Silver-catalyzed C-H insertion reactions with donor-acceptor diazoacetates

Article abstract of DOI:10.1055/s-0028-1087377

In this paper we describe the first examples of carbene transfer with donor-acceptor diazoacetates and the silver tris(pyrazolyl) borate complex {HB[3,5-(CF₃)₂Pz]₃}Ag(THF). These reactions generally proceed in good yields

Full text of DOI:10.1055/s-0028-1087377

CLUSTER
129
Silver-Catalyzed C–H Insertion Reactions with Donor–Acceptor
Diazoacetates
Silver-Catalyzed
a
C–HInsert
r
ion Reac
l
tions
w
ith
D
o
J
nor–Acce
.
ptor
D
iazoa
c
L
etates ovely,* Jaime A. Flores, Xiaofeng Meng, H. V. Rasika Dias*
Department of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, Texas 76019, USA
Fax +1(817)2723808; E-mail: lovely@uta.edu; E-mail: dias@uta.edu
Received 5 September 2009
that this combination leads to addition to and subsequent
rearrangement with aromatic systems (the Büchner reac-
tion),10 the formation and rearrangement of halonium
ylides11,12 and C–H insertion (Scheme 1).13 In the latter
case it was determined with ethyl diazoacetate (EDA) that
these reactions proceed with high efficiencies, but sub-
strates containing heteroatoms did not participate effi-
ciently in this reaction. Interestingly it was discovered that
this catalyst showed unusual selectivities with substantial
levels of C–H insertion occurring at primary sites in acy-
clic alkanes, although not at this point with synthetically
useful selectivities.9,13 All of these initial studies have
been limited to reactions of EDA and in some limited cas-
es with tert-butyl diazoacetate and therefore we have be-
gun to investigate the utility of donor–acceptor
diazoacetate derivatives to determine whether the catalyst
will tolerate more substituted substrates and whether these
reactions proceed with useful selectivities. Previous work,
most notably by Davies and co-workers with rhodium
complexes has demonstrated that these metallocarbene
precursors exhibit very different reactivity profiles and
quite often enhanced selectivities, including diastereo-
and enantioselectivities in appropriate cases.14
Abstract: In this paper we describe the first examples of carbene
transfer with donor–acceptor diazoacetates and the silver tris(pyra-
zolyl)borate complex {HB[3,5-(CF3)2Pz]3}Ag(THF). These reac-
tions generally proceed in good yields and exhibit improved
selectivities compared to simple diazoacetates.
Key words: organometallic, tris(pyrazolyl)borate, silver, atom
transfer, chemoselective
The functionalization of unactivated C–H bonds is a topic
of considerable current interest, with specific focus on
accomplishing this transformation with high levels of se-
lectivity (chemoselectivity, diastereoselectivity, enantio-
selectivity, etc.).1 Several approaches to this problem have
been investigated including intramolecular reactions,2,3
appropriately placed activating groups4–6 and varying the
steric or electronic effects.7 The derivatization of sub-
strates lacking directing groups is more challenging and
requires the development of new reagents, strategies and
tactics to achieve this in a selective manner. Along these
lines we have investigated the use of silver complex
{HB[3,5-(CF3)2Pz]3}Ag(THF) (1) containing the poly-
fluorinated and highly electron-withdrawing tris(pyra-
zolyl)borate ligand (Scheme 1).1h,8,9 Previous studies from
our lab have demonstrated that this complex effectively
functions as a carbene-transfer catalyst with diazoacetates
serving as the precursor (Scheme 1). It has been found
Two diazoacetates were selected for study, methyl phe-
nyldiazoacetate (2, MPDA)14 and methyl styryldiazoace-
tate (3, MSDA),15 which were prepared by diazo transfer
to the corresponding ester according to a literature proce-
H
B
CF3
CF3
F3C
N
N
N
N
N
N
Y
Ag
F3C
CF3
CF3
1
THF
RO2C
CO2R
Y
1
1
CO2R
N2
X
X = Cl, Br
X
X
CO2R
XnCH(4–n)
RO2C
H4–nXn–1
C
Scheme 1 Diazo transfer reactions catalyzed by {HB[3,5-(CF3)2Pz]3}Ag(THF) (1)
SYNLETT 2009, No. 1, pp 0129–0132
x
x.
x
x.
2
0
0
8
Advanced online publication: 12.12.2008
DOI: 10.1055/s-0028-1087377; Art ID: S08008ST
© Georg Thieme Verlag Stuttgart · New York

