Pd-catalyzed borylative cyclization of allenynes and enallenes

Article abstract of DOI:10.1021/ol9017694

Pd-catalyzed cyclization of 1,5- and 1,6-allenynes and 1,5-enallenes with bis(pinacolato)diboron affords synthetically useful allylboronates and alkylboronates under smooth conditions in a formal hydroborylative carbocyclization reaction. One C-C and one

Full text of DOI:10.1021/ol9017694

ORGANIC
LETTERS
2009
Vol. 11, No. 20
4548-4551
Pd-Catalyzed Borylative Cyclization of
Allenynes and Enallenes
Virtudes Pardo-Rodr´ıguez, Juan Marco-Mart´ınez, Elena Bun˜uel, and
Diego J. Ca´rdenas*
Departamento de Qu´ımica Orga´nica, UniVersidad Auto´noma de Madrid,
Cantoblanco, 28049 Madrid, Spain
diego.cardenas@uam.es
Received July 31, 2009
ABSTRACT
Pd-catalyzed cyclization of 1,5- and 1,6-allenynes and 1,5-enallenes with bis(pinacolato)diboron affords synthetically useful allylboronates and
alkylboronates under smooth conditions in a formal hydroborylative carbocyclization reaction. One C-C and one C-B bond are formed in
a single operation. The reaction outcome implies that different mechanisms operate for the reactions of allenynes and enallenes, respectively,
the actual pathway depending on the relative reactivity of the alkyne or the alkene versus the allene moiety. The cyclized boronates obtained
can be functionalized by oxidation or allylation reaction with aldehydes.
Transition-metal-catalyzed carbocyclization reactions of un-
saturated species have provided useful methods for the
preparation of a wide range of carbocycles or heterocycles
with high efficiency and selectivity.1 Compared with alkynes
and alkenes, allenes have been much less studied as a
component for the catalytic formation of carbon-carbon
multiple bonds. However, allenes have proved to be versatile
intermediates for organic synthesis in recent years.2-6 Thus,
transition-metal-catalyzed cycloisomerization and carbocy-
clization reactions of allenynes (Ti, Ru, Rh, Pd, Mo, Pt,
Au)2,3 and enallenes (Ru, Rh, Ni/Cr, Pd, Au)4,5 have been
reported in the literature. Thermal cycloadditions of allenynes
and enallenes have also been described.7
Processes in which main group elements are introduced
along the cyclization reaction are especially important since
they allow the preparation of compounds which can be
further functionalized. Thus, Shibata and co-workers reported
the first hydrosilylative carbocyclization of allenynes,8 and
RajanBabu and co-workers the first silylstannylation-cy-
(2) Selected recent references: Ti: (a) Urabe, H.; Takeda, T.; Hideura,
D.; Sato, F. J. Am. Chem. Soc. 1997, 119, 11295–11305. Ru: (b) Saito, N.;
Tanaka, Y.; Sato, Y. Organometallics 2009, 28, 669–671. Rh: (c) Brum-
mond, K. M.; Chen, H.; Sill, P.; You, L. J. Am. Chem. Soc. 2002, 124,
15186–15187. Pd: (d) Oh, C. H.; Jung, S. H.; Park, D. I.; Choi, J. H.
Tetrahedron Lett. 2004, 45, 2499–2502. Mo: (e) Shen, Q.; Hammond, G. B.
J. Am. Chem. Soc. 2002, 124, 6534–6535. Pt: (f) Zriba, R.; Gandon, V.;
Aubert, C.; Fensterbank, L.; Malacria, M. Chem.sEur. J. 2008, 14, 1482–
1491. Au: (g) Lemie`re, G.; Gandon, V.; Agenet, N.; Goddard, J.-P.; de
Kozak, A.; Aubert, C.; Fensterbank, L.; Malacria, M. Angew. Chem., Int.
Ed. 2006, 45, 7596–7599. (h) Cheong, P. H.-Y.; Morganelli, P.; Luzung,
M. R.; Houk, K. N.; Toste, F. D. J. Am. Chem. Soc. 2008, 130, 4517–
4526.
(1) (a) Lautens, M.; Klute, W.; Tam, W. Chem. ReV. 1996, 96, 49–92.
(b) Negishi, E.; Cope´ret, C.; Ma, S.; Liou, S.-Y.; Liu, F. Chem. ReV. 1996,
96, 365–393. (c) Ojima, I.; Tzamarioudaki, M.; Li, Z.; Donovan, R. Chem.
