Cyclopropanation and carbonyl olefination utilizing 2-(Alk-1-yn-1-yl)-2- (trialkylsilyl)-1,3-dithianes via regioselective generation of titanium alkynylcarbene complexes

Article abstract of DOI:10.1021/jo050122f

Cp₂Ti[P(OEt)₃]₂-promoted reactions of 2-(alk-1-yn-1-yl)-2-(trialkylsilyl)-1,3-dithianes (RS)₂C(Si)C≡ CR with terminal olefins and carbonyl compounds produced (trialkylsilylethynyl) cyclopropanes and 1-(trialkyls

Full text of DOI:10.1021/jo050122f

Cyclopropanation and Carbonyl Olefination Utilizing
2-(Alk-1-yn-1-yl)-2-(trialkylsilyl)-1,3-dithianes via Regioselective
Generation of Titanium Alkynylcarbene Complexes
Takeshi Takeda,* Makoto Ozaki, Shuichi Kuroi, and Akira Tsubouchi
Department of Applied Chemistry, Graduate School of Engineering, Tokyo University of Agriculture and
Technology, Koganei, Tokyo 184-8588, Japan
takeda-t@cc.tuat.ac.jp
Received January 21, 2005
Cp2Ti[P(OEt)3]2-promoted reactions of 2-(alk-1-yn-1-yl)-2-(trialkylsilyl)-1,3-dithianes (RS)2C(Si)Ct
CR with terminal olefins and carbonyl compounds produced (trialkylsilylethynyl)cyclopropanes and
1-(trialkylsilyl)alk-3-en-1-ynes, respectively. These compounds were suggest to be produced via the
formation of intermediary titanium R-(trialkylsilylethynyl)carbene complexes Cp2TidC(R)CtCSi
in preference to their regioisomers, R-(trialkylsilyl)alkynylcarbene complexes Cp2TidC(Si)CtCR.
Introduction
pared and applied to organic synthesis,1 only limited
work has been done on the chemistry of nonheteroatom-
substituted alkynylcarbene complexes.6 Therefore we
were intrigued with the generation of highly substituted
alkynylcarbene complexes from the acetylenic thioacetals
bearing an R-substituent. We expected that the less bulky
alkynyl group would alleviate the steric crowding of the
thioacetals, and hence these organotitanium species could
be obtained. Our major interest in the chemistry of highly
substituted alkynylcarbene complexes is their regiose-
lective formation, which is of crucial importance for their
synthetic application.
The unique reactivities of transition metal carbene
complexes and their application to organic synthesis
including olefin metathesis, cyclopropanation, and car-
bonyl olefination have attracted considerable attention.1
We have developed a variety of transformations of
organic compounds utilizing a thioacetal-titanocene(II)
system, in which titanium carbene complexes are as-
sumed to be formed as active intermediates. Thus alkyl-,
alkenyl-, and alkynylcarbene complexes were readily
generated by desulfurizative titanation of thioacetals and
related organosulfur compounds with the titanocene(II)
species Cp2Ti[P(OEt)3]2 (1).2 This methodology, however,
suffers a serious drawback in that the formation of
R-substituted alkylidenetitanocenes is seriously affected
by steric hindrance;3 only thioacetals derived from less
hindered ketones such as cyclobutanone can be employed
for the generation of the alkylidene complexes.4
Here we report highly regioselective cyclopropanation
and carbonyl olefination utilizing R-silylalkynyl thio-
acetals 2 which involve unprecedented allylic rearrange-
ment directed by the trialkylsilyl group.7
Results and Discussion
Preparation of 2-(Alk-1-yn-1-yl)-2-(trialkylsilyl)-
1,3-dithianes 2. The alkynyl thioacetals employed in this
Previously, we have found that cyclopropanes were
produced by reaction of terminal olefins with the titanium
alkynylcarbene complexes generated from â,γ-acetylenic
thioacetals.5 Although various types of heteroatom-
substituted alkynylcarbene complexes have been pre-
(5) Takeda, T.; Kuroi, S.; Yanai, K.; Tsubouchi, A. Tetrahedron Lett.
2002, 43, 5641.
(6) For Re-complexes, see: (a) Casey, C. P.; Kraft, S.; Powell, D. R.
J. Am. Chem. Soc. 2000, 122, 3771. (b) Casey, C. P.; Kraft, S.; Kavana,
M. Organometallics 2001, 20, 3795. (c) Casey, C. P.; Kraft, S.; Powell,
D. R. Organometallics 2001, 20, 2651. (d) Casey, C. P.; Kraft, S.; Powell,
D. R. J. Am. Chem. Soc. 2002, 124, 2584. For Mn-complexes, see: (e)
Ortin, Y.; Coppel, Y.; Lugan, N.; Mathieu, R.; McGlinchey, M. J. Chem.
Commun. 2001, 1690. (f) Casey, C. P.; Dzwiniel, T. L.; Kraft, S.; Kozee,
M. A.; Powell, D. R. Inorg. Chem. Acta 2003, 345, 320. (g) Ortin, Y.;
Sournia-Saquet, A.; Lugan, N.; Mathieu, R. Chem. Commun. 2003,
1060. For Rh-complexes, see: (h) Padwa, A.; Austin, D. J.; Gareau,
Y.; Kassir, J.; Xu, S. L. J. Am. Chem. Soc. 1993, 115, 2637. For
W-complexes, see: (i) Iwasawa, N.; Maeyama, K.; Saitou, M. J. Am.
