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Cage-Walking: Vertex Differentiation by Palladium-Catalyzed Isomerization of B(9)-Bromo-meta-Carborane

01 Jun 2017-Journal of the American Chemical Society (American Chemical Society)-Vol. 139, Iss: 23, pp 7729-7732

TL;DR: This "cage-walking" process provides a unique pathway to preferentially introduce functional groups at the B(2) vertex using B(9)-bromo-meta-carborane as the sole starting material through substrate control.
Abstract: We report the first observed Pd-catalyzed isomerization (“cage-walking”) of B(9)-bromo-meta-carborane during Pd-catalyzed cross-coupling, which enables the formation of B–O and B–N bonds at all boron vertices (B(2), B(4), B(5), and B(9)) of meta-carborane. Experimental and theoretical studies suggest this isomerization mechanism is strongly influenced by the steric crowding at the Pd catalyst by either a biaryl phosphine ligand and/or substrate. Ultimately, this “cage-walking” process provides a unique pathway to preferentially introduce functional groups at the B(2) vertex using B(9)-bromo-meta-carborane as the sole starting material through substrate control.
Topics: Isomerization (53%), Carborane (52%)

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Summary

  • The authors report the first observed Pd-catalyzed isomerization (“cage-walking”) of B(9)-bromo-meta-carborane during Pd-catalyzed cross-coupling, which enables the formation of B−O and B−N bonds at all boron vertices (B(2), B(4), B(5), and B(9)) of meta-carborane.
  • Experimental and theoretical studies suggest this isomerization mechanism is strongly influenced by the steric crowding at the Pd catalyst by either a biaryl phosphine ligand and/or substrate.
  • I somerization mechanisms such as chain-walking via βhydride elimination/reinsertion and aryne-based rearrangements are ubiquitous in metal-catalyzed transformations of organic molecules.
  • Through judicious choice of catalyst design, these mechanistic pathways can be biased to form specific regioisomers.
  • Boron clusters are unique molecular scaffolds that feature three-dimensional (3D) electronic delocalization.
  • Specifically, in the case of icosahedral carboranes (C2B10H12) this delocalization is nonuniform.
  • Because of their inherent robustness, carboranes can be promising molecular building blocks for applications ranging from pharmacophores to photoactive materials.
  • Even so, these approaches provide limited access to rational, vertex-specific B−H functionalization.
  • Herein the authors disclose their discovery of a Pd-catalyzed activation of B(9)-bromo-meta-carborane (Br−B(9)), which can undergo subsequent “cage-walking”, leading to the formation of B(2)-, B(4)-, B(5)-, and B(9)-functionalized clusters in the presence of a suitable nucleophile .
  • Recently the authors reported the Pd-catalyzed cross-coupling of Br− B(9) to generate B(9)−O and B(9)−N bonds with a wide range of substrates.
  • To their surprise, during the course of subsequent investigations, when the DavePhos (L1) or SPhos (L2) ligand was replaced with the bulkier XPhos Received: April 25, 2017 Published: May 25, 2017 Figure 1.
  • (A) Pd-catalyzed olefin isomerization through β-hydride elimination and arene regioisomer formation through a proposed benzyne intermediate.

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Lawrence Berkeley National Laboratory
Recent Work
Title
Cage-Walking: Vertex Differentiation by Palladium-Catalyzed Isomerization of B(9)-Bromo-
meta-Carborane.
Permalink
https://escholarship.org/uc/item/0x57v855
Journal
Journal of the American Chemical Society, 139(23)
ISSN
0002-7863
Authors
Dziedzic, Rafal M
Martin, Joshua L
Axtell, Jonathan C
et al.
Publication Date
2017-06-01
DOI
10.1021/jacs.7b04080
Peer reviewed
eScholarship.org Powered by the California Digital Library
University of California

