Regioselective cobalt-catalyzed alder-ene reaction toward silicon-and boron-functionalized building blocks

Article abstract of DOI:10.1021/ol102764w

The cobalt-catalyzed formal Alder-ene reaction of functionalized alkenes and alkynes leads to bifunctionalized 1,4-dienes in high yields and excellent regio-and stereoselectivities. The silicon-functionalized building blocks are easily converted into iodo

Full text of DOI:10.1021/ol102764w

ORGANIC
LETTERS
2011
Vol. 13, No. 2
304-307
Regioselective Cobalt-Catalyzed
Alder-ene Reaction toward Silicon- and
Boron-Functionalized Building Blocks
Gerhard Hilt,* Florian Erver, and Klaus Harms
Fachbereich Chemie, Philipps-UniVersita¨t Marburg, Hans-Meerwein-Str.,
35043 Marburg, Germany
hilt@chemie.uni-marburg.de
Received November 15, 2010
ABSTRACT
The cobalt-catalyzed formal Alder-ene reaction of functionalized alkenes and alkynes leads to bifunctionalized 1,4-dienes in high yields and
excellent regio- and stereoselectivities. The silicon-functionalized building blocks are easily converted into iodo-functionalized derivatives and
in combination with boron-functionalized building blocks polyenes can be generated utilizing a Suzuki cross-coupling. In addition, building
blocks incorporating allylic silane functionalities can be used in Sakurai allylation or Prins-type cyclization reactions for the synthesis of
heterocyclic products such as tetrahydrofuranes or tetrahydropyranes.
Cobalt-catalyzed transformations of unsaturated compounds
have steadily gained importance in modern organic synthesis.
Specifically atom economic carbon-carbon bond formations
are of increasing interest.1 Especially the 1,4-hydrovinylation
of substituted 1,3-butadienes with terminal alkenes as well
as the Alder-ene reaction of terminal alkenes with internal
alkynes are relevant for the construction of linear carbon-
skeletons.2 The application of the 1,4-hydrovinylation reac-
tion in the synthesis of 1,3-dicarbonyl derivatives3 and the
chemoselective cobalt-catalyzed Alder-ene reaction4 versus
the competing [2 + 2] cycloaddition have been explored in
more detail.5 Herein, we specifically report the generation
of silicon- and boron-functionalized 1,4-dienes via the cobalt-
catalyzed Alder-ene reaction.
For the synthesis of 1,4-dienes via the cobalt-catalyzed Alder-
ene reaction of arene substituted alkynes, the [CoBr2(dppp)]
catalyst precursor proved to be the most efficient.6 On the other
hand, when electron-deficient alkynes were applied, the
[CoBr2(dppe)] complex gave the best results7 (Scheme 1).
Nevertheless, in both cases various functional groups were
tolerated both in the internal alkynes 1 and in the terminal
alkenes 2.8 In this study, we focused our attention upon the
generation of silicon- and boron-functionalized 1,4-dienes, in
which these functional groups are located in the vinylic or allylic
(1) (a) Hess, W.; Treutwein, J.; Hilt, G. Synthesis 2008, 3537. (b) Omae,
I. Appl. Organomet. Chem. 2007, 21, 318. (bb) Laschat, S.; Becheanu, A.;
Bell, T.; Baro, A. Synlett 2005, 2547. (c) Varela, J. A.; Saa´, C. Chem. ReV.
2003, 103, 3787. (d) Malacria, M.; Aubert, C.; Renaud, J. L. In Science of
Synthesis: Houben-Weyl Methods of Molecular Transformations; Lautens,
M., Trost, B. M., Eds.; Thieme: Stuttgart, 2001; Vol. 1, p 439. (e) Welker,
M. E. Curr. Org. Chem. 2001, 5, 785. (f) Saito, S.; Yamamoto, Y. Chem.
ReV. 2000, 100, 2901. (g) Ojima, I.; Tzamarioudaki, M.; Li, Z.; Donovan,
R. J. Chem. ReV. 1996, 96, 635. (h) Lautens, M.; Klute, W.; Tam, W. Chem.
ReV. 1996, 96, 49.
(4) (a) Hilt, G.; Treutwein, J. Angew. Chem. 2007, 119, 8653. (b) Hilt,
G.; Treutwein, J. Angew. Chem., Int. Ed. 2007, 46, 8500.
(5) Hilt, G.; Paul, A.; Treutwein, J. Org. Lett. 2010, 12, 1536.
(6) [CoBr2(dppp)] ) cobalt(1,2-bis(diphenylphosphino)propane) dibro-
mide.
(7) [CoBr2(dppe)] ) cobalt(1,2-bis(diphenylphosphino)ethane) dibro-
mide.
(2) Hilt, G.; Treutwein, J. Chem. Commun. 2009, 1395.
(3) (a) Kersten, L.; Roesner, S.; Hilt, G. Org. Lett. 2010, 12, 4920. (b)
Arndt, M.; Reinhold, A.; Hilt, G. J. Org. Chem. 2010, 75, 5203. (c) Hilt,
G.; Arndt, M.; Weske, D. F. Synthesis 2010, 1321.
10.1021/ol102764w  2011 American Chemical Society
Published on Web 12/16/2010