130
C. J. Lovely et al.
CLUSTER
Table 1 C–H Insertion Reactions with {HB[3,5-(CF3)2Pz]3}Ag(THF) (1) with Methyl Phenyldiazoacetate (2, MPDA) and Methyl Styryl-
diazoacetate (3, MSDA)18
Entry
Substrate
Product(s)
EDA (%)
(R = H)
MPDA (%)a
(R = Ph)
MSDA (%)a
[R = (E)-CH=CHPh]
CO2R'
1
8813
8719
84
77
R
CO2R'
2
3
8813
7619
R
R
O
CO2R'
R
O
CO2R'
5
71 (3:2)b
88 (3:2)
O
CO2R'
CO2R'
4
5
24
0
91 (3:2)b
0
0
0
O
O
O
O
O
R
R
CO2R'
O
O
O
R
CO2R'
O
O
6
7
0
0
0
R
O
85c,13
(2 isomers)
6914
7414
66
CO2R'
R
R
87d,13
(4 isomers)
CO2R'
CO2R'
8
9
73
81e,13
(3 isomers)
73
R
R
CO2R'
85f
(1.2:1)b,20
H
H
13
(1:1)/38
R
10
–
–
CO2R'
CO2R'
R
a Yields correspond to chromatographically isolated products and are the average of at least two independent experiments.
b Ratios correspond to crude reaction products, and were determined from 1H NMR spectroscopy by integration of benzylic or vinylic methine
signals of the crude reaction mixture.
c For R = H the product was isolated as mixture of C1 and C2 insertion products (C1/C2 = 80:20).
d For R = H the product was isolated as a mixture of C1,C2, C3, and C4 insertion products (C1 + C4/C2/C3 = 59:14:27).
e For R = H the product was isolated as a mixture of C1, C2, and C3 insertion products (C1/C2/C3 = 41:47:12).
f The diastereomeric ratio could not be determined for this product.
dure.15 Initial experiments were conducted with cyclic hy- room temperature by syringe pump (Scheme 2). Gratify-
drocarbons and 5 mol% of the tris(pyrazolyl)boratosilver ingly, both 2 and 3 underwent efficient C–H insertion with
catalyst 1 and the diazo compound was introduced at both cyclopentane and cyclohexane in excellent yield,
comparable in efficiencies to EDA (entries 1 and 2,
Table 1). We had found with EDA that C–H insertion ad-
H
MeO2C
R
jacent to oxygen was not efficient, a result we attributed
to competitive coordination between the ether oxygen and
the diazo compound (entries 3–6, Table 1).13 With the do-
nor–acceptor carbenoids different reactivity trends
emerge. Both MPDA (2) and MSDA (3) insert efficiently
into the C–H bond adjacent to the oxygen in diethyl ether
and in both cases, a 3:2 mixture of diastereomers was ob-
tained. Unlike with EDA, MPDA provided an insertion
{HB[3,5-(CF3)2Pz]3}Ag(THF)
CO2Me
N2
R
2: R =
3: R =
Scheme 2
Synlett 2009, No. 1, 129–132 © Thieme Stuttgart · New York

