Paper
Organic & Biomolecular Chemistry
product by column chromatography (hexane–t-BuOMe, 3 : 1). the Reaction diagram and r09, r10 in Table 3):
1H NMR (CDCl3, 500 MHz) δ 6.37 (s, 2H), 3.82 (s, 6H), 3.80 (s,
d½RHꢀ=dt ¼ k09½TiCl3Rꢀ½TiCl3OHꢀ þ k10½TiCl3Rꢀ½HClꢀ with
k09 ¼ A expðꢁb09=RTÞ; k10 ¼ A expðꢁb10=RTÞ and
3H), 2.29 (s, 3H), 2.27 (m, 2H)‡ ppm. 13C NMR (CDCl3,
125 MHz) δ 153.0, 137.3, 133.5, 106.0, 60.8, 56.0, 21.5 ppm.
HRFABMS calcd for C10H14O3Na [M + Na]+ 205.0841, found
205.0835. (‡ Signals corresponding to deuterated derivative.)
A ¼ 4 ꢂ 107 Mꢁ1 sꢁ1
:
1,2-Bis(3,4,5-trimethoxyphenyl)ethane
(10).5c 1H
NMR
(CDCl3, 500 MHz) δ 6.37 (s, 4H), 3.82 (s, 9H), 2.85 (s, 4H) ppm.
13C NMR (CDCl3, 125 MHz) δ 153.1, 137.4, 136.3, 105.5, 61.0,
Acknowledgements
56.1, 38.6 ppm. HRFABMS calcd for C20H26O6Na [M + Na]+ This project was supported by the Spanish Ministry of
385.1627, found 385.1629.
Economy and Competitiveness (project CTQ2010-16818-BQ)
and Consej. Educ. JCyL, (project SA221U13).
Reduction/homocoupling procedure for 11
Notes and references
The lithium derivative 11 was prepared, reacted and the result-
ing crude product was purified following a similar experi-
mental procedure as for compound 5.
Results corresponding to the experiments carried out for
the study and the optimization of the reduction/homocoupling
methodology (Tables 1–2) were calculated by reaction yields
and 1H NMR integrals in the case of the mixtures of 2–3 or
9–10 obtained from the first silica gel flash chromatography.
1 The single electron transfer of bis(cyclopentadienyl)-Ti(III)
chloride, can be generated in situ by stirring commercial
Cp2TiCl2 with dust Mn. For pioneering reports on the use
of this reagent, see: T. V. RajanBabu and W. A. Nugent,
J. Am. Chem. Soc., 1994, 116, 986–997 and references cited
therein. For pertinent reviews on the use of this reagent,
see: (a) A. Gansäuer and H. Bluhm, Chem. Rev., 2000, 100,
2771–2788; (b) A. Gansäuer, T. Lauterbach and S. Narayan,
Angew. Chem., Int. Ed., 2003, 42, 5556–5573;
(c) A. F. Barrero, J. F. Quílez, E. M. Sánchez and
J. F. Arteaga, Eur. J. Org. Chem., 2006, 1627–1641;
(d) J. Justicia, L. Álvarez de Cienfuegos, A. Campaña,
D. Miguel, V. Jakoby, A. Gansäuer and J. M. Cuerva, Chem.
Soc. Rev., 2011, 40, 3525–3537; (e) B. Rossi, S. Prosperini,
N. Pastori, A. Clerici and C. Punta, Molecules, 2012, 17,
14700–14732.
2 (a) B. Giese, in Radicals in Organic Synthesis: Formation of
Carbon–Carbon Bonds, Pergamon Press, Oxford, 1986;
(b) D. P. Curran, N. A. Porter and B. Giese, in Stereo-
chemistry of Radical Reactions, VCH, Weinheim, 1996;
(c) D. P. Curran and D. M. Rakiewicz, J. Am. Chem. Soc.,
1985, 107, 1448–1449; (d) S. L. Danishefsky and J. S. Panek,
J. Am. Chem. Soc., 1987, 109, 917–918.
3 H. R. Diéguez, A. López, V. Domingo, J. F. Arteaga,
J. A. Dobado, M. M. Herrador, J. F. Quílez and A. F. Barrero,
J. Am. Chem. Soc., 2010, 132, 254–259.
4 A. Millán, A. Campaña, B. Bazdi, D. Miguel, L. Álvarez de
Cienfuegos, A. M. Echavarren and J. M. Cuerva, Chem. –
Eur. J., 2011, 17, 3985–3994.
5 (a) A. F. Barrero, M. M. Herrador, J. F. Quílez, P. Arteaga,
J. F. Arteaga, H. R. Diéguez and E. M. Sánchez, J. Org.
Chem., 2007, 72, 2988–2995; (b) A. F. Barrero,
M. M. Herrador, J. F. Quílez, P. Arteaga, J. F. Arteaga,
M. Piedra and E. M. Sánchez, Org. Lett., 2005, 7, 2301–
2304; (c) A. F. Barrero, M. M. Herrador, J. F. Quílez,
P. Arteaga, M. Akissira, F. El Hanbali, J. F. Arteaga,
H. R. Diéguez and E. M. Sánchez, J. Org. Chem., 2007, 72,
2251–2254.
Theoretical calculations
Geometry optimizations and energy calculations were per-
formed with GAUSSIAN 09 using DFT at the B3LYP/6-31+G(d,p)
level of theory in vacuo. To simulate the solvent effect used
in the experimental reactions (THF), a single point calculation
was performed at the same level described before, using the
SMD continuum model. Transition state structures were opti-
mized as saddle points at the same level of calculation. A
vibrational analysis was performed at the same level of theory
in order to determine the zero-point vibrational energy and to
characterize each stationary point as a minimum or transition
state structure. Transition states were identified by the pres-
ence of a single imaginary frequency that corresponded to the
expected motion along the reaction coordinate. The reported
energies are expressed in Hartrees (au) and include zero-point
energy corrections. The same energies expressed in Kcal mol−1
as relative energies appear in Scheme 4 in the paper. To verify
that the TSs correspond to the expected reactant and product
wells, intrinsic reaction coordinate (IRC) calculations were
performed at the same level b3lyp/6-31+g(d,p). In the IRC
plots, energies do not include zero point energy corrections.
Structural drawings were produced by Spartan’08.
Conformational studies were performed using an MMFF94
force-field with Spartan 08 prior to quantum mechanical
optimization.
The reaction set listed in Table 3 and shown in the Reaction
Diagram above was implemented in Copasi (Complex Pathway
SiImulator). The kinetics of a chemical species is determined
by the rate law associated with individual reactions. For
example, the concentration of R–H evolves with time as (see
6 A. F. Barrero, J. F. Quílez, E. M. Sánchez and J. F. Arteaga,
Org. Lett., 2006, 8, 667–672.
3468 | Org. Biomol. Chem., 2015, 13, 3462–3469
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