride along with catalytic
amount of AIBN (0.1 equiv) and excess sodium bicarbon-
ate fine powder (15 equiv) in refluxing benzene. The
crude reaction mixture was analyzed by gas chromatog-
raphy using tetradecane as internal standard, and the
1
yield of silyl enol ether 30 was determined as 85%. H
NMR analysis showed that a single isomer was formed.
An authentic sample of a mixture of silyl enol ethers 30
and 63 (30/63 ) 3/2) was prepared from 3-methylcyclo-
pentanone through deprotonation and silylation. The two
isomers can be differentiated by their 1H NMR signals
(in CDCl3) of the vinyl hydrogens. The characteristic
signal of 30 appears at δ 4.50 (br s), and that of 63
appears at δ 4.54 (br s). It should be noted that when we
used 10 equiv of sodium bicarbonate in the cyclization of
acylsilane 62, a 9/1 mixture of silyl enol ethers 30 and
63 in favor of 30 was obtained. We assumed that this is
due to slow scavenge of phenylsulfinic acid (44) by sodium
bicarbonate. The small amount of acid reacted with the
silyl enol ether and yielded 3-methylcyclopentanone. Silyl
enol ether 30 may exchange the silyl group with 3-me-
thylcyclopentanone or its enol form (Scheme 10) to
produce the isomeric silyl enol ether 63. When 15 equiv
Xanthate 58 reacted with catalytic amount of tribu-
tyltin hydride (0.15 equiv) in refluxing benzene and
yielded silyl enol ether 63. Without purification of 63,
the crude concentrate of the cyclization reaction mixture
was redesolved in dichloromethane and treated with
phenylselenenyl bromide at -78 °C to afford selenide 64
(68%) as a mixture of E- and Z-isomers (E/ Z ) 2/1).42
(39) Bonafoux, D.; Bordeau, M.; Biran, C.; Cazeau, P.; Dunogues,
J . J . Org. Chem. 1996, 61, 5532-5536.
(40) Collins, D. J .; J ames, A. M. Aust. J . Chem. 1989, 42, 223-228.
(41) Castro, B. R. Org. React. 1983, 29, 1-162.
(42) Toru, T.; Okumura, T.; Ueno, Y. J . Org. Chem. 1990, 55, 1277-
1280.

Regiospecific Formation of Cyclic Silyl Enol Ethers
J . Org. Chem., Vol. 66, No. 26, 2001 8989
prepared from the corresponding 2-silyl-1,3-dithianes 8 ac-
Sch em e 10
cording to the general procedure described before.43
Gen er a l P r oced u r e for th e P r ep a r a tion of Acylsila n es
12. 5-Br om o-5-t r ibu t ylst a n n yl-1-(m et h yld ip h en ylsilyl)-
1-p en ta n on e (12b). To a solution of 0.34 mL (2.4 mmol) of
diisopropylamine in 2 mL of dry THF cooled at 0 °C under
argon was added over 10 min a solution of 1.5 N butyllithium
in hexane (1.6 mL, 2.4 mmol). The resulting solution was
stirred at the same temperature for 30 min followed by the
addition of 0.64 mL (2.4 mmol) of tributyltin hydride over 10
min. The reaction mixture was stirred for another 30 min at
0 °C and then cooled in a dry ice/acetone bath. To this cold
solution was added dropwise over 1 h a solution of 773 mg
(2.0 mmol) of aldehyde 10b in 2 mL of dry THF. The reaction
mixture was stirred at the same temperature for 1 h and then
poured into a mixture of ether and a 0.05 N ammonium
chloride solution. The organic layer was washed with brine,
dried (MgSO4), and concentrated in vacuo. The resulting
residue and 1.06 g (3.2 mmol) of carbon tetrabromide were
dissolved in 5 mL of dichloromethane and then cooled in an
ice/water bath. To this solution was added dropwise over 20
min a solution of 839 mg (3.2 mmol) of triphenylphosphine in
2.5 mL of dichloromethane. The resulting mixture was stirred
at room temperature for 1 h and filtered over a short pad of
silica gel column (washed with hexane/ethyl acetate, 9/1). The
filtrate was concentrated, and the residual oil was chromato-
graphed with MPLC over a Lobar size B column (eluted with
hexane/ethyl acetate, 98/2) to give 771 mg (57%) of 11b as a
