Regio- and stereoselective synthesis of 1,4-dienes

Article abstract of DOI:10.1039/c1cc14765j

Titanocene(ii)-promoted cross-coupling between (Z)-alkenyl methyl sulfones and terminal allenes produced 1,4-dienes regioselectively via the formation of 2-alkylidenetitanacyclopentanes. Preferential formation of E,Z-dienes was observed in the reaction us

Full text of DOI:10.1039/c1cc14765j

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COMMUNICATION
Regio- and stereoselective synthesis of 1,4-dienesw
Shigeki Oishi, Keisuke Hatano, Akira Tsubouchi and Takeshi Takeda*
Received 2nd August 2011, Accepted 5th September 2011
DOI: 10.1039/c1cc14765j
Titanocene(II)-promoted cross-coupling between (Z)-alkenyl methyl
sulfones and terminal allenes produced 1,4-dienes regioselectively
via the formation of 2-alkylidenetitanacyclopentanes. Preferential
formation of E,Z-dienes was observed in the reaction using aryl-,
amino-, and phosphinylallenes.
Skipped dienes are important substructures in biological
molecules and also valuable intermediates in organic synthesis.
Therefore, a variety of methods for the preparation of
1,4-pentadienes have been reported.1 Most investigated ways
Scheme 1
of arylallene 3b with 2a proceeded with complete regio- and
stereoselectivity to produce E,Z-pentadiene 1b (entry 2).
The observed regio- and stereoselectivity of the reaction is
well explained by the formation of 2-alkylidenetitanacyclo-
pentane intermediate 5 with retention of the configuration of
alkenyl sulfone 2 (Scheme 2). Similarly to the reported
alkenylation with (Z)-alkenyl sulfones 2,2b–d the syn-elimination
of the methylsulfonyl group results in the formation of an
E-double bond. The stereochemistry of the double bond
originated from allene 3 is rationalized by the relative stability
of the titanacycle intermediates 5a and 5b. Unlike the reaction
of the aliphatic allene 3a (R2 = Hex), the titanacycle intermediate
5b would be largely destabilized by steric repulsion between
R2 and Cp rings when the arylallene 3b (R2 = 4-tert-
butylphenyl) was employed. Hence, the Z-double bond was
predominantly produced on hydrolysis of the alkenyltitanium
species 6a with retention of configuration.
to construct such skipped dienes include the allylation of
alkenylmetals1a,e,g,n,s and the transition metal-catalyzed 1,4-
hydrovinylation of 1,3-dienes.1f,k,l,o,p Although preparations of
1,4-dienes by the low-valent titanium or zirconium-mediated
cross-coupling of alkynes with allylic alcohols,1i allenic alcohols1j
and allenes1q have been investigated, these reactions are
disadvantageous in that high regioselectivity is achieved only
when silylacethylenes are employed. Most of the foregoing
methods are well applicable for the preparation of highly
substituted 1,4-dienes, but there are only a few reports on the
stereoselective preparation of unbranched 1,5-disubstituted
1,4-pentadienes. As for the preparation of such 1,4-dienes with
E,Z-stereochemistry, the iridium-catalyzed cross-coupling of
o-aminostyrene derivatives with allylic carbonates1m was studied.
Recently, highly stereoselective preparation of 1,4-dienes by the
titanium-mediated reductive cross-coupling of vinylcyclo-
propanes with alkynes was reported.1t
Based on the above assumption, we further examined the
reaction of functionalized allenes. As expected, good Z-selec-
tivity was observed in the reaction using homoallenylamines
(Table 1, entries 3, 4, 5, 8, 10). Furthermore, (1Z,4E)-1,4-
pentadienylamines were obtained with complete stereo-
selectivity when allenylamines were employed (Table 1, entries
6, 9, 11).4 The reaction of allenylphosphine oxide 3g also produced
the stereoisomerically pure 1,4-diene 1g (Table 1, entry 7). All
these results indicate that the stereochemistry of formation of
titanacycle 5 is primarily determined by the steric interaction.
In conclusion, we have established the first straightforward
method for the regio- and stereoselective preparation of linear
E,Z-pentadienes by the titanocene(II)-promoted cross-
coupling of (Z)-alkenyl sulfones with terminal allenes.5 Further
study on the extension of this new methodology is now under
investigation.
During the course of study on the titanocene(II)-promoted
cross-coupling of unsaturated compounds via the formation of
five-membered titanacycles,2 we have found that (Z)-alkenyl
sulfones are useful for the E-alkenylation of a variety of
alkynes.2b–d The results prompted us to investigate the regio-
and stereoselective preparation of 1,4-pentadienes 1 using (Z)-
3
alkenyl sulfones 2 and terminal allenes 3 (Scheme 1).z
The treatment of 1,2-nonadiene (3a) with the alkenyl sulfone
2a (2.6 equiv.) in the presence of the titanocene(II) reagent 4 (2.4
equiv.) in THF at 10 1C for 1 h gave the 1,5-disubstituted 1,4-
pentadiene 1a regioselectively as an almost 1 : 1 mixture of the
stereoisomers (Table 1, entry 1). In contrast, the similar reaction
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: All charac-
terization data for 1,4-pentadienes 1. See DOI: 10.1039/c1cc14765j
This work was supported by Grant-in-Aid for Scientific
Research (No. 21350026) from the Ministry of Education,
Culture, Sports, Science and Technology, Japan.
c
This journal is The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 11639–11640 11639

