Highly selective metal catalysts for intermolecular carbenoid insertion into primary C-H bonds and enantioselective C-C bond formation

Article abstract of DOI:10.1002/anie.200803157

(Figure Presented) Primary C-H bond activation! A Rh complex of bis-pocket porphyrin I catalyzes carbenoid insertion into the C-H bonds of n-alkanes with a primary/secondary selectivity (per C-H bond) of up to 11.4:1 (see picture). Enantioselective secondary C-H bond functionalization catalyzed by a Rh complex of Halterman's chiral porphyrin features up to 93% ee. These reactions exhibit up to 6477 turnovers after the catalyst was recycled five times.

Full text of DOI:10.1002/anie.200803157

Angewandte
Chemie
DOI: 10.1002/anie.200803157
À
C H Activation
Highly Selective Metal Catalysts for Intermolecular Carbenoid
À
À
Insertion into Primary C H Bonds and Enantioselective C C Bond
Formation**
Hung-Yat Thu, Glenna So-Ming Tong, Jie-Sheng Huang, Sharon Lai-Fung Chan,
Qing-Hai Deng, and Chi-Ming Che*
À
À
Direct functionalization of C H bonds is an appealing
feature lower selectivity for primary C H bonds than for
strategy in organic synthesis[1] but its practical application
has so far been difficult to realize. The selective functional-
secondary and tertiary C H bonds. For example, a selectivity
À
À
order of primary < secondary < tertiary C H bonds has been
À
ization of primary C H bonds of alkanes that also contain
secondary and/or tertiary C H bonds is a great challenge, as
observed for the extensively investigated carbene insertion
catalyzed by rhodium complexes,[4,5] possibly because of the
À
À
À
C H bond energy follows an order primary > secondary >
electron density order of primary < secondary < tertiary C H
bonds, which renders primary C H bonds the least suscep-
tertiary.[1c,d] In seminal works by Bergman,[1b] Jones,[1c] and
their respective co-workers, stoichiometric reactions of alka-
nes with [Cp*(Me3P)M] (Cp* = C5Me5; M = Rh, Ir) resulted
À
tible to attack by electrophilic rhodium–carbene intermedi-
ates.[5] By manipulating the steric or electronic properties of
À
À
in the formation of C M bonds by selective activation of
the metal catalysts, a selectivity for primary C H bonds of
À
À
primary C H bonds. Subsequent work by Hartwig and co-
alkanes comparable to that for secondary or tertiary C H
workers[1g,i,2] demonstrated C B bond formation by stoichio-
metric and catalytic functionalization of primary C H bonds
mediated by tungsten, rhodium, or ruthenium complexes. The
bonds was observed,[6] with the highest primary/secondary
À
and primary/tertiary ratio per C H bond being 1.17:1.0[6b] and
À
À
1.0:0.9,[6c] respectively.
À
À
high selectivity for primary C H bond functionalization in
Herein we report a highly selective primary C H bond
functionalization by metal-catalyzed carbenoid insertion into
À
À
these C M or C B bond-formation reactions (Scheme S1 in
the Supporting Information) is considered to result from
kinetic factors or steric interaction between the metal
complexes and alkanes.[1i,3]
À
the C H bonds of alkanes (Scheme 1), which features a
À
A well-established process in C C bond formation by
À
direct C H bond functionalization is the metal-catalyzed
À
intra- and intermolecular carbenoid insertion into C H
bonds, with diazo compounds as the carbene source.[1o,4]
Scheme 1. Selective functionalization of primary (18) over secondary
À
These catalytic C C bond-formation reactions generally
À
À
(28) C H bonds of alkanes in the metal-mediated C C bond-formation
reactions reported in this work.