ReV. 1996, 96, 635–662. (d) Mori, M. Top. Organomet. Chem. 1998, 1,
133–154. (e) Aubert, C.; Buisine, O.; Malacria, M. Chem. ReV. 2002, 102,
813–834. (f) Trost, B. M.; Toste, D. F.; Pinkerton, A. B. Chem. ReV. 2002,
101, 2067–2096. (g) Trost, B. M.; Krische, M. J. Synlett 1998, 1–16.
10.1021/ol9017694 CCC: $40.75
Published on Web 09/24/2009
 2009 American Chemical Society

clization of allenynes.9 We have recently reported a novel
reaction for the formation of alkyl (homoallylic) boronates
from enynes by a formal 1,7-hydroboration with concomitant
carbocyclization (Scheme 1) and have extended the reaction
to enediynes to obtain allylboronates.10
formation of C-C bonds from carbonyl compounds and
derivatives.15 Boronates are usually prepared by hydrobo-
ration of alkenes or by reaction of Li and Mg reagents
with borate esters.16 Herein, we report a novel Pd-
catalyzed borylative cyclization reaction for the formation
of allylboronates and alkylboronates from allenynes and
enallenes, respectively, which avoids the use of highly
nucleophilic or basic reagents. The resulting boronates
have been used as substrates for subsequent oxidation and
allylation reactions.
Scheme 1. Borylative Cyclization of 1,6-Enynes
When 1,5-allenyne 1a was subjected to reaction with
bis(pinacolato)diboron in the presence of Pd(OAc)2 and
MeOH in toluene, a mixture of two five-membered ring
allylboronates, 2a and 3a, was formed (Scheme 2). The
Alkylboronates11 and alkyltrifluoroborates12 are useful
nucleophilic partners in the Suzuki cross-coupling,13 and
allylboronates14 are important in the stereoselective
Scheme 2. Pd-Catalyzed Borylative Cyclization of an Allenyne
(3) Alternative mechanisms for allenyne cycloisomerization: For Co:
(a) Llerena, D.; Aubert, C.; Malacria, M. Tetrahedron Lett. 1996, 37, 7027–
7030. For Ga: (b) Lee, S. I.; Sim, S. H.; Kim, S. M.; Kim, K.; Chung,
Y. K. J. Org. Chem. 2006, 71, 7120–7123. For Hg: (c) Sim, S. H.; Lee,
S. I.; Seo, J.; Chung, Y. K. J. Org. Chem. 2007, 72, 9818–9821. For Mo-
catalyzed allenyne metathesis: (d) Murakami, M.; Kadowaki, S.; Matsuda,
T. Org. Lett. 2005, 7, 3953–3956. For Rh-catalyzed reactions not involving
cycloisomerization: (e) Miura, T.; Ueda, K.; Takahashi, Y.; Murakami, M.
Chem. Commun. 2008, 5366–5368.
formation of these two regioisomers implies a formal 1,7-
and 1,5-hydroboration of the allenyne, respectively, with
concomitant carbocyclization, affording one C-C and one
B-C bond in a single operation. In all cases, i.e., both
terminal and internal allenyne (referred to the alkyne moiety),
the major regioisomer is that in which the boronate is located
in the exocyclic position (2). Noteworthy, high yields are
obtained despite the potential ꢀ-hydrogen elimination that
could take place on the intermediates.
(4) Ru: (a) Mukai, C.; Itoh, R. Tetrahedron Lett. 2006, 47, 3971–3974.
Rh: (b) Makino, T.; Itoh, K. J. Org. Chem. 2004, 69, 395–405. (c) Wender,
P. A.; Glorius, F.; Husfeld, C. O.; Langkopf, E.; Love, J. A. J. Am. Chem.
Soc. 1999, 121, 5348–5349. Ni/Cr: (d) Trost, B. M.; Tour, J. M. J. Am.
Chem. Soc. 1988, 110, 5231–5233. Pd: (e) Trost, B. M.; Matsuda, K. J. Am.
Chem. Soc. 1988, 110, 5233–5235. (f) Na¨rhi, K.; Franze´n, J.; Ba¨ckvall,
J.-E. Chem. Eur. J. 2005, 11, 6937–6943. Au: (g) Lee, J. H.; Toste, F. D.
Angew. Chem., Int. Ed. 2007, 46, 912–914. (h) Luzung, M. R.; Mauleo´n,
P.; Toste, F. D. J. Am. Chem. Soc. 2007, 129, 12402–12403. (i) Tarselli,
M. A.; Chianese, A. R.; Lee, S. J.; Gagne´, M. R. Angew. Chem., Int. Ed.
2007, 46, 6670–6673. (j) Horino, Y.; Yamamoto, T.; Ueda, K.; Kuroda,
S.; Toste, F. D. J. Am. Chem. Soc. 2009, 131, 2809–2811. (k) Marion, N.;
Lemie`re, G.; Correa, A.; Costabile, C.; Ramo´n, R. S.; Moreau, X.; de
Fre´mont, P.; Dahmane, R.; Hours, A.; Lesage, D.; Tabet, J.-C.; Goddard,
J.-P.; Gandon, V.; Cavallo, L.; Fensterbank, L.; Malacria, M.; Nolan, S. P.