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Silver Catalyzed C–H Insertion Reactions with Donor-Acceptor Diazoacetates
131
partial support of the NMR spectrometers used in the course of this
investigation.
product with THF leading to a 3:2 mixture of separable
adducts, whereas MSDA did not provide insertion prod-
ucts. Interestingly, and similar to EDA, substrates con-
taining two oxygen atoms did not undergo reaction with
MPDA or MSDA. Earlier investigations with simple acy-
clic alkanes and EDA had revealed that insertion occurs
very effectively (entries 7 and 8, Table 1), but these reac-
tions occur at all sites, including insertion into primary
C–H bonds.9 This was not the case with MPDA and
MSDA where these reactions occurred with much higher
selectivities. In the case of 2,3-dimethylbutane, this reac-
tion led to the formation of a single insertion product in
good yield, with insertion occurring at the tertiary C–H.
Similarly, 2-methylbutane provided one major insertion
product, again occurring at the tertiary C–H. Somewhat
surprisingly, it was found that with pentane insertion into
C2 was the major pathway, providing a 1:1.2 mixture of
two diastereomeric adducts in good yield. Approximately
2–3% of insertion at C3 occurs, but no detectable (1H
NMR spectroscopy of the crude reaction mixture) inser-
tion at the primary carbons occurs.
References and Notes
(1) (a) Davies, H. M. L.; Manning, J. R. Nature (London) 2008,
451, 417. (b) Skouta, R.; Li, C.-J. Tetrahedron 2008, 64,
4917. (c) Kuninobu, Y.; Nishina, Y.; Kawata, A.; Shouho,
M.; Takai, K. Pure Appl. Chem. 2008, 80, 1149.
(d) Herrerias, C. I.; Yao, X.; Li, Z.; Li, C.-J. Chem. Rev.
2007, 107, 2546. (e) Ferreira, E. M.; Zhang, H.; Stoltz,
B. M. Tetrahedron 2008, 64, 5987. (f) Diaz-Requejo,
M. M.; Perez, P. J. Chem. Rev. 2008, 108, 3379. (g) Diaz-
Requejo, M. M.; Belderrain, T. R.; Nicasio, M. C.; Perez,
P. J. Dalton Trans. 2006, 5559. (h) Dias, H. V. R.; Lovely,
C. J. Chem. Rev. 2008, 108, 3223. (i) Davies, H. M. L.; Loe,
O. Synthesis 2004, 2595. (j) Davies, H. M. L. Angew. Chem.
Int. Ed. 2006, 45, 6422.
(2) (a) Du Bois, J. Chemtracts 2006, 18, 1. (b) Zalatan, D. N.;
Du Bois, J. J. Am. Chem. Soc. 2008, 130, 9220. (c) Fiori,
K. W.; Du Bois, J. J. Am. Chem. Soc. 2007, 129, 562.
(3) (a) Taber, D. F.; Tian, W. J. Org. Chem. 2007, 72, 3207.
(b) Taber, D. F.; Joshi, P. V. J. Org. Chem. 2004, 69, 4276.
(4) (a) Daugulis, O.; Zaitsev, V. G.; Shabashov, D.; Pham,
Q.-N.; Lazareva, A. Synlett 2006, 3382. (b) Do, H.-Q.;
Daugulis, O. J. Am. Chem. Soc. 2007, 129, 12404.
(c) Chiong, H. A.; Pham, Q.-N.; Daugulis, O. J. Am. Chem.
Soc. 2007, 129, 9879. (d) Zaitsev, V. G.; Shabashov, D.;
Daugulis, O. J. Am. Chem. Soc. 2005, 127, 13154.
(e) Shabashov, D.; Daugulis, O. Org. Lett. 2005, 7, 3657.
(5) (a) Kalyani, D.; Dick, A. R.; Anani, W. Q.; Sanford, M. S.
Tetrahedron 2006, 62, 11483. (b) Kalyani, D.; Dick, A. R.;
Anani, W. Q.; Sanford, M. S. Tetrahedron 2006, 62, 11483.
(c) Desai, L. V.; Hull, K. L.; Sanford, M. S. J. Am. Chem.
Soc. 2004, 126, 9542. (d) Dick, A. R.; Hull, K. L.; Sanford,
M. S. J. Am. Chem. Soc. 2004, 126, 2300. (e) Kalyani, D.;
Deprez, N. R.; Desai, L. V.; Sanford, M. S. J. Am. Chem.
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(6) (a) Campeau, L.-C.; Fagnou, K. Chem. Commun. 2006,
1253. (b) Campeau, L.-C.; Fagnou, K. Chem. Soc. Rev.
2007, 36, 1058. (c) Campeau, L.-C.; Stuart, D. R.; Fagnou,
K. Aldrichimica Acta 2007, 40, 35. (d) Liegault, B.;
Fagnou, K. Organometallics 2008, 27, 4841. (e) Campeau,
L.-C.; Schipper, D. J.; Fagnou, K. J. Am. Chem. Soc. 2008,
130, 3266.
(7) (a) Chen, M. S.; White, M. C. Science 2007, 318, 783.
(b) Reed, S. A.; White, M. C. J. Am. Chem. Soc. 2008, 130,
3316. (c) Delcamp, J. H.; White, M. C. J. Am. Chem. Soc.
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(8) Dias, H. V. R.; Jin, W. Inorg. Chem. 1996, 35, 267.
(9) For related work with other silver tris(pyrazolyl)borates, see:
Urbano, J.; Belderrain, T. R.; Nicasio, M. C.; Trofimenko,
S.; Diaz-Requejo, M. M.; Perez, P. J. Organometallics 2005,
24, 1528.
(10) Lovely, C. J.; Browning, R. G.; Badarinarayana, V.; Dias,
H. V. R. Tetrahedron Lett. 2005, 46, 2453.
Davies and Thompson have shown that AgSbF6 will cata-
lyze the selective cyclopropanation of a variety of olefins
with both MPDA and MSDPA with high levels of chemo-
and diastereoselectivity16 and therefore we performed one
scouting experiment with cyclohexene and MPDA. Un-
like the simple silver salt, it was found that both insertion
and addition occur with relatively low selectivity and
modest yield (entry 10, Table 1).
At this point some conclusions can be drawn from these
experiments. The insertion reactions with these donor–ac-
ceptor carbenes appear to be substantially more selective
compared to EDA. These results are consistent with the
development of positive character at the insertion site as
these reactions occur at the most substituted carbon, or in
the case of the oxygen-containing substrates the a-posi-
tion is most able to stabilize positive charge, this is consis-
tent with results obtained with rhodium-based
catalysts.14,17 The result obtained with n-pentane is inter-
esting in that insertion occurs at C2 with minimal inser-
tion at the other secondary site at C3. Presumably in this
case, selectivity is a result of a combination of steric and
statistical factors, and it is of note that the reaction of n-
pentane with EDA favors insertion at C2 over C3, but to a
much reduced extent.13
In summary, our investigation demonstrates that a sil-
ver(I) complex effectively catalyzes C–H insertion of do-
nor–acceptor carbenes. These reactions generally proceed
in good to high yields and with good chemoselectivities.
These observations are in contrast with the results ob-
served with simple diazoacetates, in which substantial in-
sertion occurs at primary sites.
(11) Krishnamoorthy, P.; Browning, R. G.; Singh, S.; Sivappa,
R.; Lovely, C. J.; Dias, H. V. R. Chem. Commun. 2007, 731.
(12) Dias, H. V. R.; Browning, R. G.; Polach, S. A.;
Diyabalanage, H. V.; Lovely, C. J. J. Am. Chem. Soc. 2003,
125, 9270.
(13) (a) Dias, H. V. R.; Browning, R. G.; Richey, S. A.; Lovely,
C. J. Organometallics 2004, 23, 1200. (b) Dias, H. V. R.;
Browning, R. G.; Richey, S. A.; Lovely, C. J.
Organometallics 2005, 24, 5784.
(14) Davies, H. M. L.; Hansen, T.; Churchill, M. R. J. Am. Chem.
Soc. 2000, 122, 3063.
Acknowledgment
We are grateful to the Robert A. Welch Foundation [Y-1362 (CJL)
and Y-1289 (HVRD)] for the provision of financial support for this
program and to the NSF (CHE-9601771 and CHE-0234811) for
Synlett 2009, No. 1, 129–132 © Thieme Stuttgart · New York