[*] Dr. H.-Y. Thu, Dr. G. S.-M. Tong, Dr. J.-S. Huang, Dr. S. L.-F. Chan,
Prof. Dr. C.-M. Che
primary/secondary selectivity (that is, the primary/secondary
Department of Chemistry and Open Laboratory of Chemical Biology
of the Institute of Molecular Technology for
Drug Discovery and Synthesis, The University of Hong Kong
Pokfulam Road (Hong Kong)
Fax: (+852)2857-1586
E-mail: cmche@hku.hk
À
ratio per C H bond) of up to 11.4:1. We have also
accomplished highly enantioselective functionalization of
À
secondary C H bonds with ee values of up to 93% and
product turnovers up to 6100 through metal-mediated carbe-
À
noid C H bond insertion reactions.
Q.-H. Deng, Prof. Dr. C.-M. Che
Our studies in this work were inspired by previous work
Shanghai-Hong Kong Joint Laboratory in Chemical Synthesis
Shanghai Institute of Organic Chemistry,
The Chinese Academy of Sciences
from the research groups of Callot[6a,b] and Suslick.[7] In the
À
1980s, Callot and co-workers reported that the primary C H
bond selectivity for the reaction of linear alkanes with ethyl
diazoacetate (N2CHCO2Et, EDA) catalyzed by [Rh(por)I]
(H2(por) = meso-tetraarylporphyrin) increases with the size
of the ortho groups H, Me, or Cl of the meso-aryl rings. We
envisioned that replacing these ortho groups with bulkier
phenyl groups, coupled with changing the a hydrogen atom of
EDA to a phenyl group, would enhance the selectivity for
354 Feng Lin Road, Shanghai 200032 (China)
[**] This work was supported by The University of Hong Kong
(University Development Fund), the University Grants Council of
HKSAR (the Area of Excellence Scheme: AoE 10/01P), and the Hong
Kong Research Grants Council (HKU 7012/05P). We thank Dr.
Nianyong Zhu for solving the crystal structure of [Rh(N-CH2CO2Et-
ttp)(Me)]ClO4 and Dr. Herman H. Y. Sung (The Hong Kong
University of Science and Technology) for collecting the X-ray
diffraction data of catalyst III. Q.-H.D. is gratefully to the Croucher
Foundation of Hong Kong for a postgraduate studentship.
À
primary C H bonds. Therefore, our attention was directed to
À
developing an intermolecular C H bond insertion reaction of
alkanes with N2C(Ph)CO2R[4b,c] catalyzed by the rhodium
complex of meso-tetrakis(2,4,6-triphenylphenyl)porphyrin
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.200803157.
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[H2(ttppp)]. The H2(ttppp) ligand, a bis-pocket porphyrin
metal–carbene intermediates for subsequent reactions with
alkanes, in a similar fashion to metal catalysts for carbenoid
transfer reactions.[4a,b] We found that I is an active catalyst for
the reaction of N2C(Ph)CO2Me with n-hexane (1), n-octane
first synthesized in 1983 by Suslick and Fox,[7a] was previously
shown to dramatically enhance the selectivity in the hydrox-
ylation of alkanes, with a primary/secondary selectivity of up
to approximately 0.82:1 obtained for [Mn(ttppp)(OAc)].[7b]
To insert rhodium into H2(ttppp), we employed a method
analogous to that for the preparation of [Rh(ttp)(Me)][8a] and
[Rh(tmp)(Me)].[8b] Reaction of [Rh(CO)2Cl]2 with H2(ttppp)
in toluene, followed by treatment with NaBH4, MeI, and
MeOH, afforded [Rh(ttppp)(Me)(MeOH)] (I). Complex I
À
(2), and n-decane (3). These reactions afforded the C H bond
insertion products 4–6 with remarkably high selectivity for the
À
primary C H bonds (Scheme 2).
1
was characterized by H NMR and UV/Vis spectroscopy as
well as mass spectrometry. Its structure has been determined
by X-ray crystallography[9] and is shown in Figure 1 (see also
À
Scheme 2. Intermolecular C H bond insertion of n-alkanes 1–3 with
N2C(Ph)CO2Me catalyzed by I. Reaction conditions: N2C(Ph)CO2Me
(0.1 mmol), alkane (4 mL), I (2.5 mol%), 808C under N2, 24 h.
