Introducing axial chirality into mesoionic 4,4′-Bis(1,2,3-triazole) dicarbenes

Article abstract of DOI:10.1021/ol3004657

Mesoionic 4,4′-bis(1,2,3-triazole-5,5′-diylidene) Rh(I) complexes having a C2 chiral 4,4′-axis were accessed from 3-alkyltriazolium salts in virtually complete de. Their structure and configurational integrity were assessed by NMR spectroscopy, X-ray crys

Full text of DOI:10.1021/ol3004657

ORGANIC
LETTERS
2012
Vol. 14, No. 7
1866–1868
Introducing Axial Chirality into Mesoionic
4,40-Bis(1,2,3-triazole) Dicarbenes
Jesus M. Aizpurua,*,† Maialen Sagartzazu-Aizpurua,† Zaira Monasterio,† Itxaso Azcune,†
†
†
‡
‡
´
Claudio Mendicute, Jose I. Miranda, Eva Garcıa-Lecina, Ainhoa Altube, and
Raluca M. Fratila§
´
Departamento de Quımica Organica-I, Universidad del Paıs Vasco UPV/EHU, Joxe
Mari Korta R&D Center, Avda Tolosa-72, 20018 San Sebastian, Spain, Departamento
ꢀ
´
ꢀ
ꢀ
de Tratamientos de Superficie, CIDETEC-ik4, Paseo Miramon-196, 20009 San
Sebastian, Spain, and Faculty of Science and Technology, Institute of Biomedical
ꢀ
Technology and Technical Medicine (MIRA), University of Twente, 7500 AE Enschede,
The Netherlands
jesusmaria.aizpurua@ehu.es
Received February 24, 2012
ABSTRACT
Mesoionic 4,40-bis(1,2,3-triazole-5,50-diylidene) Rh(I) complexes having a C2 chiral 4,40-axis were accessed from 3-alkyltriazolium salts in virtually
complete de. Their structure and configurational integrity were assessed by NMR spectroscopy, X-ray crystallography, and chiral HPLC.
Computational analysis of the MICs involved in the reaction suggested the formation of a highly stable and unprecedented cation-carbene
intermediate species, which could be evidenced experimentally by cyclic voltammetry analysis.
Mesoionic carbenes (MICs) constitute a novel, yet
scarcely studied, class of divalent carbon species possessing
unique electronic features and transition coordination
ability.1 Very recently, 1H-1,2,3-triazole-derived MICs2 1
(Scheme 1) haveattracted special attention because oftheir
high ligand donation ability and ease of preparation
following “click” chemistry methodologies.3 Introduction
of chirality elements close to the carbene center in such
MIC compounds is a particularly challenging problem,
which was first addressed by Sankararaman et al.4
Inspired by noncarbene atropoisomeric 5,50-bistriazoles
2 described by Burgess,5 we envisioned the dicarbene
† Universidad del Paı
´
s Vasco UPV/EHU.
‡ CIDETEC-ik4.
§ University of Twente.
€
(3) (a) Lalrempuia, R.; McDaniel, N. D.; Muller-Bunz, H.; Bernhard,
S.; Albrecht, M. Angew. Chem., Int. Ed. 2010, 49, 9765–9768. (b) Kilpin,
K. J.; Paul, U. S. D.; Lee, A.-L.; Crowley, J. D. Chem. Commun. 2011, 47,
328–330. (c) Prades, A.; Peris, E.; Albrecht, M. Organometallics 2011, 30,
1162–1167. (d) Poulain, A.; Canseco-Gonzalez, D.; Hynes-Roche, R.;
(1) MICs can only be represented as zwitterions. (a) Araki, S.; Yokoi,
K.; Sato, R.; Hirashita, T.; Setsune, J.-I. J. Heterocyclic Chem. 2009, 46,
164–171. (b) Schuster, O.; Yang, L.; Raubenheimar, H. G.; Albrecht, M.
Chem. Rev. 2009, 109, 3448–3478. (c) Crowley, J. D.; Lee, A.-L.; Kilpin,
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Chem.;Eur. J. 2011, 17, 8269–8272.
€
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50, 5834–5837. See also: (b) Enders, D.; Gielen, H.; Runsink, J.; Breuer,
K.; Brode, S.; Bohen, K. Eur. J. Inorg. Chem. 1998, 913–919.
(5) Angell, Y.; Burgess, K. Angew. Chem., Int. Ed. 2007, 46, 3649–
3651.
(6) For a study on the rotation around the CꢀPdꢀC axis in
achiral complexes containing two 1,2,3-triazole-5-ylidene ligands, see:
Saravanakumar, R.; Ramkumar, V.; Sankararaman, S. Organometallics
2011, 30, 1689–1694.
(2) (a) Mathew, P.; Neels, A.; Albrecht, M. J. Am. Chem. Soc. 2008,
130, 13534–13535. (b) Guisado-Barrios, G.; Bouffard, J.; Donnadieu,
B.; Bertrand, G. Angew. Chem., Int. Ed. 2010, 49, 4759–4762. (c)
Bouffard, J.; Keitz, B. K.; Tonner, R.; Guisado-Barrios, G.; Frenking,
G.; Grubbs, R. H.; Bertrand, G. Organometallics 2011, 30, 2617–2627.
(d) Nakamura, T.; Ogata, K.; Fukuzawa, S.-I. Chem. Lett. 2010, 39,
920–922. (e) Nakamura, T.; Terashima, T.; Ogata, K.; Fukuzawa, S.-I.
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2012, 31, 405–412.
r
10.1021/ol3004657
Published on Web 03/20/2012
2012 American Chemical Society