Cage-Walking: Vertex Dierentiation by Palladium-Catalyzed
Isomerization of B(9)-Bromo-meta-Carborane
Rafal M. Dziedzic,
Joshua L. Martin,
Jonathan C. Axtell,
Liban M. A. Saleh,
Ta-Chung Ong,
Yun-Fang Yang,
Marco S. Messina,
Arnold L. Rheingold,
K. N. Houk,
and Alexander M. Spokoyny*
,,§
Department of Chemistry and Biochemistry, University of California, Los Angeles, 607 Charles E. Young Drive East, Los Angeles,
California 90095, United States
Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093,
United States
§
California NanoSystems Institute (CNSI), University of California, Los Angeles, 570 Westwood Plaza, Los Angeles, California
90095, United States
*
S
Supporting Information
ABSTRACT: We report the rst observed Pd-catalyzed
isomerization (cage-walking) of B(9)-bromo-meta-car-
borane during Pd-catalyzed cross-coupling, which enables
the formation of BO and BN bonds at all boron
vertices (B(2), B(4), B(5), and B(9)) of meta-carborane.
Experimental and theoretical studies suggest this isomer-
ization mechanism is strongly inuenced by the steric
crowding at the Pd catalyst by either a biaryl phosphine
ligand and/or substrate. Ultimately, this cage-walking
proces s provides a unique pathway to preferentially
introduce functional groups at the B(2) vertex using
B(9)-bromo-meta-carborane as the sole starting material
through substrate control.
I
somerization mechanisms such as chain-walking via β-
hydride elimination/reinsertion and aryne-based rearrange-
ments (Figure 1A) are ubiquitous in metal-catalyzed trans-
formations of organic molecules.
1,2
Through judicious choice of
catalyst design, these mechanistic pathways can be biased to
form specic regioisomers. Thus, metal-catalyzed isomerization
control can provide a means of incorporating functional groups
in molecules at positions remote from where initial bond
activation occurs.
13
Boron clusters are unique molecular scaolds that feature
three-dimensional (3D) electronic delocalization.
4
Specically,
in the case of icosahedral carboranes (C
2
B
10
H
12
)this
delocalization is nonuniform.
5
This charge distribution makes
carboranes an interesting alternative to classical carbon-based
structural building blocks such as aryl and alkyl groups.
6
Because of their inherent robustness, carboranes can be
promising molecular building blocks for applications ranging
from pharmacophores to photoactive materials.
7
Ultimately,
vertex-specic functionalization routes (vertex dierentiation)
are critical for constructing carborane-containing molecules and
materials.
7,8
Recent developments in carborane functionalization have
relied on several metal-catalyzed routes, including B H
activation (either directed or undirected) and cross-coupling
of halogenated carborane electrophiles at both C and B
vertices.
8,9
Even so, these approaches provide limited access to
rational, vertex-specicBH functionalization. Surprisingly,
metal-catalyzed isomerization reactivity commonly observed
with classical organic substrates (vide supra) has never been
reported for any boron cluster systems, including carboranes.
Herein we disclose our discovery of a Pd-catalyzed activation of
B(9)-bromo-meta-carborane (BrB(9)), which can undergo
subsequent cage-walking, leading to the formation of B(2)-,
B(4)-, B(5)-, and B(9)-functionalized clusters in the presence
of a suitable nucleophile (Figure 1B).
Recently we reported the Pd-catalyzed cross-coupling of Br
B(9) to generate B(9) O and B(9)N bonds with a wide
range of substrates.
9
This cross-coupling relied on biaryl
phosphine ligands to generate monoligated palladium(0)
species ([LPd]) capable of undergoing oxidative addition
into the BBr bond of BrB(9). To our surprise, during the
course of subsequent investigations, when the DavePhos (L1)
or SPhos (L2) ligand was replaced with the bulkier XPhos
Received: April 25, 2017
Published: May 25, 2017
Figure 1. (A) Pd-catalyzed olen isomerization through β-hydride
elimination and arene regioisomer formation through a proposed
ben zyne intermediate. (B) Pd-catalyzed isomerization of meta-
carboranyl through cage-walking.
Communication
pubs.acs.org/JACS
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J. Am. Chem. Soc. 2017, 139, 7729 7732