Soc. Chem. 1997, 119, 1486.
(1) Do¨rwald, F. Z. Metal Carbenes in Organic Synthesis; Wiley-
VCH: Weinheim, Germany, 1999.
(2) (a) Takeda, T. In Titanium and Zirconium in Organic Synthesis;
Marek, I., Ed.; Wiley-VCH: Weinheim, Germany, 2002; p 480. (b)
Takeda, T.; Tsubouchi, A. In Modern Carbonyl Olefination; Takeda,
T., Ed.; Wiley-VCH: Weinheim, Germany, 2004; p 178. (c) Takeda, T.
Bull. Chem. Soc. Jpn. 2005, 78, 195.
(3) Takeda, T.; Sasaki, R.; Fujiwara, T. J. Org. Chem. 1998, 63, 7286.
(4) Fujiwara, T.; Iwasaki, N.; Takeda, T. Chem. Lett. 1998, 741.
10.1021/jo050122f CCC: $30.25 © 2005 American Chemical Society
Published on Web 04/21/2005
J. Org. Chem. 2005, 70, 4233-4239
4233

Takeda et al.
TABLE 1. Regioselective Formation of the
(Trialkylsilylethynyl)cyclopropanes 11
SCHEME 1. Preparation of Alkynyl Thioacetals
SCHEME 2. Cyclopropanation with
2-Methyl-2-(5-phenylpent-1-yn-1-yl)-1,3-dithiane (7)
study were prepared as summarized in Scheme 1. Trans-
thioacetalization of â,γ-acetylenic acetals 3 with 1,3-
propanedithiol in the presence of AlCl3 gave the 2-alky-
nyl-1,3-dithianes 4. The R-(trialkylsilyl)-â,γ-acetylenic
thioacetals 2 were obtained by successive treatment of 4
with buthyllithium and trialkylchlorosilanes. 2-Methyl-
2-(trimethylsilylethynyl)-1,3-dithiane (5) was prepared by
the treatment of 2-(trimethylsilylethynyl)-1,3-dithiane
(6)8 with butyllithium followed by the alkylation with
methyl iodide. The alkylation of the dithiane 4a with
methyl iodide also gave 2-methyl-2-(5-phenylpent-1-yn-
1-yl)-1,3-dithiane (7).
Reaction of Alkynyl Thioacetals with Terminal
Olefins in the Presence of the Titanocene(II) Re-
agent. Initially we examined the titanocene(II)-promoted
cyclopropanation of the R-methyl-â,γ-acetylenic thioacetal
7 under ethylene (8a). Treatment of 7 with the titano-
cene(II) reagent 1 (3 equiv) under ethylene atmosphere
afforded a mixture of the alkynylcyclopropane 9 and its
regioisomer 10 in 61% yield with a ratio of 79:21 in favor
of the less steric crowding cyclopropane (Scheme 2).
When more sterically hindered 2-(5-phenylpent-1-yn-
1-yl)-2-(trimethylsilyl)-1,3-dithiane (2a) was treated with
1 (2 equiv) under 8a at 25 °C for 1 h, the trimethylsilyl-
ethynyl-substituted cyclopropane 11a was exclusively
produced in 68% yield (Table 1, entry 1). Similar ti-
tanocene(II)-promoted reactions of the R-trialkylsilyl-â,γ-
acetylenic thioacetals 2 with various terminal olefins 8
a Carried out under ethylene. b 3 equiv of 1 and 4 equiv of 8e
were used.
SCHEME 3. Silyl Group Directed Regioselective
Cyclopropanation with the
r-(Trialkylsilyl)-â,γ-acetylenic Thioacetals 2
also gave the (trialkylsilylethynyl)cyclopropanes 11 with-
out formation of their possible regioisomers 12 (Scheme
3). When styrene (8e) was used as an olefin component,
partial reduction of the triple bond of the alkynylcyclo-
propane proceeded to form the alkenylsilane 13 (entry
5). The coupling constant of its vinyl protons (14.5 Hz)
suggests that its configuration is Z.9 This reduction was
(7) Preceding paper: Takeda, T.; Kuroi, S.; Ozaki, M.; Tsubouchi,
A. Org. Lett. 2004, 6, 3207.
(8) Andersen, N. H.; Dennistone, A. D.; McCrae, D. A. J. Org. Chem.
1982, 47, 1145.
4234 J. Org. Chem., Vol. 70, No. 11, 2005

Reactions via Titanium Alkynylcarbene Complexes
SCHEME 4. Reaction Pathway for the
Regioselective Formation of
(Trialkylsilylethynyl)cyclopropanes 11
SCHEME 6. Reaction of the Alkynylcarbene
Complexes with Dimethylphenylsilanes
SCHEME 5. Formation of the Dideuterio
Alkynylsilanes 16
5). It is rational to assume that 16b is produced by
deuteration of the alkynylcarbene complex 14a with
allylic rearrangement. However, the result does not
exclude the formation of the R-(trimethylsilyl)alkynyl-
carbene complex 17.
