Zinc(II)-Mediated Carbene Insertion into C-H Bonds in Alkanes

Article abstract of DOI:10.1021/acs.inorgchem.5b02134

The cationic zinc adduct {[HB(3,5-(CF₃)₂Pz)₃]Zn(NCMe)₂}ClO₄ catalyzes the functionalization of tertiary, secondary, and primary C-H bonds of alkanes via carbene insertion. Ethyl diazoacetate serves as the:CHCO₂Et carbene precursor. The counteranion, supporting ligand, and coordinating solvents affect the catalytic activity. An in situ generated {[HB(3,5-(CF₃)₂Pz)₃]Zn}⁺ species containing a bulkier {B[3,5-(CF₃)₂C₆H₃]₄}^- anion gives the best results among the zinc catalysts used.

Full text of DOI:10.1021/acs.inorgchem.5b02134

Communication
pubs.acs.org/IC
Zinc(II)-Mediated Carbene Insertion into C−H Bonds in Alkanes
Naveen V. Kulkarni,† Chandrakanta Dash,† Naleen B. Jayaratna,† Shawn G. Ridlen,†
Sarah Karbalaei Khani,‡ Animesh Das,† Xiaodi Kou,† Muhammed Yousufuddin,† Thomas R. Cundari,*,‡
and H. V. Rasika Dias*,†
†Department of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, Texas 76019, United States
‡Department of Chemistry, Center for Advanced Scientific Computing and Modeling, University of North Texas, Denton, Texas
76203, United States
S
* Supporting Information
The primary catalyst {LZn(NCMe)2}ClO4 (L = [HB(3,5-
(CF3)2Pz)3]; Figure 1) used in this work was synthesized in 71%
ABSTRACT: The cationic zinc adduct {[HB(3,5-
(CF3)2Pz)3]Zn(NCMe)2}ClO4 catalyzes the functionaliza-
tion of tertiary, secondary, and primary C−H bonds of
alkanes via carbene insertion. Ethyl diazoacetate serves as
the :CHCO2Et carbene precursor. The counteranion,
supporting ligand, and coordinating solvents affect the
catalytic activity. An in situ generated {[HB(3,5-
(CF3)2Pz)3]Zn}+ species containing a bulkier {B[3,5-
(CF3)2C6H3]4}− anion gives the best results among the
zinc catalysts used.
he activation of unfunctionalized C−H bonds is of
Tsignificant importance because it allows the synthesis of a
variety of complex organic compounds from more widely
available hydrocarbon precursors.1−4 Among the routes available
for the functionalization of aliphatic C−H bonds, metal-
mediated carbene insertion processes are some of the most
promising and attracted the interest of several groups.3−8
Diazoacetates like ethyl diazoacetate (EDA) are the most
common carbene source, while copper- and rhodium-based
compounds are the earliest and most widely used catalysts for
this process.3,5,7,9,10
We have been working on the development of highly
fluorinated tris(azolyl)borates (scorpionates)11 and their utility
in the stabilization of molecules possessing very electrophilic
metal sites.6,12,13 During the course of this work, Dias, Lovely,
and co-workers discovered that silver(I) adducts like [HB(3,5-
(CF3)2Pz)3]Ag(THF) containing highly fluorinated scorpio-
nates [where [HB(3,5-(CF3)2Pz)3]− = hydrotris[3,5-bis-
(trifluoromethyl)pyrazolyl]borate] very effectively catalyze
carbene insertion into unfunctionalized C−H bonds including
primary C−H bonds under remarkably mild conditions.14 We
have also showed that it is possible to modulate this reactivity by
using sterically and electronically different ligands like [MeB(3-
(C2F5)Pz)3]−, [HB(3,5-(CF3)2,4-(Cl)Pz)3]−, and [HB(3,5-
(CF3)2,4-(NO2)Pz)3]− or by varying the carbene source.13,15,16
The utility of silver adducts of fluorinated scorpionates in
methane activation chemistry has also been noted.17 In this
paper, we describe the use of 3d-metal-based zinc(II)
scorpionates as efficient catalysts to functionalize tertiary,
secondary, and primary C−H bonds of hydrocarbons via carbene
insertion. We recently reported C−halogen bond functionaliza-
tion via a similar route using zinc.18
Figure 1. Zinc(II) catalyst {[HB(3,5-(CF3)2Pz)3]Zn(NCMe)2}ClO4
and a view of its molecular structure. Selected bond lengths (Å) and
angles (deg): Zn−N1 = 2.2028(19), Zn−N3 = 2.058(2), Zn−N5 =
2.0507(19), Zn−N7 = 1.982(2), Zn−N8 = 2.164(2); N3−Zn−N5 =
95.96(7), N5−Zn−N7 = 141.19(8), N3−Zn−N7 = 122.85(8), N1−
Zn−N8 = 174.28(7), N7−Zn−N8 = 88.67(8).