Conversion of N2C(Ph)CO2Me: 100%. The yields (based on
N2C(Ph)CO2Me) are for isolated products. The primary/secondary
ratio was normalized for the relative number of hydrogen atoms.
Figure 1. X-ray crystal structure of I with omission of hydrogen atoms.
Thermal ellipsoid probability: 30%.
Table S1 in the Supporting Information). This complex has
Rh–C(Me) and Rh–O(MeOH) distances of 2.028(15) ꢀ and
2.507(16) ꢀ, respectively; the former is similar to that of
Addition of N2C(Ph)CO2Me (0.1 mmol) in n-hexane
(2 mL) to a mixture of I (2.5 mol%) and n-hexane (2 mL)
at 808C over 20 h, followed by stirring the mixture at 808C for
4 h, gave 4a–c in an overall yield of 51% (based on
N2C(Ph)CO2Me), with a primary/secondary selectivity of
9.8:1. Changing the catalyst to [Rh(ttp)(Me)] or [Rh-
(tmp)(Me)] (both 1.5 mol%; H2(ttp) = meso-tetrakis(p-tol-
yl)porphyrin, H2(tmp) = meso-tetramesitylporphyin) which
contain a sterically less demanding porphyrin ligand lowered
the primary/secondary selectivity of 4a–c to 0.9:1 or 3.4:1,
respectively (Scheme S2 in the Supporting Information). For
2.027(4) ꢀ
in
[Rh(F28-tpp)(Me)]
(H2(F28-tpp) =
2,3,7,8,12,13,17,18-octafluoro-meso-tetrakis(pentafluorophe-
nyl)porphyrin).[10]
Access to the rhodium atom in I is difficult because of
steric hindrance (Figure 1 and Figure S1 in the Supporting
Information). We investigated whether this rhodium bis-
pocket porphyrin complex could react with the sterically
encumbered N2C(Ph)CO2R to form the corresponding
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substrates n-octane and n-decane, the primary/secondary
selectivities of catalyst I reached 10.5:1 (5a–d) and 11.4:1
(6a–e).
carbene complex intermediate in the cyclopropanation of
alkenes with EDA catalyzed by rhodium porphyrins,[12]
although such a metal–carbene species has not been observed.
We propose that the reaction of EDA or N2C(Ph)CO2Me with
When EDA was used instead of N2C(Ph)CO2Me, the I-
À
catalyzed C H bond insertion products for substrates 1 and 3
I
generates the carbene complexes [Rh(ttppp)-
were obtained in up to 63% yield (reaction time: 24 h), with a
primary/secondary selectivity of (2.7–3.2):1 (Table S2 in the
Supporting Information).
(CHCO2Et)(X)] or [Rh(ttppp)(C(Ph)CO2Me)(X)] (X could
be, for example, Me or solvent) in a fashion analogous to the
reactions catalyzed by other rhodium complexes.[13] We have
performed density functional theory (DFT) calculations on
the hypothetical compounds [Rh(ttppp)(C(Ph)CO2Me)(Cl)]
and [Rh(por0)(C(Ph)CO2Me)(Cl)] (where por0 is the unsub-
stituted porphyrin ring), which showed that these complexes
are, at least in theory, stable species (see
Branched alkanes 2,2-methylbutane (7) and 2,3-methyl-
butane (8) also underwent C H bond insertion with
N2C(Ph)CO2Me in the presence of catalyst I, affording 9a,b
or 10a,b in 48–54% yields (Scheme 3). The primary/secon-
À
the Supporting Information). Figure 2
shows the optimized structure of [Rh-
(ttppp)(C(Ph)CO2Me)(Cl)]; the calcu-
lated Rh–C distance of 1.982 ꢀ is slightly
longer than that in the optimized struc-
ture of [Rh(por0)(C(Ph)CO2Me)(Cl)]
(1.969 ꢀ, Figure S3 in the Supporting
Information). Based on the optimized
structure in Figure 2, it is evident that
the axial phenyl groups of ttppp would
impose a significantly larger steric hin-
drance for secondary than for primary
À
C H bonds that attack the carbene
group in a concerted manner,[13] which
accounts for the high primary/secondary
selectivity shown in Scheme 2 and
Scheme 3.