Reaction of the Alkynylcarbene Complexes with
Dimethylphenylsilane. A more persuasive evidence for
the intermediary trialkylsilylethynly-substituted carbene
complex 14 was obtained by using a carbenoid insertion-
type reaction of titanium carbene complexes with group
14 metal hydrides10 as a probe. Desulfurizative titanation
of 2a with 1 in the presence of dimethylphenylsilane
produced propargylsilane 18a as a major product along
with the allenylsilane 19 (Scheme 6). It is apparent that
these compounds are formed by the [2+1] and [2+3]
carbenoid insertion-type reactions of the (trialkylsilyl-
ethynyl)carbene complex 14a (Scheme 7). No formation
of the propargylsilane 20 or allenylsilane 21, which would
be formed via the R-trialkylsilyl carbene complex 17, was
observed, thus indicating exclusive formation of 14a by
the desulfurization of 2a with 1. The selective generation
of the silylethynyl carbene complex is further supported
by the fact that a similar reaction of 2c with dimeth-
ylphenylsilane gave only the propargylsilane 18b, which
was also produced by the reaction of the isomeric silyl-
ethynyl thioacetal 5. The mechanism for the regioselec-
tive formation of 14a is obscure at present. Although it
is reasonable to assume that the desulfurizative titana-
tion of 2 with 1 proceeds with allylic rearrangement to
give 14, the isomerization of the initially formed carbene
complexes such as 17 to 14 cannot be excluded because
the equilibrium between regioisomers of rhenium,6b,d
manganese,6e and rhodium6h alkynylcarbene complexes,
LnMdC(R)CtCR′ and LnMdC(R′)CtCR, was observed.
suppressed by use of more bulky tert-butyldimethylsilyl-
substituted acetylenic thioacetals (entries 6 and 9).
Interestingly, the position γ to the thioacetal group of 2
was predominantly cyclopropanated in all the reactions
examined. This regioselectivity is in sharp contrast to
that observed in the reaction of R-unsubstituted thio-
acetals, in which cyclopropanation took place at the
R-position.5 Furthermore, it is noteworthy that both the
cyclopropanation of 4-phenylbut-1-ene (8c) with the
R-(trimethylsilyl)-â,γ-acetylenic thioacetal 2c and its
regioisomer, γ-(trimethylsilyl)-â,γ-acetylenic thioacetal 5,
regioselectively produced the (trimethysilylethynyl)cy-
clopropane 11j with the same ratio of stereoisomers
(entries 10 and 11). These results indicate that the
regioselectivity of the cyclopropanation depends on the
relative steric bulkiness of R (R1)- and γ (R2)-substituents
of acetylenic thioacetals R2CtCC(SR)2R1.
The regioselectivity of the formation of (trialkylsilyl-
ethynyl)cyclopropanes 11 strongly suggests exclusive
formation of intermediary R-(trialkylsilylethynyl)carbene
complexes 14 (Cp2TidC(R)CtCSi). Accordingly, we as-
sume that the cyclopropanation proceeds through the
formation of the titanacyclobutane intermediate 15 formed
from 14 and a terminal olefin 8. Subsequent reductive
elimination affords the cyclopropane 11 (Scheme 4).
Indeed, the formation of alkynylcarbene complex 14
was supported by the fact that the dideuterated 1- and
2-alkynylsilanes 16a and 16b (>95% D) were produced
by successive treatment of the thioacetal 2a with the
titanocene(II) reagent 1 and deuterium oxide (Scheme
Titanocene(II)-Promoted Reaction of the R-Sub-
stituted Alkynyl Thioacetals 2 with Carbonyl Com-
pounds. On the basis of the regioselective formation of
14 suggested by the above investigation, we next exam-
ined the regioselective preparation of enynes 22 by the
olefination of carbonyl compounds 23 with the alkynyl-
carbene complexes 14 (Scheme 8). Contrary to our
expectations, the successive treatment of acetylenic thio-
acetal 2a with the titanocene(II) reagent 1 (3 equiv) and
(9) (a) Miura, K.; Oshima, K.; Utimoto, K. Bull. Chem. Soc. Jpn.
1993, 66, 2356. (b) Dash, A. K.; Wang, J. Q.; Eisen, M. S. Organome-
tallics 1999, 18, 4724.
(10) Takeda, T.; Nozaki, N.; Fujiwara, T. Tetrahedron Lett. 1998,
39, 3533.
J. Org. Chem, Vol. 70, No. 11, 2005 4235

Takeda et al.
SCHEME 7. Reaction Pathway for the Formation of Propargyl- and Allenylsilanes
TABLE 3. Reaction of the Acetylenic Thioacetals 2 with
Sterically Less Hindered Ketones 23
SCHEME 8. Carbonyl Olefination Utilizing the
Acetylenic Thioacetals 2
TABLE 2. Reaction of the Acetylenic Thioacetals 2 with
Dialkyl Ketones 23
a Ratio of stereoisomers.
3-pentanone (23a) (1.2 equiv) produced a mixture of the
two regioisomers of the carbonyl olefination products, the
conjugated dienes 22a and 24a (80:20) in 75% yield
(Table 2, entry 1). The regioselectivity increased when
the more sterically hindered tert-butyldimethylsilyl-
substituted counterpart 2d was employed (entry 2).
Although the reactions of dialkyl ketones and acetophe-
none with acetylenic thioacetals generally gave mixtures
of regioisomers, complete regioselectivity was observed
a Ratio of stereoisomers.
when the less bulky methyl-substituted thioacetal 2f was
employed (entries 6 and 7).