complexes 3 as candidates to display analogous axial
chirality, provided that the very strong carbeneꢀmetal
bonds in these MICs could hold configurational stability.6
Herein we report the preparation and full structural anal-
ysis of the first enantiopure C2-type MIC dicarbenes 3
with a C4ꢀC40-chiral axis created during the metalation
process.
The absolute configuration of the newly created C4ꢀC40
chiral axis for 3bꢀc was unambiguously established as (R)
for both compounds from the X-ray crystallograms
(Figure 1, top). Their optical purities were further con-
firmed by chiral HPLC analysis (Figure 1, bottom), show-
ingsinglepeaksforenantiopure3bꢀcbuttwopeaksfor the
racemic mixture 3a. Optical rotations were also in full
agreement with these data.
Scheme 1. Mesoionic 1,2,3-Triazole-derived Carbenes 1 and
Chiral 4,40-Bis(1,2,3-triazole) Dicarbene Complexes 3;
Synthesis from 4,40-Bis(1,2,3-triazolium) Salts 4aꢀca
a Cod = 1,5-cyclooctadienyl group.
In previous work to prepare 4,40-bis(1H-1,2,3-triazole)s,
we developed a fully site-controlled method to synthesize
unsymmetrically substituted N-alkylated 4,40-bis(1,2,3-
triazolium) salts 4,7 which can be considered as the natural
precursors of MICs 3. Upon deprotonation/metalation of
4 with Ag2O in acetonitrile, the intermediate silver dicar-
bene complexes were obtained quantitatively after 24 h at
80 °C.8 1H NMR monitoring at the early stages of the
reaction revealed a mixture of the two possible diastereo-
mers around the C4ꢀC40 biaryl bond for the silver dicar-
benes 3bꢀc [M = Ag], although they experienced a
thermodynamic equilibration to a single complex in each
case (see Supporting Information (SI) Figures S3ꢀS4).
Subsequent transmetalation with [Rh(cod)Cl]2 to afford
the complexes3 [M = Rh(cod)Cl] occurredwithtotal axial
configuration integrity, as judged from the single set of
Figure 1. (Top) ORTEP plot of the X-ray crystal structure of the
chiral carbene complex 3b. (Bottom) Chiral stationary phase
HPLC chromatograms of rhodium complexes 3a (racemic) and
3c (enantiopure).
In order to gain insight into the intermediate carbene
species involved in the Ag-metalation reaction that could
explain the efficient thermodynamic equilibration ob-
served, ab initio calculations were conducted to estimate
the protonation affinities (PA1),9 HOMO energies, and
HOMO/LUMO gaps of carbenes 5ꢀ7 (R1 = R2 = Me,
Figure 2; SI Figure S17). In all instances, singlet carbenes
were the more stable electronic configurations with
1
proton signals observed in the H NMR spectra and the
large singletꢀtriplet band gaps2b (54ꢀ57 kcal molꢀ1).
sharp double doublets for the benzylic diastereotopic
protons in 3a and 3b. Characteristic 13C NMR doublets
of Rh(I) carbenes at δ ≈ 170 ppm (1JRhꢀC ≈ 46 Hz) were
also recorded. Compounds 3aꢀc were completely stable to
the air and moisture at room temperature.
3
We found that neutral carbene 5 and dicarbene 7 gave
,
protonation affinities in the range ∼270ꢀ280 kcal molꢀ1
3
in line with previous results reported for monotriazole
carbenes 1 and classical 1,3-imidazolium carbenes.2b,c In
contrast, the cationic MIC 6 yielded dramatically low PA1,
HOMO energy, and HOMO/LUMO energy gap values,
likely resulting from the strong stabilization of the carbene
by the conjugated electrodeficient triazolium moiety.
Seeking an experimental confirmation of the antici-
pated stability of cation carbenes 6, we studied the depro-
tonation reaction of bistriazolium dication salt 4a under
cathodic electroreduction conditions to generate the naked
(7) (a) Aizpurua, J. M.; Sagartzazu-Aizpurua, M.; Monasterio, Z.;
Azcune, I.; Miranda, J. I.; Garcıa-Lecina, E.; Fratila, R. M. Synthesis
´
2011, 2737–2742. (b) Aizpurua, J. M.; Azcune, I.; Fratila, R. M.;
Balentova, E.; Sagartzazu-Aizpurua, M.; Miranda, J. I. Org. Lett.
2010, 12, 1584–1587. See also: (c) Fiandanese, V.; Bottalico, D.;
Marchese, G.; Punzi, A.; Capuzzola, F. Tetrahedron 2009, 65, 10573–
10580. (d) Doak, B. C.; Scanlon, M. J.; Simpson, J. S. Org. Lett. 2011, 13,
537–539.
(8) This double metallation of 1,4-bis(1,2,3-triazolium) salts con-
trasted with the formation of 1,4-bidentated monometallated Rh(I)
complexes upon deprotonation of the bistriazolium salts with NaOEt
followed by trapping with [Rh(cod)(OEt)]2, as reported recently by
Bertrand et al.; see: Guisado-Barrios, G.; Bouffard, J.; Donnadieu, B.;
Bertrand, G. Organometallics 2011, 30, 6017–6021.
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Org. Lett., Vol. 14, No. 7, 2012
1867