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Table
sulfones with terminal allenes
1
Titanocene(II)-promoted cross-coupling of (Z)-alkenyl
10 min and stirring was continued for 15 min. A THF (10 cm3)
solution of the allene 3f (116 mg, 0.5 mmol) was added to the reaction
mixture over 2 h by using a syringe pump. Stirring was continued for
further 1 h and then the reaction was quenched with 1 M NaOH. The
insoluble materials were filtrated off through Celite and washed with
CH2Cl2. The layers were separated, and the aqueous layer was
extracted with CH2Cl2. After the combined organic extracts were
dried over Na2SO4, the solvent was removed under reduced pressure
and the residue was purified by alumina gel column chromatography
(eluted with hexane/AcOEt (95 : 5) containing a trace amount of
hydroquinone) to give 1f (148 mg, 88%); nmax (neat)/cmꢀ1 3060,
3028, 2978, 2930, 1712, 1657, 1495, 1323, 1302, 1254, 1165, 740 and
693; dH (300 MHz, CDCl3; Me4Si) 1.47 (s, 9H), 2.45 (dd, J = 7.5,
6.5 Hz, 2H), 5.00 (dt, J = 8.7, 7.5 Hz, 1H), 5.87 (dt, J = 15.9, 6.5 Hz,
1H), 6.10 (d, J = 15.9 Hz, 1H), 6.55 (d, J = 8.7 Hz, 1H) and 7.14–7.39
(m, 10H); dC (75 MHz; CDCl3) 28.2, 30.0, 81.3, 117.5, 125.8, 125.9,
126.7, 126.9, 127.5, 128.1, 128.4, 128.6, 130.3, 137.5, 141.9 and
153.4; m/z (FAB) 334.1809 [(M ꢀ H)+] (C22H24NO2 requires 334.1802).
Entry
2
3
1,4-Diene 1
Yielda, % (E : Z)b
1
2
2a 3a
2a 3b
1a
1b
76 (54 : 46)c
74 (0 : 100)
3
4
5
6
7
8
9
2a 3c
2a 3d
2a 3e
2a 3f
2a 3g
2b 3c
2b 3f
1c
1d
1e
1f
84 (14 : 86)
89 (13 : 87)
78 (25 : 75)
88 (0 : 100)
70 (0 : 100)
82 (16 : 84)
74 (0 : 100)
1 For recent examples, see: (a) H. Taguchi, K. Ghoroku, M. Tadaki,
A. Tsubouchi and T. Takeda, J. Org. Chem., 2002, 67, 8450;
(b) A. N. Thadani and V. H. Rawal, Org. Lett., 2002, 4, 4317;
(c) D. C. Braddock and A. Matsuno, Synlett, 2004, 2521;
(d) D. C. Braddock, D. M. Badine, T. Gottschalk, A. Matsuno
and M. Rodriguez-Lens, Synlett, 2003, 345; (e) Y. Kayaki, T. Koda
and T. Ikariya, Eur. J. Org. Chem., 2004, 4989; (f) A. Zhang and
T. V. Rajan Babu, J. Am. Chem. Soc., 2006, 128, 54;
(g) G. W. Kabalka and M. Al-Masum, Org. Lett., 2006, 8, 11;
(h) G. Hilt and J. Treutwein, Angew. Chem., Int. Ed., 2007, 46, 8500;
(i) F. Kolundzic and G. C. Micalizio, J. Am. Chem. Soc., 2007,
129, 15112; (j) H. L. Shimp, A. Hare, M. McLaughlin and
G. C. Micalizio, Tetrahedron, 2008, 64, 3437; (k) B. Moreau,
J. Y. Wu and T. Ritter, Org. Lett., 2009, 11, 337; (l) G. Hilt and
J. Treutwein, Chem. Commun., 2009, 1395; (m) H. He, W.-B. Liu,
L.-X. Dai and S.-L. You, J. Am. Chem. Soc., 2009, 131, 8346;
(n) K. Akiyama, F. Gao and A. H. Hoveyda, Angew. Chem., Int.
Ed., 2010, 49, 419; (o) R. K. Sharma and T. V. Rajan Babu, J. Am.
Chem. Soc., 2010, 132, 3295; (p) M. Arndt, A. Reinhold and G. Hilt,
J. Org. Chem., 2010, 75, 5203; (q) W. Zheng, Y. Wu, F. Zheng,