pale yellow liquid: 1H NMR (CDCl3, 300 MHz) δ 0.78 (s, 3 H),
0.83-0.95 (two overlapped t, J ) 7 Hz, at 0.89 and 0.93, 15
H), 1.29 (sextet, J ) 7 Hz, 6 H), 1.41-2.28 (m, 14 H), 2.42 (dt,
J ) 13.5, 4 Hz, 2 H), 2.98 (ddd, J ) 13.5, 11, 4 Hz, 2 H), 3.48
(dd, J ) 9.5, 5 Hz, 1 H), 7.28-7.42 (m, 6 H), 7.78-7.84 (m, 4
H); 13C NMR (CDCl3, 75 MHz) δ -3.9, 9.9 (J C-Sn ) 315 Hz),
13.6, 24.0, 24.6, 27.3 (J C-Sn ) 60 Hz), 27.6, 28.9 (J C-Sn ) 20
Hz), 37.2, 38.0, 39.0, 127.5, 129.6, 134.2, 135.9. Bromide 11b
was not stable at room temperature and should be hydrolyzed
as soon as possible. To a mixture of 771 mg (1.04 mmol) of
11b, 71 mg (0.85 mmol) of sodium bicarbonate, and 48 mg of
Celite in dichloromethane/acetonitrile (3 mL/2 mL) cooled at
-15 °C (dry ice/carbon tetrachloride bath) was added dropwise
over 10 min a solution of 1.72 g (3.1 mmol) CAN in aqueous
acetonitrile (acetonitrile/water ) 15 mL/1 mL). The resulting
mixture was stirred at the same temperature for another 10
min, diluted with ether, and filtered. The filtrate was parti-
tioned between ether and water. The organic layer was washed
with brine, dried (MgSO4), and concentrated in vacuo. The
residue was chromatographed over silica gel (eluted with
hexane/ethyl acetate, 98/2) to give 377 mg (55%) of 12b as a
of sodium bicarbonate was used, phenylsulfinic acid (44)
can be removed more efficiently. Therefore, isomerization
of silyl enol ether 30 was not observed.
Con clu sion s
In this study, we have successfully developed two
routes in the synthesis of regiospecific cyclic silyl enol
ethers employing intramolecular radical cyclizations of
acylsilanes. Both approaches involve â-fragmentation of
the cyclized R-silyloxy radical intermediates. The cycliza-
tions of acylsilanes carrying terminal R-tributylstannyl
bromide or xanthate functionalities adopt the tributyl-
stannyl group as the radical leaving group for the â-frag-
mentation. This approach works only for five-membered
ring formation. The other approach uses R-phenylsulfo-
nylacylsilanes as the substrates. The R-phenylsulfonyl
group serves as the radical leaving group. Although the
latter approach works well for both five- and six-mem-
bered ring formations, the concomitant formation of
phenylsulfinic acid causes some trouble. This side product
can be removed by the use of excess (15 equiv) sodium
bicarbonate powder. Because of the difference in the
direction of bond formation, the two radical approaches
are complementary regarding the regiochemistry of cyclic
silyl enol ether formation. Within the same route, tuning
the position of the substituents on the acylsilane back-
bone will also lead to the formation of the desired
regioisomer.
This study extended the synthetic utility of acylsi-
lanes.15 Although there are many methods for the prepa-
ration of silyl enol ethers, most of them employ strongly
basic conditions.18 Our radical approach works under
neutral conditions and may offer some advantages when
base-sensitive functionalities are present. However, the
efficiency of our method depends on how easily the
acylsilanes can be synthesized, and it is successful only
for five- and six-membered cyclic silyl enol ethers.
pale yellow oil: IR (neat) 1634 cm-1 1H NMR (CDCl3, 300
;
MHz) δ 0.74 (s, 3 H), 0.78-1.10 (m, 15 H), 1.28 (sextet, J ) 7
Hz, 6 H), 1.37-1.67 (m, 6 H), 1.67-1.95 (m, 4 H), 2.65 (br t, J
) 7 Hz, 2 H), 3.49 (dd, J ) 8.5, 6 Hz, 1 H), 7.27-7.48 (m, 6
H), 7.50-7.62 (m, 4 H); 13C NMR (CDCl3, 50 MHz) δ -5.3, 9.9
(J C-Sn ) 315 Hz), 13.6, 22.6, 27.3 (J C-Sn ) 60 Hz), 28.9 (J C-Sn
) 20 Hz), 37.0, 39.1, 48.5, 128.1, 130.1, 132.7, 135.0, 243.8.
Anal. Calcd for C30H47BrOSiSn: C, 55.40; H, 7.28. Found: C,
55.65; H, 6.87.
