Unexpected TiIII/Mn-promoted pinacol coupling of ketones

Article abstract of DOI:10.1021/jo9005238

Titanocene(III) chemistry has emerged in the last decades as an indispensable tool in C-C bond-forming reactions. In this context, pinacol and related reactions allow the stereoselective synthesis of vicinal diols. In this work, we present new applications of these reactions using as starting materials aromatic ketones. Simple and smooth reaction conditions have been developed and have been applied for inter- and intramolecular processes. We also describe that although Cp₂TiCl is usually used as a monoelectronic reducing agent, it can be also used as an efficient Lewis acid.

Full text of DOI:10.1021/jo9005238

Unexpected TiIII/Mn-Promoted Pinacol Coupling
of Ketones
SCHEME 1.
Mn
Pinacol Coupling of 1 Promoted by Cp2TiCl2/
Miguel Paradas, Araceli G. Campan˜a, Rosa E. Este´vez,
´
Luis Alvarez de Cienfuegos, Tania Jime´nez, Rafael Robles,
Juan M. Cuerva,* and J. Enrique Oltra*
Department of Organic Chemistry, Faculty of Sciences,
UniVersity of Granada, E-18071 Granada, Spain
alkenes and alkynes,6 a divergent C-C bond-forming reaction
with modulation by Ni or Pd,7 or the metal-catalyzed Barbier-
type cyclization and R-prenylation of carbonyl derivatives.8
Moreover, several authors have shown how Nugent’s reagent
is capable of promoting pinacol couplings of conjugated
aldehydes,9 but in contrast, Barden and Schwartz reported that
Nugent’s reagent showed low reactivity toward pinacol coupling
of aromatic ketones.10
jmcuerVa@ugr.es; joltra@ugr.es
ReceiVed March 09, 2009
Nevertheless, we have serendipitously found that treatment
of acetophenone (1) with Nugent’s reagent, generated in situ
by stirring Cp2TiCl2 with an excess of Mn dust,11 provided
pinacol-coupling products 2 and 3 with good overall yield (81%)
and considerable stereoselectivity (dl/meso ratio ) 9/1) (Scheme
1).12 The above result attracted our attention due not only to
the potential synthetic value of this selective C-C bond-forming
reaction but also to the apparent discrepancy with the Barden
and Schwartz’s observations.
To clarify this discrepancy, we prepared solid (Cp2TiCl)2 as
described by these authors10 and treated model ketone 1 with
this dinuclear form of Nugent’s reagent. In this manner, we
obtained only 10% of a 2/3 mixture (dl/meso ) 2/1) confirming
the relatively low reactivity of the (Cp2TiCl)2 dimer. We
subsequently treated 1 with (Cp2TiCl)2 and an excess of Mn
dust. Under these conditions, similar to those employed in the
reaction with Nugent’s reagent generated in situ, we obtained
products 2 and 3 with overall yield (72%) and stereoselectivity
(dl/meso ) 16/1) similar to those depicted in Scheme 1.
Moreover, when we used the combination of (Cp2TiCl)2 and
Titanocene(III) chemistry has emerged in the last decades
as an indispensable tool in C-C bond-forming reactions. In
this context, pinacol and related reactions allow the stereo-
selective synthesis of vicinal diols. In this work, we present
new applications of these reactions using as starting materials
aromatic ketones. Simple and smooth reaction conditions
have been developed and have been applied for inter- and
intramolecular processes. We also describe that although
Cp2TiCl is usually used as a monoelectronic reducing agent,
it can be also used as an efficient Lewis acid.
During the last two decades, bis(cyclopentadienyl)titanium(I-
II) chloride, Nugent’s reagent (Cp2TiCl), has become a formi-
dable tool in organic synthesis,1 facilitating unprecedented
chemical transformations as useful as the homolytic ring-opening
of epoxides,2 the radical cascade cyclization of epoxypolyenes,3
