Selective, catalytic carbon-carbon bond activation and functionalization promoted by late transition metal catalysts

Article abstract of DOI:10.1021/ja028912j

The selective catalytic activation and functionalization of carbon-carbon bonds in a series of substituted cyclopropane substrates has been developed using commercially available transition metal catalysts. Catalytic hydrogenation and olefination procedures, tolerant of a range of functional groups, have been discovered. Introduction of a chelate-assisting substituent such as [PPh₂] is effective in altering the kinetic selectivity and lowering the activation barrier for the catalytic processes. Copyright

Full text of DOI:10.1021/ja028912j

Published on Web 01/04/2003
Selective, Catalytic Carbon-Carbon Bond Activation and Functionalization
Promoted by Late Transition Metal Catalysts
Suzanne C. Bart and Paul J. Chirik*
Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell UniVersity, Ithaca, New York 14853
Received October 11, 2002 ; E-mail: pc92@cornell.edu
The selective cleavage and subsequent elaboration of aliphatic
carbon-carbon bonds into more valuable commodity and specialty
chemicals presents a fundamental challenge in synthesis.1 Relatively
high bond strengths (typically 85 kcal/mol) and directional σ orbitals
provide both thermodynamic and kinetic obstacles to C-C bond
activation. Relief of ring strain with substrates such as cyclopropane2
and cubane3 has provided favorable conditions for stoichiometric
carbon-carbon bond cleavage. This strategy has recently evolved
to include catalytic hydrogenation,4 decarbonylation,5 and ring
expansion/opening6 reactions of strained substrates.
Despite these significant advances, the general applicability of
carbon-carbon bond activation in synthetically useful transforma-
tions remains limited.5,7 Although the ring opening hydrosilylation
of methylenecyclopropanes has been described, these reactions
provide mixtures of products and are believed to proceed via olefin
insertion into a metal hydrogen bond followed by â-alkyl elimina-
tion.8 To achieve hydrocarbon cleavage and derivatization for a
range of functional groups, methodologies that couple carbon-
carbon activation with other bond-forming processes are desirable.
Considering the metallocyclobutane product of C-C bond oxidative
addition as a typical metal alkyl suggests that traditional organo-
metallic bond-forming reactions (insertion, elimination, etc.) may
be coupled to bond activation processes (eq 1). Such a pairing may
extend the utility of numerous catalytic reactions to otherwise inert
substrates.
The scope of the catalytic hydrogenation reaction was explored
with a series of substituted cyclopropane substrates (Table 1).
Wilkinson’s catalyst, (PPh3)3RhCl, was chosen for subsequent
experiments because it displays good activity and is the most readily
available. In general, the hydrogenation reactions are tolerant of a
range of functional groups including alcohols, ethers, carbonyls,
and thiophenes with little influence on activity. Notable exceptions
are the presence of long alkyl chains (entries 4 and 7). Pure
hydrocarbon substrates such as cyclopropylbutane (entry 7) as well
as butyl ethers (entry 4) undergo preferential C-H activation and
dehydrogenation10 of the alkyl chain, even in the presence of
dihydrogen,11 forming a mixture (∼1:1) of 2-olefins. Catalytic,
acceptorless alkane dehydrogenation at 130 °C represents one of
the lowest temperatures reported for this process.12 Interestingly,
ethyl ethers (entry 5) are compatible with the C-C cleavage
reaction, participating in ring opening and hydrogenation with no
complications arising from C-H activation.
Performing the C-C bond activation reactions with (PPh3)3RhCl
under an atmosphere of N2 rather than H2 results in catalytic alkane
olefination (Table 2). In each case, gem-olefins arising from C-C
activation of the least hindered face of the cyclopropane are formed.
Olefination most likely occurs via C-C oxidative addition followed
by both â-hydrogen and reductive eliminations, respectively. Unlike
hydrogenation, the olefination procedure is not effective for alcohol
substrates (entry 2) or for the dehydrogenation of the butyl ether
derivative (entry 4). However, (PPh3)3RhCl does promote the
dehydrogenation, albeit with low activity, of the alkyl chain of
cyclopropylbutane (entry 7).
In principle, the regioselectivity of both catalytic hydrogenation
and olefination can be altered by incorporation of functional groups
that can serve as ligands for rhodium and direct the activation of
the most hindered C-C bond.4c,13 Because oxygen14 and sulfur
donors are ineffective in providing chelate-assisted selectivity, a
[PPh2] group was chosen given the high affinity of rhodium for
phosphine-based ligands.15 This approach was successfully applied
in both the catalytic hydrogenation and the olefination of the [PPh2]-
substituted cyclopropylcarbinol (I), resulting in exclusive cleavage
of the most hindered C-C bond (eq 2). As observed previously in
Table 2, the terminal olefin is formed initially but undergoes
isomerization to a mixture (∼1:1) of 2-olefins during the course of
the reaction.
In this communication, we describe the regioselective catalytic
hydrogenation, olefination, and, in one case, hydrosilylation, of
aliphatic carbon-carbon bonds for a range of substituted cyclo-
propane derivatives. Each reaction may be performed under typical
laboratory conditions with commercially available transition metal
catalysts. The regioselectivity of the C-C cleavage and subsequent
functionalization reaction can be controlled by the appropriate
choice of cyclopropyl substituent.
Initial studies focused on the hydrogenation of the [SiMe3]-
c
protected cyclopropylcarbinol, PrCH2OSiMe3, with a series of
commercially available late transition metal catalysts (Table S1,
Supporting Information). The hydrogenation reactions proceeded
readily at 130 °C with 1-4 atm of dihydrogen and with low (0.5-2
mol %) catalyst loadings. To compare relative rates, hydrogenation
reactions were carried out under standard conditions of 4 atm of
H2, 2 mol % catalyst, and were assayed at 18 h. In each case, Me2-
CHCH2OSiMe3 was the sole product formed, arising from cleavage
of the most sterically accessible C-C bond. The activity of the
hydrogenation reaction showed only a modest dependence on the
metal catalyst and was unaffected by the addition of elemental
mercury, consistent with a homogeneous process.9 The observed
turnover frequencies (∼1 mol/h for the best cases) are some of the
most active catalytic C-C hydrogenation reactions reported to date.4
In addition to altering the kinetic selectivity, chelate assistance
is also effective in providing a lower energy pathway for C-C
cleavage. The reactions presented in Table 2 take place over the
9
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J. AM. CHEM. SOC. 2003, 125, 886-887
10.1021/ja028912j CCC: $25.00 © 2003 American Chemical Society