Exp er im en ta l Section
Gen er a l P r oced u r e for In tr a m olecu la r Ra d ica l Cy-
cliza tion s of r-Sta n n yl Br om id es. Cycliza tion of 12b. To
a refluxing solution of 325 mg (0.50 mmol) of 12b in 2.5 mL of
benzene was added via syringe pump over 1 h a solution of 19
µL (0.060 mmol) of tributyltin hydride and 4.0 mg (0.024 mmol)
of AIBN in 2.5 mL of benzene. The resulting solution was
heated for 1 h and then cooled to room temperature. To the
resulting reaction mixture was added a solution of 197 mg (1.0
mmol) 2,4-dinitrophenylhydrazine in 5 mL of methanol, and
0.25 mL of 98% sulfuric acid. The resulting mixture was stirred
overnight, poured into a saturated sodium bicarbonate solu-
tion, and then extracted with ether. The combined organic
phases were washed with brine, dried (MgSO4), and concen-
trated in vacuo. The residue was chromatographed over silica
Melting points are uncorrected. 1H NMR spectra were
recorded at 200 or 300 MHz; 13C NMR spectra were recorded
at 50 or 75 MHz. Tetramethysilane (δ ) 0 ppm) or CHCl3 (δ
) 7.24 ppm) were used as internal standards, and CDCl3 was
used as the solvent. Benzene and THF were distilled from
sodium/benzophenone ketyl under N2. Diisopropylamine and
acetonitrile were dried with CaH2 and distilled. The benzene
used for cyclization reactions was deoxygenated by passing a
gentle stream of argon through it for 0.5 h before use. All
reactions were performed under a blanket of N2 or Ar. Lobar
LiChroprep Si 60 (40-63 µm) prepacked columns purchased
from Merck were used for medium-pressure liquid chroma-
tography (MPLC). Gas chromatography was performed on a
Shimadzu GC-8A apparatus with TCD using a 3.3 mm × 2 m
column of 10% SE-30 on Chromosorb W (AW-DMCS), 80-100
mesh, and hydrogen as carrier gas. Aldehydes 10 were
(43) Chuang, T.-H.; Fang, J .-M.; J iaang, W.-T.; Tsai, Y.-M. J . Org.
Chem. 1996, 61, 1794-1805.

8990 J . Org. Chem., Vol. 66, No. 26, 2001
Huang et al.
gel (eluted with hexane/ethyl acetate, 9/1) to give 110 mg (84%)
of cyclopentanone 2,4-dinitrophenylhydrazone (19) as an or-
ange solid: mp 148-150 °C (lit.44 146-148 °C).
reaction mixture was stirred at the same temperature for
another 30 min and then cooled in an dry ice/acetone bath. To
the cold solution was added dropwise over 30 min a solution
of 403 mg (1.0 mmol) of 26 in 1 mL of THF. The resulting
mixture was stirred at the same temperature for 1 h, followed
by the addition of 68 µL (1.1 mmol) of carbon disulfide, and
then warmed to room temperature. The reaction mixture was
stirred at room temperature for 30 min and then cooled in a
dry ice/acetone bath. To the cold mixture was added 94 µL (1.5
mmol) of methyl iodide, and the reaction mixture was warmed
to room temperature. The resulting mixture was stirred at
room temperature for 1 h and partitioned between ether and
water. The organic layer was washed with brine, dried
(MgSO4), and concentrated in vacuo. The residue was chro-
matographed over silica gel (eluted with hexane/ethyl acetate,
98/2) to give 716 mg (100%) of 27 as a yellow oil. This material
is a 1:1 mixture of two diastereomers: 1H NMR (CDCl3, 200
MHz) δ 0.65-1.00 (m, 21 H), 1.10-2.50 (m, 21 H), 2.49 (s, 1.5
H, S-Me of one isomer), 2.54 (s, 1.5 H, S-Me of another isomer),
2.75-3.04 (m, 2 H), 5.69-5.89 (m, 1 H), 7.26-7.44 (m, 6 H),
7.73-7.90 (m, 4 H). Anal. Calcd for C36H58OS4SiSn: C, 55.30;
H, 7.48. Found: C, 54.89; H, 7.49.
2-(4-Br om o-3-m eth ylp r op yl)-1,3-d ioxola n e (24). Ozone
gas was bubbled into a solution of 3.87 g (23.7 mmol) of
5-bromo-4-methyl-1-pentene45 in 20 mL of methanol cooled at
-78 °C until the solution turned into pale blue. To the reaction
mixture was added 20 mL of dimethyl sulfide, and the
resulting solution was stirred at room temperature for 3 days.