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congener (L3) in the presence of alcohol or amine substrates,
we consistently observed not one but rather three distinct peaks
with identical m/z by gas chromatographymass spectrometry
(GCMS). For example, using 3,5-dimethylphenol (R1)asa
cross-coupling partner with BrB(9), we observed several
products with identical m/z (see the Supporting Information
(SI)). Upon chromatographic separation of the reaction
mixture on silica gel, we identied four distinct R1-carborane
compounds by
11
B,
1
H, and
13
C NMR spectroscopy (Figure 2).
The isolated carborane-containing molecules show a distinct
downeld singlet in the
11
B NMR spectrum corresponding to
R1 bound at a B(2), B(4), B(5), or B(9) vertex of meta-
carborane (R1B(2), R1B(4), R1B(5), and R1B(9),
respectively). Although we were unable to chromatographically
separate R1B(5) and R1B(4), we identied the isomer ratio
as 15:85 by
11
B and
1
H NMR spectroscopy: R1B(4) is C
1
-
symmetric, resulting in 10
11
B NMR resonances (one singlet
and nine doublets), whereas R1B(5) contains a mirror plane,
resulting in six
11
B NMR resonances (one singlet and ve
doublets). Thus, the more intense singlet at 3 ppm ( Figure
2B) is assigned to the dominant pattern of R1B(4). Similarly,
two sets of
1
H and
13
C NMR resonances corresponding to R1
B(5) and R1B(4) were observed in a 15:85 signal ratio for
the CH aromatic and aliphatic regions, respectively (see the SI).
These structural assignments are further supported by single-
crystal X-ray diraction studies of the four regioisomers (Figure
2C). Interestingly, R1B(4) is the only monofunctionalized
meta-carborane regioisomer that exhibits chirality. R1B(4)
crystallized as two distinct polymorphs, with both polymorphs
containing equal amounts of the two enantiomers in the unit
cell. Chiral HPLC analysis further supports the presence of two
R1B(4) enantiomers in the isolated mixture (Figure S12).
To further assess the generality of this isomerization process,
we examined three biaryl phosphine ligands and several
substrates to ge nerate BO- and B N-bound carborane
regioisomers (Figure 3). Consistent with our previous report,
[L1Pd] and [L2Pd] generate B(9) isomers almost exclusively
with O- and N-based nucleophiles.
9
However, [L3Pd]
generates appreciable amounts of regioisomers under the
same conditions. Noteworthy was the presence of bromo-
meta-carborane regioisomers when the cross-coupling reactions
were stopped early, indicating that isomerization of BrB(9)
occurs in addition to the cross-coupling reaction. Furthermore,
BrB(9) forms bromo-meta-carborane isomers in the presence
of [L3Pd] precatalyst and triethylamine, implying that
isomerization can occur prior to transmetalation of a cross-
coupling partner and subsequent reductive elimination of the
B-functionalized meta-carborane. Hence, this metal-catalyzed
isomerization may provide a convenient pathway to B(2)-,
B(4)-, and B(5)-functionalized meta-carborane species that
circumvents laborious and often low-yielding protocols such as
deboronation/capitation o r thermal isomerization strat-
egies.
10,11
Since bromo-meta-carboranyl isomerization can occur before
all of the carborane regioisomers are depleted by cross-coupling
(vide supra), we hypothesized that the isomerization process
might operate separately from the main cross-coupling cycle.
To further explore the isomerization mechanics, we attempted
Figure 2. (A) Reaction conditions that result in the formation of R1-meta-carborane regioisomers. (B)
11
B NMR spectra of the isolated regioisomers.
Singlet resonances (no
11
B
1
H coupling) corresponding to the B O-bonded vertex are labeled; all other resonances correspond to doublet
resonances arising from
11
B
1
H couplings. (C) Single-crystal X-ray structures of R1-B(n), n = 2, 4, 5, 9 (ellipsoids drawn at 50% probability and H
atoms omitted for clarity).
Figure 3. Reaction conditions for forming B-functionalized meta-
carborane isomers using dierent substrates (R1R3) and biaryl
phosphine ligands (L1L3). Yields were obtained by GCMS. See
the SI for full experimental conditions.
Journal of the American Chemical Society Communication
DOI: 10.1021/jacs.7b04080
J. Am. Chem. Soc. 2017, 139, 7729 7732
7730

