Pd-catalyzed borylative polycyclization of enediynes to allylboronates

Article abstract of DOI:10.1021/ol801424m

(Chemical Equation Presented) Pd-catalyzed dicyclization of 6-ene-1,11-diynes with bis(pinacolato)diboron affords synthetically useful allylboronates under smooth conditions. Two new C-C and one C-B bonds are stereospecifically formed in a single operation. The stereochemical outcome depends on the starting alkene configuration. The reaction is general and has been applied to differently substituted enediynes. Isolation of intermediate 1,3-dienes suggests a regioselective β-hydrogen elimination along the reaction pathway.

Full text of DOI:10.1021/ol801424m

ORGANIC
LETTERS
2008
Vol. 10, No. 16
3619-3621
Pd-Catalyzed Borylative Polycyclization
of Enediynes to Allylboronates
Juan Marco-Mart´ınez, Elena Bun˜uel, Rebeca Mun˜oz-Rodr´ıguez, and
Diego J. Cárdenas*
Departamento de Qu´ımica Orga´nica, UniVersidad Auto´noma de Madrid,
Cantoblanco, 28049 Madrid, Spain
diego.cardenas@uam.es
Received June 24, 2008
ABSTRACT
Pd-catalyzed dicyclization of 6-ene-1,11-diynes with bis(pinacolato)diboron affords synthetically useful allylboronates under smooth conditions.
Two new C-C and one C-B bonds are stereospecifically formed in a single operation. The stereochemical outcome depends on the starting
alkene configuration. The reaction is general and has been applied to differently substituted enediynes. Isolation of intermediate 1,3-dienes
suggests a regioselective ꢀ-hydrogen elimination along the reaction pathway.
Alkylboronates and alkyltrifluoroborates are becoming more
and more important intermediates for synthetic purposes,1,2
since they can be used as nucleophilic partners in the Suzuki
cross-coupling3 and other C-C bond-forming reactions. 1,2-
Diborylated alkanes prepared by diboration of CdC bonds
have been recently used for the enantioselective synthesis
of 1,2-diols.4 Alkyl- and allylboronates are usually prepared
by hydroboration of alkenes or reaction of main-group
organometallic derivatives with borate esters.5 C-H activa-
tion of alkanes is a promising alternative for the preparation
of primary alkylboronates.6 We have recently developed a
novel reaction for the formation of alkyl (homoallylic)
boronates from enynes by a formal 1,7-hydroboration with
concomitant carbocyclization (Scheme 1).7
The success of this reaction relies on the absence of
ꢀ-hydrogen elimination on the putative alkylpalladium
intermediate I. In our aim to exploit the synthetic utility of
this process, we explored the reaction of 6-ene-1,11-diynes.
(1) (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
.
(2) 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.-
(6) (a) Murphy, J. M.; Lawrence, J. D.; Kawamura, K.; Incarvito, C.;
Hartwig, J. F. J. Am. Chem. Soc. 2006, 128, 13684–13685. (b) Chen, H.;
Schlecht, S.; Semple, T. C.; Hartwig, J. F. Science 2000, 287, 1995–1997.
(c) Lawrence, J. D.; Takahashi, M.; Bae, C.; Hartwig, J. F. J. Am. Chem.
Soc. 2004, 126, 15334–15335. (d) Hartwig, J. F.; Cook, K. S.; Hapke, M.;
Incarvito, C.; Fan, Y.; Webster, C. E.; Hall, M. B. J. Am. Chem. Soc. 2005,
127, 2538–2552.
H.; Yan, Z.-J.; Deng, M.-Z. Org. Lett. 2004, 6, 357–360
.
(3) (a) Miyaura, N.; Suzuki, A. Chem. ReV. 1995, 95, 2457–2483. (b)
Suzuki, A. J. Organomet. Chem. 1999, 576, 147–168.
(4) Diboration of allenes: (a) Pelz, N. F.; Woodward, A. R.; Burks, H. E.;
Sieber, J. D.; Morken, J. P. J. Am. Chem. Soc. 2004, 126, 16328–16329.
Diboration of alkenes: (b) Morgan, J. B.; Miller, S. P.; Morken, J. P J. Am.
Chem. Soc. 2003, 125, 8702–8703.
(7) 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.
(8) 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. Metal-
catalyzed synthesis of allylboronates: (a) Ishiyama, T.; Ahiko, T.; Miyaura,
N Tetrahedron Lett. 1996, 37, 6889–6992. Enantioselective synthesis: (b)
Ito, H.; Ito, S.; Sasaki, Y.; Matsuura, K.; Sawamura, M J. Am. Chem. Soc.
2007, 129, 14856–14857. See references cited therein.
(5) Boronic Acids; Hall, D. G., Ed.; Wiley-VCH: Weinheim, 2005; pp
1-99.
10.1021/ol801424m CCC: $40.75
Published on Web 07/19/2008
2008 American Chemical Society