The resulting reaction mixture was partitioned between ether
and water. The organic layer was washed with brine, dried
(MgSO4), and concentrated in vacuo. To the resulting residue
was added 1.44 mL of ethylene glycol, 380 mg (2.0 mmol) of
p-toluenesulfonic acid, and 30 mL of benzene. The resulting
mixture was heated under reflux for 24 h, and water was
removed via a Dean-Stark apparatus. The reaction mixture
was partitioned between ether and water. The organic layer
was washed with brine, dried (MgSO4), and concentrated in
vacuo. The residue was distilled to give 3.87 g (78%) of 24 as
1
a colorless liquid: bp 72-73 °C/1.5 mmHg; H NMR (CDCl3,
200 MHz) δ 1.08 (d, J ) 6.6 Hz, 3 H), 1.52-1.70 (m, 1 H),
1.71-1.80 (m, 1 H), 1.95-2.16 (m, 1 H), 3.32-3.58 (m, 2 H),
3.72-4.01 (m, 4 H), 4.89 (t, J ) 5 Hz, 1 H). Anal. Calcd for
C7H13BrO2: C, 40.21; H, 6.27. Found: C, 39.89; H, 6.10.
Gen er a l P r oced u r e for th e Hyd r olysis of Dith ia n e
Xan th ates. O-(1-Tr ibu tylstan n yl-3-m eth yl-5-m eth yldiph e-
n ylsilyl-5-oxop en tyl) S-Meth yl Dith ioca r bon a te (29). To
a mixture of 781 mg (1.0 mmol) of 27 and 126 mg (1.5 mmol)
of sodium bicarbonate in 4.5 mL of THF, 4.5 mL of acetonitrile,
and 1 mL of water was added over 5 min a solution of 602 mg
(1.4 mmol) of iodobenzenebis(trifluroacetate) in 2 mL of
acetonitrile. The resulting mixture was stirred at room tem-
perature for 15 min and then partitioned between ether and
water. The organic layer was washed with brine, dried
(MgSO4), and concentrated in vacuo. The residue was chro-
matographed over silica gel (eluted with hexane/ethyl acetate,
98/2) to give 483 mg (70%) of 29 as a yellow oil. This material
2-(2-Meth yl-3-(2,5-d ioxa cyclop en tyl)p r op yl)-2-(m eth yl-
d ip h en ylsilyl)-1,3-d ith ia n e (25). To a solution of 2.53 g (8.0
mmol) of 8b in 8 mL of dry THF under argon cooled at 0 °C
was added dropwise over 10 min a solution of 1.53 N butyl-
lithium in hexane (5.5 mL, 8.4 mmol). The resulting solution
was stirred at 0 °C for 20 min followed by the addition of 1.3
mL (8.0 mmol) of 24 over a period of 20 min. The resulting
mixture was stirred at room temperature for 2 h and then
partitioned between ether and water. The organic layer was
washed with brine, dried (MgSO4), and concentrated in vacuo.
The residual oil was chromatographed with MPLC over a
Lobar size B column (eluted with hexane/ethyl acetate, 9/1)
to give 2.90 g (82%) of 25 as a white solid: mp 87.5-88.0 °C;
1H NMR (CDCl3, 300 MHz) δ 0.85 (s, 3 H), 0.95 (d, J ) 6.5
Hz, 3 H), 1.38 (ddd, J ) 13.5, 8.5, 4.5 Hz, 1 H), 1.77 (dt, J )
13.5, 4.5 Hz, 1 H), 1.82-2.15 (m, 4 H), 2.25 (dd, J ) 14.5, 4.5
Hz, 1 H), 2.44 (dt, J ) 13.5, 4.5 Hz, 2 H), 2.91 (br t, J ) 13.5
Hz, 2 H), 3.69-3.90 (m, 4 H), 4.63 (t, J ) 5.5 Hz, 1 H), 7.30-
7.43 (m, 6 H), 7.83 (d, J ) 7 Hz, 4 H); 13C NMR (CDCl3, 75
MHz) δ -4.0, 21.7, 24.3, 24.4, 28.2, 39.0, 41.8, 44.9, 64.2, 64.4,
103.4, 127.4, 129.3, 134.6, 135.8. Anal. Calcd for C24H32O2S2-
Si: C, 64.82; H, 7.25. Found: C, 64.49; H, 7.17.
1
is a 1:1 mixture of two isomers: IR (CH2Cl2) 1633 cm-1; H
NMR (CDCl3, 200 MHz) δ 0.70-1.10 (m, 21 H), 1.23-1.70 (m,
13 H), 2.02-2.28 (m, 2 H), 2.34-2.83 (m overlapped with two
s at 2.53 and 2.55, 5 H), 5.82-5.89 (m, 0.5 H, OCH of one
isomer), 5.89-5.95 (m, 0.5 H, OCH of another isomer), 7.27-
7.48 (m, 6 H), 7.50-7.68 (m, 4 H). Anal. Calcd for C33H52O2S2-
SiSn: C, 57.31; H, 7.58. Found: C, 57.39; H, 7.58.