L. Hu and Y. Hong, Tetrahedron Lett., 2010, 51, 4702;
(r) W.-B. Liu, H. He, L.-X. Dai and S.-L. You, Chem.–Eur. J.,
2010, 16, 7376; (s) F. Gao, K. P. McGrath, Y. Lee and
A. H. Hoveyda, J. Am. Chem. Soc., 2010, 132, 14315;
(t) T. K. Macklin and G. C. Micalizio, Nat. Chem., 2010, 2, 638.
2 (a) A. Ogata, M. Nemoto, K. Arai, K. Kobayashi, A. Tsubouchi
and T. Takeda, Eur. J. Org. Chem., 2006, 878; (b) A. Ogata,
M. Nemoto, K. Kobayashi, A. Tsubouchi and T. Takeda, J. Org.
Chem., 2007, 72, 3816; (c) A. Ogata, M. Nemoto, K. Kobayashi,
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39, 723.
1g
1h
1i
10
2c
2c
3c
3f
1j
80 (18 : 82)
11
1k 70 (0 : 100)
a
b
Isolated yield based on allene 3 used. The stereoisomeric ratio of
c
the double bond originated from 3. The ratio of stereoisomers.
3 The (Z)-alkenyl sulfones 2 were prepared by the DIBAL reductiona
of alkynyl sulfidesb followed by oxidation with oxones
(a) M. J. Dabdoub and P. G. Guerrero Jr., Tetrahedron Lett., 2001,
;
42, 7167; (b) H. A. Stefani, R. Cella, F. A. Dorr, C. M. P. de Pereira,
¨
F. P. Gomes and G. Zeni, Tetrahedron Lett., 2005, 46, 2001.
Homoallenylamines 3c, 3d, 3e were obtained by the reaction of
propargylamines with paraformaldehyde in the presence of diisopro-
pylamine and copper(I) bromide; S. Searles, Y. Li, B. Nassim,
M. R. Lopes, P. T. Tran and P. Crabbe, J. Chem. Soc., Perkin Trans.
´
1, 1984, 747. The allenylamine 3f was prepared by isomerization of
the corresponding propargylamine with t-BuOK in THF at ꢀ78 1C
for 30 min; for example, see: F. Le Strat and J. Maddaluno, Org.
Lett., 2002, 4, 2791. The allenylic diphenyl phosphine oxide 3g was
synthesized by the reaction of propargyl alcohol with Ph2PCl in the
presence of Et3N; H. Guo, R. Qian, Y. Guo and S. Ma, J. Org.
Chem., 2008, 73, 7934.
4 For the stereoselective preparation of (1E,4E)-1,4-pentadienylamines, see:
B. M. Trost and J.-P. Surivet, Angew. Chem., Int. Ed., 2001, 40, 1468.
5 Similarly to the alkenylation of alkynes,2b (E)-alkenyl sulfones are
ineffective for the alkenylation of allenes; the reaction of E-enriched
2a (E : Z = 73 : 27) with 3c produced 1c only in a poor yield (10%;
E : Z = 11 : 89) and a substantial amount of E-2a was recovered.
Scheme 2
Notes and references
z A typical experimental procedure is as follows: magnesium turnings
(32 mg, 1.3 mmol), finely powdered molecular sieves 4A (120 mg) and
Cp2TiCl2 (299 mg, 1.2 mmol) were placed in a flask and dried by
heating with a heat gun under reduced pressure (2–3 mmHg). After
cooling, THF (2 cm3) and P(OEt)3 (0.42 cm3, 2.4 mmol) were added
successively with stirring at 25 1C under Ar. After 3 h, the reaction
mixture was cooled to 10 1C and then a THF (2 cm3) solution of
the alkenyl sulfone 2a (237 mg, 1.3 mmol) was added dropwise over
c
11640 Chem. Commun., 2011, 47, 11639–11640
This journal is The Royal Society of Chemistry 2011