The reaction of [Rh(oep)(Me)] (H2-
(oep) = 2,3,7,8,12,13,17,18-octaethylpor-
phyrin) with EDA in the presence of
acetic acid has been shown to give an N-
substituted rhodium–porphyrin complex
[Rh(N-CH2CO2Et-oep)(Me)]ClO4.[14] In
this work, we isolated and structurally
À
Scheme 3. Intermolecular C H bond insertion of 7, 8, and 11 with N2C(Ph)CO2Me catalyzed
by I. The reaction conditions are the same as those indicated in the legend of Scheme 2.
Conversion of N2C(Ph)CO2Me: 100%. The primary/secondary or primary/tertiary ratio was
normalized for the relative number of hydrogen atoms.
characterized
[Rh(N-CH2CO2Et-
ttp)(Me)]ClO4 from the reaction of [Rh-
dary selectivity for 7 is 6.7:1. Notably, although 7 contains two
(ttp)(Me)] with EDA (Figure 3 and Figure S2 in the Support-
ing Information).[9] However, treatment of this complex with
À
types of primary C H bonds—one bonded to the secondary
À
carbon atom and the other bonded to the quaternary carbon
n-hexane or cyclohexane (13) at reflux afforded no C H bond
À
atom, only the former underwent C H bond insertion with
insertion product; this observation suggests that the N-
N2C(Ph)CO2Me. This demonstrates an excellent regioselec-
À
tivity in the I-catalyzed primary C H bond insertion.
N2C(Ph)CO2Me was reacted with toluene (11) in the
À
presence of I for 24 h to give the primary C H bond insertion
product 12 in 62% yield (Scheme 3). No cyclopropanation
product was observed in the 1H NMR spectrum of the
reaction mixture. In contrast, the previously reported reaction
of toluene with N2C(p-BrC6H5)CO2Me catalyzed by [Rh2((S)-
dosp)4] ((S)-dosp = N-[(4-dodecylphenyl)sulfonyl]-(S)-proli-
nate) mainly gave cyclopropanation products with the
[11]
À
primary C H bond insertion product formed in 14% yield.
À
The high selectivity in the I-catalyzed C H bond insertion
Figure 2. Optimized structure (B3LYP) of [Rh(ttppp)(C(Ph)
CO2Me)(Cl)]. The inset shows a part of the structure with axial phenyl
groups of ttppp in spacefill representation. A spacefill representation
reactions can be rationalized by the steric interaction between
the substrates and the putative rhodium–carbene complexes
of the bis-pocket porphyrin. Previously, Kodadek and co-
workers provided strong evidence for a rhodium–porphyrin–
À
of alkanes with either primary and secondary C H bonds approaching
the carbene group is shown in the lower left corner.
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(Table 1). The best enantiocontrol (92 and 93% ee) was
achieved for cyclohexane and cyclopentane (Table 1, entries 3
and 4).
À
Table 1: Enantioselective intermolecular C H bond insertion catalyzed
by II.[a]
Entry Substrate Product
Yield[b] ee[c,d]
Primary/
[%]
[%]
secondary[e]
1
2
4a+4b+4c
9a+9b
66
55
68 (4a) 3.5:1
65 (9a) 3.8:1
3
4
80
64
92
93
Figure 3. X-ray crystal structure of [Rh(N-CH2CO2Et-ttp)(Me)]ClO4 with
omission of the counterion. Thermal ellipsoid probability: 30%.