Ra d ica l Cycliza tion of 29 a n d Dir ect Con ver sion to
Selen id e. 4-Meth yl-2-(p h en ylselen en yl)cyclop en ta n on e
(31). According to the general cyclization procedure of R-stan-
nyl bromides, 483 mg (0.70 mmol) of 29 was cyclized with
tributyltin hydride (29 µL, 0.11 mmol) and AIBN (6 mg, 0.037
mmol) in benzene. At the end of the cyclization, the solvent
was removed in vacuo, and the residue was taken up into 2
mL of dichloromethane. The solution was cooled in a dry ice/
acetone bath followed by the addition of a solution of 164 mg
(0.70 mmol) of phenylselenenyl bromide in 2 mL of dichlo-
romethane over a period of 10 min. The resulting solution was
stirred at the same temperature for 1 h and then partitioned
between ether and water. The organic layer was washed with
brine, dried (MgSO4), and concentrated in vacuo. To the
residue was added a few drops of wet triethylamine,46 and the
resulting mixture was chromatographed over silica gel (eluted
with hexane/ethyl acetate, 8.8/1) to give 136 mg (77%) of 31
as a pale yellow oil. This material is a 9:1 mixture of two
3-Meth yl-4-(1-m eth yldiph en ylsilyl-2,6-dith iacycloh exyl)-
bu ta n a l (26). A solution of 2.90 g (6.53 mmol) of 25 in 7 mL
of acetic acid and 1 mL of water was heated at 60 °C overnight.
The resulting mixture was carefully added to a saturated
sodium bicarbonate solution followed by extraction with ether.
The organic layer was washed with brine, dried (MgSO4), and
concentrated in vacuo. The residue was chromatographed over
silica gel (eluted with hexane/ethyl acetate, 9/1) to give 1.933
mg (74%) of 26 as a white solid: mp 85-87 °C; IR (CH2Cl2)
1
1712 cm-1; H NMR (CDCl3, 300 MHz) δ 0.83 (d, J ) 6 Hz, 3
H), 0.84 (s, 3 H), 1.80-2.35 (m, 6 H), 2.35-2.63 (m, 3 H), 2.98-
3.01 (m, 2 H), 7.28-7.46 (m, 6 H), 7.71-7.87 (m, 4 H), 9.35 (t,
J ) 1.5 Hz, 1 H); 13C NMR (CDCl3, 75 MHz) δ -3.9, 22.1, 24.3,
24.4, 24.5, 27.7, 39.0, 43.9, 51.6, 127.6, 129.7, 134.3, 135.8,
202.4; HRMS calcd for C22H28OS2Si m/z 400.1351, found
400.1351.
1
isomers: IR (neat) 1725 cm-1; H NMR (CDCl3, 200 MHz) δ
1.08 (d, J ) 6.5 Hz, 3 H), 1.48-2.02 (m, 2 H), 2.02-2.25 (m, 1
H), 2.35-2.68 (m, 2 H), 3.72 (dd, J ) 11, 8.5 Hz, 0.12 H, SeCH
of the minor isomer), 3.82 (br d, J ) 6.5 Hz, 0.88 H, SeCH of
the major isomer), 7.18-7.46 (m, 3 H), 7.48-7.70 (m, 2 H);
HRMS calcd for C12H14OSe m/z 254.0210, found 254.0215.
Gen er a l P r oced u r e for th e P r ep a r a tion of Dith ia n e
Xa n th a tes. O-[1-Tr ibu tylsta n n yl-3-m eth yl-4-(1-m eth yl-
diph en ylsilyl-2,6-dith iacycloh exyl)]bu tyl S-Meth yl Dith io-
ca r bon a te (27). To a solution of 0.16 mL (1.1 mmol) diiso-
propylamine in 1 mL of dry THF cooled at 0 °C under argon
was added over 10 min a solution of 1.5 N butyllithium in
hexane (0.73 mL, 1.1 mmol). The resulting solution was stirred
at the same temperature for 10 min, followed by the addition
of 0.30 mL (1.1 mmol) of tributyltin hydride over 10 min. The
Gen er a l P r oced u r e for r-Su lfen yla tion of Acylsila n es.