to inhibit transmetalation by increasing the steric bulk of the
cross-coupling partner, thereby allowing the active catalyst
species to operate in the isomerization pathway for a longer
time (Figure 4, step II). Indeed, cross-coupling reactions using
bulky L3 and sterically congested 2,6-dimethylphenol (R3)
yielded R3B(2) as the major product (Figure 3). As a control
experiment, equimolar amounts of 3,5-dimethylphenol (R1)
and 2,4,6-trimethylphenol (R3, a variant of R3 to permit
separation of the products by GCMS) were reacted with Br
B(9) in the presence of [L3Pd] and K
3
PO
4
in 1,4-dioxane at 80
°C(Figures S5 and S6). GCMS analysis of the reaction
mixture showed complete consumption of BrB(9) with R1-
meta-carborane isomers as the major products, suggesting that
the size of the nucleophile is linked to the rate of product
formation. Since oxidative addition is likely rapid in this
process,
12
it appears that by decreasing the rate of trans-
metalation and/or reductive elimination one can increase the
yield of the B(2) regioisomer (Figure 4B). This type of Pd-
catalyzed remote vertex functionalization is unprecedented and
demonstrates the utility of a metal-catalyzed route to meta-
carborane vertex dierentiation. Importantly, it contrasts with
known thermal rearrangements that are limited to thermally
resistant functional groups (above 300 °C) and produce isomer
mixtures with B(2) substituted meta -carboranes as the minor
product.
11
We attribute this dierence in reactivity between cage-
walking (when using L3) and cross-coupling exclusively at the
B(9) vertex (when using L1/L2) to steric crowding at the Pd
center. The combination of a sterically demanding ligand and
nucleophile appears to inhibit transmetalation,
13
allowing the
catalyst to operate through several cage-walking steps before
re-entering the traditional cross-coupling cycle (vide supra). On
the basis of these observations, we propose a Pd-catalyzed
cage-walking mechanism for isomerization of BrB(9)
(Figure 4B). Beginning with the oxidative addition complex
[LPdBrB(9)], an open Pd(II) coordination site is generated
by bromide dissociation
2d
(Figure 4, step II-a) to form [LPd
B(9)]
+
. Consistent with this hypothesis, cross-coupling experi-
ments between Br B(9) and R3 inthepresenceof
tetrabutylammonium bromide sh ow decreased BrB(9)
consumption and decreased formation of R3-meta-carborane
(Figure S7). These experiments suggest that bromide
dissociation is an important step in the overall cross-coupling
process.
14
After bromide dissociation, two possible cage-
walking pathways were envisioned for the formally cationic
[LPdB(9)]
+
: (1) deprotonation of an adjacent BH vertex to
form a B(4),B(9)-bound carborane species that isomerizes
upon reprotonation to form [LPdB(4)]
+
(Figure S9) and (2)
a Pd-mediated BH activation that leads to an intramolecular
β-hydride shift (Figure S10). Deuterium labeling experiments
in which 2,6-Me
2
C
6
H
4
OD was used as the nucleophile did not
result in deuterium incorporation at any BH vertex, as judged
by GCMS and
2
H and
11
B NMR spectroscopy, likely ruling
out isomerization pathway 1. However, with the deuterated
congener of BrB(9), 9-Br-10-D-meta-C
2
B
10
H
10
, and 2,6-
Me
2
C
6
H
4
OH as the nucleophile, we observed ve B
2
H
resonances in the
2
H{
11
B} NMR spectrum of R3B(2),
indicating deuterium scrambling across the carborane BH
framework (Figure 4A). We postulate that this β-hydride shift
exchanges the B(10) deuterium with an adjacent B(5) proton
and enables cage-walking to form [LPdB(4)]
+
(Figure 4 B,
step II-b). The cage-walking process can occur again to
generate [LPdB(2)]
+
(Figure 4B, step II-c). Similar reports of
metal-catalyzed carborane BH activation processes have been
reported;
8,15,16
however, they are limited to BH vertices
adjacent to carborane-bound directing groups, whereas the
presently reported cage-walking accesses all of the meta-
carborane BH vertices from one starting point in a diversity-
oriented fashion.
Through the cage-walking process, the carboranyl fragment
eventually binds the Pd center through the most electron-
decient boron vertex, B(2), resulting in a more electrophilic
Pd center that can overcome the steric repulsion between the
cationic [LPdB(2)]
+
and the anionic cross-coupling partner.
Density functional theory (DFT) calculations (B3LYP/
LANL2DZ 6-31G* and M06/SDD/6-311++G**, SMD(1,4-
dioxane)) on [LPdB(9)]
+
,[LPdB(4)]
+
, and [LPdB(2)]
+
indicate that [LPdB(2)]
+
has the most cationic Pd center,
which likely results in a lower transmetalation barrier due to a
stronger electrostatic attraction between the Pd center and the
Figure 4. (A) Deuterium labeling experiments. The resonance at 2.7 ppm is present from polydeuterated BrB(9). See the SI for full experimental
details. (B) Proposed metal-catalyzed isomerization of bromo-meta-carborane through a cage-walking mechanism: (I) oxidative addition; (II-a)
bromide dissociation; (II-b, II-c) cage-walking; (II-d) bromide association; (III) transmetalation; (IV) reductive elimination.
Journal of the American Chemical Society Communication
DOI: 10.1021/jacs.7b04080
J. Am. Chem. Soc. 2017, 139, 7729 7732
7731