5
6
78
88
substituted rhodium–porphyrin complex is not the catalyti-
cally active intermediate. Similarly, rhodium–corrole ana-
logues have been shown not to be true intermediates in the
related catalytic cyclopropanation reaction of styrenes.[15]
Davies et al. demonstrated that [Rh2((S)-dosp)4] exhibits
high enantio- and chemoselectivity in catalyzing intermolec-
43[f]
71[g]
7
45
16
85
77
À
ular C H bond insertion reactions of alkanes with aryl
diazoacetates N2C(Ar)CO2R.[4b] These [Rh2((S)-dosp)4]-cata-
À
lyzed reactions exclusively occur at secondary or tertiary C H
[16]
À
bonds, leaving the primary C H bonds unfunctionalized.
Therefore, the quest for an enantioselective carbenoid trans-
[a] Reaction conditions: N2C(Ph)CO2Me (0.1 mmol); 1, 7, 13, or 14
(4 mL); 15 (2 equiv), 16 or 17 (5 equiv) in 1,2-dichloroethane (4 mL); II
(0.1 mol% for 13–17, 1.5 mol% for 1 and 7); 608C under N2; 4 h (13–15)
or 24 h (others). Conversion of N2C(Ph)CO2Me: 100%. [b] Determined
by GC–MS after chromatography (based on N2C(Ph)CO2Me). [c] Deter-
mined by HPLC with chiral-OD column. [d] Absolute configuration not
determined. [e] Normalized for the relative number of hydrogen atoms.
[f] The ratio of two diastereomers is 60:40. The reaction was performed
in the presence of 4 ꢀ molecular sieves. The cyclopropanation product
was also formed in 14% yield. [g] Determined after catalytic hydro-
genation of 21 (H2/Pd on C).
À
fer reaction that is highly selective for primary C H bonds of
alkanes remains a challenge.
In view of the high primary/secondary selectivity obtained
with catalyst I, we examined the enantioselective intermo-
À
lecular C H bond insertion with N2C(Ph)CO2Me catalyzed
by [Rh(D4-por*)(Me)(MeOH)] (II, H2(D4-por*) = meso-tet-
À
Two features of the enantioselective C H bond insertion
reactions catalyzed by II were noted: 1) For 2,2-dimethylbu-
tane, an unreactive substrate for catalyst [Rh2((S)-dosp)4],[16b]
À
the C H bond insertion products 9a,b were obtained in 55%
yield by employing II as catalyst (Table 1, entry 2) and 2) in
À
contrast to the selective secondary or tertiary C H bond
functionalization catalyzed by [Rh2((S)-dosp)4],[16] the II-
catalyzed reactions of n-hexane and 2,2-dimethylbutane with
À
N2C(Ph)CO2Me preferentially afforded primary C H bond
insertion products 4a and 9a, respectively, albeit with
moderate enantioselectivity (65–68% ee). For both sub-
À
rakis-{(1S,4R,5R,8S)-1,2,3,4,5,6,7,8-octahydro-1,4:5,8-dime-
thano-anthracen-9-yl}porphyrin), which contains a sterically
encumbered chiral porphyrin ligand first synthesized by
Halterman and Tan.[17] The preparation of II is similar to
that of I. Reaction of N2C(Ph)CO2Me with n-hexane, 2,2-
dimethylbutane, cyclohexane, cyclopentane (14), adamantane
(15), cyclohexene (16), or ethylbenzene (17) in the presence
strates, the selectivity for primary C H bonds is about four
times that for secondary bonds (Table 1, entries 1 and 2). To
the best of our knowledge, these are the first metal-catalyzed
enantioselective carbenoid insertion reactions that feature
significantly higher selectivity for primary than for secondary
À
C H bonds.
