Coupling reaction of terminal allenes with themselves or acetylenes mediated by (η2-propene)Ti(O-i-Pr)2: some new selectivities and synthetic application

Article abstract of DOI:10.1039/a706998g

Treatment of an allene alone or with an acetylene with (η²-propene)Ti(O-i-Pr)2 generates a new titanacycle, which reacts with some electrophiles to give useful intermediates for organic synthesis.

Full text of DOI:10.1039/a706998g

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Coupling reaction of terminal allenes with themselves or acetylenes mediated
2
i
by (h -propene)Ti(OPr ) : some new selectivities and synthetic application
2
Daigaku Hideura, Hirokazu Urabe and Fumie Sato*
Department of Biomolecular Engineering, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama, Kanagawa
226, Japan
Treatment of an allene alone or with an acetylene with
Table 1 Coupling of allene mediated by 1
2
(
2
h -propene)Ti(O-i-Pr) generates a new titanacycle, which
Entry
Allene
Product Yield (%)
reacts with some electrophiles to give useful intermediates
for organic synthesis.
1
2
3
2
5
8
4
7
10
75
65
80
a
b
Low-valent early transition metal complexes are well known to
effect the coupling reactions of olefins and acetylenes to yield
metallacycles via olefin– (or acetylene)–metal intermediates,
a
b
E:Z ratio = 24:76 (or vice versa).
Z isomer only.
1
which show wide application in organic synthesis. Although
some examples of allene coupling reactions based on
with 1 under the same conditions as above initiated cyclization
to afford the single product 10 after aqueous workup (Scheme 2
and entry 3, Table 1). The internal double bond of 10 had
exclusively the Z configuration, as determined via examination
5 5 2 5 5 2
(C H ) Ti– or (C H ) Zr–allene complexes have been docu-
2–4
mented, † the small number of reactions utilizing just allenes
as the starting material (rather than any other appropriate
precursors) and, accordingly, the critical issues in organic
synthesis of regio- and stereo-selectivity and the feasibility of
the reaction with respect to various substrates, have not been
sufficiently investigated. As some of the aforementioned
cyclometallation reactions have recently been carried out with
an inexpensive, readily available low-valent titanium species,
of the coupling constants and an NOE study in the 1
H NMR
spectrum. The titanacycle structure 9‡ was verified by deuter-
2
olysis that gave the bis-deuterated product [
at each position) as a single regioisomer.
2
H ]-10 (93 atom%
More importantly, addition of 9 to aldehydes proceeded in a
regioselective manner to give the adducts 11 and 12 as an
approximately 3:1–4:1 mixture of diastereoisomers, which
2
i
5
(
2
h -propene)Ti(OPr ) 1, we reinvestigated the coupling reac-
tion of allenes themsleves and with other unsaturated com-
pounds by taking advantage of this new method.
could be separated on silica gel. The addition of the vinyl–
titanium bond in 9 to the aldehyde was not observed,5b,9
The homo-coupling reaction of 1,1-dimethylallene 2 with 1
proceeded at 250 °C for 2 h to give the symmetrically
substituted 3 having two vinyl–metal bonds as a virtually single
isomer (Scheme 1) as shown by the production of 4 (Table 1,
although its presence was confirmed by the subsequent workup
with deuteriochloric acid to give the product 12 having vinylic
deuterium (93 atm%). Upon treatment with KH in THF,10 the
entry 1) in accord with precedents of the (C
5
H
5
)
2
Ti- or
Me2PhSi
Me2PhSi
2,3a,4b
5 5 2
(C H ) Zr-mediated reactions.
However, mono-substi-
6
SiPhMe2
tuted allene 5 showed a completely different regioselectivity
from 2 to give the titanabicycle 6, which was identified by
isolation of 7 as a mixture of E- and Z-olefinic isomers after
aqueous workup (Table 1, entry 2). The latter regioselectivity is
not seen in the homo-coupling reactions of representative types
of allenes mediated by a low-valent titanium complex having
cyclopentadienyl ligands.2
H+ (or D+)
1
H(D)
i
Ti(OPr)2
•
Me2PhSi
Me2PhSi
SiPhMe2
H(D)
8
9
10
i, RCHO
+
+
The E/Z ratio of the double bond in the above product could
Me2PhSi
ii, H (or D )
7c
be controlled by the use of a silylallene. Thus, treatment of 88
H(D)
H(D)
Me
Me
Me
+
OPri
Me
Me2PhSi
HO
Me2PhSi
Me
Me
Ti
1
OPri
H +
i
R
HO
R
Ti(OPr)2
•
1
1a R = C8H17
78:22 (83%)
11b R = C8H17
12b R = Pri
12a R = Pri
Me
77:23 (95%)
Me
Me
Me
KH
KH
2
3
4
Me2PhSi
Me2PhSi
BnO
BnO
H
OBn
H +
1
i
Ti(OPr)2
•
BnO
Pri
13a 94%
Pri
OBn
5
6
7
13b 89%
Scheme 1
Scheme 2
Chem. Commun., 1998
271