Unlike the reactions of dialkyl ketones, less bulky
ketones such as acetone, butan-2-one, and 4-substituted
cyclohexanones were exclusively transformed into the
corresponding silylacetylenes 22, regardless of the γ-sub-
4236 J. Org. Chem., Vol. 70, No. 11, 2005

Reactions via Titanium Alkynylcarbene Complexes
TABLE 4. Reaction of the Acetylenic Thioacetals 2 with
Esters and Lactones 23
SCHEME 9. Protodesilylation of the
(Trialkylsilylethynyl)cyclopropanes 11 and
1-(Trialkylsilyl)alk-3-en-1-ynes 22
TABLE 5. Protodesilylaton of the
(Trimethylsilylethynyl)cyclopropanes 11 and
1-(tert-Butyldimethylsilyl)alk-3-en-1-ynes 22
silylacetylene
11 or 22
terminal alkyne
yield/% (ratio of
stereoisomers)
entry
25 or 26
1
2
11b
11c
11g
22b
22d
22f
22h
22i
22j
25a
25b
25c
26a
26b
26c
26d
26e
26f
92 (56:44)
78 (62:38)
93 (83:17)
74
75 (70:30)
76
76
77 (82:18)
80
82
93
3
4
5
6
7
8
9
10
11
22k
22o
26g
26h
SCHEME 10. Pathways for the Reactions of the
Alkynylcarbene Complexes 14
a Single stereoisomers were obtained.
stituents of the â,γ-acetylenic thioacetals 2 (Table 3). The
dienyne 22m was also obtained in good yield by the
reaction of 2d with cyclohex-2-en-1-one (23i) (entry 6).
Similarly to the conventional carbonyl olefinations with
titanium carbene complexes,11 the present reaction is
applicable to the transformation of esters and lactones
into enynes 22 (Table 4). In contrast to the reactions of
dialkyl ketones, the reaction proceeded regioselectively
to produce silylethynyl group-substituted enol ethers as
sole products. It is also of special interest that every
reaction examined gave a single stereoisomer. Olefination
of carboxylic acid derivatives utilizing a thioacetal-
titanocene(II) system generally produces Z stereoisomers,
in which there is less steric interaction between the alkyl
group originating from the acyl group and the alkyl
substituent at the â carbon.12 Therefore, it is reasonable
to assume that the configuration of these enol ethers is
E. A similar stereoselectivity was also observed in other
olefination reactions of esters with use of titanium
carbene complexes.13
Protodesilylation of the (Trialkylsilylethynyl)-
cyclopropanes 11 and 1-(Trialkylsilyl)alk-3-en-1-
ynes 22. The major products of the reactions can be
transformed into synthetically useful terminal alkynes
(Scheme 9). Treatment of the (trialkylsilyethynyl)cyclo-
propanes 11 with tetrabutylammonium fluoride (TBAF)
gave the ethynylcyclopropanes 25. Similarly the trialkyl-
silyl group-substituted enynes 22 were transformed to
the terminal alkynes 26 (Table 5).
Reaction Pathways. The results of the carbenoid
insertion-type reactions indicate that only the R-(trialkyl-
silylethynyl)carbene complex 14 is generated by the
desulfurization of the alkynyl thioacetal 2 with the low-
valent titanocene 1. Therefore all the reactions of 2 are
explained by the formation of two types of organotita-
nium intermediates 27 and 28 (Scheme 10). The reaction
sequence involving the formation of the propargyltita-
nium intermediate 27 via the more stable 4-membered
transition state 29 and its metathesis-type degradation
or reductive elimination affords the major products of
cyclopropanation 11, carbenoid insertion-type reaction
18, or carbonyl olefination 22. The minor products of the
latter two reactions 19 and 24 are produced by similar
degradations of the allenyltitanium intermediate 28,
(11) Pine, S. H. Org. React. 1993, 43, 1.
(12) (a) Horikawa, Y.; Watanabe, M.; Fujiwara, T.; Takeda, T. J.
Am. Chem. Soc. 1997, 119, 1127. (b) Takeda, T.; Watanabe, M.; Nozaki,
N.; Fujiwara, T. Chem. Lett. 1998, 115.
(13) (a) Petasis, N. A.; Bzowej, E. I. J. Org. Chem. 1992, 57, 1327.
(b) Petasis, N. A.; Akritopoulou, I. Synlett 1992, 665. (c) Hart, S. L.;
McCamley, A.; Taylor, P. C. Synlett 1999, 90.
J. Org. Chem, Vol. 70, No. 11, 2005 4237

Takeda et al.
34.3, 35.1, 80.2, 86.3, 125.9, 128.4, 128.5, 141.7. Anal. Calcd
for C21H32S2Si: C, 66.96; H, 8.56. Found: C, 66.75; H, 8.52.
The R-(trialkylsilyl)-â,γ-acetylenic thioacetals 2a-c,e,f were
also obtained by a similar procedure described above.
which is formed via the less stable 6-membered transition
state 30. In the case of the reactions of sterically hindered
dialkyl ketones or dimethylphenylsilane, the four-
membered transition state 29 is destabilized by steric
repulsion between the R-substituent of the carbene
complex and the substrate, hence the reaction partially
follows the pathway involving the six-membered transi-
tion state 30 to produce the minor products. On the
contrary, a bulky tert-butyldimethylsilyl group destabi-
lizes 30, which would be the reason the carbonyl olefi-
nation with tert-butyldimethylsilyl group-substituted
acetylenic thioacetals is more regioselective than the
reaction of the trimethylsilyl group-substituted counter-
parts.