Chem. Eur. J. 2009, 15, 3243–3260.
Terminal allenynes afford the corresponding boronates
with moderate to good yields (Table 1).17,18 The best results
(11) (a) Chemler, S. R.; Trauner, D.; Danishefsky, S. J. Angew. Chem.,
Int. Ed. 2001, 40, 4544–4568. (b) Netherton, M.; Dai, C.; Neuschu¨tz, K.;
Fu, G. C. J. Am. Chem. Soc. 2001, 123, 10099–10100.
(5) Recent references for Pd-catalyzed reactions not involving cycloi-
somerization ,(a) Piera, J.; Persson, A.; Caldentey, X.; Ba¨ckvall, J.-E. J. Am.
Chem. Soc. 2007, 129, 14120–14121, and references cited therein. (b) Ohno,
H.; Miyamura, K.; Mizutani, T.; Kadoh, Y.; Takeoka, Y.; Hamaguchi, H.;
Tanaka, T. Chem. Eur. J. 2005, 11, 3728–3741. (c) Hashmi, A. S. K. Angew.
Chem., Int. Ed. 2000, 39, 3590–3593.
(12) Recent examples of synthetic applications of alkyltrifluoroborates:
(a) Molander, G. A.; Yokoyama, Y. J. Org. Chem. 2006, 71, 2493–2498.
(b) Molander, G. A.; Figueroa, R. Org. Lett. 2006, 8, 75–78. (c) Molander,
G. A.; Ito, T. Org. Lett. 2001, 3, 393–396. (d) Molander, G. A.; Yun, C.-
S.; Ribagorda, M.; Biolatto, B. J. Org. Chem. 2003, 68, 5534–5539. (e)
Matteson, D. S.; Kim, G. Y. Org. Lett. 2002, 4, 2153–2155. (f) Fang, G.-
H.; Yan, Z.-J.; Deng, M.-Z. Org. Lett. 2004, 6, 357–360.
(6) (a) Pelz, N. F.; Woodward, A. R.; Burks, H. E.; Sieber, J. D.; Morken,
J. P. J. Am. Chem. Soc. 2004, 126, 16328–16329. (b) Pelz, N. F.; Morken,
J. P. Org. Lett. 2006, 8, 4557–4559. (c) Sieber, J. D.; Morken, J. P. J. Am.
Chem. Soc. 2006, 128, 74–75. (d) Burks, H. E.; Liu, S.; Morken, J. P. J. Am.
Chem. Soc. 2007, 129, 8766–8773.
(13) (a) Miyaura, N.; Suzuki, A. Chem. ReV. 1995, 95, 2457–2483. (b)
Suzuki, A. J. Organomet. Chem. 1999, 576, 147–168.
(7) Thermal reactions of allenynes: (a) Ohno, H.; Mizutani, T.; Kadoh,
Y.; Miyamura, K.; Tanaka, T. Angew. Chem., Int. Ed. 2005, 44, 5113–
5115. (b) Oh, C. H.; Gupta, A. K.; Park, D. I.; Kim, N. Chem Commun.
2005, 5670–5672. (c) Mukai, C.; Hara, Y.; Miyashita, Y.; Inagaki, F. J.
Org. Chem. 2007, 72, 4454–4461. (d) Buisine, O.; Gandon, V.; Fensterbank,
L.; Aubert, C.; Malacria, M. Synlett 2008, 751–754. (e) Ovaska, T. V.;
Kyne, R. E. Tetrahedron Lett. 2008, 49, 376–378. Thermal reactions of
enallenes: (f) Na¨rhi, K.; Franze´n, J.; Ba¨ckvall, J.-E. J. Org. Chem. 2006,
71, 2914–2917. (g) Ohno, H.; Mizutani, T.; Kadoh, Y.; Aso, A.; Miyamura,
K.; Fujii, N.; Tanaka, T. J. Org. Chem. 2007, 72, 4378–4389.
(8) Shibata, T.; Kadowaki, S.; Takagi, K. Organometallics 2004, 23,
4116–4120.
