Olefin-Directed Palladium-Catalyzed Regio- and Stereoselective Hydroboration of Allenes

Article abstract of DOI:10.1002/chem.201505130

An olefin-directed palladium-catalyzed regio- and stereoselective hydroboration of allenes has been developed to afford fully substituted alkenylboron compounds. The reaction showed a broad substrate scope: a number of functionalized allenes, including 2,3-dienoate, 3,4-dienoate, 3,4-dienol, 1,2-allenylphosphonate, and alkyl-substituted allenes, could be used in this olefin-directed allene hydroboration. The olefin unit was proven to be an indispensable element for this transformation.

Full text of DOI:10.1002/chem.201505130

DOI: 10.1002/chem.201505130
Communication
&
Allene Hydroboration
Olefin-Directed Palladium-Catalyzed Regio- and Stereoselective
Hydroboration of Allenes
Can Zhu+, Bin Yang+, Youai Qiu, and Jan-E. Bäckvall*[a]
Abstract: An olefin-directed palladium-catalyzed regio-
and stereoselective hydroboration of allenes has been de-
veloped to afford fully substituted alkenylboron com-
pounds. The reaction showed a broad substrate scope:
a number of functionalized allenes, including 2,3-dienoate,
3,4-dienoate, 3,4-dienol, 1,2-allenylphosphonate, and alkyl-
substituted allenes, could be used in this olefin-directed
allene hydroboration. The olefin unit was proven to be an
indispensable element for this transformation.
Organoboranes are a class of highly useful building blocks for
the construction of complex molecules in organic synthesis.[1,2]
They have attracted considerable attention and found wide ap-
plications in various carbon–carbon bond-forming reactions,
such as the Suzuki cross-coupling reaction,[3,4] and transition-
metal-catalyzed 1,2-/1,4-additions.[5] Selective monohydrobora-
tion of allenes,[6,7] in principle, could be an efficient approach
to afford organoboranes.[8] However, the challenge will be the
control of the regio- and stereoselectivity involved in the reac-
tion.[9] In recent years, copper-catalyzed selective hydrobora-
Scheme 1. Previous reports and this approach.
tion of allenes has emerged as an effective strategy for the
construction of useful organoboranes.[9,10] In 2011, Santos and
co-workers first reported the copper-catalyzed borylation of
2,3-dienoates (Scheme 1a). In this reaction, a preactivated di-
boron reagent is required to produce vinyl boronic esters in
moderate yields (33–78%).[10a] Moreover, Hoveyda et al. devel-
oped NHC–Cu-catalyzed hydroboration of monosubstituted al-
lenes with ligand-controlled site selectivity to afford vinyl boro-
nates A and B respectively (Scheme 1b).[10b] In addition, enan-
tioselective formation of type-A product from 1,1-disubstituted
allenes was described (Scheme 1b).[10c] In 2013, Ma and co-
workers reported a highly selective amide-controlled catalytic
borylation of allenes proceeding by means of borylcupration.
Amide was needed as the directing group to control the site
selectivity, thus alkenyl boronates could be obtained from 2,3-
dienamide.[10d] Herein, we wish to disclose our observation on
olefin-directed palladium-catalyzed regio- and stereoselective
hydroboration of allenes, in which the olefin unit was indispen-
sable in controlling the exclusive selectivity. To the best of our
knowledge, there is no report on the palladium-catalyzed
highly selective hydroboration of allenes.
We initially chose an easily accessible 3,4-dienoate as the
standard substrate.[11] When allyl-substituted 3,4-dienoate 1a
was treated with B2pin2 (1.3 equiv) and MeOH (1.0 equiv) in the
presence of Pd(OAc)2 (5 mol%) in toluene at 508C for 15 h, in-
spiringly, the hydroborylated product (Z)-2a was observed in
85% yield as a single regio- and stereoisomer (Scheme 2a). The
stereochemistry was determined by NOE measurements.[12] The
exclusive stereoselectivity for the (Z)-isomer in this hydrobory-
lative transformation implies a coordination of the olefin group
during the reaction.[13] Comparative experiments were carried
out using 3,4-dienoate 1ab with a propyl-substituent, or 1ac
with a smaller methyl substituent instead of the allyl group;
however, only complex reaction mixtures were obtained (Sche-
me 2b,c; for details see the Supporting Information). These ob-
servations indicate that the olefin unit is required as a directing
group in this regio- and stereoselective hydroboration of al-
lenes. Thus, coordination of the olefin unit to the palladium
center during the reaction would account for the exclusive ste-
reoselectivity of the (Z)-isomer.