phenoxide nucleophile (Figures S13S16). Furthermore, the
ΔG of BO and BN bond formation decreases accordingly,
B(9) > B(5) B(4) > B(2), for the cross-coupling between
BrB(9) and R1R3. Similar electronic eects of substrate
and ligand were observed in Pd-catalyzed aryl halide cross-
coupling.
17
In summary, we have discovered the rst example of metal-
catalyzed isomerization (cage-walking)ofmeta-carboranyl
fragment. The isomerization process appears to operate in
conjunction with a classical cross-coupling mechanism, leading
to a distribution of carborane regioisomers. The rate of cross-
coupling relative to cage-walking can be adjusted to achieve
selective B-vertex functionalization. We have demonstrated this
selectivity by controlling the steric crowding at the Pd center by
appropriate choice of catalyst ligand and cross-coupling
substrate. Preliminary studies have shown that this cage-
walking strategy can be applied to carborane B(2)C
aryl
bond
formation using an arylboronic acid (Figure S17). Overall, this
approach provides a unique pathway to vertex dierentiation of
boron clusters.
ASSOCIATED CONTENT
*
S
Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/jacs.7b04080.
Full procedures and additional data (PDF)
Crystallographic data (CIF)
AUTHOR INFORMATION
Corresponding Author
*spokoyny@chem.ucla.edu
ORCID
Yun-Fang Yang: 0000-0002-6287-1640
K. N. Houk: 0000-0002-8387-5261
Alexander M. Spokoyny: 0000-0002-5683-6240
Notes
The authors declare no competing nancial interest.
ACKNOWLEDGMENTS
We thank the donors of the American Chemical Society
Petroleum Research Fund (56562-DNI3 to A.M.S.), UCLA
(startup funds to A.M.S.), NSF (CHE-1048804 and
CHE1361104), 3M (Non-Tenured Faculty Award to A.M.S.),
and the National Defense Science and Engineering Graduate
Fellowship Program (to R.M.D.) for support.
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Citations
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Journal ArticleDOI
Xiaolei Zhang1, Hongning Zheng1, Jie Li1, Fei Xu1  +2 moreInstitutions (2)
TL;DR: The direct arylation of o-carboranyl aldehydes has been developed via Pd-catalyzed cage B-H bond functionalization via glycine to generate a directing group (DG) in situ and obtained good to excellent yields with high selectivity.
Abstract: Carboranyl aldehydes are among the most useful synthons in derivatization of carboranes. However, compared to the utilization of carboranyl carboxylic acids in selective B–H bond functionalizations, the synthetic application of carboranyl aldehydes is limited due to the weakly coordinating nature of the aldehyde group. Herein, the direct arylation of o-carboranyl aldehydes has been developed via Pd-catalyzed cage B–H bond functionalization. With the help of glycine to generate a directing group (DG) in situ, a series of cage B(4,5)-diarylated- and B(4)-monoarylated-o-carboranyl aldehydes were obtained in good to excellent yields with high selectivity. A wide range of functional groups are tolerated. The aldehyde group in the B–H arylated products could be readily removed or transformed into o-carboranyl methanol. A plausible catalytic cycle for B–H arylation was proposed based on control experiments and stoichiometric reactions, including the isolation of a key bicyclic palladium complex.

