Phosphine-catalyzed anti-carboboration of alkynoates with alkyl-, alkenyl-, and arylboranes

Article abstract of DOI:10.1021/ja506310v

We found that trialkylphosphine organocatalysts promoted unprecedented anti-carboboration of alkynoates with alkyl-, alkenyl-, or arylboranes to form β-boryl acrylates. The regioselectivity of the carboboration across the polar C-C triple bond exhibited inverse electronic demand, with the less electronegative B atom being delivered to the positively charged β carbon atom. The regioselectivity and the anti stereoselectivity were both complete and robust. In addition, the substrate scope was broad with excellent functional group compatibility.

Full text of DOI:10.1021/ja506310v

Communication
pubs.acs.org/JACS
Phosphine-Catalyzed Anti-Carboboration of Alkynoates with Alkyl‑,
Alkenyl‑, and Arylboranes
Kazunori Nagao, Hirohisa Ohmiya,* and Masaya Sawamura*
Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo 060-0810, Japan
S
* Supporting Information
borabicyclo[3.3.1]nonane) due to the convenience of their
preparation, alkenyl or aryl-9-BBN reagents also worked as
suitable substrates.
ABSTRACT: We found that trialkylphosphine organo-
catalysts promoted unprecedented anti-carboboration of
alkynoates with alkyl-, alkenyl-, or arylboranes to form β-
boryl acrylates. The regioselectivity of the carboboration
across the polar C−C triple bond exhibited inverse
electronic demand, with the less electronegative B atom
being delivered to the positively charged β carbon atom.
The regioselectivity and the anti stereoselectivity were
both complete and robust. In addition, the substrate scope
was broad with excellent functional group compatibility.
Specifically, a solution of alkylborane 2a (6 mmol) was first
prepared through hydroboration of styrene (1a) with a 9-
borabicyclo[3.3.1]nonane dimer [(9-BBN-H)2] (3 mmol) in
THF (24 mL) at 60 °C (1a/B 1.05:1). Subsequently, PBu3 (10
mol %) and ethyl 3-phenylpropionate (3a) (1.1 g, 6 mmol) were
added, and the mixture was heated at 80 °C over 8 h for complete
conversion of 3a (eq 1). Evaporation of volatiles followed by
purification by recrystallization gave trisubstituted alkenylborane
4aa in an isomerically pure form in 95% yield (based on 3a).
Single-crystal X-ray diffraction analysis of 4aa confirmed that the
alkyl group and the B atom were bound at the α and β positions
of the alkynoate, respectively, and that the carbonyl oxygen
coordinated to the boron atom (Figure 1). Thus, the C−B bond
addition across the C−C triple bond was completely anti-
stereoselective.
arboboration of internal alkynes with organoboron
C
compounds offers an efficient strategy for the synthesis
of trisubstituted alkenylboron derivatives, which can be utilized
as precursors to tetrasubstituted alkenes.1,2 Suginome and co-
workers reported the palladium- and nickel-catalyzed carbobora-
tions of internal alkynes with cyano-1a−d and alkynylboron1e
derivatives. These reactions introduced carbon and boron atoms
with syn stereochemistry. However, alkyne carboboration has not
yet been expanded to the use of more common organoboron
compounds such as alkyl-, alkenyl-, or arylboron compounds.3
This is mainly due to resistance of the C−B bond in these
compounds against oxidative addition to transition metals.4
In our study on metal-catalyzed transformations of organo-
boron compounds,5 we unexpectedly found that an alkylborane
(2a) reacted with an alkynoate (3a) in the presence of a catalytic
amount of tributylphosphine (PBu3) in a carboboration mode to
give a β-boryl acrylate derivative (4aa) with a B−O coordination
bond (eq 1).6−8 Interestingly, the carboboration exhibited an
Figure 1. Molecular structure of 4aa was confirmed by single-crystal X-
ray diffraction analysis.