[a] Dr. C. Zhu,+ B. Yang,+ Dr. Y. Qiu, Prof.Dr. J.-E. Bäckvall
Department of Organic Chemistry, Arrhenius Laboratory
Stockholm University, SE-10691, Stockholm (Sweden)
E-mail: jeb@organ.su.se
[+] Both authors contributed equally to this work.
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201505130.
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Table 1. Substrate scope the olefin-directed palladium-catalyzed regio-
and stereoselective hydroboration of allenes 1.[a]
Entry Enallene (1)
Product (2)
t [h] Yield of 2 [%][b,c]
1
15
19
17
85 (method A)
87 (method A)
81 (method A)
2
3
Scheme 2. Comparative experiments using different substituents on allenes
for the Pd-catalyzed allene-hydroboration. In reaction b, 1ab was recovered
in 6% yield as determined by 1H NMR using anisole as the internal standard.
39 (method A)[d]
90 (method B)
4
20
With these results in hand, we next examined the scope of
allenes 1 in the hydroborylative transformation. First, 2,3-dien-
oate 1b, as well as tosyl 3,4-dienol 1c reacted well and pro-
duced the corresponding vinyl boronates in good yields with
methanol as the proton source (method A, Table 1, entries 2
and 3). It is interesting to observe that the reaction of 1,2-alle-
nylphosphonate 1d using method A produced 2d in only 39%
yield, probably due to the high electron-deficiency of the
allene moiety (entry 4).[14] However, the use of 1.0 equivalents
of AcOH (method B), in place of MeOH as the proton source,[15]
improved the yield of 2d dramatically to 90%. Trisubstituted
allenes could also be employed with method A, affording
products 2e and 2 f in 74 and 77% yields, respectively (en-
tries 5 and 6). The reaction of fully-substituted allenes 1g and
1h failed with method A, but reacted well using 0.8 equiva-
lents of AcOH (method C) as the proton source to give product
2g and 2h in good yields (entries 7 and 8). It is worth noting
that cycloalkylidene allenes also exhibited good reactivity with
method C (entries 9 and 10). To our delight, phenyl or two
methyl substituents on the olefin moiety turned out to be
compatible with the hydroboration reaction (entries 11 and
12). Further studies showed that nBu and benzyl-substituted
allenes performed excellently in this hydroborylative transfor-
mation, thus producing the corresponding vinyl boronates 2m
and 2n in 87 and 91% yield, respectively (entries 13 and 14).
Hydroboration of 1,1-disubstituted allene 1o, in which the allyl
group is significantly larger than the other substituent (3,3-di-
methylallyl vs. propyl), afforded only product 2o in 78% yield,
strongly supporting the directing effect of the olefin group
(Table 1, entry 15). The stereochemistry of 2n and 2o was fur-
ther confirmed by NOE measurements (for details, see the Sup-
porting Information). Finally, the reaction of 1n with B2pin2
was carried out on a one-gram scale to afford 2n in 94% yield
(Scheme 3).
5
6
7
8
38
19
18
20
74 (method A)
77 (method A)
9 (method A)[e]
43 (method B)
60 (method C)
71 (method C)
70 (method C)
9
18
18
10
64 (method C)
11
12
17
24
58 (method C)
74 (method B)
To demonstrate the utility of this highly regio- and stereose-
lective hydorboration reaction, the transformations in
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pling of vinyl boronate 2n with iodobenzene afforded product
4 in 80% yield without loss of geometrical purity.[10g] Further-
more, hydroxylation of 2n could also be conducted to give
g,d-unsaturated methyl ketone 5 in 81% yield.[10g] Cross-meta-
thesis of 2n with methyl acrylate promoted by Grubbs II cata-
lyst produced 6 in 78% yield with complete E selectivity
(Scheme 4).[16]
Table 1. (Continued)
Entry Enallene (1)
Product (2)
t [h] Yield of 2 [%][b,c]
To gain a deeper insight into the allene hydroboration,
mechanistic studies on kinetic isotope effects (KIE) were done.
