Trialkylsilyl group-directed regioselective transformations of 2-(alk-1-yn-1-yl)-2-(trialkylsilyl)-1,3-dithianes to alkynylcyclopropanes and enynes

Article abstract of DOI:10.1021/ol0486066

(Chemical Equation Presented) The Cp₂Ti[P(OEt)₃] ₂-promoted reaction of 2-(alk-1-yn-1-yl)-2-(trialkylsilyl)-1,3- dithianes with 1-alkenes regioselectively produced [(trialkylsilyl)-ethynyl] cyclopropanes with a formal ally

Full text of DOI:10.1021/ol0486066

ORGANIC
LETTERS
2004
Vol. 6, No. 18
3207-3210
Trialkylsilyl Group-Directed
Regioselective Transformations of
2-(Alk-1-yn-1-yl)-2-(trialkylsilyl)-1,3-dithianes
to Alkynylcyclopropanes and Enynes
Takeshi Takeda,* Shuichi Kuroi, Makoto Ozaki, and Akira Tsubouchi
Department of Applied Chemistry, Tokyo UniVersity of Agriculture and Technology,
Koganei, Tokyo 184-8588, Japan
takeda-t@cc.tuat.ac.jp
Received July 20, 2004
ABSTRACT
The Cp2Ti[P(OEt)3]2-promoted reaction of 2-(alk-1-yn-1-yl)-2-(trialkylsilyl)-1,3-dithianes with 1-alkenes regioselectively produced [(trialkylsilyl)-
ethynyl]cyclopropanes with a formal allylic rearrangement. The reaction of the thioacetals with ketones proceeded with the same regioselectivity
to produce 1-(trialkylsilyl)alk-3-en-1-ynes predominantly. It is suggested that these reactions proceed via the formation of titanium r-(silylethynyl)-
carbene complexes Cp2TidC(R)CtCSi in preference to their regioisomers, r-silylalkynylcarbene complexes Cp2TidC(Si)CtCR.
We have developed a variety of synthetic reactions utilizing
a thioacetal-titanocene(II) system, in which titanium carbene
complexes are assumed to be formed as active intermediates.1
This methodology, however, suffers the drawback that the
formation of intermediary organotitanium species is seriously
affected by steric hindrance;2 hence thioacetals prepared from
ketones cannot be employed except for those of less hindered
ketones such as cyclobutanone.3
R-substituted alkynyl thioacetals because a less bulky alkynyl
group would alleviate the steric crowding of the thioacetals.
After several attempts, we found that the reaction proceeded
Scheme 1
Recently, we reported the preparation of alkynylcyclo-
propanes 1 by the reaction of terminal olefins 2 with the
alkynylcarbene complexes generated by the desulfurization
of thioacetals of R,â-acetylenic aldehydes 3 with the ti-
tanocene(II) species Cp2Ti[P(OEt)3]2 4 (Scheme 1).4 We
expected that the cyclopropanation could be extended to the
to afford the alkynylcyclopropanes 5 even in the case when
the thioacetals 6 bearing a bulky trialkylsilyl group at the
R-position were employed (Scheme 2).
(1) (a) Takeda, T. In Titanium and Zirconium in Organic Synthesis;
Marek, I., Ed.; Wiley-VCH: Weinheim, 2002; p 480. (b) Takeda, T.;
Tsubouchi, A. In Modern Carbonyl Olefination; Takeda, T., Ed.; Wiley-
VCH: Weinheim, 2004; p 178.
(2) Takeda, T.; Sasaki, R.; Fujiwara, T. J. Org. Chem. 1998, 63, 7286.
(3) Fujiwara, T.; Iwasaki, N.; Takeda, T. Chem. Lett. 1998, 741.
The treatment of 2-(5-phenylpent-1-yn-1-yl)-2-(trimeth-
ylsilyl)-1,3-dithiane 6a with 2 equiv of titanocene(II) reagent
(4) Takeda, T.; Kuroi, S.; Yanai, K.; Tsubouchi, A. Tetrahedron Lett.
2002, 43, 5641.
10.1021/ol0486066 CCC: $27.50 © 2004 American Chemical Society
Published on Web 08/07/2004

