Regio- and stereoselective formation of conjugated dienes by titanocene(ii)-promoted alkylation of propargyl carbonates

Article abstract of DOI:10.1039/b905782j

Conjugated dienes were produced with complete regio- and stereoselectivity by the titanocene(ii)-promoted alkylation of propargyl carbonates via the formation of 2,3,4-trisubstituted titanacyclobutenes.

Full text of DOI:10.1039/b905782j

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COMMUNICATION
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Regio- and stereoselective formation of conjugated dienes by
titanocene(II)-promoted alkylation of propargyl carbonatesw
Yasutaka Yatsumonji, Yuichiro Atake, Akira Tsubouchi and Takeshi Takeda*
Received (in Cambridge, UK) 23rd March 2009, Accepted 9th April 2009
First published as an Advance Article on the web 28th April 2009
DOI: 10.1039/b905782j
Conjugated dienes were produced with complete regio- and
stereoselectivity by the titanocene(II)-promoted alkylation of
propargyl carbonates via the formation of 2,3,4-trisubstituted
titanacyclobutenes.
alcohol derivatives with the titanocene(II) reagent 2.4 Further
treatment of 5 with 2 generates the titanacyclopropanes 6
which are then alkylated to form gem-dititanium species 7.
Elimination of the titanium(IV) species Cp2TiXY affords
titanium carbene complexes 8. As for the formation of
titano-titanacycles, Marek and coworkers reported the
generation of titano-titanacyclopropenes by the reaction of
alkynyl chlorides with Ti(Oi-Pr)4–i-PrMgBr.5 Titanium
alkenylcarbene complexes 8 are present in equilibrium with
titanacyclobutenes 1 and the position of equilibrium is
dependent on their substitution patterns.3 Since the position
of equilibrium lies far toward titanacycles 1 when they possess
two substituents at the 2- and 3-positions, we expected that the
organotitanium species generated from g-monosubstituted
propargyl carbonates 4 (R1 = H) according to Scheme 1
exclusively exist as titanacyclobutenes 1 (R1 = H).
Preparation of titanacyclobutenes 1 has been the subject of
considerable recent attention because of their unique reactivity
and synthetic potential. A variety of titanacyclobutenes 1
bearing two identical substituents at the 2- and 3-positions
have been prepared by the reaction of symmetrical alkynes
with titanocene methylidene complex.1 However, poor regio-
selectivity is observed when unsymmetrical alkynes are
employed. We reported the formation of 2,3,4-trisubstituted
titanacyclobutenes 1 by the reaction of titanocene-alkylidenes
generated by the reductive titanation of thioacetals or 1,1-
dichlorocyclopropanes with alkynes.2 The reaction with un-
symmetrical alkynes, however, also lacks regioselectivity.
Indeed, successive treatment of the organotitanium species,
generated by the reductive titanation of the g-monosubstituted
propargyl carbonate 4a with the titanocene(II) reagent 2
(3 equiv.) at 25 1C for 35 min, with benzyl chloride (9a)
(3 equiv., 25 1C, 2 h) and D2O (55 equiv., 25 1C, 18 h)
produced the dideuterated Z-alkene 10 with retention of the
stereochemistry of the double bond of 1a. Similar stereo-
selective formation of alkenes by the protonation of titana-
cyclobutenes has been observed.2b The formation of 10 clearly
indicates that the titanacycle 1a was formed by the sequential
reactions of 4a (Scheme 2).
Therefore, the preparation of
1 bearing a variety of
substituents at any positions is crucial for the development
of unsaturated titanacycle chemistry. In this context, recently
we disclosed a new method for the preparation of mono- and
disubstituted titanacyclobutenes by the reaction of g-chloro-
allylic sulfides with the titanocene(II) reagent Cp2Ti[P(OEt)3]2
2.3 We have further explored a straightforward and general
method for the generation of titanacyclobutenes 1, and here
we describe a novel method for the stereoselective preparation
of conjugated dienes 3 via the formation of titanacycles 1
starting from propargyl carbonates 4.
The thermal stability of titanacyclobutenes is also
dependent on their substitution pattern. As shown in
Scheme 3, 2,3,4-trisubstituted titanacyclobutenes 1 having a
b-hydrogen on the substituent at the 4-position are thermally
unstable and readily decompose through b-elimination to
afford conjugated dienes 3 stereoselectively.2a,c We therefore
Our new approach for the generation of titanacycles 1 is
outlined in Scheme 1. We recently reported that allenyltitano-
cenes 5 were produced by the reductive titanation of propargyl
Scheme 1
Scheme 2
Department of Applied Chemistry, Graduate School of Engineering,
Tokyo University of Agriculture and Technology, Koganei,
Tokyo 184-8588, Japan. E-mail: takeda-t@cc.tuat.ac.jp;
Fax: +81 42 388 7034; Tel: +81 42 388 7034
w Electronic supplementary information (ESI) available: Character-
ization data for all compounds. See DOI: 10.1039/b905782j
Scheme 3
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Table 1 Reaction of the propargyl carbonate 4b with alkylating
agents 9
oxide (9f) could also be employed for the alkylation of
dititanium species 6a and the dienyl alcohol 3d was obtained
(entry 6).
Regio- and stereoselective formation of a variety of
conjugated dienes 3 was also achieved by using various
