Regio- and Stereoselective Rhodium(II)-Catalyzed C-H Functionalization of Organosilanes by Donor/Acceptor Carbenes Derived from Aryldiazoacetates

Article abstract of DOI:10.1021/acs.orglett.9b01833

The regioselective and enantioselective intermolecular sp³ C-H functionalization of silicon-substituted alkanes with aryl diazoacetates was accomplished using the recently developed dirhodium catalyst Rh₂(S-TPPTTL)₄. These reactions generate a diverse array of stereodefined substituted silacycloalkanes with high enantioselectivity and diastereoselectivity.

Full text of DOI:10.1021/acs.orglett.9b01833

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Regio- and Stereoselective Rhodium(II)-Catalyzed C−H
Functionalization of Organosilanes by Donor/Acceptor Carbenes
Derived from Aryldiazoacetates
Zachary J. Garlets,† Elliot F. Hicks,† Jiantao Fu,† Eric A. Voight,‡ and Huw M. L. Davies*,†
†Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, Georgia 30322, United States
‡Research & Development, AbbVie, 1 North Waukegan Road, North Chicago, Illinois 60064, United States
S
* Supporting Information
ABSTRACT: The regioselective and enantioselective intermo-
lecular sp3 C−H functionalization of silicon-substituted alkanes
with aryl diazoacetates was accomplished using the recently
developed dirhodium catalyst Rh2(S-TPPTTL)4. These reac-
tions generate a diverse array of stereodefined substituted
silacycloalkanes with high enantioselectivity and diastereose-
lectivity.
Scheme 1. Recent Developments in Selective C−H
Functionalization Reactions with Donor/Acceptor
Carbenes
he selective functionalization of unactivated C−H bonds
Thas rapidly matured into a useful and attractive synthetic
strategy for constructing complex organic molecules.1 One
approach to C−H functionalization is the selective inter-
molecular insertion of donor/acceptor carbenes stabilized by
dirhodium tetracarboxylate catalysts into C−H bonds.2 Over
the course of the development of this reaction, several
functional groups have emerged which serve to stabilize the
putative positive charge development in the transition state
and ultimately enhance the lability of specific C−H bonds.
These effects include conjugation, inductive, and steric effects.
In addition to understanding and implementing these effects,
our group is currently developing a suite of catalysts that can
functionalize C−H bonds at will depending on the catalyst and
the functional groups present.3 As shown in Scheme 1, several
new catalysts can pinpoint specific C−H bonds through
carbene-induced sp3 C−H functionalization at a variety of
different sites. For example, while transformations at activated
benzylic sites are precedented,3a,b three different catalysts,
Rh2(R-3,5-di(p-tBuC6H4)TPCP)4, Rh2(S-TCPTAD)4, and
Rh2(R-tris(p-tBuC6H4)TPCP)4, can selectively functionalize
either secondary,3c tertiary,3d or primary3e unactivated C−H
bonds, respectively. Furthermore, Rh2(S-2-Cl-5BrTPCP)4
achieved selective functionalization of remote C−H bonds in
the presence of electronically activated benzylic C−H bonds.3f
Most recently, Rh2(S-TPPTTL)4 was shown to be capable of
desymmetrizing substituted cyclohexane derivatives, generating
three stereocenters by the conversion of one C−H bond.3g
Despite extensive work in the functionalization of C−H
bonds, hyperconjugation has been understudied as a
prominent interaction for enhancing site-selective and stereo-
selective C−H bond functionalization. While early work
demonstrated the feasibility of utilizing the β-silicon effect to
control regioselectivity in carbene reactions, none of these
studies showcased a stereoselective reaction.4 Additional
interest in organosilanes is evident in the literature related to
the agrochemical,5 materials,6 and pharmaceutical industries.7
Received: May 27, 2019
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.9b01833
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Organic Letters
Letter
In particular, silicon can be incorporated into bioactive
compounds for manipulating pharmacokinetic properties.7
Due to the paucity of stereoselective investigations for
elucidating the role of hyperconjugation toward enhancing
specific C−H bond lability, the selective C−H functionaliza-
tion of organosilanes using Rh2(S-NTTL)4 and 1,2,3-N-
sulfonyl triazoles as carbene precursors was recently reported.8
These reactions were effective for generating functionalized
organosilanes bearing amino groups, but several limitations
prompted our inquiries into improving this reaction. First, the
most effective catalyst for the transformation of 1,2,3-N-
sulfonyl triazoles was Rh2(S-NTTL)4, but this catalyst was only
able to achieve modest diastereoselectivity (∼5:1 dr) in
reactions with unsymmetrical silanes. Additionally, challenges
arose in expanding the substrate scope of the donor group on
the donor/acceptor carbene. For example, the incorporation of
heteroaromatic groups as the donor on 1,2,3-N-sulfonyltriazole
has yet to be reported for carbene C−H insertion reactions.