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SiMe3
Table 2 Coupling of allene and acetylene mediated by 1
a
SiPhMe2
Me3Si
H13C6
i
Ti(OPr)2
1
R2
R2
+
R1
•
1
C6H13
14
SiPhMe2
+
•
R3
8
15
R3
R1
El +
El
14 R2 = SiMe2,
5
R1 = (CH2)2OBn
16, 20, 21, 23
8 R1 = SiPhMe2
2 R1 = OC8H17
Me3Si
H13C6
El
R3 = C H
9 R2 = R3 = Bu
6
13
2
1
Entry
Allene
Acetylene Product
E:Z ratiob Yield (%)c
SiPhMe2
1
1
1
6 El = H 94%
7 El = D 94% 97–99 atom% D
8 El = I 54%
1
2
3
4
5
5
5
5
8
22
19
19
14
14
14
20
20
21
16
23
64:36
64:36
25:75
Z only
Z only
74
70
72
94
45
d
Scheme 3
a
Allene (1.5 equiv.) and acetylene (1.0 equiv.), unless otherwise stated.
Refers to double bond substituted with R . Isolated yields based on
b
1 c
major stereoisomer 12a afforded the Z,Z-triene 13a, while the
minor 12b gave Z,E-13b. These results not only established the
orientation of the hydroxy group in 12 (and, hence, 11 by
limiting substrate. d Allene (1.0 equiv.) and acetylene (1.5 equiv.).
Footnotes and References
analogy) based on the well-precedented stereochemical course
of the Peterson olefination,10 but also demonstrated a synthetic
* E-mail: fsato@bio.titech.ac.jp
†
The intramolecular cyclization of allenes and acetylenes has also been
documented (ref. 7).
Two simple rules, namely that (i) the formation of the transient allene–
application of the homo-coupling of the allene followed by
aldehyde addition for the stereoselective preparation of tri-
enes.
‡
titanium complex takes place from the less hindered side and (ii) the
titanium atom is better located at the less crowded terminus of the allylic
system (ref. 9), support the depicted structure of 9 (and also 6) over the other
possible isomeric formulations.
The hetero-coupling reaction between an allene and an
acetylene is another important feature of the transformation
involving allenes.3 † However, little information is available
on the regio- and stereo-chemical aspects of the coupling
reaction starting from unsymmetrical allenes and acetylenes.4b
Thus, we first attempted the reaction of unsymmetrical
substrates, a mono-substituted allene 8 and silylacetylene 14,
and found that the desired products 16 could be obtained in good
yield and as an essentially single stereoisomer (Scheme 3). The
stereochemistry of both double bonds in 16 was elucidated by
a,4
1
H. Yasuda, K. Tatsumi and A. Nakamura, Acc. Chem. Res., 1985, 18,
20; S. L. Buchwald and R. B. Nielsen, Chem. Rev., 1988, 88, 1047;
1
E. Negishi, in Comprehensive Organic Synthesis, ed. B. M. Trost and I.
Fleming, Pergamon, Oxford, 1991, vol. 5, p. 1163; E. Negishi and
T. Takahashi, Acc. Chem. Res., 1994, 27, 124; F. Sato and H. Urabe, in
Handbook of Grignard Reagents, ed. G. S. Silverman and P. E. Rakita,
Marcel Dekker, New York, 1966, p. 23.
1
2 P. Binger, F. Langhauser, P. Wedemann, B. Gabor, R. Mynott and
C. Kr u¨ ger, Chem. Ber., 1994, 127, 39.
H NMR analysis. The high regioselectivity found for this
unsymmetrical acetylene, as verified by the absence of another
regioisomer, is also noteworthy. The presence of the inter-
mediate titanacycle 15 was confirmed by the deuterolysis (1 m
3
4
(a) J. Yin and W. M. Jones, Tetrahedron, 1995, 51, 4395; (b)
J. R. Schmidt and D. M. Duggan, Inorg. Chem., 1981, 20, 318; (c)