Figure 2. PA1 protonation affinities (kcal molꢀ1), HOMO en-
3
3
ergies (eV), and HOMO/LUMO gap (kcal molꢀ1) for bis(1,2,3-
triazole) carbenes 5ꢀ7 (R1 = R2 = Me) calculated with
Gaussian09 optimized energies and BP86/def2-SVP gradients.
carbenes (Figure 3).10 The monoalkylated triazolium salt
9a and the parent bistriazole 8a were analyzed by cyclic
voltammetry (CV) for comparison purposes. Unlike 8a,
which shows no electrochemical activity in the potential
window studied, a well-defined cathodic peak was mea-
sured at ꢀ1.6 V for monocation 9a, denoting the electro-
reduction to the neutral carbene 5a (see SI Figure S18). In
contrast, the bis(triazolium) salt 4a showed two different
reduction potentials, consistent with the stepwise forma-
tion of the stabilized cation carbene 6a at a lower reduction
potential (ꢀ1.3 V) and the neutral dicarbene 7a at ꢀ1.6 V.
In conclusion, we have demonstrated that mesoionic
dicarbenes derived from 4,40-bis(1,2,3-triazolium) salts can
be endowed with axial chirality at one bond distance from
the carbene center by promoting a double metalation
reaction at positions C5 and C50. When the starting bis-
triazoles bear stereogenic groups at positions N1 and/or
N10 a perfect stereoinduction assisted by thermodynamic
equilibration can be achieved at the newly created C4ꢀC40
chiral axis. The metalation reaction occurs through a
cation-carbene intermediate, strongly stabilized by conju-
gative effects. This species has been identified by cyclic
voltammetry in the first example of an electrogenerated
Figure 3. Cyclic voltammograms of 4,40-bis(1,2,3-triazole) deriv-
atives 4a, 9a, and 8a. Conditions: 25 °C, 2 ꢁ 10ꢀ3 M in DMF/
TBAFP(10ꢀ1 M), referenced to Ag/AgCl, using ferrocene/fer-
rocenium (Fc/Fcþ) redox couple (E° = 0.508 V vs Ag/AgCl,
labeled with an asterisk). TBAFP = tetrabutylammonium
hexafluorophosphate.
mesoionic carbene. It can be expected that these novel
chiral carbene ligands could be structurally tuned to
meet interesting applications in the field of asymmetric
catalysis.11
Acknowledgment. This work was supported by the
ꢀ
Ministerio de Ciencia e Innovacion (MICINN, Spain)
(Project: CTQ2010-21625-C02-01), UPV/EHU, and Gobierno
Vasco (ETORTEK-nanoIKER IE-11/304). We thank SGIker
UPV/EHU for NMR and X-ray crystallography facilities.
Grantsfrom GobiernoVasco toM.S.A. and UPV/EHUto
Z.M. are acknowledged.
Supporting Information Available. Preparation proce-
dures and full characterization data for compounds 3aꢀc,
4aꢀc, and 9a. NMR spectra of 3aꢀc. Cyclic voltammo-
gram analysis data. Gaussian output data of structures
5ꢀ7. CIF files of 3aꢀc. This material is available free of
charge via the Internet at http://pubs.acs.org.
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E307–E311. (b) Gorodetsky, B.; Ramnial, T.; Branda, N. R.; Clyburne,
J. A. C. Chem. Commun. 2004, 1972–1973. (c) Feroci, M.; Chiarotto, I.;
Orsini, M.; Sotgiu, G.; Inesi, A. Adv. Synth. Catal. 2008, 350, 1355–1359.
ꢀ
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´
The authors declare no competing financial interest.
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