100 citations


Journal ArticleDOI
Yangjian Quan1, Zuowei Xie1Institutions (1)
TL;DR: A review of recent advances in transition metal catalyzed vertex-specific BH functionalization of carbon-boron molecular clusters concludes that selection of a cage C-H bonds for functionalization is very challenging.
Abstract: Carboranes, a class of carbon-boron molecular clusters, are often viewed as three-dimensional analogues of benzene. They are finding increasing applications as useful functional building blocks in materials science, medicine, organometallic/coordination chemistry and more. Thus, functionalization of carboranes has received considerable attention. In comparison with the weakly acidic cage C-H bonds that can be readily functionalized, selective cage B-H functionalization among ten chemically similar BH vertices in o-carboranes is very challenging. Only in the recent few years, considerable progress has been made in transition metal catalyzed vertex-specific BH functionalization. This review summarizes recent advances in this research area.

83 citations


01 Apr 2015
TL;DR: Advances enabled the arylation of a wide array of sterically encumbered amines, highlighting the importance of rational ligand design in facilitating challenging Pd-catalyzed cross-coupling reactions.
Abstract: In Pd-catalyzed CN cross-coupling reactions, α-branched secondary amines are difficult coupling partners and the desired products are often produced in low yields. In order to provide a robust method for accessing N-aryl α-branched tertiary amines, new catalysts have been designed to suppress undesired side reactions often encountered when these amine nucleophiles are used. These advances enabled the arylation of a wide array of sterically encumbered amines, highlighting the importance of rational ligand design in facilitating challenging Pd-catalyzed cross-coupling reactions.

57 citations


Journal ArticleDOI
Furong Lin1, Jing-Lu Yu1, Yunjun Shen1, Shuo-Qing Zhang1  +4 moreInstitutions (2)
TL;DR: A series of cage penta-arylated carboranes have been synthesized by palladium-catalyzed intermolecular coupling of the C-carboxylic acid of the monocarba- closo-dodecaborate anion with iodoarenes by direct cage B-H bond functionalization, setting a record in terms of one-pot directing group-mediated activation of inert bonds in a single molecule.
Abstract: A series of cage penta-arylated carboranes have been synthesized by palladium-catalyzed intermolecular coupling of the C-carboxylic acid of the monocarba-closo-dodecaborate anion [CB11H12]− with iodoarenes by direct cage B–H bond functionalization. These transformations set a record in terms of one-pot directing group-mediated activation of inert bonds in a single molecule. The methodology is characterized by high yields, good functional group tolerance, and complete cage regioselectivity. The directing group COOH can be easily removed during or after the intermolecular coupling reaction. The mechanistic pathways were probed using density functional theory calculations. A Pd(II)–Pd(IV)–Pd(II) catalytic cycle is proposed, in which initial coupling is followed by preferred B–H activation of the adjacent boron vertex, and continuation of this selectivity results in a continuous walking process of the palladium center. The methodology opens a new avenue toward building blocks with 5-fold symmetry.

48 citations


Journal ArticleDOI
Ruofei Cheng1, Bowen Li1, Jie Wu1, Jie Zhang2  +6 moreInstitutions (2)
TL;DR: This work reports an efficient method to achieve chiral-at-cage arylation of o-carboranes with high regio- and enantioselectivities by a strategy of palladium-catalyzed asymmetric intramolecular B-H arieslation and cyclization.
Abstract: Carborane cage chirality is an outstanding issue of great interest as the icosahedral carboranes have wide applications in medicinal and materials chemistry. The synthesis of optically active carborane derivatives, whose chirality is associated with the substitution patterns on the polyhedron, will open new avenues to carborane chemistry. We report herein an efficient method to achieve chiral-at-cage arylation of o-carboranes with high regio- and enantioselectivities by a strategy of palladium-catalyzed asymmetric intramolecular B–H arylation and cyclization. This represents the first example of the enantioselective reaction on carboranes, providing an efficient way for the construction of chiral-at-cage compounds with new skeletons.