We reasoned that changing to aryl diazoacetate compounds
could provide an opportunity to improve the stereoselectivity
of the chiral substituted silacycloalkanes by testing the catalyst
collection we have developed. Moreover, utilization of aryl
diazoacetates would allow the exploration of heteroaromatic
donors on the carbene precursor.9
available catalysts were unsuitable for attaining enantioselec-
tivities higher than 90% ee (entries 1−6). Even the use of
Rh2(S-NTTL)4, which was effective for 1,2,3-N-sulfonyltria-
zoles,8 failed to provide satisfactory results (entry 4).
Fortunately, the implementation of a recently developed
catalyst, Rh2(S-TPPTTL)4, was able to achieve product
formation in 74% yield and 96% ee (entry 7). This catalyst
is readily made in two steps from commercially available
reagents, and it has recently demonstrated a remarkable ability
to desymmetrize cyclohexane derivatives,3g but its utility with
other types of substrates had not been reported. Further
optimization studies indicated that the trichloroethyl ester
provided the best results compared to other ester derivatives
(entries 8−10). In addition, a small increase in enantiose-
lectivity was obtained from a solvent screen in which α,α,α-
trifluorotoluene was deemed optimal (entries 11−14). Finally,
the reaction could be conducted on 1 mmol scale (entry 16)
without negatively influencing the outcome of the reaction.
Next, the substrate scope was examined, and a number of
different aryl diazoacetates were found to be effective. This
included a variety of different substituted aryl rings that were
competent in this transformation (Scheme 2). The reaction
tended to suffer from lower yields for silanes bearing bulky aryl
groups even though the enantioselectivity remained high.10
Importantly, the substrate scope of the aryl donor could be
expanded to heteroaromatic donors such as pyridine,
pyrimidine, and thiophene (entries 15−17). The absolute
configuration was determined by X-ray crystallographic
analysis of 8.
To this end, we set out to optimize the reaction using
commercially available silacyclobutane 1 and aryl diazoacetate
2 (Table 1). It was quickly determined that the current set of
Table 1. Catalyst Optimization Studies
We also evaluated 5-membered ring silacyclopentane to
determine if high levels of diastereoselectivity could be
achieved using Rh2(S-TPPTTL)4. When 1-sulfonyl-1,2,3-
triazoles were used previously for the C−H insertion of five-
membered rings, lower levels of diastereoselectivity were
achieved (up to 5:1 dr). To investigate the unique aptitude of
this new catalyst for controlling diastereoselectivity, a catalyst
screen was conducted using a variety of catalysts that have
demonstrated recent success with similar transformations
(Scheme 3).11 While all of the catalysts delivered the desired
compound, the levels of diastereoselectivity were low, but
when Rh2(S-TPPTTL)4 was utilized as the catalyst the dr of 20
was improved up to ∼13:1.12 The relative configuration was
assigned on the basis of shielding effects arising from preferred
conformers of the products.13 The general success of Rh2(S-
TPPTTL)4 for achieving highly stereoselective reactions was
further evidenced by the formation of 21 with 20:1 dr and 98%
ee for the major diastereomer and the formation of 22 with
10:1 dr and 87% ee for the major diastereomer. The
importance of the trichloroethyl ester group was also assessed
by using methyl 2-(4-bromophenyl)-2-diazoacetate in the
reaction for the generation of 23. The diastereoselectivity for
this reaction dropped to 3:1 dr even though both
diastereomers were produced with high enantioselectivity
(major = 93% ee; minor 86% ee).