Preparation of 2-Methyl-2-(trimethylsilylethynyl)-1,3-
dithiane (5). Similarly to the preparation of R-(trialkylsilyl)-
â,γ-acetylenic thioacetals 2, the thioacetal 5 (193 mg, 70%) was
prepared by the alkylation of 2-(trimethylsilylethynyl)-1,3-
dithiane (6) (260 mg, 1.2 mmol) with MeI (0.09 mL, 1.4 mmol).
5: IR (neat) 2957, 2903, 2157, 1419, 1252, 1159, 1067, 926,
859, 833, 764, 652 cm-1 1H NMR δ 0.22 (s, 9H), 1.72-1.85
;
(m, 1H), 1.77 (s, 3H), 2.15 (dtt, J ) 14.5, 2.8, 4.2 Hz, 1H), 2.79
(ddd, J ) 3.6, 3.6, 13.8 Hz, 2H), 3.32 (ddd, J ) 2.3, 12.7, 14.8
Hz, 2H); 13C NMR δ 0.13, 25.0, 28.8, 29.1, 41.3, 89.7, 105.1.
Anal. Calcd for C10H18S2Si: C, 52.11; H, 7.87. Found: C, 51.73;
H, 7.94.
Similarly, 2-methyl-2-(5-phenylpent-1-yn-1-yl)-1,3-dithiane
(7) (251 mg, 91%) was obtained by the alkylation of 4a (262
mg, 1 mmol) with MeI (0.08 mL, 1.2 mmol). 7: IR (neat) 2903,
Conclusion
We have demonstrated that the highly regioselective
reactions of alkynyl thioacetals with terminal olefins and
carbonyl compounds are achieved by the introduction of
the bulky trialkylsilyl group. The products of these
reactions together with the results of the reaction of the
thioacetals with dimethylphenylsilane suggested that the
reaction preceeded via the regioselective formation of
silylethynyl group-substituted titanium carbene com-
plexes. It should be noted that the reactions described
here are convenient synthetic methods for the prepara-
tion of functionalized terminal alkynes.
1
2240, 1496, 1453, 1421, 1071, 740, 700 cm-1; H NMR δ 1.80
(s, 3H), 1.77-1.93 (m, 3H), 2.11-2.14 (m, 1H), 2.34 (t, J ) 7.2
Hz, 2H), 2.75 (t, J ) 7.9 Hz, 2H), 2.80 (ddd, J ) 3.7, 3.7, 13.8
Hz, 2H), 3.35 (ddd, J ) 2.5, 13.6, 13.6 Hz, 2H), 7.17-7.32 (m,
5H); 13C NMR δ 18.4, 25.1, 29.1, 29.6, 30.6, 35.0, 41.4, 81.6,
85.1, 125.9, 128.4, 128.5, 141.5. Anal. Calcd for C16H20S2: C,
69.51; H, 7.29. Found: C, 69.43; H, 7.44.
Titanocene(II)-Promoted Reaction of 7 with Ethylene.
Cp2TiCl2 (224 mg, 0.9 mmol), magnesium turnings (26 mg, 1.1
mmol; purchased from Nacalai Tesque Inc. Kyoto, Japan), and
finely powdered molecular sieves 4 A (90 mg) were placed in
a flask and dried with heating in vacuo. After cooling, THF
(1.8 mL) and P(OEt)3 (0.31 mL, 1.8 mmol) were added
successively with stirring at 25 °C under ethylene. After 3 h,
a THF (0.9 mL) solution of 7 (83 mg, 0.3 mmol) was added to
the mixture. The mixture was stirred for 1 h at 25 °C and then
refluxed for 1 h. The reaction was quenched by addition of 1
M NaOH, and the resulting insoluble materials were filtered
off through Celite and washed with ether. The organic materi-
als were extracted with ether and dried. After removal of the
solvent, the residue was purified by PTLC (hexane) to give a
mixture of 1-methyl-1-(5-phenylpent-1-yn-1-yl)cyclopropane (9)
and 1-(3-phenylpropyl)-1-(prop-1-yn-1-yl)cyclopropane (10) (34
mg, 57%, 9:10 ) 79:21). A mixture of 9 and 10: IR (neat) 3084,
3025, 2933, 2859, 1603, 1496, 1454, 1379, 1337, 1080, 1020,
Experimental Section
Preparation of 2-(5-Phenylpent-1-yn-1-yl)-1,3-dithiane
(4a). A THF (50 mL) solution of AlCl3 (5.87 g, 44 mmol) was
cooled to 0 °C. To the solution was added 1,3-propanedithiol
(2.0 mL, 20 mmol) under argon and then a THF (10 mL)
solution of 1,1-diethoxy-6-phenylhex-2-yne (3a) (4.93 g, 20
mmol). After being stirred for 2 days, the reaction was
quenched with H2O and organic materials were extracted with
ether. The organic layer was washed with 1 M NaOH, H2O,
and brine, and dried over Na2SO4. The solvent was removed
under reduced pressure and the residue was chromatographed
on silica gel (hexane/AcOEt ) 98/2) to give 4a (3.74 g, 71%).