Catalysts I and II are recyclable and robust. For the
reaction of n-decane with EDA using catalyst I (0.1 mol%)
and the reaction of cyclohexane with N2C(Ph)CO2Me using
À
of II (0.1–1.5 mol%) at 608C afforded C H bond insertion
products 4, 9, and 18–22 in up to 80% yield and up to 93% ee
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À
catalyst II (0.1 mol%), the catalysts could be reused at least
five times without significantly lowering the primary/secon-
dary selectivity or enantioselectivity (see Table S3 in the
Supporting Information), and the total number of product
turnovers reached 6477 after recycling the catalyst five times.
When 0.01 mol% of II was used, the reaction between
cyclohexane and N2C(Ph)CO2Me at 608C for 8 h gave 18 in
61% yield and 90% ee, corresponding to a product turnover
number of 6100.
Reactions were also carried out on the gram scale.
Treatment of N2C(Ph)CO2Me (3 g) and I (2 mol%) with
toluene (150 mL) at 808C for 25 h afforded 12 (2.26 g, 56%
yield), together with the dimers (43% yield) arising from
coupling of N2C(Ph)CO2Me. The reaction of N2C(Ph)CO2Me
(3 g) and II (0.1 mol%) with cyclohexane (150 mL) at 608C
for 10 h gave 18 (2.88 g, 73% yield) in 91% ee.
Keywords: C H activation · homogeneous catalysis ·
metalloporphyrins · N ligands · rhodium
.
[1] a) T. H. Maugh II, Science 1983, 220, 1261; b) R. G. Bergman,
Science 1984, 223, 902; c) W. D. Jones, F. J. Feher, Acc. Chem.
Res. 1989, 22, 91; d) W. H. Weinberg, Y. K. Sun, Science 1991,
253, 542; e) K. A. Gardner, J. M. Mayer, Science 1995, 269, 1849;
f) J. Corker, F. Lefebvre, C. Lꢁcuyer, V. Dufaud, F. Quignard, A.
Choplin, J. Evans, J.-M. Basset, Science 1996, 271, 966; g) K. M.
Waltz, J. F. Hartwig, Science 1997, 277, 211; h) R. A. Periana,
D. J. Taube, S. Gamble, H. Taube, T. Satoh, H. Fujii, Science
1998, 280, 560; i) H. Chen, S. Schlecht, T. C. Semple, J. F.
Hartwig, Science 2000, 287, 1995; j) J.-Y. Cho, M. K. Tse, D.
Holmes, R. E. Maleczka, Jr., M. R. Smith III, Science 2002, 295,
305; k) J. A. Labinger, J. E. Bercaw, Nature 2002, 417, 507; l) K.
Godula, D. Sames, Science 2006, 312, 67; m) S. Das, C. D.
Incarvito, R. H. Crabtree, G. W. Brudvig, Science 2006, 312,
1941; n) R. G. Bergman, Nature 2007, 446, 391; o) H. M. L.
Davies, J. R. Manning, Nature 2008, 451, 417.
To circumvent the difficulty of the bis-pocket porphyrin
synthesis, we directed our attention to porphyrin ligands 23
[2] a) J. D. Lawrence, M. Takahashi, C. Bae, J. F. Hartwig, J. Am.
Chem. Soc. 2004, 126, 15334; b) J. M. Murphy, J. D. Lawrence, K.
Kawamura, C. Incarvito, J. F. Hartwig, J. Am. Chem. Soc. 2006,
128, 13684.
[3] A. H. Janowicz, R. G. Bergman, J. Am. Chem. Soc. 1983, 105,
3929.
[4] a) M. P. Doyle, D. C. Forbes, Chem. Rev. 1998, 98, 911;
b) H. M. L. Davies, R. E. J. Beckwith, Chem. Rev. 2003, 103,
2861; c) H. M. L. Davies, Angew. Chem. 2006, 118, 6574; Angew.
Chem. Int. Ed. 2006, 45, 6422; d) M. M. Dꢂaz-Requejo, T. R.