Scheme 1
.
Borylative Cyclization of 1,6-Enynes
Table 1. Pd-Catalyzed Borylative Cyclization of Enediynes
In this paper, we wish to report the formation of allylbor-
onates from enediynes by a Pd-catalyzed cascade reaction
with bis(pinacolato)diboron. Allylboronates8 are useful re-
agents involved in the stereoselective formation of C-C
bonds especially by reaction with carbonyl compounds and
derivatives.9
We considered the possibility of trapping the intermediate
alkylpalladium complexes by intramolecular reaction with
a second alkyne. This would give rise to alkenylpalladium
complexes and, eventually, to alkenylboronates. Instead,
when 6-ene-1,11-diyne 1a was subjected to reaction with
bis(pinacolato)diboron in the presence of Pd(OAc)2 and
MeOH in toluene, allylboronate 2a was formed (Scheme 2).10
Scheme 2. Pd-Catalyzed Borylative Cyclization of an Enediyne
This result is in sharp contrast with that of Ojima, who
obtained alkenyl silanes in the Rh-catalyzed cyclative hy-
drosilylation of the same kind of enediynes.10b
This cascade reaction provides two C-C and one C-B
bond in a single operation and stereoselectively. Internal
alkynes afford the corresponding boronates in higher yields
(Table 1, entries 2, 3, 6, and 7). Nonsymmetrical 1d and 1e
afford borylation of the terminal alkynes (entries 4 and 5),
in a fully regioselective process. Instead, compound 1g gives
a 1:1 mixture of the two possible regioisomers. We were
pleased to confirm the stereospecificity of the reaction by
using (E)-alkenes (entries 8-10) which provide different
stereoisomers of the final products. Yields are lower in this
case due to the presence of unseparable dienes or tricycles
a Mixture of the two possible regioisomers (60:40). Major isomer: R )
Ph, R′ ) Me (see the Supporting Information). b NMR yields in mixtures
with dienes or tricycles.
(see below).11,12 The relative stereochemistry was determined
for compound 2b by single-crystal X-ray diffraction (see the
Supporting Information).
(9) (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.
(11) Boronates tend to decompose in column chromatography when
longer retention times are used, which precludes isolation of pure compounds
(10) Silylcarbocyclization of enynes: (a) Lee, S.-Y.; Ojima, I J. Am.
Chem. Soc. 2000, 122, 2385–2386. (b) Ojima, I.; McCullagh, J. V.; Shay,
W. R. J. Organomet. Chem. 1996, 521, 421–423. (c) Bennacer, B.; Fujiwara,
M.; Lee, S.-Y.; Ojima, I. J. Am. Chem. Soc. 2005, 127, 17756–17767.
in some cases
(12) Related enediynes containg terminal alkynes with bis(sulfonyl)-
methane or NTs as tethers did not afford the desired compunds
.
.
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Org. Lett., Vol. 10, No. 16, 2008