43 citations


References
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Journal ArticleDOI
TL;DR: The motivation for studying Pd-catalyzed C-H functionalization assisted by weakly coordinating functional groups is discussed, and efforts to bring reactions of this type to fruition are chronicle.
Abstract: Reactions that convert carbon–hydrogen (C–H) bonds into carbon–carbon (C–C) or carbon–heteroatom (C–Y) bonds are attractive tools for organic chemists, potentially expediting the synthesis of target molecules through new disconnections in retrosynthetic analysis. Despite extensive inorganic and organometallic study of the insertion of homogeneous metal species into unactivated C–H bonds, practical applications of this technology in organic chemistry are still rare. Only in the past decade have metal-catalyzed C–H functionalization reactions become more widely utilized in organic synthesis.Research in the area of homogeneous transition metal–catalyzed C–H functionalization can be broadly grouped into two subfields. They reflect different approaches and goals and thus have different challenges and opportunities. One approach involves reactions of completely unfunctionalized aromatic and aliphatic hydrocarbons, which we refer to as “first functionalization”. Here the substrates are nonpolar and hydrophobic a...

2,097 citations



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26 Mar 1999-Science
TL;DR: Although the overall branching number and the distribution of short-chain branching change very slightly, the architecture or topology of the polyethylene changes from linearpolyethylene with moderate branches at high ethylene pressures to a hyperbranched polyethylenes at low pressures.
Abstract: Ethylene pressure has been used to control the competition between isomerization (chain walking) and monomer insertion processes for ethylene coordination polymerization catalyzed by a palladium-α-diimine catalyst. The topology of the polyethylene varies from linear with moderate branching to “hyperbranched” structures. Although the overall branching number and the distribution of short-chain branching change very slightly, the architecture or topology of the polyethylene changes from linear polyethylene with moderate branches at high ethylene pressures to a hyperbranched polyethylene at low pressures.

555 citations


Journal ArticleDOI
Abstract: The medicinal chemistry of dicarba-closo-dodecaboranes (otherwise referred to as carboranes) has traditionally centered on their use in boron neutron capture therapy (BNCT). More recently, work has begun to exploit the unique chemical and physical properties of carboranes for the preparation of novel inorganic pharmaceuticals and biological probes. This review is designed to highlight some of the recent work concerning medicinal carborane chemistry including the synthesis and testing of new BNCT agents. Following this review, as an appendix, is an illustrated summary of reactions involving carboranes reported in literature since 1992.

519 citations


Journal ArticleDOI
Abstract: Mechanistic studies of olefin polymerizations catalyzed by aryl-substituted α-diimine−Pd(II) complexes are presented. Syntheses of several cationic catalyst precursors, [(N∧N)Pd(CH3)(OEt2)]BAr‘4 (N∧N = aryl-substituted α-diimine, Ar‘ = 3,5-(CF3)2C6H3), are described. X-ray structural analyses of [ArNC(H)C(H)NAr]Pd(CH3)(Cl) and [ArNC(Me)C(Me)NAr]Pd(CH3)2 (Ar = 2,6-(iPr)2C6H3) illustrate that o-aryl substituents crowd axial sites in these square planar complexes. Low-temperature NMR studies show that the alkyl olefin complexes, (N∧N)Pd(R)(olefin)+, are the catalyst resting states and that the barriers to migratory insertions lie in the range 17−19 kcal/mol. Following migratory insertion, the cationic palladium alkyl complexes (N∧N)Pd(alkyl)+ formed are β-agostic species which exhibit facile metal migration along the chain (“chain walking”) via β-hydride elimination/readdition reactions. Model studies using palladium−n-propyl and −isopropyl systems provide mechanistic details of this process, which is respon...

474 citations