Presuming the role of PBu3 as a nucleophilic catalyst,9 we
examined various potential nucleophiles as catalysts for the
reaction between 2a and 3a, and PBu3 was found to be the most
effective (Table 1). The use of sterically less demanding PMe3 or
PEt3 instead of PBu3 under otherwise identical conditions
resulted in significantly decreased substrate conversions and
product yields (entries 3 and 4). Bulkier trialkylphosphines such
as PCy3 and PtBu3 were ineffective (entries 5 and 6). The weaker
electron donors such as PPh3 or P(OPh)3 also resulted in no
reaction (entries 7 and 8). DPPE or DCYPE bisphosphines
showed slight catalytic activity (entries 9 and 10). These results
can be summarized as follows. The electron-donating natures of
inverse electronic demand with regard to regioselectivity: the less
electronegative B atom was introduced at the positively charged
β carbon of the α,β-unsaturated ester (alkynoate), with the more
electronegative C atom at the electron-neutral α carbon. To our
knowledge, this mode of carboboration has not been reported.
Another interesting feature of this reaction is the anti
stereochemistry of the C−B bond addition. Both regio- and
stereoselectivities are exclusive and robust irrespective of
substrate structures. Although this study was mostly focused
on the reaction of alkyl-9-BBN reagents (9-BBN: 9-
Received: June 24, 2014
Published: July 17, 2014
© 2014 American Chemical Society
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a
a
Table 1. Catalyst Effects in Carboboration of 3a with 2a
Table 2. Scope of Alkynoates
b
entry
catalyst
yield (%)
1
PBu3 (eq 1)
PBu3 (5 mol %)
PMe3
99 (95)
2
99 (95)
3
48
29
0
4
PEt3
5
PCy3
PtBu3
6
0
7
PPh3
0
8
P(OPh)3
DPPE
0
9
9
10
11
12
13
14
15
16
17
DCYPE
SIMe
7
0
SICy
0
IMes
0
DABCO
DBU
0
0
DMAP
NBu3
0
0
a
Conditions of hydroboration: 1a, 0.315 mmol; (9-BBN-H)2, 0.15
mmol (1/B 1.05:1); THF, 60 °C, 1 h. 2a (0.3 mmol) was used
without purification. Conditions of carboboration reaction: 3a, 0.3
b
mmol; 2a, 0.3 mmol; PBu3, 10 mol %; THF, 80 °C, 8 h. 1H NMR
yield. Yield of the isolated product is in parentheses.
the P-alkyl substituents favored the phosphine catalysis, while
bulkiness around the P center inhibited the reaction probably
due to a decrease in nucleophilicity of the phosphine molecules.
No reaction occurred with N-heterocyclic carbenes (NHCs) or
amines (DABCO, DBU, DMAP, and NBu3) with different steric
and electronic natures (entries 11−17). The PBu3 loading could
be reduced to 5 mol % without affecting the yield of 4aa (95%)
(entry 2).
The use of (2-phenylethyl)boronic acid and its pinacolate ester
instead of the alkyl-9-BBN reagents did not give the
carboboration product at all, leaving both substrates almost
unreacted. As alkynic substrates, the corresponding conjugated
amides, aldehydes, or ketones as well as nonpolar internal alkenes
showed no reactivity under similar conditions. The carbobora-
tion did not occur with C−C double bonds in conjugated enone
or enoate derivatives.
Various alkynoates with different substituents at the β-position
were subjected to the carboboration of 2a with the PBu3 catalyst
(Table 2). Methoxy and fluoro groups were tolerated at the para-
position of the aromatic β-substituent of the alkynoate (entries 1
and 2). The 2-thienyl-substituted alkynoate 3d underwent the
carboboration in high yield (entry 3). The reaction of the o-tolyl-
substituted alkynoate 3e proceeded at 100 °C (1,4-dioxane) with
a 20 mol % catalyst loading to give a sterically congested
alkenylborane (4ae) in moderate yield (entry 4).10 The reaction
of 1,3-enyne derivative 3f occurred regioselectively to afford a
conjugated 2,4-dienoate (4af) (entry 5).10 The carboboration
protocol was applicable to aliphatic alkynoates such as 2-
butynoate (3g) and 2-pentynoate (3h) although the yields were
lower than those from the reaction of the Ph-substituted
alkynoate (3a) (entries 6 and 7).10
a
Conditions of hydroboration: 1, 0.315 mmol; (9-BBN-H)2, 0.15
mmol (1/B 1.05:1); THF, 60 °C, 1 h. 2a (0.3 mmol) was used
without purification. Conditions of carboboration reaction: 3, 0.3
mmol; 2a, 0.3 mmol; PBu3, 10 mol % (entries 1−3, 5 and 6) or 20 mol
b
% (entries 4 and 7); THF, 80 °C, 8 h. Yield of the isolated product
(silica gel chromatography). Reaction was carried out in 1,4-dioxane
at 100 °C.