D. M. Duggan, Inorg. Chem., 1981, 20, 1164.
(a) A. Maercker and A. Groos, Angew. Chem., Int. Ed. Engl., 1996, 35,
210; (b) K. M. Doxsee, J. J. J. Juliette, K. Zientara and G. Nieckarz,
J. Am. Chem. Soc., 1994, 116, 2147; (c) J. Yin, K. A. Abboud and
W. M. Jones, J. Am. Chem. Soc., 1993, 115, 3810.
2
DCl) and iodinolysis (excess I ) to give the bis-deuterated 17
and diiodide 18 in good yields.
This coupling reaction seems to be general for various
substrates, as shown in Table 2. Alkylallene 5 preferentially
affords the product 20 having an E-disubstituted double bond
when reacted with dialkylacetylene 19 (Table 2, entries 1 and 2),
but gives 21 carrying a Z-disubstituted olefin with silylacetylene
5 (a) H. Urabe, T. Hata and F. Sato, Tetrahedron Lett., 1995, 36, 4261; (b)
H. Urabe, T. Takeda and F. Sato, Tetrahedron Lett., 1996, 37, 1253; (c)
H. Urabe and F. Sato, J. Org. Chem., 1996, 61, 6756; (d) K. Suzuki,
H. Urabe and F. Sato, J. Am. Chem. Soc., 1996, 118, 8729.
1
4 (entry 3), both in good yields. Alkoxyallene 2211 was able to
6
P. Crabb e´ , B. Nassim and M.-T. Robert-Lopes, Organic Syntheses, ed.
G. Saucy, Wiley, NY, 1985, vol. 63, p. 203.
participate in this coupling reaction as well. Although the yield
of 23 is not particularly good due to partial decomposition of the
allene in the presence of the titanium alkoxide, the exclusive
Z-olefinic preference found in the product is somewhat
amazing, provided that the stereoselectivity was simply con-
trolled by the steric hindrance of the allenic substituent, which
is usually less pronounced in the following order: trialkylsilyl >
n-alkyl > n-alkyloxy (cf. entries 3–5). The resultant cis-vinyl
ether moiety may be stereospecifically replaced by a carbon
chain with a Grignard reagent under nickel catalysis12 or
hydrolyzed to aldehyde.
7
(a) E. Negishi, S. J. Holmes, J. M. Tour, J. A. Miller, F. E. Cederbaum,
D. R. Swanson and T. Takahashi, J. Am. Chem. Soc., 1989, 111, 3336;
(b) F. A. Hicks, N. M. Kablaoui and S. L. Buchwald, J. Am. Chem. Soc.,
1996, 118, 9450; (c) H. Urabe, T. Takeda, D. Hideura and F. Sato, J. Am.
Chem. Soc., 1997, 119, 11295.
8
9
A. G. Myers and B. Zheng, J. Am. Chem. Soc., 1996, 118, 4492.
M. T. Reetz, Organotitanium Reagents in Organic Synthesis, Springer-
Verlag, Berlin, 1986; C. Ferreri, G. Palumbo and R. Caputo, in
Comprehensive Organic Synthesis, ed. B. M. Trost and I. Fleming,
Pergamon, Oxford, 1991, vol. 1, p. 139; M. T. Reetz, in Organome-
tallics in Synthesis, ed. M. Schlosser, Wiley, Chichester, 1994,
p. 195.
The coupling reaction based on allenes described herein,
which enables the selective construction of a carbon framework
and the facile introduction of an electrophile, is a synthetically
useful entry to the metal-promoted coupling reactions of
unsaturated compounds.
We thank the Ministry of Education, Science, Sports and
Culture (Japan) for financial support.
10 D. J. Ager, Organic Reactions, ed. L. A. Paquette, Wiley, New York,
1990, vol. 38, p. 1.
1
1
1 R. Zimmer, Synthesis, 1993, 165.
2 H. Urabe and F. Sato, in Handbook of Grignard Reagents, ed. G. S.
Silverman and P. E. Rakita, Marcel Dekker, New York, 1996, p. 577.
Received in Cambridge, UK, 29th September 1997; 7/06998G
272
Chem. Commun., 1998