Scheme 1
.
Cobalt-Catalyzed Alder-ene Reaction with
Table 1. Results of the Cobalt-Catalyzed Alder-ene Reaction of
Electron-Rich and Electron-Deficient Alkynes
Silicon- And Boron-Functionalized Alkynes and Alkenesa
position in the product 3 (Scheme 2).9 The results of these
investigation are summarized in Table 1.
Scheme 2. Cobalt-Catalyzed Alder-ene Reaction for the
Generation of Polysubstituted 1,4-Dienes
Concerning the configuration of the double bonds in the
1,4-dienes in 3, the products are formed predominantly as
the E,E-isomers concerning double bond a or b (see Scheme
2). Nevertheless, the most striking finding in this series of
experiments is the fact that the configuration of double bond
b is altered depending on whether a trialkylsilicon-function-
alized alkene or a pinacolboronic ester alkene is applied
(compare entries 8 and 11). While the E-configuration of
double bond b is adopted when trialkylsilicon based groups
are used the corresponding Z-configured double bond is
formed predominantly with the boron-functionalized alkenes.
This observation can be explained by postulating coordina-
tion of one of the pinacol oxygen lone pairs to the cobalt
center. In the case of a bulky silyl-group a transoid
conformation in transition state BSi leads predominantly to
a ꢀ-hydride elimination via Ha toward an E-configured double
bond. When the allyl pinacolboronic ester is used a cisoid
comformation is adopted in transition state BB which favors
the ꢀ-hydride elimination via the proton Hb toward the
predominantly formed Z-isomer (Scheme 3).
In addition, when allylpinacolboronic ester is used,
the results suggest that the smaller the substituent R2 in the
alkyne is the higher the ratio for the formation of the
Z-configured double bond becomes (Bu vs Me, entries 6,7).
Moreover, this finding is hard to explain by the mechanistic
sketch proposed in Scheme 3. Also, the application of the
diisopropylsilane group in the alkyne (entries 4,5) and in
the alkene component (entries 12, 15) resulted in unexpected
findings. In these cases a rather low or in some cases an
even ratio of E/Z-isomers concerning double bond a or b is
obtained no matter if this functional group adopts a vinylic
or an allylic position in the product of type 3. The only option
to rationalize the formation of E/Z-isomers in these cases
seems to be the intermediate formation of an attractive
hydrogen bridge between the cobalt center and the silicon
a Method A: CoBr2(dppp) (10 mol %), zinc dust (20 mol %), zinc iodide
(20 mol %), alkyne addition (1.5 equiv) in one portion. Method B:
CoBr2(dppe) (20 mol %), zinc dust (40 mol %), zinc iodide (40 mol %);
alkyne addition (3.0 equiv) over 7 h. b Pin ) pinacol. c E/Z ratios were
determined by 1H NMR spectroscopy. d Performed according to method A
utilizing CoBr2(dppp) (20 mol %); zinc dust (40 mol %); zinc iodide (40
mol %).
Org. Lett., Vol. 13, No. 2, 2011
305

a in the product and regenerates the active catalyst unless
the coordination of functional groups interferes with this
reaction pathway to induce double bond isomerizations.
Scheme 3. Rationale for the E-Selectivity for
Silyl-Functionalized Educts and Z-Selectivity for
Boron-Functionalized Alkenes
If both components lack such coordinating groups, the
Alder-ene reaction usually leads to E,E-configured 1,4-dienes
3.
We envisage that many of the silicon- and boron-
functionalized 1,4-dienes generated by the atom economic
cobalt-catalyzed Alder-ene reaction are useful building blocks
for further transformations to generate advanced products
in a concise manner. In fact, the allyl silane 3i can be reacted
with propionaldehyde leading to the rapid generation of the
polysubstituted tetrahydropyran 4 by Prins-type cyclization
in good yields (Scheme 5). On the other hand, when
atom via the hydrogen atom (Co-H-Si bridge). Neverthe-
less, only the E,E-configured product 3c utilizing the
diisopropylsilane group (entry 3) could be observed. How-
ever, in most cases good yields, exclusive regioselectivities
concerning the site of the carbon-carbon bond formation
in both the alkyne and the alkene, and the exclusive formation
of the desired E,E-configured isomers can be reported.
Finally, for the first time an alkynone could be deployed in
the cobalt-catalyzed Alder-ene reaction leading to the cor-
responding 1,4-diene 3p in a moderate yield (entry 16). The
proposed mechanism is initiated by the coordination of the
alkyne and the alkene component to the active cationic cobalt
complex leading to the generation of intermediate A (Scheme
4).
Scheme 5. Alder-ene Product in the Generation of a
Polysubstituted Tetrahydropyran and -Furan
Scheme 4
.
Mechanism of the Cobalt-Catalyzed Alder-ene
Reaction
isobutyraldehyde was used under slightly modified condi-
tions, alcohol 5 was generated via a Sakurai allylation in a
72% yield. In this proof-of-principle investigation catalytic
amounts of sodium hydride converted this compound smoothly
into the corresponding polysubstituted tetrahydrofuran 6 in
an excellent 88% yield as a mixture of diastereomers.10
The boron- and silicon-functionalized building blocks were
then applied in a palladium-catalyzed coupling reaction. To
do so, the vinyl silane 3k was first converted into the
(8) When terminal alkynes were used the cyclotrimerization of the
alkynes to the corresponding 1,2,4-trisubstituted benzene derivatives became
the predominent reaction pathway, see: (a) Hilt, G.; Hengst, C.; Hess, W.
Eur. J. Org. Chem. 2008, 2293. (b) Hilt, G.; Hess, W.; Harms, K. Synthesis
2008, 75. (c) Hilt, G.; Hess, W.; Vogler, T.; Hengst, C. J. Organomet. Chem.
2005, 690, 5170.
Then the regioselective carbon-carbon bond formation
process leads to intermediate B from which a ꢀ-hydride
elimination furnishes the intermediate cobalt-hydride com-
plex C.
Finally, a reductive elimination under retention of double
bond configuration generates the E-configured double bond
(9) For cobalt-catalyzed reactions involving borylated partners, see: (a)
Geny, A.; Leboef, D.; Rouquie´, G.; Vollhardt, K. P. C.; Malacria, M.;
Gandon, V.; Aubert, C. Chem.sEur. J. 2007, 13, 5408. (b) Leboef, D.;
Iannazzo, L.; Geny, A.; Malacria, M.; Vollhardt, K. P. C.; Aubert, C.;
Gandon, V. Chem.sEur. J. 2010, 16, 8904.
(10) Reddipalli, G.; Venkataiah, M.; Mishra, M. K.; Fadnavis, N. W.
Tetrahedron: Asymmetry 2009, 20, 1802.
306
Org. Lett., Vol. 13, No. 2, 2011