a
b
yield
ee
entry
catalyst
product
solvent
CH2Cl2
CH2Cl2
(%)
(%)
1
2
Rh2(S-DOSP)4
3a
3a
55
67
58
−62
Rh2(R-3,5-
di(p-tBuC6H4)
TPCP)4
Rh2(S-pPhTPCP)4
Rh2(S-NTTL)4
3
4
5
6
7
8
9
3a
3a
3a
3a
3a
3b
3c
3d
3a
3a
3a
3a
3a
3a
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CHCl3
ClCH2CH2Cl
TFT
45
70
59
57
74
67
54
68
72
61
64
61
69
74
72
38
−40
88
96
88
92
93
94
94
Rh2(S-PTAD)4
Rh2(S-TCPTAD)4
Rh2(S-TPPTTL)4
Rh2(S-TPPTTL)4
Rh2(S-TPPTTL)4
Rh2(S-TPPTTL)4
Rh2(S-TPPTTL)4
Rh2(S-TPPTTL)4
Rh2(S-TPPTTL)4
Rh2(S-TPPTTL)4
Rh2(S-TPPTTL)4
Rh2(S-TPPTTL)4
10
11
c
12
13
14
95
98
98
98
d
15
e
TFT
TFT
The success of Rh2(S-TPPTTL)4 in generating highly
diastereoselective reactions made us curious about the
possibility of selectively functionalizing either an equatorial
or axial C−H bond when the substituents on silicon were
different (Scheme 4). For this to be accomplished, substrates
like 24 and 25 needed to undergo preferential C−H insertion
at either an equatorial or axial C−H bond relative to the aryl
substitution. Normally, C−H functionalization occurs prefer-
entially at equatorial C−H bonds where sterics are minimized,
16
a
Reaction conditions: 2 (0.25 mmol) in 3.0 mL of solvent was added
over 3 h to a solution of the silane substrate (0.75 mmol, 3.0 equiv)
and catalyst (1.0 mol %) in 1.5 mL of solvent at room temperature.
The reaction was allowed to stir for an additional 2 h. All yields are
isolated yields. The enantioselectivity was determined by chiral
HPLC analysis of the isolated product. The reaction was conducted
b
c
d
e
at reflux. 0.5 mmol scale. 1 mmol scale.
B
DOI: 10.1021/acs.orglett.9b01833
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Organic Letters
Letter
Scheme 2. Scope of Silacyclobutane C−H
Functionalization*
Scheme 3. Diastereoselective Silacylopentane C−H
Functionalization
Scheme 4. Diastereoselective C−H Functionalization of
Silacyclobutanes with Different Silyl Substituents
*
Reaction conditions: diazo compound (0.5 mmol) in 6.0 mL of
PhCF3 was added over 3 h to a solution of the silane substrate (1.5
mmol, 3.0 equiv) and catalyst Rh2(S-TPPTTL)4 (0.5−1.0 mol %) in
3.0 mL of PhCF3 at room temperature, and then the reaction was
allowed to stir for an additional 2 h. All yields are isolated yields. The
enantioselectivity was determined by chiral HPLC analysis of the
a
isolated product. Reaction conducted on 3 mmol scale.
so if any conformational bias is present in the molecule, some
diastereoselectivity may be achieved. Indeed, the slight
conformational bias of 24 was evidenced by the modest
diastereoselectivity of 2:1−3:1 when Rh2(OAc)4 was utilized as
the catalyst for formation of 26 and 27. This suggested that a
catalyst framework was necessary to further enhance selectivity.
This was confirmed by evaluating Rh2(S-TPPTTL)4 as the
catalyst, where the generation of 26 and 27 was achieved with
high levels of diastereoselectivity (>20:1) in addition to high
levels of enantioselectivity (96% ee and 99% ee). Additionally,
the formation of 28 and 29 was accomplished with good
diastereoselectivity (9:1 dr and 7:1 dr) and great enantiose-
lectivity (97% ee and 96% ee for each major compound).14
The relative configuration was established by 1H NOE analysis
of the products, and the absolute stereochemistry was
tentatively assigned by analogy to 8 (see the Supporting
Information).