4a: IR (neat) 3060, 3024, 2901, 2231, 1602, 1496, 1454, 1275,
1243, 1223, 1030, 910, 744, 700 cm-1 ;1H NMR δ 1.87 (tt, J )
7.2, 7.2 Hz, 2H), 2.01-2.08 (m, 2H), 2.30 (dt, J ) 2.2, 7.1 Hz,
2H), 2.71-2.85 (m, 4H), 3.17 (ddd, J ) 5.9, 5.9, 13.8 Hz, 2H),
4.65 (s, 1H), 7.17-7.32 (m, 5H); 13C NMR δ 18.3, 25.7, 28.4,
30.2, 33.6, 34.8, 76.7, 86.3, 125.9, 128.3, 128.5, 141.4. Anal.
Calcd for C15H18S2: C, 68.65; H, 6.91. Found: C, 69.01; H, 7.03.
In a similar manner, the 2-(alk-1-yn-1-yl)-1,3-dithianes 4b
and 4c were prepared.
1
745, 699 cm-1; H NMR δ 0.48 (dd, J ) 4.0, 6.4 Hz, 0.42H),
0.53 (dd, J ) 4.0, 6.4 Hz, 1.58H), 0.79 (dd, J ) 4.0, 6.4 Hz,
0.42H), 0.82 (dd, J ) 4.0, 6.4 Hz, 1.58H), 1.25 (s, 2.37H), 1.72-
1.83 (m, 2.42H), 1.76 (s, 0.63H), 2.14 (t, J ) 7.1 Hz, 1.58H),
2.64 (t, J ) 7.2 Hz, 0.42H), 2.69 (t, J ) 7.5 Hz, 1.58H), 7.14-
7.32 (m, 5H); 13C NMR δ 3.6, 6.7, 11.8, 14.9, 16.1, 18.2, 24.6,
29.5, 30.7, 34.8, 35.6, 38.1, 71.9, 75.0, 83.9, 86.8, 125.6, 125.8,
128.2, 128.3, 128.4, 128.5, 141.8, 142.6. Anal. Calcd for
C15H18: C, 90.85; H, 9.15. Found: C, 90.38; H, 9.23.
Titanocene(II)-Promoted Cyclopropanation of Ter-
minal Olefins 8 with the r-(Trialkylsilyl)-â,γ-acetylenic
Thioacetals 2. To a THF (1.2 mL) solution of 1, prepared from
Cp2TiCl2 (149 mg, 0.6 mmol), magnesium turnings (17 mg, 0.7
mmol), molecular sieves 4 A (60 mg), and P(OEt)3 (0.21 mL,
1.2 mmol) in the presence of 8c (0.36 mL, 2.4 mmol), was added
a THF (0.9 mL) solution of 2a (100 mg, 0.3 mmol) at 25 °C
under argon. The mixture was stirred for 1 h at 25 °C. The
workup and purification described above gave 11c (73 mg,
67%). 11c: IR (neat) 3063, 3025, 2938, 2858, 2156, 1603, 1495,
1454, 1248, 1031, 840, 758, 698, 635 cm-1; 1H NMR δ 0.13 (s,
5.49H), 0.16 (s, 3.51H), 0.24 (dd, J ) 4.3, 6.5 Hz, 0.61H), 0.58
(dd, J ) 3.8, 5.4 Hz, 0.39H), 0.67-0.76 (m, 0.78H), 1.04 (dd, J
) 4.2, 8.8 Hz, 0.61H), 1.14-1.53 (m, 3.61H), 1.66-1.95 (m,
3H), 2.56-2.86 (m, 4H), 7.15-7.30 (m, 10H); 13C NMR δ -0.03,
0.00, 16.4, 18.2, 21.4, 21.6, 25.5, 26.7, 29.0, 29.2, 30.4, 31.2,
32.6, 35.1, 35.2, 35.3, 35.5, 37.7, 79.6, 82.7, 109.3, 112.9, 125.3,
125.4, 127.86, 127.88, 127.90, 127.94, 128.01, 128.07, 128.12,
Preparation of 2-(tert-Butyldimethylsilyl)-2-(5-phen-
ylpent-1-yn-1-yl)-1,3-dithiane (2d). To a THF (3.0 mL)
solution of the dithiane 4a (262 mg, 1.0 mmol) was added
butyllithium (1.37 M in hexane, 0.73 mL, 1.0 mmol) at -78
°C under argon. After the solution was stirred for 2 h, a THF
(2 mL) solution of tert-butylchlorodimethylsilane (151 mg, 1.0
mmol) was added and the mixture was gradually warmed to
room temperature and stirred overnight. The reaction was
quenched by addition of a saturated aqueous solution of NH4-
Cl, and organic materials were extracted with ether. The
extract was washed with H2O and brine, dried over Na2SO4,
and concentrated. The residue was chromatographed on silica
gel (hexane/AcOEt ) 99/1) to give 2d (263 mg, 70%). 2d: IR
1
(neat) 3026, 2930, 2210, 1496, 1249, 917, 824, 698 cm-1; H
NMR δ 0.29 (s, 6H), 1.79 (s, 9H), 1.79-2.18 (m, 4H), 2.39 (t, J
) 7.1 Hz, 2H), 2.60 (ddd, J ) 3.5, 3.5, 14.1 Hz, 2H), 2.76 (t, J
) 7.6 Hz, 2H), 3.52 (ddd, J ) 2.6, 13.3, 13.3 Hz, 2H), 7.15-
7.33 (m, 5H); 13C NMR δ -7.3, 18.8, 19.6, 25.9, 26.4, 28.0, 30.8,
4238 J. Org. Chem., Vol. 70, No. 11, 2005

Reactions via Titanium Alkynylcarbene Complexes
141.7, 142.1, 142.18, 142.23. Anal. Calcd for C25H32Si: C, 83.27;
H, 8.94. Found: C, 83.57; H, 9.21.