corresponding vinyl iodide 7 under slightly modified Kishi
conditions.11
Unfortunately, this conversion was always accompanied
by isomerization of the affected double bond (Scheme 6).
of such a dehydrogenative oxidation process has not been
described. We were very pleased to isolate the pentaene
product 9 in a moderate yield of 37% as a solid of intense
yellow color crystallizing directly from the crude reaction
mixture. The all-trans configuration of the double bonds, as
was determined by X-ray analysis (Figure 1) of the isolated
Scheme 6. Synthesis of a Pentaene via Suzuki Cross-Coupling
of Alder-ene Products with Subsequent DDQ Oxidation
Figure 1. Crystal structure of compound 9.
solid, must be generated during the course of the DDQ
oxidation which can be best explained by a radical type
intermediate.14 The generation of such polyenes via such a
short reaction sequence from four simple starting materials
(two alkynes and two alkenes) is very appealing, leading to
either a 1,4,6,9-tetraene or a 1,3,5,7,9-pentaene product after
DDQ oxidation.
In conclusion we have demonstrated that the cobalt-
catalyzed Alder-ene reaction can be used to generate E-
configured silicon- or Z-configured boron-functionalized 1,4-
diene building blocks. These adducts were transformed in
proof-of-principle transformations into polysubstituted het-
erocycles. Moreover, the generation of unprecedented 1,4,6,9-
tetraene and conjugated 1,3,5,7,9-pentaene derivatives, by
simple DDQ oxidation, was accomplished.
Nevertheless, the iodo-substituted 1,4-diene 7 could be
obtained in good yield.
The Suzuki cross-coupling with the Z-configured enriched
vinyl pinacolboronic ester 3g proceeded smoothly at room
temperature within 2 h to yield the tetraenoate 8 in a nearly
quantitative yield.12
In previous studies concerning cobalt-catalyzed Diels-Alder
reactions we utilized DDQ for the oxidation of the dihy-
droaromatic compounds to the corresponding aromatic prod-
ucts.13 Based on these results we envisaged that the oxidation
of the 1,4,6,9-tetraene derivative 8 substituted with an ester
functionality and a phenyl substituent at both ends of the
molecule could be used to generate a conjugated push-pull
substituted pentaene 9 by DDQ dehydrogenation. To the best
of our knowledge, such an interconversion has not been
described in the literature. Accordingly, the ratio of retention
or inversion of double bond configurations over the course
Acknowledgment. This work was supported by the Fonds
der Chemischen Industrie by a fellowship (FE) and the
German Science Foundation. Their support is gratefully
acknowledged.
Supporting Information Available: Experimental pro-
cedures and full characterization of the compounds obtained
in pure form. This material is available free of charge via
the Internet at http://pubs.acs.org.
OL102764W
(11) Jiang, X.; Ma, S. J. Am. Chem. Soc. 2007, 129, 11600.
(12) Tortosa, M.; Yakelis, N. A.; Roush, W. R. J. Org. Chem. 2008,
73, 9657.
(14) The crystal structure has been deposited at the Cambridge
Crystallographic Data Centre and allocated the deposition number CCDC
798849.
(13) For a recent reference, see: Auvinet, A.-L.; Harrity, J. P. A.; Hilt,
G. J. Org. Chem. 2010, 75, 3893.
Org. Lett., Vol. 13, No. 2, 2011
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