The structure of Rh2(S-TPPTTL)4 has been studied by
means of X-ray-crystallographic analysis and computational
C
DOI: 10.1021/acs.orglett.9b01833
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Organic Letters
Letter
studies.3g The catalyst has a deep cavity, as illustrated in Figure
1, and the 16 phenyl rings on the four phthalimido groups
Eric A. Voight: 0000-0002-9542-5356
Huw M. L. Davies: 0000-0001-6254-9398
Notes
The authors declare the following competing financial
interest(s): H.M.L.D. is a named inventor on a patent entitled
Dirhodium Catalyst Compositions and Synthetic Processes
Related There-to (US 8,974,428, issued 3/10/2015).
ACKNOWLEDGMENTS
■
Financial support was provided by AbbVie, NSF under the
CCI Center for Selective C−H Functionalization (CHE-
1700982) and the NIH (GM099142-05). Z. J. G. was
supported on a fellowship from the NIH (F32GM130020).
Instrumentation used in this work was supported by the
National Science Foundation (CHE 1531620 and CHE
1626172). We wish to thank the members of the NSF Center
for C−H Functionalization (CHE-1700982) for helpful
discussions regarding this work. We thank Dr. John Bacsa
and Mr. Thomas Pickel at the Emory X-ray Crystallography
Facility for the X-ray structural analysis.
Figure 1. Space-filling representation of the structure of Rh2(S-
TPPTTL)4 (top-down view; 16 phenyl rings in blue).
adopt an orientation resulting in propeller chirality. When
Rh2(S-TPPTTL)4 was used for the desymmetrization of
alkylcyclohexanes, the enantioselectivity at the carbene center
was very high, favoring the R configuration, and the shape of
the cavity within the catalyst caused the reactions to be highly
site-selective and diastereoselective. In the case of the current
studies, the asymmetric induction at the carbene site again
favors the formation of the R configuration. The distinctive
shape of the pocket is likely to be a major factor explaining why
reactions with this catalyst proceed with higher levels of
diastereocontrol compared to all other chiral dirhodium
catalysts examined.
In conclusion, the regio- and stereoselective C−H
functionalization reaction of silicon-substituted alkanes was
realized using aryl diazoacetates and the sterically encumbered
catalyst Rh2(S-TPPTTL)4. These reactions show high stereo-
selectivity, including diastereoselectivity at the β position of
silacycloalkanes, and are amenable to the incorporation of
heteroaromatic donors.
REFERENCES
■
(1) (a) Gutekunst, W. R.; Baran, P. S. C−H functionalization logic
in total synthesis. Chem. Soc. Rev. 2011, 40, 1976−1991. (b) New-
house, T.; Baran, P. S. If C−H bonds could talk: selective C-H bond
oxidation. Angew. Chem., Int. Ed. 2011, 50, 3362−3374. (c) Yama-
guchi, J.; Yamaguchi, A. D. Itami, K. C−H bond functionalization:
emerging synthetic tools for natural products and pharmaceuticals.
Angew. Chem., Int. Ed. 2012, 51, 8960−9009.
(2) Davies, H. M. L.; Morton, D. Guiding principles for site selective
and stereoselective intermolecular C−H functionalization by donor/
acceptor rhodium carbenes. Chem. Soc. Rev. 2011, 40, 1857−1869.
(3) (a) Guptill, D. M.; Davies, H. M. L. 2,2,2-Trichloroethyl
Aryldiazoacetates as Robust Reagents for the Enantioselective C−H
Functionalization of Methyl Ethers. J. Am. Chem. Soc. 2014, 136,
17718−17721. (b) Qin, C.; Davies, H. M. L. Role of Sterically
Demanding Chiral Dirhodium Catalysts in Site-Selective C−H
Functionalization of Activated Primary C−H Bonds. J. Am. Chem.