Belderrain, M. C. Nicasio, P. J. Pꢁrez, Dalton Trans. 2006, 5559.
[5] D. F. Taber, R. E. Ruckle, Jr., J. Am. Chem. Soc. 1986, 108, 7686.
[6] a) H. J. Callot, F. Metz, Tetrahedron Lett. 1982, 23, 4321; b) H. J.
Callot, F. Metz, Nouv. J. Chim. 1985, 9, 167; c) M. R. Fructos, P.
de Frꢁmont, S. P. Nolan, M. M. Dꢂaz-Requejo, P. J. Pꢁrez,
Organometallics 2006, 25, 2237.
[7] a) K. S. Suslick, M. M. Fox, J. Am. Chem. Soc. 1983, 105, 3507;
b) B. R. Cook, T. J. Reinert, K. S. Suslick, J. Am. Chem. Soc.
1986, 108, 7281.
[8] a) H. Ogoshi, J. Setsune, T. Omura, Z. Yoshida, J. Am. Chem.
Soc. 1975, 97, 6461; b) B. B. Wayland, S. Ba, A. E. Sherry, J. Am.
Chem. Soc. 1991, 113, 5305.
[9] CCDC 693047, 693048, 693049 contain the supplementary
crystallographic data for this paper. These data can be obtained
free of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
[10] A. P. Nelson, S. G. DiMagno, J. Am. Chem. Soc. 2000, 122, 8569.
[11] H. M. L. Davies, Q. Jin, P. Ren, A. Y. Kovalevsky, J. Org. Chem.
2002, 67, 4165.
[12] J. L. Maxwell, K. C. Brown, D. W. Bartley, T. Kodadek, Science
1992, 256, 1544.
[13] E. Nakamura, N. Yoshikai, M. Yamanaka, J. Am. Chem. Soc.
2002, 124, 7181.
[14] H. J. Callot, E. Schaeffer, Nouv. J. Chim. 1980, 4, 311.
[15] L. Simkhovich, A. Mahammed, I. Goldberg, Z. Gross, Chem.
Eur. J. 2001, 7, 1041.
[16] a) H. M. L. Davies, T. Hansen, J. Am. Chem. Soc. 1997, 119,
9075; b) H. M. L. Davies, T. Hansen, M. R. Churchill, J. Am.
Chem. Soc. 2000, 122, 3063.
and prepared 1,3,5,7-tetramethyl-2,4,6,8-tetraterphenylpor-
phyrin (H2ttmp), reported by Chang and co-workers,[18] in
35% yield. Its rhodium complex, [Rh(tmttp)(Me)(MeOH)]
(III), was subsequently prepared, the X-ray crystal structure
of which is shown in Figure S4 in the Supporting Informa-
tion.[9] The reactions of N2C(Ph)CO2Me (0.1 mmol) with n-
hexane, n-octane, and n-decane (4 mL) catalyzed by III (2.5
mol%) at 808C for 24 h gave 4–6 in 50–55% yields, with a
primary/secondary selectivity of 6.5:1 (4a–c), 6.7:1 (5a–d),
and 7.2:1 (6a–e). Further studies are underway to enhance the
primary/secondary selectivity by tuning the Ar groups in 23.
In conclusion, by employing N2C(Ph)CO2Me and robust
sterically encumbered rhodium–porphyrin catalysts, we have
À
demonstrated highly selective primary C H bond function-
À
alization and enantioselective secondary C H bond function-
À
alization in C C bond formations by metal-catalyzed carbe-
noid transfer reactions.
[17] R. L. Halterman, S.-T. Jan, J. Org. Chem. 1991, 56, 5253.
[18] N. Bag, S.-S. Chern, S.-M. Peng, C. K. Chang, Tetrahedron Lett.
1995, 36, 6409.
Received: July 1, 2008
Published online: October 15, 2008
Angew. Chem. Int. Ed. 2008, 47, 9747 –9751
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