132
C. J. Lovely et al.
CLUSTER
(15) Manning, J. R.; Davies, H. M. L. Org. Synth. 2007, 84, 334.
(16) Thompson, J. L.; Davies, H. M. L. J. Am. Chem. Soc. 2007,
129, 6090.
(17) Choi, M. K.-W.; Yu, W.-Y.; So, M.-H.; Zhou, C.-Y.; Deng,
Q.-H.; Che, C.-M. Chem. Asian J. 2008, 3, 1256.
(18) General Procedure for Catalysis by Carbene-Transfer
Reactions with Catalyst {HB[3,5-(CF3)2Pz]3}Ag(THF):
Methyl phenyldiazoacetate or methyl styryldiazoacetate
(0.25 mmol) dissolved in the substrate (5 mL) was added by
syringe pump over a period of ca. 3 h to a stirred solution of
the catalyst (0.005 g, 0.01 mmol) in the substrate (10 mL) in
a foil-shielded, round-bottomed flask. The resulting mixture
was stirred for 6 h at r.t., concentrated and the residue was
purified by flash chromatography on silica gel (2% Et2O–PE
for hydrocarbons, 5–20% Et2O–PE for ethers) to yield oily
transparent or white solid products. The isolated yields are
based on the average of at least two experiments and on the
amount of diazoacetate used.
(19) Davies, H. M. L.; Hansen, T. J. Am. Chem. Soc. 1997, 119,
9075.
(20) Methyl 2-Phenyl-3-methylhexanoate: yield: 40.2 mg
(73%); diastereoisomer ratio = 1.2:1. 1H NMR (300 MHz,
CDCl3): d = 7.19–7.36 (m, 10 H, ArH), 3.624 (s, 3 H, OMe),
3.620 (s, 3 H, OMe), 3.24 (d, J = 10.7 Hz, 1 H, CHPh), 3.23
(d, J = 10.3 Hz, 1 H, CHPh), 2.11–2.28 (m, 2 H, CH), 1.01–
1.50 (m, 8 H, CH2), 0.98 (d, J = 6.5 Hz, 3 H, Me), 0.89 (t,
J = 6.9 Hz, 3 H, Me), 0.73 (t, J = 6.9 Hz, 3 H, Me), 0.65 (d,
J = 6.9 Hz, 3 H, Me). 13C NMR (125 MHz, CDCl3): d =
174.54, 174.49, 138.19, 138.14, 128.61, 128.58, 128.42,
128.39, 127.14, 58.8, 55.5, 51.7, 37.6, 36.2, 36.1, 35.6, 19.9,
19.4, 17.8, 16.6, 14.2, 14.0. IR (neat): 3087, 3064, 3029,
2959, 2932, 2873, 1738 cm–1. HRMS (ESI): m/z [M + H]+
calcd for C14H21O2: 221.1536; found: 221.1537.
Synlett 2009, No. 1, 129–132 © Thieme Stuttgart · New York

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