c
groups on aromatic rings as well as acetal, phthalimide, ester,
carbamate, and silyl ether moieties in aliphatic chains of
alkylboranes (entries 1−8).
The tolerance toward steric demand in the alkylboranes (2)
was also evaluated, and the results are shown in Table 3. The
sterically more demanding alkylborane 2g, which was derived
from a terminal alkene 1g bearing a tertiary alkyl substituent,
served as a substrate to afford the corresponding product in high
yield (entry 6). However, the use of secondary alkylborane 2j
prepared from cyclohexene resulted in low conversion and poor
yield (entry 9).
Ethyl-9-BBN (2k), which was derived from hydroboration of
ethylene (1k), was a suitable substrate (Table 3, entry 10). This
reaction delivered an ethyl group to the α carbon atom of the
alkynoate in high yield (87%). However, the carboboration with
Et3B (5a) resulted in a lower product yield (47%) (eq 2).
Various terminal alkenes were subjected to 9-BBN-hydro-
boration and were used for carboboration of 3a (Table 3). The
reaction tolerated functional groups such as chloro and methoxy
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a
a
Table 3. Scope of Alkylboranes
Table 4. Scope of Alkenyl- and Arylboranes
a
Conditions of carboboration reaction: 3a, 0.3 mmol; 2, 0.3 mmol;
PBu3, 10 mol % (entries 1−3 and 5) or 20 mol % (entry 4); THF, 80
b
°C, 8 h. Yield of the isolated product (silica gel chromatography). 1H
NMR yield is in parentheses. The isolated yield was significantly
reduced as compared with the H NMR yield because of the material
c
1
loss during silica gel chromatography.
Phosphine catalysis triggered by conjugate addition of the P
center of the phosphine to the alkynoate is known in the
literature.9 On the basis of this knowledge, we propose a catalytic
mechanism as shown in Figure 2, which involves the conjugate
a
Conditions of hydroboration: 1, 0.315 mmol; (9-BBN-H)2, 0.15
mmol (1/B 1.05:1); THF, 60 °C, 1 h. 2 (0.3 mmol) was used without
purification. Conditions of carboboration reaction: 3a, 0.3 mmol; 2,
b
0.3 mmol; PBu3, 10 mol %; THF, 80 °C, 8 h. Yield of the isolated
product (silica gel chromatography).
The phosphine-catalyzed carboboration was also possible with
alkenyl- and arylboranes, allowing the introduction of sp2
carbons to the α carbon atom of the alkynoate (Table 4). For
instance, the carboboration with β-borylstyrene 2l, which was
prepared in advance through hydroboration of phenylacetylene
(1l), occurred to afford the 1,3-dienylborane derivative 4la
(entry 1). Alkyl-substituted alkenylborane 2m was also a suitable
substrate (entry 2).
The reaction of phenyl-9-BBN (2n) with 3a proceeded
efficiently, giving the corresponding tetrasubstituted alkenylbor-
ane 4na (Table 4, entry 3). The reactions of aryl-9-BBN
derivatives with electron-donating (2o: p-MeO) or -withdrawing
(2p: p-F) substituents afforded the corresponding products
(entries 4 and 5).