6-Br om o-1-(m eth yldiph en ylsilyl)-2-ph en ylsu lfen yl-1-h ex-
a n on e (40). A mixture of 2.10 g (5.60 mmol) of 32, 2.55 g (12.3
mmol) of N-phenylthiosuccinimide, and 106 mg (0.559 mmol)
of p-toluenesulfonic acid in 28 mL of dry acetonitrile was
stirred under argon at room temperature for 5.5 h. The
(44) Burgstahler, A. W.; Lewis, T. B.; Abdel-Rahman, M. O. J . Org.
Chem. 1966, 31, 3516-3522.
(45) Becker, D.; Haddad, N. Tetrahedron 1993, 49, 947-964.
(46) Curran, D. P.; Chang, C.-T. J . Org. Chem. 1989, 54, 3140-
3154.

Regiospecific Formation of Cyclic Silyl Enol Ethers
J . Org. Chem., Vol. 66, No. 26, 2001 8991
resulting mixture was partitioned between ether and water.
The organic layer was washed with brine, dried (MgSO4), and
concentrated in vacuo. The residual oil was chromatographed
with MPLC over a Lobar size B column (eluted with hexane/
ethyl acetate, 95/5) to give 2.39 g (88%) of 40 as a greenish
yellow oil: IR (neat) 1623 cm-1; 1H NMR (CDCl3, 300 MHz) δ
0.89 (s, 3 H), 1.38-1.45 (m, 1 H), 1.45-1.60 (m, 2 H), 1.66-
1.84 (m, 3 H), 3.27 (t, J ) 6.7 Hz, 2 H), 3.86 (t, J ) 7.0 Hz, 1
H), 7.03 (br d, J ) 7.0 Hz, 2 H), 7.10-7.23 (m, 3 H), 7.34-
7.48 (m, 6 H), 7.62-7.70 (m, 4 H); 13C NMR (CDCl3, 75 MHz)
δ -3.9 (q), 25.7 (t), 27.2 (t), 32.4 (t), 33.2 (t), 60.5 (d), 127.9
(d), 128.0 (d), 128.1 (d), 128.8 (d), 130.0 (d), 131.5 (s), 132.8
(s), 133.0 (d), 135.2 (d), 231.9 (s). Anal. Calcd for C25H27BrOSSi:
C, 62.10; H, 5.63. Found: C, 61.16; H, 5.61.
by gas chromatography. The yield of 50 determined this way
was 99%: tR ) 16.06 min (column temperature ) 210 °C, flow
rate ) 19 mL/min).
Ra d ica l Cycliza tion of 53. 5-Meth yl-1-(m eth yld ip h e-
n ylsiloxy)cyclop en ten e (54). Similar as the cyclization of
49, the cyclization of 53 was analyzed with gas chromatogra-
phy using tetradecane as internal standard. The yield of 54
was determine as 92%: tR ) 12.40 min (column temperature
) 220 °C, flow rate ) 18 mL/min). Characteristic 1H NMR
signals of 54: (CDCl3, 200 MHz) δ 0.70 (s, 3 H), 1.06 (d, J )
7 Hz, 3 H), 2.50-2.62 (m, 1 H), 4.43 (br s, 1 H), 7.30-7.50 (m,
6 H), 7.56-7.70 (m, 4 H).
2-Met h yl-5-[1-(m et h yld ip h en ylsilyl)-2,6-d it h ia cyclo-
h exyl]bu ta n ol (59). A mixture of 1.43 g (3.57 mmol) of 57
and 162 mg (4.28 mmol) of sodium borohydride in 6 mL of
ethanol and 1 mL of dichloromethane was stirred in an ice/
water bath for 2 h and then partitioned between ether and
water. The organic layer was washed with brine, dried
(MgSO4), and concentrated in vacuo. The residue was chro-
matographed over silica gel (eluted with hexane/ethyl acetate,
8/2) to give 1.26 g (88%) of 59 as a pale yellow oil: IR (neat)
Gen er a l P r oced u r e for th e Oxid a tion of r-P h en ylsu fe-
n yla cylsila n es. 6-Br om o-1-(m eth yld ip h en ylsilyl)-2-p h e-
n ylsu lfon yl-1-h exa n on e (41). To a mixture of 2.39 g (4.94
mmol) of 40 and 4.15 g (49.4 mmol) of sodium bicarbonate in
33 mL of dichloromethane cooled in an ice/water bath was
added 2.68 g (10.9 mmol) of MCPBA (70%). The resulting
mixture was stirred at 0 °C for 30 min, quenched by stirring
with 146 mg (0.987 mmol) of sodium thiosulfate for 5 min, and
then partitioned between dichloromethane and water. The
organic layer was dried (MgSO4) and concentrated in vacuo.