isolated yield by treating LNa with Zn(ClO4)2·6H2O in
acetonitrile in the presence of a few grains of activated molecular
sieves (to remove water). Suitable crystals for X-ray analysis were
obtained from a dichloromethane solution of the complex stored
at −20 °C. The X-ray crystal structure of the bis(acetonitrile)
adduct {LZn(NCMe)2}ClO4 is illustrated in Figure 1. It has a
distorted trigonal-bipyramidal zinc center. The pyrazolyl nitro-
gen atoms of a κ3-bound L− ligand occupy two equatorial and one
axial sites with two long and one short Zn−N distances. Not
surprisingly, the equatorial and axial Zn−acetonitrile bond
distances are also different, e.g., Zn−N7 = 1.982(2) Å and Zn−
N8 = 2.164(2) Å. The bis(isocyanide)zinc adduct {LZn-
(CNtBu)2}{B[3,5-(CF3)2C6H3]4} is known, and, interestingly,
it also adopts a similar trigonal-bipyramidal structure.18
In a typical catalytic process, 1 equiv of catalyst was placed in
1.5 mL of hydrocarbon (substrate and also the solvent) and
stirred at 60 °C. This mixture was slowly treated with a solution
of 20 equiv of EDA (which is the carbene precursor) in the same
hydrocarbon (5 mL) using a syringe pump (rate: 1 mL/h). After
the mixture was stirred at 60 °C overnight, the resulting products
were analyzed using NMR spectroscopy and gas chromatog-
raphy−mass spectrometry methods. The results are summarized
Received: June 26, 2015
© XXXX American Chemical Society
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DOI: 10.1021/acs.inorgchem.5b02134
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Inorganic Chemistry
Communication
Table 1. Metal-Catalyzed Carbene Insertion into C−H Bonds of Hydrocarbons with EDA (L = [HB(3,5-(CF3)2Pz)3]; L′ =
a
[MeB(3-(CF3)Pz)3])
b
b
b
b
catalyst
substrate
total C−H % yield
1° C−H
2° C−H
3° C−H
{LZn(NCMe)2}ClO4
{LZn(NCMe)2}ClO4
{LZn(NCMe)2}ClO4
LZnCl
cyclohexane
91
75
74
57
98
23
85
99
95
40
10
12
91
2-methylpentane
2,3-dimethylbutane
cyclohexane
37 (1)
56 (1)
30 (1.82)
8 (1.95)
18 (1.93)
57
98
23
{LZn}{B[3,5-(CF3)2C6H3]4}
Zn(OTf)2
cyclohexane
cyclohexane
{LZn}{B[3,5-(CF3)2C6H3]4}
LAg(THF)
2,3-dimethylbutane
cyclohexane
66 (1)
75 (1)
0
19 (1.72)
20 (1.60)
10
99
40
12
LAg(THF)
2,3-dimethylbutane
cyclohexane
LCu(C2H4)
LCu(C2H4)
2,3-dimethylbutane
cyclohexane
{L′Zn(NCMe)}ClO4
a
b
Reactions at 60 °C. Total C−H insertion product yields (%) and primary, secondary, and tertiary C−H insertion product yields (%) are based on
1
the EDA used and calculated by integration of H NMR signals. The remaining EDA either was found to be unreacted or was converted into a
mixture of dimethyl fumarate and maleate (see the Supporting Information for details). Normalized C−H insertion selectivity values were calculated
using the ratio of :CHCO2Et carbene insertion products and the number of each type of C−H bonds and are provided in parentheses.
in Table 1 (provided in more detail in Table S1 in the Supporting
Information). Results show that {LZn(NCMe)2}ClO4 is an
excellent catalyst for inserting a :CHCO2Et carbene fragment
from EDA into C−H bonds of cyclohexane, providing ethyl 2-
cyclohexylacetate in 91% yield. The elevated temperature is
necessary for higher activity. When the same process was carried
out at room temperature, only 13% ethyl 2-cyclohexylacetate was
produced, while about 80% EDA remained unreacted. The
sluggish activity at room temperature is probably a result of
acetonitrile being retained on zinc(II), which not only lowers the
Lewis acidity but also hinders the interaction of EDA with zinc.