Figure 2. A possible catalytic cycle.
addition of PBu3 to the alkynoate 3 with the assistance of Lewis
acidic activation of the carbonyl group with the organoborane 2
to form a zwitterionic allenolate intermediate (A). The B-
substituent (R1) in A migrates to the sp-hybridized central carbon
of the allene moiety to form a phosphonium ylide (B1).11 After
conversion of B1 to its geometrical isomer B2, the ylide carbon
forms a bond with the proximal boron atom to afford cyclic
borate C. Finally, elimination of Bu3P associated with B−O bond
cleavage affords the alkenylborane 4. The B−O interaction in C
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(4) For a proposed C−B oxidative addition to Ni(0) in the
hydroarylation of internal alkynes with arylboronates, see: Shirakawa,
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2688.
and the concerted nature of the final elimination step is
responsible for the anti stereochemistry of the carboboration.
The trisubstituted alkenylborane obtained by the phosphine-
catalyzed carboboration was used to demonstrate the synthetic
utility (eq 3). Although attempts at direct Suzuki−Miyaura
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coupling with 4aa were unsuccessful, the conversion of the ester
group into a secondary amide gave an organoboron derivative
suitable for Pd-catalyzed coupling with 4-iodotoluene to afford
tetrasubstituted alkene 7aa.12
In summary, phosphine-catalyzed anti-selective carboboration
of alkynoates with alkyl-, alkenyl-, or arylboranes to form β-boryl
acrylates was reported. Interestingly, the carboboration across
the polar C−C triple bond occurred with inverse electronic
demand with regard to the regioselectivity, with the less
electronegative B atom being delivered to the positively charged
β carbon atom. The regioselectivity and anti stereoselectivity
were both complete and robust. In addition, a broad substrate
scope with excellent functional group compatibility was
confirmed. Accordingly, this phosphine-catalyzed protocol
provides a new and efficient strategy for organic synthesis
mediated by organoboron compounds.
(7) For Cu-catalyzed carboborations of internal alkynes with
bis(pinacolato)diboron and carbon electrophiles, see: (a) Alfaro, R.;
́
Parra, A.; Aleman, J.; Ruano, J. L. G.; Tortosa, M. J. Am. Chem. Soc. 2012,
134, 15165. (b) Zhang, L.; Cheng, J.; Carry, B.; Hou, Z. J. Am. Chem. Soc.
2012, 134, 14314. (c) Yoshida, H.; Kageyuki, I.; Takaki, K. Org. Lett.
2013, 15, 952.
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Hiyama, T. Angew. Chem., Int. Ed. 2001, 40, 790. (b) Shimizu, M.;
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Am. Chem. Soc. 2005, 127, 12506. (c) Itami, K.; Kamei, T.; Yoshida, J. J.
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(9) For reviews on nucleophilic catalysis by phosphines, see:
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(b) Ye, L.-W.; Zhou, J.; Tang, Y. Chem. Soc. Rev. 2008, 37, 1140. (c) Lu,
X.; Zhang, C.; Xu, Z. Acc. Chem. Res. 2001, 34, 535. For a review on
Lewis base catalysis in organic synthesis, see: (d) Denmark, S. E.;
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(10) For Table 2, entries 4 and 5, unreacted alkynoate was detected in
the crude materials. For Table 2, entries 6 and 7, the conversion of 3g
and 3h was 100% with unidentified compounds observed in the crude
materials.
(11) For recent papers on 1,2-metalate rearrangement of borate
complexes, see: (a) Stymiest, J. L.; Bagutski, V.; French, R. M.; Aggarwal,
V. K. Nature 2008, 456, 778. (b) Bagutski, V.; French, R. M.; Aggarwal,
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ASSOCIATED CONTENT
* Supporting Information
Experimental details and characterization data for all new
compounds (PDF). This material is available free of charge via
the Internet at http://pubs.acs.org.
■
S
AUTHOR INFORMATION
■
Corresponding Authors
ohmiya@sci.hokudai.ac.jp
sawamura@sci.hokudai.ac.jp
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by Grants-in-Aid for Young Scientists
(A) and Challenging Exploratory Research, JSPS to H.O. and by
CREST, JST to M.S. K.N. thanks JSPS for scholarship support.
We thank Prof. Tomohiro Iwai (Hokkaido University) for the X-
ray crystal structure analysis.
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