The residual oil was chromatographed with MPLC over a
Lobar size B column (eluted with hexane/ethyl acetate, 9/1 and
then 8/2) to give 2.16 g (85%) of 41 as a greenish yellow oil:
1
3622, 3482 (br) cm-1; H NMR (CDCl3, 300 MHz) δ 0.72 (d, J
) 6.6 Hz, 3 H), 0.76 (s, 3 H), 1.10-1.28 (m, 1 H), 1.30-1.52
(m, 3 H), 1.81-2.05 (m, 2 H), 2.08-2.30 (m, 2 H), 2.43 (dt, J
) 14, 4 Hz, 2 H), 2.98 (br t, J ) 14 Hz, 2 H), 3.23-3.30 (m, 2
H), 7.25-7.48 (m, 6 H), 7.79 (d, J ) 6 Hz, 4 H); 13C NMR
(CDCl3, 75 MHz) δ -3.8, 16.4, 23.9, 24.7, 30.3, 35.0, 36.0, 39.1,
67.7, 127.5, 129.7, 134.2, 135.8; HRMS calcd for C22H30OS2Si
m/z 402.1507, found 402.1507.
1
IR (neat) 1640 cm-1; H NMR (CDCl3, 300 MHz) δ 0.91 (s, 3
H), 1.07 (q, J ) 7.5 Hz, 2 H), 1.48-1.70 (m, 3 H), 1.75-1.90
(m, 1 H), 3.05-3.15 (m, 2 H), 4.66 (dd, J ) 10.3, 3.8 Hz, 1 H),
7.35-7.50 (m, 10 H), 7.55-7.65 (m, 5 H); 13C NMR (CDCl3, 75
MHz) δ -4.9 (q), 25.3 (t), 25.6 (t), 32.1 (t), 32.6 (t), 74.6 (d),
128.2 (d), 128.4 (d), 128.9 (d), 129.3 (d), 130.4 (d), 130.5 (d),
131.5 (s), 134.0 (d), 135.3 (d), 135.4 (d), 137.0 (s), 237.7 (s).
Anal. Calcd for C25H27BrO3SSi: C, 58.24; H, 5.28. Found: C,
58.10; H, 5.46.
5-B r o m o -4-m e t h y l-1-(m e t h y ld ip h e n y ls ily l)-1-p e n -
ta n on e (60). To a solution of 1.60 g (3.97 mmol) of 59 and
1.58 g (4.77 mmol) of carbon tetrabromide in 4 mL of dichlo-
romethane cooled in an ice/water bath was added over 20 min
a solution of 1.24 g (4.77 mmol) of triphenylphosphine in 5
mL of dichloromethane. The reaction mixture was stirred at
the same temperature for 2 h and then directly filtered over a
short pad of silica gel (eluted with ether). The filtrate was
concentrated in vacuo, and the residue was dissolved in 3 mL
of dry THF. This THF solution was added to a mixture of 1.72
g (7.95 mmol) of red mercury oxide, 1.72 g of Celite, and 1 mL
(7.95 mmol) of borontrifluoride etherate in aqueous THF (H2O/
THF ) 3 mL/17 mL). The resulting mixture was stirred at
room temperature for 2 h and filtered. The filtrate was
partitioned between ether and water. The organic layer was
washed with brine, dried (MgSO4), and concentrated in vacuo.
The residue was chromatographed over silica gel (eluted with
hexane/ethyl acetate, 95/5) to give 0.95 g (63%) of 60 as a
yellow oil: IR (neat) 1641 cm-1; 1H NMR (CDCl3, 300 MHz) δ
0.76 (s, 3 H), 0.89 (d, J ) 7 Hz, 3 H), 1.43 (dq, J ) 14, 7 Hz,
1 H), 1.55-1.75 (m, 2 H), 2.66 (t, J ) 7 Hz, 2 H), 3.17 (dd, J
) 9.5, 6 Hz, 2 H), 3.25 (dd, J ) 9.5, 4.5 Hz, 1 H), 7.33-7.50
(m, 6 H), 7.67 (d, J ) 7 Hz, 4 H); 13C NMR (CDCl3, 75 MHz)
δ -5.0, 18.5, 27.1, 34.5 40.7, 46.7, 128.2, 130.1, 132.6, 134.9,
243.7; HRMS calcd for C19H23BrOSi m/z 376.0702, found
376.0699.