Higher temperatures, in contrast, would facilitate the dissociation
of acetonitrile from zinc, thus creating open coordination sites for
EDA. Interestingly, LZnCl is also capable of catalyzing carbene
insertion into C−H bonds of cyclohexane at 60 °C, producing
57% ethyl 2-cyclohexylacetate (while 40% EDA remains
unreacted). A lower product yield compared to that of the
{LZn(NCMe)2}ClO4-mediated reaction (which produces 91%
carbene insertion product under similar conditions) is not
primary, secondary, and tertiary C−H bonds were found to be 1,
1.82, and 1.95, respectively, which are in line with the relative C−
H bond energies1,7 in which the weaker tertiary bonds get
activated at a relatively greater level compared to stronger
primary C−H bonds. The C−H bond functionalization
chemistry of cyclohexane and 2,3-dimethylbutane was also
probed under similar conditions using the well-established silver
catalyst LAg(THF) for comparison.6,15 The results show that
LAg(THF) (which is a neutral complex and a 4d-metal-based
catalyst and more soluble in hydrocarbons) is still the better
catalyst compared to {LZn(NCMe)2}ClO4 (Table 1), but
zinc(II) adducts like {LZn}{B[3,5-(CF3)2C6H3]4} with very
weakly coordinating counterions display respectable catalytic
activity, approaching those of LAg(THF) and LAg(C2H4).15
The related 3d-metal-based copper(I) catalyst LCu(C2H4), in
contrast, shows relatively poor C−H functionalization activity via
this route under similar conditions and also demonstrates its
inability to facilitate the primary C−H bond activation. Carbene
dimers diethyl fumarate and maleate are formed as byproducts in
significant quantities. While this study was underway, a report
appeared that showed the use of copper(I) and a fluorinated
scorpionate, [HB(3,5-(CF3)2,4-(Br)Pz)3]−, in primary C−H
bond functionalization chemistry.20 It features a ligand like
[HB(3,5-(CF3)2,4-(Cl)Pz)3]−, which we reported earlier with
silver(I) chemistry.13
The proposed C−H bond functionalization process is
illustrated in Scheme 1. The cationic {LZn}+ species reacts
with EDA, resulting in a zinc carbene/zinc-bound carbocation
(resonance forms), which then inserts the carbene moiety into
C−H bonds of the substrate, releasing the catalyst. A detailed
computational study (see the Supporting Information) of the
likely intermediate suggests that it is best described as a zinc-
bound carbocation rather than a zinc carbene21 form (although a
neutral :CHCO2Et carbene moiety gets transferred to the
substrate during the reaction).
Preliminary studies indicate that {LZn(NCMe)2}ClO4 can
also functionalize the C−H bonds of tetrahydrofuran (THF) but
the activities are relatively low, presumably because of the
competition between THF molecules (present in large excess)
with EDA to coordinate to the Lewis acidic zinc center, which
hinders the zinc-mediated decomposition of EDA. These
cationic zinc adducts also mediate other types of chemistry like
−
surprising because the latter has a weakly coordinating ClO4
counterion, while LZnCl is a neutral species with a covalently
bound chloride ion. In fact, {LZn}{B[3,5-(CF3)2C6H3]4}, which
has one of the weakest coordinating counterions,19 shows the
highest activity under comparable conditions, affording ethyl 2-
cyclohexylacetate from cyclohexane and EDA in essentially
quantitative yield. This catalyst was generated in situ from LZnEt
and [Ph3C]{B[3,5-(CF3)2C6H3]4} (and in the absence of donors
like acetonitrile). A less acidic {[MeB(3-(CF3)Pz)3]Zn-
(NCMe)}ClO4-mediated reaction produced only 12% carbene
insertion product with cyclohexane (compared to the 91%
{LZn(NCMe)2}ClO4-catalyzed reaction), illustrating the effect
of the supporting ligand on zinc(II).
We have also investigated the catalytic activity of {LZn-
(NCMe)2}ClO4 with other hydrocarbon substrates like 2,3-
dimethylbutane (which contains tertiary and primary C−H
bonds) and 2-methylpentane (which contains primary, secon-
dary, and tertiary C−H bonds). With 2,3-dimethylbutane, C−H
functionalization products were obtained in a total of 74% yield
with a relative selectivity of 1:1.93 toward primary versus tertiary
C−H bonds. When 2-methylpentane was used as the substrate, a
total of 75% of the C−H functionalization products was
obtained. The relative selectivities of carbene insertion into
B
DOI: 10.1021/acs.inorgchem.5b02134
Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
Communication
Scheme 1. {[HB(3,5-(CF3)2Pz)3]Zn}+ (Denoted as [LZn]+)-
Mediated :CHCO2Et Carbene Insertion into C−H Bonds
Involving EDA
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ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.inorg-
chem.5b02134.
■
(19) Diaz-Torres, R.; Alvarez, S. Dalton Transactions 2011, 40, 10742−
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2015, 5, 3726−3730.
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Synthesis and characterization of zinc adducts, details on
catalysis, computational work, additional figures, and X-
ray crystallographic data tables (PDF)
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X-ray crystallographic data in CIF format (CIF)
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AUTHOR INFORMATION
■
Corresponding Authors
*E-mail: tomc@unt.edu.
*E-mail: dias@uta.edu.
Author Contributions
The manuscript was written through contributions of all authors.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the National Science Foundation (Grant CHE-
1265807) and Welch Foundation (Grant Y-1289) for support of
this research. T.R.C. and S.K.K. acknowledge partial support of
this research through Grant CHE-1057785.
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DOI: 10.1021/acs.inorgchem.5b02134
Inorg. Chem. XXXX, XXX, XXX−XXX