a,g-disubstituted propargyl carbonates 4. As shown in
Table 2, the carbonates 4 having a primary alkyl or aryl
substituent at the g-position reacted with alkylating agents 9
to give the conjugated dienes 3 in good yields. The intro-
duction of a bulky secondary alkyl group at the a- or
g-position, however, significantly decreased the yields of 3
(see entries 8 and 9). Since the starting materials, propargyl
carbonates 4, are available by the addition of alkynyllithiums
to aldehydes followed by esterification with ethyl chloro-
formate, the present method enjoys an advantage in that
1,3-butadienes having various substituents at the 1-, 2- and
4-positions are readily obtained with complete regio- and
stereoselectivity.
Yield
(%)a
Entry Alkylating agent 9
Product
1
2
9b
9a
3a
83
3b
73
3
4
9c
9d
3b
3c
Trace
60
Table 2 Reaction of propargyl carbonates 4 with alkylating agents 9
5
9e
11
3d
31
78
6
9f
a
Isolated yield.
Propargyl
Entry carbonate 4
Alkylating
agent 9
Yield
(%)a
Conjugated diene 3
anticipated that 3 would be produced by a similar reaction
using a,g-disubstituted propargyl carbonates via
4
1
4c
3e
66
trisubstituted titanacyclobutenes 1 illustrated in Scheme 3.
Then the generation of organotitanium species by the treat-
ment of a,g-disubstituted propargyl carbonates 4 with the
titanocene(II) reagent 2 and the following reaction with
various alkylating agents 9 were examined. As was expected,
the conjugated E,E-diene 3a was produced with complete
regio- and stereoselectivity by the treatments of 4b with 2
(3 equiv.) at 25 1C for 35 min and then with methallyl chloride
(9b) (3 equiv.) for 2 h (Table 1, entry 1).z In a similar fashion,
the titanocene(II) 2-promoted reactions of 4b with various
alkylating agents 9 were examined. The reaction using benzyl
chloride (9a) gave the corresponding diene 3b in good yield
(entry 2). In contrast, a similar reaction of 4b with benzyl
bromide (9c) was complicated and the formation of only a
trace amount of 3b was observed (entry 3). Although the
reaction with the secondary chloride 9d produced the diene
3c, the alkene 11 was produced as the only isolable product
when butyl chloride (9e) was employed (entry 5). The forma-
tion of 11 could be explained by the difference between the
modes of alkylation: the dititanium species 6a acts as an
allyltitanium species toward the primary halide 9e exclusively
and the subsequent hydrolysis of the resulting titanacyclo-
propene 12 affords the Z-alkene 116 (Scheme 4). Styrene
9g
9b
2
3
4
5
6
4c
4c
4c
4d
4d
3f
3g
3h
3i
72
73
68
70
71
9a
9f
9b
9a
3j
7
8
4e
9b
3k
70
4f
9b
9b
3l
36b
48
9
4g
3m
a
b
Isolated yield. 1-Cyclohexyl-5-phenyl-1-pentyne was obtained in
31% yield.
Scheme 4
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In conclusion, we have developed a general and complete
regioselective method for the generation of highly substituted
titanacyclobutenes, which are difficult to generate regio-
selectively by conventional methods using titanium carbene
complexes and alkynes. The present titanocene(II)-promoted
reaction of propargyl carbonates and alkylating agents is
useful for the complete regio- and stereoselective preparation
of conjugated 1,3-dienes.
removal of the solvent, the residue was purified by PTLC (hexane)
to give (5E)-2-methyl-7-phenyl-4-[(E)-phenylmethylidene]-1,5-hepta-
diene (3a) (91 mg, 83%). 3a: found: C, 91.72; H, 8.20. C21H22 requires
C, 91.92; H, 8.08%; dH (300 MHz, CDCl3, Me4Si) 1.80 (s, 3 H), 3.07
(s, 2 H), 3.48 (d, J = 7.0 Hz, 2 H), 4.72–4.79 (m, 1 H), 4.83–4.89 (m, 1 H),
5.85 (dt, J = 15.6, 7.0 Hz, 1 H), 6.25 (d, J = 15.6 Hz, 1 H), 6.60 (s, 1 H)
and 7.12–7.36 (m, 10 H); dC (75 MHz, CDCl3) 23.5, 36.2, 39.2, 111.0,
126.0, 126.7, 128.2, 128.4, 128.55, 128.59, 128.8, 131.4, 135.4, 137.2,
137.6, 140.5 and 143.0; nmax/cmꢁ1 3081, 3025, 2968, 2910, 1651, 1599,
1495, 1451, 1030, 962, 891, 750 and 698.
This work was supported by a Grant-in-Aid for Scientific
Research (no. 18350018) and a Grant-in-Aid for Scientific
Research on Priority Areas ‘‘Advanced Molecular
Transformations of Carbon Resources’’ (no. 19020016) from
the Ministry of Education, Culture, Sports, Science and
Technology, Japan.
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Notes and references
z A representative experimental procedure is as follows: finely
powdered molecular sieves
4 A (120 mg), magnesium turning
(35 mg, 1.44 mmol) and Cp2TiCl2 (299 mg, 1.2 mmol) were placed
in a flask and dried by heating with a heat gun under reduced pressure.
After cooling, THF (3 mL) and P(OEt)3 (0.41 mL, 2.4 mmol) were
successively added with stirring at 25 1C under argon. After 3 h, a
THF (2 mL) solution of 3-(ethoxycarbonyloxy)-1,5-diphenyl-1-
pentyne (4b) (123 mg, 0.40 mmol) was added to the reaction mixture
at 25 1C. After 35 min, a THF (1 mL) solution of methallyl chloride
(9b) (109 mg, 1.2 mmol) was added dropwise over 3 min and the
mixture was further stirred for 2 h. The reaction was quenched by
addition of 1 M NaOH, and the insoluble materials were filtered off
through Celite and washed with diethyl ether. The organic materials
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This journal is The Royal Society of Chemistry 2009
Chem. Commun., 2009, 3375–3377 | 3377