Ra d ica l Cycliza tion of 41. Meth od (A). 1-(Meth yl-
d ip h en ylsiloxy)cycloh exen e (42). To a refluxing mixture
of 394 mg (0.763 mmol) of 41 and 642 mg (7.64 mmol) of finely
ground sodium bicarbonate in 10.2 mL of benzene was added
via syringe pump over 2 h a solution of 0.25 mL 0.916 mmol)
of tributyltin hydride and 12.5 mg (0.076 mmol) of AIBN in 5
mL of benzene. The resulting mixture was stirred at 80 °C for
another 2 h, filtered, and concentrated in vacuo. The residue
was mixed with 0.1 mL of anhydrous triethylamine and
chromatographed over silica gel (eluted with hexane) to give
109 mg (88%) of 42 as a colorless liquid: IR (neat) 1670 cm-1
;
1H NMR (CDCl3, 300 MHz) δ 0.70 (s, 3 H), 1.38-1.50 (m, 2
H), 1.55-1.65 (m, 2 H), 1.87-1.98 (m, 2 H), 1.98-2.05 (m, 2
H), 4.85-4.89 (m, 1 H), 7.30-7.42 (m, 6 H), 7.56-7.63 (m, 4
H); 13C NMR (CDCl3, 75 MHz) δ -2.5 (q), 22.2 (t), 23.1 (t),
23.8 (t), 29.8 (t), 105.1 (d), 127.8 (d), 129.8 (d), 134.3 (d), 136.3
(s), 150.2 (s). Meth od (B). To a refluxing mixture of 118 mg
(0.228 mmol) of 41 and 87.0 µL (0.273 mmol) of allyl(tributyl)-
stannane in 3.9 mL of benzene was added via syringe pump
over 1 h a solution of 7.0 µL (0.023 mmol) of tributyltin hydride
and 3.7 mg (0.023 mmol) of AIBN in 0.7 mL of benzene. The
resulting mixture was stirred at 80 °C for another 3 h and
concentrated in vacuo, and the residue was chromatographed
over silica gel (eluted with hexane) to give 53 mg (79%) of 42.
Further elution with hexane/ethyl acetate (9/1 and then 8/2)
gave 34 mg (81%) of allyl phenyl sulfone.38
Ra d ica l Cycliza tion of 62. 4-Meth yl-1-(m eth yld ip h e-
n ylsiloxy)cyclop en ten e (30). Similar to the cyclization of
49, the cyclization of 62 was analyzed with gas chromatogra-
phy using tetradecane as internal standard. The yield of 30
was determined as 85%: tR ) 10.40 min (column temperature
) 220 °C, flow rate ) 24 mL/min). Characteristic 1H NMR
signals of 30: (CDCl3, 300 MHz) δ 0.72 (s, 3 H), 0.98 (d, J )
6 Hz, 3 H), 1.78 (br d, J ) 13 Hz, 1 H), 1.89 (br d, J ) 13 Hz,
1 H), 2.20-2.50 (m, 3 H), 4.45-4.53 (m, 1 H), 7.35-7.50 (m, 4
H), 7.56-7.70 (m, 4H).
Ra d ica l Cycliza tion of 49. 1-(Meth yld ip h en ylsiloxy)-
cyclop en ten e (50). According to the procedure for the cy-
clization of 41, 200 mg (0.399 mmol) of 49 reacted with 0.13
mL (0.48 mmol) of tributyltin hydride, 6.4 mg (0.039 mmol) of
AIBN, and 0.503 g (5.98 mmol) of sodium bicarbonate.
Purification of the product through silica gel column chroma-
tography (eluted with hexane) gave 59 mg (52%) of 50 as a
Ack n ow led gm en t . Financial support by the
National Science Council of the Republic of China is
gratefully acknowledged.
Su p p or tin g In for m a tion Ava ila ble: Characterization
data for compounds 9b,c, 10b,c, 11a ,c, 12a ,c, 14, 15, 17, 23,
48, 49, 52, 53, 56-58, 61, and 62 and copies of 1H and 13C
NMR spectra of new compounds. This material is available
free of charge via the Internet at http://pubs.acs.org.
colorless liquid: IR (neat) 1645 cm-1 1H NMR (CDCl3, 200
;
MHz) δ 0.75 (s, 3 H), 1.81 (quartet, J ) 5.9 Hz, 2 H), 2.16-
2.35 (m, 4 H), 4.55-4.62 (m, 1 H, vinyl CH), 7.30-7.50 (m, 6
H, ArH), 7.56-7.70 (m, 4 H, ArH). In another experiment, 2
equiv of decane was added to the reaction mixture as an
internal GC standard, and the resulting solution was analyzed
J O010883S