Scheme 2
Scheme 3
4 in the presence of 1-hexene 2a (8 equiv) at 25 °C for 1 h
gave the [(trimethylsilyl)ethynyl]cyclopropane 5a in 67%
yield (Table 1, entry 1). Interestingly the cyclopropanation
took place exclusively at the γ-position of 6a in contrast to
the reaction of R-unsubstituted thioacetals 3, the cyclopro-
panation of which proceeded at the R-position. When an
excess amount of the low-valent titanium 4 was used, the
reduction of the triple bond partly proceeded to give the
corresponding alkenylcyclopropane as a byproduct. The
reaction of organotitanium species generated from several
acetylenic thioacetals 6 with various terminal olefins 2 gave
the alkynylcyclopropanes 5 with excellent regioselectivity.
In all of the reactions examined, formation of the other
possible regioisomer, (trimethylsilyl)cyclopropane 7, was not
observed. When styrene was used as the olefin component,
reduction of the carbon-carbon triple bond partially pro-
ceeded to produce the alkenylcyclopropanes as byproducts.
We found that use of bulky tert-butyldimethylsilyl-substituted
acetylenic thioacetals could eliminate the reduction of the
triple bond, giving [(tert-butyldimethylsilyl)ethynyl]cy-
clopropanes 5 as sole products in good yields (entries 5 and
6). The cyclopropane 5i was regioselectively produced by
both the reactions of R-(trimethylsilyl)-â,γ-acetylenic thio-
acetal 6e and its isomer, γ-(trimethylsilyl)-â,γ-acetylenic
thioacetal 8 (entries 7 and 8). 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.
Table 1. Regioselective Formation of the
(Silylethynyl)cyclopropanes 5
Similar regioselectivity was also observed in the titano-
cene(II)-promoted reaction of the alkynyl thioacetals 6 with
ketones 9 (Scheme 3, Table 2).5 The successive treatment
of the acetylenic thioacetal 6a with the titanocene(II) reagent
4 (3 equiv) and 3-pentanone 9a (1.2 equiv) produced the
conjugated enyne 10a as a major product along with the
vinylsilane 11a (entry 1). The formation of silylacethylene
10a indicates that the process involves a formal allylic
rearrangement. The reaction of more the sterically hindered
tert-butyldimethylsilyl-substituted counterpart 6b gave the
enyne 10b with higher regioselectivity (entry 2). Essentially
complete regioselectivity was observed when less bulky
ketones such as acetone and cyclohexanones were employed.
Furthermore, even when the sterically hindered ketone 9e
was employed, the silylacetylene 10i was produced with
complete regioselectivity by use of the â,γ-acetylenic thio-
acetal 6d bearing a less bulky methyl group at the γ-position
(entry 9). Several enynes 10 possessing the (trialkylsilyl)-
acetylene moiety were protodesilylated to give the terminal
alkynes 12 on treatment with TBAF in THF.
a Carried out under ethylene. b Performed with 3 equiv of 4 and 4 equiv
of styrene.
(5) In contrast to the reaction of 6, a similar reaction of R-unsubstituted
alkynyl thioacetals 3 with ketones 6 was complicated and no carbonyl
olefination product was obtained under the same reaction conditions.
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Org. Lett., Vol. 6, No. 18, 2004

Table 2. Regioselective Formation of 1-(Trialkylsilyl)alk-3-en-1-ynes 10
a Ratio of stereoisomers.
On the basis of the regioselective formation of (silyleth-
ynyl)cyclopropanes 5 and enynes 10, we tentatively propose
that the reactions proceed via preferential formation of the
intermediary R-(silylethynyl)carbene complexes 13 (Scheme
4). The reaction sequence involving the formation of the
propargyltitanium intermediate 14 via the four-membered
transition state 15 affords the cyclopropane 5 by further
reductive elimination or the carbonyl olefination product 11
by metathesis-type degradation. In the case of the reaction
of 13 with sterically hindered ketones, the transition state
15 is destabilized to a certain extent by steric repulsion
between the R-substituent of 13 (R1) and the substrate. As a
result, the reaction partially follows the path involving the
transition state 16, and hence the reaction is more regiose-
lective than that of the thioacetals bearing a trimethylsilyl
group.
The mechanism for the formation of the carbene complex
13 from the thioacetal 6 is obscure at present; the isomer-
ization of R-trialkylsilyl-substituted alkynylcarbene com-
plexes [Cp2TidC(Si)CtCR], initially formed from the
R-silyl thioacetal 6, to 13 cannot be excluded because an
equilibrium between the regioisomers of rhenium,6 rhodium,7
and manganese8 alkynylcarbene complexes, LnMdC(R1)Ct
CR2 and LnMdC(R2)CtCR1, was observed.
(6) (a) Casey, C. P.; Kraft, S.; Kavana, M. Organometallics 2001, 20,
3795. (b) Casey, C. P.; Kraft, S.; Powell, D. R. J. Am. Chem. Soc. 2001,
124, 2584.
(7) Padwa, A.; Austin, D. J.; Gareau, Y.; Kassir, J.; Xu, S. L. J. Am.
Chem. Soc. 1993, 115, 2637.
(8) Ortin, Y.; Coppel, Y.; Lugan, N.; Mathieu, R.; McGlinchey, M. J.
Chem. Commun. 2001, 1690.
six-membered transition state 16, and the metathesis-type
degradation of the allenyltitanium intermediate 17 affords
the minor product 11. In the case of carbonyl olefination, a
bulky tert-butyldimethylsilyl group in 13 disfavored the
Org. Lett., Vol. 6, No. 18, 2004
3209

and 1-(trialkylsilyl)-3-en-1-ynes. These products were readily
protodesilylated to give synthetically useful terminal alkynes.
Further study on the reactions of (trialkylsilyl)ethynylcarbene
complexes with a variety of organic molecules is currently
in progress.
Scheme 4
Acknowledgment. This research was supported by a
Grant-in-Aid for Scientific Research (No. 14340228) and
Grant-in-Aid for Scientific Research on Priority Areas (A)
“Exploitation of Multi-Element Cyclic Molecules” (No.
14044022) from the Ministry of Education, Culture, Sports,
Science and Technology, Japan. This work was carried out
under the 21st Century COE program of “Future Nanoma-
terials” at Tokyo University of Agriculture & Technology.
Supporting Information Available: Experimental pro-
cedures and characterization data for compounds 5a-i, 10a-
j, 11a, 11b, 11f, and 12a-f. This material is available free
of charge via the Internet at http://pubs.acs.org.
In summary, we have developed trialkylsilyl group-
directed, highly regioselective transformations of R-silyl-
alkynyl thioacetals into [(trialkylsilyl)ethynyl]cyclopropanes
OL0486066
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Org. Lett., Vol. 6, No. 18, 2004