Soc. 2014, 136, 9792−9796. (c) Liao, K.; Negretti, S.; Musaev, D. G.;
Bacsa, J.; Davies, H. M. L. Site-selective and stereoselective
functionalization of unactivated C−H bonds. Nature 2016, 533,
230−234. (d) Liao, K.; Pickel, T. C.; Boyarskikh, V.; Bacsa, J.;
Musaev, D. G.; Davies, H. M. L. Site-selective and stereoselective
functionalization of non-activated tertiary C−H bonds. Nature 2017,
551, 609−613. (e) Liao, K.; Yang, Y.-F.; Li, Y.; Sanders, J. N.; Houk,
K. N.; Musaev, D. G.; Davies, H. M. L. Design of catalysts for site-
selective and enantioselective functionalization of non-activated
primary C−H bonds. Nat. Chem. 2018, 10, 1048−1055. (f) Liu,
W.; Ren, Z.; Bosse, A. T.; Liao, K.; Goldstein, E. L.; Bacsa, J.; Musaev,
D. G.; Stoltz, B. M.; Davies, H. M. L. Catalyst-Controlled Selective
Functionalization of Unactivated C−H Bonds in the Presence of
Electronically Activated C−H Bonds. J. Am. Chem. Soc. 2018, 140,
12247−12255. (g) Fu, J.; Ren, Z.; Bacsa, J.; Musaev, D. G.; Davies, H.
M. L. Desymmetrization of cyclohexanes by site- and stereoselective
C−H functionalization. Nature 2018, 564, 395−399.
(4) (a) Seyferth, D.; Washburne, S. S.; Attridge, C. J.; Yamamoto, K.
Halomethylmetal compounds. XXXIV. Insertion of phenyl-
(bromodichloromethyl)mercury-derived dichlorocarbene into car-
bon-hydrogen bonds. Tetraalkylsilicon and tetraalkyltin compounds.
J. Am. Chem. Soc. 1970, 92, 4405−4417. (b) Seyferth, D.; Damrauer,
R.; An-drews, S. B.; Washburne, S. S. Halomethyl metal compounds.
XLIV. Reactions of phenyl (bromodichloromethyl) mercury derived
dichlorocarbene with silacyclobutanes. Novel ring expansion reaction.
J. Am. Chem. Soc. 1971, 93, 3709−3713. (c) Seyferth, D.; Shih, H.-M.;
Dubac, J.; Mazerolles, P.; Serres, B. The insertion of phenyl-
(bromodichloromethyl)mercury-derived dichlorocarbene into the Si-
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.9b01833.
Complete experimental data and images of the NMR
spectra and HPLC traces (PDF)
Accession Codes
CCDC 1902706 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
via www.ccdc.cam.ac.uk/data_request/cif, or by emailing
data_request@ccdc.cam.ac.uk, or by contacting The Cam-
bridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: hmdavie@emory.edu.
ORCID
Jiantao Fu: 0000-0002-1067-6915
D
DOI: 10.1021/acs.orglett.9b01833
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C(ring) and βC−H bonds of the cis and trans isomers of 1,3-
dimethyl-1-n-butyl-1-silacyclobutane J. J. Organomet. Chem. 1973, 50,
39−45. (d) Ando, W.; Konishi, K.; Migita, T. Reactions of
carboalkoxycarbenes with alkylsilanes. J. Organomet. Chem. 1974,
67, C7−C9. (e) Danilkina, L. P.; Sidorenko, G. V. Interposition of
Thermocatalytically Generated (ethoxycarbonyl)carbene in a C−H
Bond in a Tetraorganosilane. J. Gen. Chem. USSR (Engl. Transl.)
1979, 49, 2460−2461. (f) Hatanaka, Y.; Watanabe, M.; Onozawa, S.;
Tanaka, M.; Sakurai, H. Rhodium-Catalyzed Insertion of Carbenoids
into β C−H Bonds of Silacycloalkanes: A Facile and General
Approach to Functionalized Silacycloalkanes. J. Org. Chem. 1998, 63,
422−423.
(5) (a) Cash, G. G. Use of Graph-Theoretical Parameters to Predict
Activity of Organosilane Insecticides. Pestic. Sci. 1997, 49, 29−34.
(b) Moberg, W. K.; Basarab, G. S.; Cuomo, J.; Liang, P. H.
Biologically Active Organosilicon Compounds: Fungicidal Silylme-
thyltriazoles. In Synthesis and Chemistry of Agrochemicals; ACS
Symposium Series 355; American Chemical Society: Washington,
DC, 1987; pp 288−301.