The cyclopropanes 11a,b,d-k were also obtained by similar
reactions of 2 with terminal olefins 8.
13C NMR δ -4.4, 16.7, 18.4, 26.2, 34.1, 34.2, 34.7, 37.5, 94.0,
107.4, 114.1, 125.8, 126.0, 128.3, 128.36, 128.41, 141.7, 142.1,
147.9. Anal. Calcd for C27H36Si: C, 83.44; H, 9.34. Found: C,
83.74; H, 9.24.
Deuteration of the Organotitanium Intermediate. To
a THF (1.8 mL) solution of 1, prepared from Cp2TiCl2 (224
mg, 0.9 mmol), magnesium turnings (26 mg, 1.1 mmol),
molecular sieves 4 A (90 mg), and P(OEt)3 (0.31 mL, 1.8 mmol),
was added a THF (0.9 mL) solution of 2a (100 mg, 0.3 mmol)
at 25 °C under argon. After the solution was stirred for 10
min, D2O (0.3 mL) was added and the mixture was further
stirred for 30 min. The usual workup and purification afforded
a mixture of the dideuterated 1- and 2-alkynylsilanes 16a
(>95% D) and 16b (>95% D) (43 mg, 61%, 16a:16b ) 15:85).
A mixture of 16a and 16b: 1H NMR δ 0.11 (s, 7.56H), 0.15 (s,
1.35H), 1.50-1.57 (m, 0.3H), 1.67-1.72 (m, 0.3H), 1.78 (tt, J
) 7.3, 7.3 Hz, 1.7H), 2.17 (t, J ) 6.9 Hz, 1.7H), 2.62 (t, J ) 7.6
Hz, 0.3H), 2.72 (t, J ) 7.7 Hz, 1.7H), 7.13-7.32 (m, 5H); 13C
NMR (major isomer) δ -2.24, 0.00, 18.3, 31.0, 34.7, 77.8, 78.2,
125.6, 128,1, 128.4, 142.1.
The enynes 22a-e,g-p and their isomers 24a-e were also
obtained by similar reactions of 2 with ketones 23.
Titanocene(II)-Promoted Olefination of Esters and
Lactones 23j-n with 2. To a THF (1.8 mL) solution of 1,
prepared from Cp2TiCl2 (224 mg, 0.9 mmol), magnesium
turnings (26 mg, 1.1 mmol), molecular sieves 4 A (90 mg), and
P(OEt)3 (0.31 mL, 1.8 mmol), was added a THF (0.9 mL)
solution of 2d (113 mg, 0.3 mmol) at 25 °C. After 10 min,
γ-butyrolactone (23k) (31 mg, 0.36 mmol) in THF (0.9 mL) was
added and the mixture was stirred for 3 h. The usual workup
and purification by chromatography on Al2O3 (eluted with 1%
triethylamine in hexane) gave 2-[1-(tert-butyldimethylsilyl)-
6-phenylhex-1-yn-3-ylidene]oxorane (22r) (72 mg, 70%). 22r:
IR (neat) 2929, 2129, 1655, 1459, 1251, 1177, 827, 776, 699
1
cm-1; H NMR δ 0.11 (s, 6H), 0.95 (s, 9H), 1.82 (tt, J ) 7.7,
7.7 Hz, 2H), 2.02 (tt, J ) 7.2, 7.2 Hz, 2H), 2.18 (t, J ) 7.3 Hz,
2H), 2.63 (t, J ) 7.8 Hz, 2H), 2.76 (t, J ) 7.6 Hz, 2H), 4.18 (t,
J ) 6.8 Hz, 2H), 7.12-7.30 (m. 5H); 13C NMR δ -4.2, 16.7,
24.5, 26.2, 28.0, 29.6, 30.0, 35.4, 72.1, 91.7, 92.4, 107.1, 125.4,
128.1, 128.5, 142.9, 164.8. Anal. Calcd for C22H32OSi: C, 77.59;
H, 9.47. Found: C, 77.40; H, 9.76.
Reaction of 2 with Dimethylphenylsilane. To a THF
(1.2 mL) solution of 1, prepared from Cp2TiCl2 (224 mg, 0.9
mmol), magnesium turnings (26 mg, 1.1 mmol), molecular
sieves 4 A (90 mg), and P(OEt)3 (0.31 mL, 1.8 mmol), was
added a THF (0.9 mL) solution of 2a (100 mg, 0.3 mmol) at 25
°C under argon. After the solution was stirred for 10 min,
dimethylphenylsilane (0.54 mL, 3.6 mmol) was added and the
mixture was stirred for 3 h. The usual workup and purification
afforded 3-(dimethylphenylsilyl)-6-phenyl-1-(trimethylsilyl)-
hex-1-yne (18a) (53 mg, 48%) and 1-(dimethylphenylsilyl)-2-
(3-phenylpropyl)-1-(trimethylsilyl)hex-1,2-diene (19) (12 mg,
11%). 18a: IR (neat) 2957, 2157, 1427, 1249, 1115, 840, 646
The enynes 22q,s-u were also obtained by similar reactions
of 2 with the esters 23j,m,n and lactone 23l.