C O M M U N I C A T I O N S
Table 1. Catalytic Hydrogenation of Cyclopropyl Substrates with
(PPh3)3RhCl
entrya
R
tofb
1
2
3
4
5
6
7
OSiMe3
OH
OAc
OCH2CH2CH2CH3
OCH2CH3
C(O)(2-C4H3S)
0.98
0.25
0.56
2.4
0.21
0.25
0.25
most hindered carbon-carbon bond. Further studies aimed at
elucidating the mechanistic details of both catalytic reactions as
well as coupling them to additional organometallic bond-forming
reactions are now in progress.
c
c
Acknowledgment. We would like to thank the Coates group
for access to their gas chromatograph, Johnson-Matthey for a gift
of iridium trichloride hydrate, and the Department of Chemistry
and Chemical Biology at Cornell University for generous financial
support.
CH2CH2CH3
a 2.75 mM (PPh3)3RhCl and 0.138 M substrate in anhydrous toluene.
b Turnover frequency determined with 4 atm of H2 at 18 h. c Undergoes
alkane dehydrogenation of the alkyl chain to a mixture of internal olefins.
Table 2. Catalytic Olefination of Cyclopropyl Substrates with
(PPh3)3RhCl
Supporting Information Available: Results for catalytic hydro-
genation of cPrCH2OSiMe3 as a function of metal catalyst and all
experimental procedures (PDF). This material is available free of charge
via the Internet at http://pubs.acs.org.
entrya
R
tofb
1.78
no reaction
0.28
no reaction
0.68
0.92
References
1
2
3
4
5
6
7
OSiMe3
OH
OAc
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c
OCH2CH2CH2CH3
OCH2CH3
C(O)(2-C4H3S)
CH2CH2CH3
0.05
a 2.75 mM (PPh3)3RhCl and 0.138 M substrate in anhydrous toluene.
b Turnover frequency determined at 18 h. c Undergoes alkane dehydroge-
nation of the alkyl chain to a mixture of internal olefins.
course of 55 h, whereas the catalytic hydrogenation or olefination
of I is complete within 6 h. Likewise, both of these catalytic
processes can be conducted at temperatures as low as 100 °C. In
addition to (PPh3)3RhCl, other catalysts such as [Rh(COD)Cl]2 and
Pd(PPh3)4 are effective for the chelate-assisted hydrogenation or
olefination protocol.
Catalytic carbon-carbon bond activation may also be coupled
to hydrosilylation. In a one-pot procedure, olefination of I followed
by addition of Et3SiH under conditions where (PPh3)3RhCl is active
for hydrosilylation16 produced the terminal silane in >95% yield
(eq 3). As typically observed with olefin hydrosilylation reactions,
mixtures of internal alkenes undergo isomerization and hydrosilyl-
ation to the terminal product.16
In summary, we have successfully coupled carbon-carbon bond
activation to reactions traditionally available to metal alkyls. Using
commercially available catalysts under convenient laboratory condi-
tions, we have achieved catalytic hydrocarbon functionalization.
Introduction of functional groups such as [PPh2] is effective in
promoting accelerated reactions with exclusive selectivity for the
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