Palladium-catalyzed trans- and cis-carboboration of alkynes tethered to chloroborane with organozirconium reagents: Ligand-dependent complementary stereoselectivity

Article abstract of DOI:10.1021/ja711160h

Cyclizative carboboration of carbon-carbon triple bonds has been achieved with a wide range of organozirconium reagents, including alkenyl, aryl, and alkylzirconium, with chloroboranes tethered to alkynes in the presence of palladium catalysts. The carboboration takes two distinctive stereochemical courses depending upon the phosphine ligands used: PMe₃ induces highly selective cis-carboboration, while bulkier phosphines such as P^tBu₃, PCy₃, and PAr₃ induce trans-carboboration selectively. Copyright

Full text of DOI:10.1021/ja711160h

Published on Web 02/16/2008
Palladium-Catalyzed trans- and cis-Carboboration of Alkynes Tethered to
Chloroborane with Organozirconium Reagents: Ligand-Dependent
Complementary Stereoselectivity
Masaki Daini, Akihiko Yamamoto, and Michinori Suginome*
Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto UniVersity
Katsura, Nishikyo-ku, Kyoto 615-8510, Japan
Received December 17, 2007; E-mail: suginome@sbchem.kyoto-u.ac.jp
Scheme 1. Ni-Catalyzed Carboboration with a Zr Reagent
There are increasing demands for organoboronic acid derivatives
in synthetic organic chemistry because they exhibit remarkable
reactivities upon appropriate activation, while being stable, storable,
and nonpoisonous.1 Their applications are spreading over the
pharmaceutical and material sciences in recognition of the unique
properties of organoboron compounds. Therefore, development of
efficient methods for the synthesis of stereodefined, functionalized
organoboronic acids is highly desirable.
Catalytic borylation reactions have gained much attention with
respect to efficiency, selectivity, and functional group compat-
ibility.2,3 Recent efforts have focused on the additions of boron-
element bonds across carbon-carbon multiple bonds,4 such as
diboration5 and silaboration.6 Our attention has been focused on
the development of catalytic carboboration reactions, in which B-C
and C-C bonds are formed concurrently. We have so far reported
two distinctive classes of carboborations, i.e., direct7 and trans-
metalative8 carboborations. While direct carboboration involves the
activation of B-C bonds of the boron reagents, transmetalative
carboboration uses haloborane as the source of the boryl group,
with organometallic reagents as the source of the organic group.
As the first example of the latter class of carboboration, we recently
established that a carbon-carbon triple bond tethered to chloro-
bound boron underwent nickel-catalyzed carboboration upon use
of alkynylstannanes as the transmetalation reagents.8 In contrast to
our mechanism-based assumption, the carboboration proceeded with
a trans-addition mode. In this paper, we report a new carboboration
system utilizing organozirconium reagents with palladium catalysts.
The Pd/Zr system not only allows significant expansion of the
substrate scope but also brings about highly stereoselective car-
boboration with either stereochemical course, which critically
depends on the phosphine ligands.
Table 1. Ligand-Dependent Stereoselectivities in the
Palladium-Catalyzed Reactions of 1a with 2aa
entry
ligand
% yield (NMR)
trans/cis (NMR)
1
2
3
4
5
6
PtBu3
86
91
80
77
58
75
96:4
PCy3
88:12
71:29
41:59
17:83
6:94
PPh3
PMePh2
PMe2Ph
PMe3
a
1a (0.2 mmol) and 2a (0.3 mmol) in toluene (0.25 mL) were heated
at 110 °C in the presence of PdCp(π-allyl) (0.010 mmol) with a phosphine
ligand (0.020 mmol).
between the stereoselectivities and the bulkiness of the phosphine
ligands was observed.
The ligand-dependent stereoselectivity can be rationalized well
by the reaction mechanism. As shown in Scheme 2, the catalysis
is triggered by the oxidative addition of a B-Cl bond to a Pd(0)
complex.10,11 Subsequent intramolecular insertion of the carbon-
carbon triple bond into the B-Pd bond of A leads to the formation
of â-borylalkenylpalladium intermediate cis-B. As proposed for the
Ni/Sn system, the trans-addition pathway may involve isomerization
of cis-B to trans-B before the transmetalation step. The isomer-
ization pathway can be rationalized by the large steric repulsion
between the L2PdCl and the isopropyl groups on the nitrogen atom,
which are inevitably coplanar with the boron-containing five-
membered ring due to the double bond character of the B-N bond.
On the other hand, with less bulky phosphine ligands such as PMe3,
transmetalation with the organozirconium reagent proceeds without
isomerization, giving the cis-carboboration products cis-3 directly
through cis-C. To support this assumption, palladium complex 5,
which corresponds to cis-B in Scheme 2, was isolated in high yield
in the stoichiometric reaction of 1e with PdCp(allyl) and PMe3
(Scheme 3). The observed cis stereochemistry of the CdC bond in
After screening various alkenyl organometallics as the trans-
metalation reagents, we found that reaction of alkenylzirconium
reagent 2a with chloroborane 1a, which was tethered to an aryl-
substituted alkyne, gave the carboboration product trans-3aa in good
yield in the presence of nickel catalysts (Scheme 1). The Ni/Zr
system still gave a trans-addition product with high selectivity, as
did the Ni/Sn system. However, no carboboration products were
obtained in the reaction of terminal or alkyl-substituted alkynes
1b or 1c, even with the Ni/Zr system.
We then reexamined the transition metal catalysts for use with
the organozirconium reagent. We found that palladium catalysts
exhibited high catalytic activity. On using bulky trialkylphosphines
such as PtBu3 or PCy3 with palladium complexes such as PdCp-
(allyl) or Pd(acac)2, the alkenylboration proceeded with high
stereoselectivities for the trans-addition product, as observed in the
Ni-catalyzed reaction (Table 1, entries 1 and 2).9 To our surprise,
however, the stereochemical course was completely switched to
favor cis-addition, when PMe3 was used as a ligand in the reaction
of 1a with 2a (entry 6). As shown in Table 1, a clear relationship
9
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J. AM. CHEM. SOC. 2008, 130, 2918-2919
10.1021/ja711160h CCC: $40.75 © 2008 American Chemical Society