Protodesilylation. To the enyne 22j (35 mg, 0.1 mmol) was
added TBAF (1 M in THF, 1 mL, 1 mmol) at 0 °C. After being
stirred for 2 h, the reaction was quenched by addition of H2O.
The organic materials were extracted with ether, successively
washed with 1 M HCl and H2O, and dried over Na2SO4. The
solvent was removed under reduced pressure and the crude
product was purified by PTLC (hexane) to give (6-phenylhex-
1-yne-3-ylidene)cyclohexane (26f) (19 mg, 80%). 26f: IR (neat)
3305, 3026, 2927, 2854, 2087, 1604, 1496, 1452, 1030, 745, 699
1
cm-1; H NMR δ 0.13 (s, 9H), 0.37 (s, 6H), 1.41 (dt, J ) 7.5,
7.5 Hz, 2H), 1.59-1.98 (m, 2H), 1.93 (t, J ) 7.3 Hz, 1H), 2.46-
2.66 (m, 2H), 7.11-7.57 (m, 10H); 13C NMR δ -5.2, -4.5, 0.3,
20.8, 28.5, 31.0, 35.2, 85.5, 109.2, 125.6, 127.6, 128.2, 128.4,
129.3, 134.1, 136.8, 142.5. Anal. Calcd for C23H32Si2: C, 75.75;
H, 8.84. Found: C, 75.72; H, 9.03. 19: IR (neat) 2955, 1919,
1
cm-1; H NMR δ 1.45-1.66 (m, 6H), 1.83 (tt, J ) 7.7,7.7 Hz,
2H), 2.16-2.24 (m, 4H), 2.43-2.54 (m, 2H), 2.62 (t, J ) 7.9
Hz, 2H), 3.01 (s, 1H), 7.14-7.30 (m, 5H); 13C NMR δ 26.5, 27.9,
30.0, 30.5, 30.9, 34.0, 35.3, 79.0, 84.5, 112.8, 125.6, 128.2, 128.4,
142.5, 149.7. Anal. Calcd for C18H22: C, 90.70; H, 9.30.
Found: C, 90.49; H, 9.34.
1
1248, 1111, 896, 839, 805, 698 cm-1; H NMR δ 0.04 (s, 9H),
0.44 (s, 6H), 1.72 (tt, J ) 7.8, 7.5 Hz, 2H), 2.04 (dt, J ) 6.9,
7.5 Hz, 2H), 2.68 (t, J ) 7.8 Hz, 2H), 4.52 (t, J ) 6.9 Hz, 1H),
7.21-7.25 (m, 3H), 7.30-7.41 (m, 5H), 7.33-7.57 (m, 2H); 13
C
NMR δ -1.39, -1.35, 0.04, 27.1, 32.0, 35.5, 76.0, 125.6, 127.6,
128.2, 128.4, 128.9, 133.9, 139.2, 142.6, 211.9. Anal. Calcd for
C23H32Si2: C, 75.75; H, 8.84. Found: C, 75.74; H, 8.71.
3-(Dimethylphenylsilyl)-1-(trimethylsilyl)but-1-yne (18b) was
also obtained by the reactions of both 2c and 5 with dimeth-
ylphenylsilane.
The alkenylcyclopropanes 25a-c and enynes 26a-e,g,h
were also obtained by a similar procedure.
Acknowledgment. This research was supported by
a Grant-in-Aid for Scientific Research (No. 14340228)
from the Ministry of Education, Culture, Sports, Science
and Technology, Japan. This work was carried out
under the 21st Century COE program of “Future Nano-
materials” at the Tokyo University of Agriculture &
Technology.
Titanocene(II)-Promoted Olefination of Ketones 23a-i
with 2. To a THF (1.8 mL) solution of 1, prepared from Cp2-
TiCl2 (224 mg, 0.9 mmol), magnesium turnings (26 mg, 1.1
mmol), molecular sieves 4 A (90 mg), and P(OEt)3 (0.31 mL,
1.8 mmol), was added a THF (0.9 mL) solution of 2f (82 mg,
0.3 mmol) at 25 °C. After 10 min, 1,5-diphenylpentan-3-one
(23b) (86 mg, 0.36 mmol) in THF (0.9 mL) was added dropwise
over 5 min and the mixture was stirred for 1 h. The usual
workup and purification gave 1-(tert-butyldimethylsilyl)-3-
methyl-4-phenethyl-6-phenylhex-3-en-1-yne (22f) (83 mg, 71%).
Supporting Information Available: Characterization
data for the compounds 4b,c, 2a-c,e,f, 11a,b,d-k, 13, 18b,
22a-e,g-q,s-u, 24a-e, 25a-c, and 26a-e,g,h. This mate-
rial is available free of charge via the Internet at http://
pubs.acs.org.
22f: IR (neat) 2928, 2137, 1604, 1496, 1454, 1249, 697 cm-1
;
1H NMR δ 0.14 (s, 6H), 0.96 (s, 9H), 1.79 (s, 3H), 2.40 (dd, J
) 6.1, 10.4 Hz, 2H), 2.63-2.81 (m, 6H), 7.16-7.32 (m, 10H);
JO050122F
J. Org. Chem, Vol. 70, No. 11, 2005 4239