With the aim of obtaining some evidence about the
mechanism, enediynes were subjected to the reaction condi-
tions in the absence of B2(pin)2. Diene 3a(Z) (R ) H) was
obtained stereoselectively from 1a (Scheme 3).13,14
terminal alkyne. After 1,2-insertion of the alkene into
alkenyl-Pd intermediate A (Scheme 4) a regioselective
ꢀ-hydrogen elimination would afford 1,3-diene C.
Scheme 4. Proposed Reaction Pathway
Scheme 3
.
Reaction in the Absence of B2(pin)2 Affords
1,3-Dienes
Compound 3a(Z) led to 2a when treated with B2(pin)2 and
Pd(OAc)2 under the above-mentioned conditions in ca. 25%
yield,15 which suggests the intermediacy of 1,3-dienes in the
reaction pathway. In contrast, the only product that could
be isolated from the reaction of 1i under the same conditions
was the corresponding (E)-alkene 3b(E) (R ) Me), which
is consistent with a regio- and stereoselective ꢀ-hydrogen
elimination.
Reaction of trans derivative 1h in the absence of B2(pin)2
led to tricycle 4a (R ) H) in 30% yield (no 1,3-diene was
detected). Tricyclic compounds seem to be formed from
compounds 3 by Diels-Alder intramolecular cycloaddition,16
rather than coming from Pd-catalyzed reactions, since heating
of 3a(Z) led to aromatized 4a through the likely intermediacy
of 5a (R ) H). Diphenyl derivative 5b (R ) Ph) was isolated
from 1j from the reaction in the absence of B2(pin)2. This
compound also aromatizes upon heating a solution in the
presence of oxygen, although more slowly.17 Higher cy-
cloaddition ability of 3(E) compared with 3(Z) due to the
configuration of the disubstituted alkene explains why the
former are not detected in some cases.
Although related intermediates involved in the Oppolzer
reaction usually evolve through elimination of the exocyclic
H atoms,18 the stereospecificity of the overall process
suggests the opposite regioselectivity in this case.19 Insertion
of the other alkyne into the Pd-H bond in C to give D
stereoselectively, followed by carbometalation of the diene
would give rise to allyl-Pd intermediate E. This 1,2-insertion
explains the relative stereochemistry observed in the final
products. Methoxide-promoted transmetalation of E with the
boron reagent and reductive elimination would lead to the
observed final products.
In summary, we have developed a cascade reaction in
which formation of two C-C and one C-B bonds affords
allylboronates in smooth conditions. The stereochemical
information contained in the starting double bond travels
along the multistep reaction pathway giving rise to the
stereospecific formation of two asymmetric centers.
Acknowledgment. We thank Ce´sar Pastor (SIdI-UAM)
for the X-ray studies We gratefully acknowledge the MEC
(projects CTQ2004-02040/BQU and CTQ2007-60494/BQU)
for financial support and for a FPU fellowship to J.M.-M.
The reaction probably takes place by formation of a Pd
hydride complex which promotes hydropalladation of the
Supporting Information Available: Experimental details,
spectra for new compounds, and crystal structure determi-
nation of 2b.This material is available free of charge via the
Internet at http://pubs.acs.org.
(13) The same double-bond configuration was observed in dienes
obtained from 1b and 1c (NOESY), although low yields (<15%) were
observed in these cases. Partial decomposition of these compounds precludes
isolating them in higher yields
(14) Related carbocycles by Rh-catalyzed reactions: Shibata, T.; Kuroka-
wa, H.; Kanda, K J. Org. Chem. 2007, 72, 6521–6525
.
.
OL801424M
(15) Approximate yield since starting diene 3a(Z) was not pure. These
compounds tend to decompose and are difficult to purify.
(16) Cycloisomerization of enynes and enediynes: (a) Trost, B. M.; Shi,
Y. J. Am. Chem. Soc. 1993, 115, 12491–12509. (b) Trost, B. M.; Tanoury,
G. J.; Lautens, M.; Chan, C.; MacPherson, D. T. J. Am. Chem. Soc. 1994,
116, 4255–4267.
(18) Reviews: (a) Oppolzer, W. In ComprehensiVe Organometallic
Chemistry II; Abel, E. W., Stone, F. G. A., Wilkinson, G., Eds.; Pergamon:
Oxford, 1995; Vol. 12, Chapter 8.3. (b) Oppolzer, W. Angew. Chem., Int.
Ed. Engl. 1989, 28, 38–52.
(17) Probably, the steric hindrance between the phenyl rings precludes
oxidation of the benzylic position in 4j.
(19) A ꢀ-hydrogen elimination involving the exocyclic chain would
destroy the stereochemical information contained in the starting alkene.
Org. Lett., Vol. 10, No. 16, 2008
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