C O M M U N I C A T I O N S
of PtBu3 or PCy3. Chloroborane 1d tethered to a tertiary alcohol
was similarly reactive to give the corresponding trans products
selectively (entry 4). It was remarkable that the chloroboranes
derived from propargylic alcohol (n ) 0) and bishomopropargylic
alcohols (n ) 2) underwent the trans-carboboration selectively
(entries 5 and 6). With respect to the organometallic reagents, not
only a wide range of alkenylzirconium reagents (entries 7 and 8)
but also arylzirconium (entry 9) and even alkylzirconium reagents
(entries 10 and 11) took part in the reaction giving alkenyl-, aryl-,
and alkylboration products in high yields. These groups could not
be introduced by the previous carboboration using organostannanes
as transmetalation reagents.
Scheme 2. Proposed Mechanism for the Pd-Catalyzed trans- and
cis-Carboboration
It should be remarked that the stereochemical complementarity
held generally. Highly stereoselective cis-carboboration proceeded
in the presence of PMe3 as a ligand, regardless of the R1, R2, and
R3 substituents of the reactants as well as the ring size formed
(entries 12-19). In general, trans-carboboration using bulky
phosphine ligands shows somewhat higher yields than the corre-
sponding cis-carboboration using the PMe3 ligand.
Scheme 3. Formation and X-ray Crystal Structure of 5
In summary, we report a new cyclizative carboboration system
using alkynes tethered to chloroborane moieties, organozirconium
reagents, and palladium catalysts. The Pd/Zr system shows a
remarkably broad substrate scope, leading to alkenyl-, aryl-, and
alkylborations of terminal and internal alkynes through four-, five-,
and six-membered ring formations. Furthermore, the stereochemical
course of the addition is successfully controlled by the phosphine
ligand: trans addition is preferred with the bulky phosphines such
as PtBu3, PCy3, and PAr3, while cis addition is favored with small
phosphines such as PMe3.
Table 2. Pd-Catalyzed trans- and cis-Carboborations with 1 and
Organozirconium Reagents 2a
Acknowledgment. This work was supported by a Grant-in-Aid
for Scientific Research on Priority Areas “Advanced Molecular
Transformations of Carbon Resources” from MEXT.
Supporting Information Available: Experimental procedures and
spectral data for the new compounds. This material is available free of
charge via Internet at http://pubs.acs.org.
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a
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PCy3
3
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P(2-furyl)3
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PCy3
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d
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f
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14
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PMe3
PMe3
PMe3
PMe3
PMe3
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cis-4ba (71)
cis-4ca (69)
cis-4da (60)
cis-4ea (63)
cis-4fa (44)
cis-4ad (54)
cis-4ae (61)
6:94
<1:99
<1:99
<1:99
4:96
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b
noted. Isolated yield.
5 is in sharp contrast to the trans stereochemistry for the
corresponding Ni complex in a previous report.8
The Pd/Zr-based new carboboration system showed a remarkably
wider substrate scope than the previous Ni/Sn or Ni/Zr system
(Table 2). While the Ni/Sn and the Ni/Zr systems could utilize
neither terminal nor alkyl-substituted alkynes, the Pd/Zr system
allowed those types of alkynes to give the corresponding alkenylbo-
ration product in high yields (entries 2 and 3). In both cases, high
selectivities for the trans addition were observed in the presence
(9) Use of Pd(acac)2 instead of PdCp(allyl) with PtBu3 resulted in the formation
of trans-3aa in 66% yield with the same stereoselectivity.
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