(14) Metal-catalyzed synthesis of allylboronates: (a) Yang, F.-Y.;
Shanmugasundaram, M.; Chuang, S.-Y.; Ku, P.-J.; Wu, M.-Y.; Cheng, C.-
H. J. Am. Chem. Soc. 2003, 125, 12576–12583. (b) Ishiyama, T.; Ahiko,
T.; Miyaura, N. Tetrahedron Lett. 1996, 37, 6889–6892. Enantioselective
synthesis: (c) Ito, H.; Ito, S.; Sasaki, Y.; Matsuura, K.; Sawamura, M. J. Am.
Chem. Soc. 2007, 129, 14856–14857.
(15) (a) Ishiyama, T.; Ahiko, T.; Miyaura, N. J. Am. Chem. Soc. 2002,
124, 12414–12415. (b) Kennedy, J. W. J.; Hall, D. G. J. Am. Chem. Soc.
2002, 124, 11586–11587.
(16) Boronic Acids; Hall, D. G., Ed.; Wiley-VCH: Weinheim, 2005; pp
1-99.
(17) Endocyclic allylboronates 6b and 6c were obtained as a mixture
of geometric isomers. The crystal structure of the E-isomer of 6c was
(9) (a) Shin, S.; RajanBabu, T. V. J. Am. Chem. Soc. 2001, 123, 8416–
8417. (b) Kumareswaran, R.; Shin, S.; Gallou, I.; RajanBabu, T. V. J. Org.
Chem. 2004, 69, 7157–7170.
determined using
separation.
a pure sample from a chromatographic partial
(10) (a) Marco-Mart´ınez, J.; Lo´pez-Carrillo, V.; Bun˜uel, E.; Simancas,
R.; Ca´rdenas, D. J. J. Am. Chem. Soc. 2007, 129, 1874–1875. (b) Marco-
Mart´ınez, J.; Bun˜uel, E.; Mun˜oz-Rodr´ıguez, R.; Ca´rdenas, D. J. Org. Lett.
2008, 10, 3619–3621.
(18) Boronates tend to decompose in column chromatography when
longer retention times are used, which precludes isolation of pure compounds
in some cases. Derivatives 3a, 3b, 3d, and 3f could not be fully characterized
due to their instability and fast decomposition in solution.
Org. Lett., Vol. 11, No. 20, 2009
4549

yield. Low yields are probably due to decomposition of
starting materials since conversion was complete in all cases.
A reasonable reaction pathway for the formation of the
observed products is shown in Scheme 3. The reaction
Table 1. Pd-Catalyzed Borylative Cyclization of Allenynesa
Scheme 3. Proposed Reaction Pathway for Allenynes
probably starts with the formation of a Pd-hydride complex
by protonation of Pd(0) intermediates with the alcohol, which
promotes the hydropalladation of the alkyne.20 Subsequent
carbometalation of the allene by the alkenylpalladium
intermediate would take place regioselectively with for-
mation of the new C-C bond onto the central carbon of
the allene and would give rise to allyl-Pd intermediate
A (Scheme 3). Methoxide-promoted transmetalation of A
with bis(pinacolato)diboron, followed by reductive elimi-
nation, would lead to the observed final products 2 and 3.
Therefore, we propose that the regioselective outcome of
the reaction is a consequence of the relative feasibility of
both possible C-B reductive eliminations on the allylpal-
ladium intermediate.
a Standard conditions: allenyne 1 or 4 (1 equiv), B2(pin)2 (1.2 equiv),
Pd(OAc)2 (5 mol %), MeOH (1 equiv) in dry toluene (1 mL) were stirred
at the indicated temperature under Ar atmosphere. b Isomers 2 and 3 were
completely separated in most cases. See Supporting Information for details.
c Pd(OAc)2 (10 mol %) was added. d Additional B2(pin)2 (1 equiv) and
Pd(OAc)2 (5 mol %) were added after 48 h with no reaction at rt and then
heated at 50 °C. e A mixture of nonseparable ꢀ-elimination products was
obtained in additional 16% yield.
On the other hand, when 1,5-enallenes 7a,b were subjected
to the same reaction conditions, the following mixtures of
alkyl- and allylboronates, 8a,b and 9a,b, were obtained in
moderate yields (ca. 60%) (Table 2).
were obtained for allenynes 1a and 1d (ca. 80% yield). The
lower yields obtained for the internal allenynes, 1e-f, could
be due to the lower reactivity of the internal alkyne with
respect to the allene moiety and the potential competition
of the allene in the early stages of the reaction pathway (see
below).