An intermolecular competition experiment was carried out
using a 1:1 mixture of methanol and [D4]methanol at 408C for
25 min [Eq. (1)]. The product ratio 2a/[D]-2a (ca. 15% conv.)
was measured as 3.7:1. On the basis of this ratio, the competi-
tive KIE was caculated to be kH/kD =4.1.[17] Furthermore, in par-
allel experiments (from initial rate) a KIE of kH/kD =2.3 was ob-
tained [Eqs. (2) and (3)].[17]
13
14
15
87 (method A)
91 (method A)
14
15
10
78 (method A)
[a] The reaction was conducted with Pd(OAc)2 (5 mol%), B2pin2
(1.3 equiv), allene 1 (1.0 equiv), and proton source (indicated in different
methods) in toluene at 508C. [b] Proton source used in method A: MeOH
(1.0 equiv); method B: AcOH (1.0 equiv); method C: AcOH (0.8 equiv).
[c] Isolated yield. [d] 1d was recovered in 52% yield as determined by
1H NMR using anisole as the internal standard. [e] 1g was recovered in
53% yield as determined by 1H NMR using anisole as the internal stan-
dard.
Scheme 3. Gram-scale synthesis of 2n from 1n.
Scheme 4 were carried out. Selective hydrogenation of the
carbon–carbon double bond on the allyl moiety gave reduced
fully-substituted vinyl boronate 2n’ in 86% yield. Suzuki cou-
Based on the mechanistic studies, the stereochemical out-
come, and the comparative experiments in Scheme 2, a possi-
ble mechanism for the allene hydroboration is proposed in
Scheme 5. Pd0 is most likely formed from reaction with B2pin2,
and protonation of the Pd0 intermediate by methanol or acetic
acid would produce a Pd-hydride (Scheme 5, step A).[15,18] Si-
multaneous coordination of the allyl C=C bond and the allenyl
C=C bond of substrate 1 to the PdII center would promote the
formation of Int-1 (step B).[19] Subsequent hydropalladation of
the allene in Int-1 would give vinylpalladium intermediate Int-
2 (step C). The coordination of olefin to PdII would account for
a cis orientation of PdII and the allyl group. Transmetalation of
Int-2 with B2pin2 would produce Int-3 (step D), which on sub-
sequent reductive elimination (step E) would lead to vinyl bor-
onate 2. Here, it is worth noting that this palladium-catalyzed
hydroboration proceeds via hydrometalation and subsequent
borylation, instead of borylmetalation/protonation, which is
usually observed in copper-catalyzed reactions.[20]
Since H-transfer takes place in two different steps in
Scheme 5, that is, proton transfer in step A and hydride trans-
fer in step C, the deuterium isotope effects from Equations
Scheme 4. Versatile transformations of the hydroborylated product 2n
(Grubbs 2nd=Grubbs second-generation Ru catalyst).
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(1–3) could arise from either of these steps or both. The data
from the parallel experiments [Eqs. (2) and (3)] cannot distin-
guish which of the steps A or C is rate-limiting. From the com-
petitive experiment [Eq. (1)] one can conclude that at least one
of the H-transfer steps (A or C) has to be irreversible.[21] If both
of these steps are irreversible the isotope effect kH/kD =4.1 will
arise from both steps A and C.[22]
In conclusion, we have developed an efficient olefin-directed
palladium-catalyzed regio- and stereoselective hydroboration
of allenes under mild conditions. The reaction proceeds via hy-
dropalladation and subsequent borylation. Furthermore, the
reaction showed a broad substrate scope for various function-
alized allenes, including 2,3-dienoate, 3,4-dienoate, 3,4-dienol,
1,2-allenylphosphonate, and alkyl-substituted allenes. Compa-
rative experiments showed that the olefin is an indispensable
directing group for the regio- and stereoselective formation of
vinyl boronates. Finally, due to the success of our approach in
the selective synthesis of fully substituted alkenylborons, this
method will be highly attractive for organic and medicinal
chemists. Further studies in this area, including synthetic appli-
cations are currently underway in our laboratory.
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Acknowledgements
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Financial support from the European Research Council (ERC
AdG 247014), the Swedish Research Council (621-2013-4653),
the Berzelii Center EXSELENT, and the Knut and Alice Wallen-
berg Foundation is gratefully acknowledged.
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Keywords: allenes · directing group · hydroboration · olefin ·
palladium
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[22] If both steps A and C are irreversible there would be a first selection at
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a second selection [(kH/kD)C] of PdÀH over PdÀD in the insertion. Thus,
in this case, the competitive isotope effect would be kH/kD =(kH/kD)A ”
(kH/kD)C.
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Received: December 22, 2015
Published online on January 28, 2016
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