(6) (a) Jones, R. G.; Ando, W.; Chojnowski, J. Silicon-Containing
Polymers; Springer: Berlin, 2000. (b) Kumagai, T.; Itsuno, S.
Asymmetric Allylation Polymerization of Bis(allylsilane) and
Dialdehyde Containing Arylsilane Structure. Macromolecules 2002,
35, 5323−5325. (c) Bai, D.; Han, S.; Lu, Z.-H.; Wang, S. Bright blue
luminescent pyrenyl-containing organosilicon compounds with
contrasting charge transport functionality  SiPh2(p-C6H4-pyrenyl)-
(p-C6H4-N-benzimida-zolyl) and SiPh2(p-C6H4-pyrenyl) [p-C6H4-
NPh(1-naph)]. Can. J. Chem. 2008, 86, 230−237. (d) Su, T. A.;
Widawsky, J. R.; Li, H.; Klausen, R. S.; Leighton, J. L.; Steigerwald, M.
L.; Venkataraman, L.; Nuckolls, C. Silicon Ring Strain Creates High-
Conductance Pathways in Single-Molecule Circuits. J. Am. Chem. Soc.
2013, 135, 18331−18334.
(7) (a) Tacke, R.; Zilch, H. Sila-substitution−a useful strategy for
drug design? Endeavour 1986, 10, 191−197. (b) Tacke, R.; Linoh, H.
Bioorganosilicon Chemistry. In Organic Silicon Compounds; John
Wiley & Sons, Ltd.: New York, 1989; Vol. 2, p 1143. (c) Showell, G.
A.; Mills, J. S. Chemistry challenges in lead optimization: silicon
isosteres in drug discovery. Drug Discovery Today 2003, 8, 551−556.
(d) Mills, J. S.; Showell, G. A. Exploitation of silicon medicinal
chemistry in drug discovery. Expert Opin. Invest. Drugs 2004, 13,
1149−1157. (e) Franz, A. K.; Wilson, S. O. Organosilicon molecules
with medicinal applications. J. Med. Chem. 2013, 56, 388−405.
(f) Franz, A. K. The synthesis of biologically active organosilicon
small molecules. Curr. Opin. Drug Discovery Dev. 2007, 10, 654−671.
(g) Fujii, S.; Hashimoto, Y. Progress in the medicinal chemistry of
silicon: C/Si exchange and beyond. Future Med. Chem. 2017, 9, 485−
505. (h) Ramesh, R.; Reddy, D. S. Quest for Novel Chemical Entities
through Incorporation of Silicon in Drug Scaffolds. J. Med. Chem.
2018, 61, 3779−3798.
(8) Garlets, Z. J.; Davies, H. M. L. Harnessing the β-Silicon Effect
for Regioselective and Stereoselective Rhodium(II)-Catalyzed C−H
Functionalization by Donor/Acceptor Carbenes Derived from 1-
Sulfonyl-1,2,3-triazoles. Org. Lett. 2018, 20, 2168−2171.
(9) Fu, L.; Mighion, J. D.; Voight, E. A.; Davies, H. M. L. Synthesis
of 2,2,2,-Trichloroethyl Aryl- and Vinyldiazoacetates by Palladium-
Catalyzed Cross-Coupling. Chem. - Eur. J. 2017, 23, 3272−3275.
(10) Even the use of the smaller trifluoroethyl ester resulted in
poorer yield and enantioselectivity.
(11) See the SI for comparative details.
(12) The second best catalyst Rh2(S-NTTL)4 generated the desired
compound with 4:1 dr, which was similar to the levels of
diastereoselectivity obtained using 1-sulfonyl-1,2,3-triazoles as car-
bene precursors. See ref 8.
(13) Davies, H. M. L.; Ren, P. Conformational analysis and
stereochemical assignments of products derived from C−H activation
at secondary sites. Tetrahedron Lett. 2001, 42, 3149−3151.
(14) The opposite enantiomer of the catalyst was utilized to obtain
sufficient separation by chiral HPLC chromatography for determining
enantiomeric ratios.
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