When the reaction was performed with the 1,6-allenynes
(4), homologues of 1, six-membered ring allylboronates 5
and 6 were obtained in formal 1,8- and 1,6-hydroborylative
carbocyclizations, respectively. Reactions of 4a and 4b
afforded a single regioisomer in each case, 5a and 5b,
respectively, with moderate yields (Table 1). However,
allenyne 4d provides an excellent yield (97%), with a
significant increase in the endocyclic boronate proportion
(5d:6d, 59:41), and 4c affords the mixture of allylboronates
with the endocyclic boronate as the major regioisomer (6c).19
Finally, the methylene-bridged allenyne 4e gave 5e in lower
The reaction outcome indicates the occurrence of a
different mechanism. In this case, the mechanistic pathway
probably starts with the hydropalladation of the terminal
double bond of the allene resulting in a vinyl-Pd
intermediate.4f Then, insertion of the alkene into the C-Pd
bond would give B (Scheme 4). Finally, transmetalation of
B with the boron reagent and reductive elimination would
lead to alkylboronate 8. The formation of the regioisomer
9 could be explained by a ꢀ-hydrogen elimination in the
alkylpalladium intermediate B and subsequent hydropal-
ladation of the exocyclic alkene with the opposite regi-
oselectivity to give C. Transmetalation and reductive
elimination would afford compound 9. This proposal is
consistent with the isolation of cycloisomerization com-
(19) Probably, the steric hindrance exerted by the iPr and Cy substituents
hampers the transmetalation on the exocyclic allylpalladium intermediate,
being more favorable on the endocyclic species.
(20) We cannot rule out the presence of heterogeneous hydride-
containing catalytic species in this step, due to the absence of stabilizing
ligands and the formation of Pd-black during the reaction performance.
4550
Org. Lett., Vol. 11, No. 20, 2009

Table 2. Pd-Catalyzed Borylative Cyclization of Enallenes
Scheme 5
.
Oxidation and Allylboration Reactions of
Allylboronates
were subjected to oxidation and to reaction with aldehydes
in the presence of Lewis acids21 (Scheme 5).
Thereby, alcohols 11a,b were obtained in almost quantita-
tive yields. Allylation reaction of benzaldehyde with 2a in
the presence of different Lewis acids [Y(OTf)3 or BF3·Et2O]
provided lactone 12 in low yields (ca. 27%) as a result of
the intramolecular transesterification between the alcohol
resulting from the allylation and one of the ester groups.
Heterocyclic derivative 13 is also obtained when BF3·Et2O
is used. This compound could be the result of a Lewis acid
catalyzed hetero Diels-Alder reaction of the aldehyde with
a conjugated diene formed by decomposition of the boronate.
The optimization of this allylation reaction and other C-C
bond-forming reactions with these allylboronates and alky-
lboronates is currently under active investigation.
a ꢀ-Elimination products 10a and 10b (see Supporting Information) were
obtained in additional 20% yield each. b Yields calculated by NMR.
c Approximate yield since these compounds contain pinacol resulting from
decomposition. d The three regioisomers indicated were separated by column
chromatography (see Supporting Information for yields and details).
Scheme 4. Proposed Reaction Pathway for Enallenes
In summary, we have developed a formal hydroborylative
carbocyclization reaction of allenynes and enallenes in which
formation of one C-C and one C-B bond affords allylbo-
ronates and alkylboronates under smooth conditions. In
general, the process is regioselective. Oxidation of allylbo-
ronates and allylation of aldehydes can be performed on the
boronates to obtain functionalized derivatives. The develop-
ment of other applications of these boronates are currently
in progress.
Acknowledgment. We thank Ce´sar Pastor (SIdI-UAM)
for the X-ray studies. We gratefully acknowledge the
MICINN (project CTQ2007-60494/BQU) for financial sup-
port and for a FPU fellowship to J. M.-M. and the CAM for
a fellowship to V. P.-R.
pounds 10a,b. The case of 7c is special since the desired
product 8c is obtained along with regioisomeric alkylbo-
ronates located around the initial cyclohexene moiety, due
to the possibility of consecutive ꢀ-hydrogen eliminations
and reinsertions in this ring.
These results show the different reactivity between alkyne,
allene, and alkene moieties regarding the hydropalladation
process since alkynes are more reactive than allenes, and
the latter are more reactive than alkenes.
Supporting Information Available: Experimental details,
spectra for new compounds, and crystal structure determi-
nation of 2f and 6c. This material is available free of charge
via the Internet at http://pubs.acs.org.
OL9017694
With the aim of demonstrating the utility of these boronate
compounds in further functionalizations, allylboronates 2a,b
(21) Kennedy, J. W. J. Hall, D. Angew. Chem., Int. Ed. 2003, 42, 4732–
4739. See also ref 15.
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