the Michael-type coupling between aldehydes and conjugated
alkenals,4 the H-atom transfer from water to free radicals,5
(6) Campan˜a, A. G.; Este´vez, R. E.; Fuentes, N.; Robles, R.; Cuerva, J. M.;
Bun˜uel, E.; Ca´rdenas, D.; Oltra, J. E. Org. Lett. 2007, 9, 2195–2198.
(7) Campan˜a, A. G.; Bazdi, B.; Fuentes, N.; Robles, R.; Cuerva, J. M.; Oltra,
J. E.; Porcel, S.; Echavarren, A. M. Angew. Chem., Int. Ed. 2008, 47, 7515–
7519.
(8) (a) Rosales, A.; Oller-Lo´pez, J. L.; Justicia, J.; Gansa¨uer, A.; Oltra, J. E.;
Cuerva, J. M. Chem. Commun. 2004, 2628–2629. (b) Este´vez, R. E.; Justicia,
J.; Bazdi, B.; Fuentes, N.; Paradas, M.; Choquesillo-Lazarte, D.; Garc´ıa-Ruiz,
J. M.; Robles, R.; Gansa¨uer, A.; Cuerva, J. M.; Oltra, J. E. Chem.sEur. J. 2009,
15, 2774–2791.
(9) (a) Handa, Y.; Inanaga, J. Tetrahedron Lett. 1987, 28, 5717–5718. (b)
Gansa¨uer, A. Chem. Commun. 1997, 457–458. (c) Gansa¨uer, A.; Bauer, D. J.
Org. Chem. 1998, 63, 2070–2071. (d) Gansa¨uer, A.; Bauer, D. Eur. J. Org.
Chem. 1998, 2673–2676. (e) Hirao, T.; Hatano, B.; Asahara, M.; Muguruma,
Y.; Ogawa, A. Tetrahedron Lett. 1998, 39, 5247–5248. (f) Dunlap, M. S.;
Nicholas, K. M. J. Organomet. Chem. 2001, 630, 125–131.
(1) For pertinent reviews, see: (a) Gansa¨uer, A.; Bluhm, H. Chem. ReV. 2000,
100, 2771–2788. (b) Gansa¨uer, A.; Pierobon, M. In Radicals in Organic
Synthesis; Renaud, P., Sibi, M. P., Eds.; Wiley-VCH: Weinheim, Germany, 2001;
Vol. 2, pp 207-220. (c) Gansa¨uer, A.; Narayan, S. AdV. Synth. Catal. 2002,
344, 465–475. (d) Gansa¨uer, A.; Lauterbach, T.; Narayan, S. Angew. Chem.,
Int. Ed. 2003, 42, 5556–5573. (e) Cuerva, J. M.; Justicia, J.; Oller-Lo´pez, J. L.;
Oltra, J. E. Top. Curr. Chem. 2006, 264, 63–91.
(2) For pioneering reports on epoxide opening promoted by Nugent’s reagent,
see:(a) RajanBabu, T. V.; Nugent, W. A. J. Am. Chem. Soc. 1994, 116, 986–
997, and references cited therein. (b) Gansa¨uer, A.; Bluhm, H.; Pierobon, M.
J. Am. Chem. Soc. 1998, 120, 12849–12859. (c) Barrero, A. F.; Rosales, A.;
Cuerva, J. M.; Oltra, J. E. Org. Lett. 2003, 5, 1935–1938.
(3) (a) Justicia, J.; Rosales, A.; Bun˜uel, E.; Oller-Lo´pez, J. L.; Valdivia, M.;
Ha¨ıdour, A.; Oltra, J. E.; Barrero, A. F.; Ca´rdenas, D. J; Cuerva, J. M.
Chem.sEur. J. 2004, 10, 1778–1788. (b) Justicia, J. E; Oltra, J. M; Cuerva, J.
Org. Chem. 2004, 69, 5803–5806. (c) Justicia, J.; Oltra, J. E.; Cuerva, J. M. J.
Org. Chem. 2005, 70, 8265–8272. (d) Justicia, J.; Oller-Lo´pez, J. L.; Campan˜a,
A. G.; Oltra, J. E.; Cuerva, J. M.; Bun˜uel, E.; Ca´rdenas, D. J. J. Am. Chem. Soc.
2005, 127, 14911–14921.
(4) Este´vez, R. E.; Oller-Lo´pez, J. L.; Robles, R.; Melgarejo, C. R.; Gansa¨uer,
A.; Cuerva, J. M.; Oltra, J. E. Org. Lett. 2006, 8, 5433–5436.
(5) Cuerva, J. M.; Campan˜a, A. G.; Justicia, J.; Rosales, A.; Oller-Lo´pez,
J. L.; Robles, R.; Ca´rdenas, D.; Bun˜uel, E.; Oltra, J. E. Angew. Chem., Int. Ed.
2006, 45, 5522–5526.
(10) Barden, M. C.; Schwartz, J. J. Am. Chem. Soc. 1996, 118, 5484–5485.
(11) Nugent’s reagent generated in situ by stirring commercial Cp2TiCl2 with
Zn or Mn dust in THF exists as an equilibrium mixture of the monomer Cp2TiCl
and the dinuclear species (Cp2TiCl)2; see: (a) Enemærke, R. J.; Larsen, J.;
Skrydstrup, T.; Daasbjerg, K. J. Am. Chem. Soc. 2004, 126, 7853–7864. (b)
Daasbjerg, K.; Svith, H.; Grimme, S.; Gerenkamp, M.; Mu¨ck-Lichtenfeld, C.;
Gansa¨uer, A.; Barchuck, A.; Keller, F. Angew. Chem., Int. Ed. 2006, 45, 2041–
2044. (c) Gansa¨uer, A.; Barchuk, A.; Keller, F.; Schmitt, M.; Grimme, S.;
Gerenkamp, M.; Mu¨ck-Lichtenfeld, C.; Daasbjerg, K.; Svith, H. J. Am. Chem.
Soc. 2007, 129, 1359–1371.
(12) Oller-Lo´pez, J. L.; Campan˜a, A. G.; Cuerva, J. M.; Oltra, J. E. Synthesis
2005, 2619–2622.
3616 J. Org. Chem. 2009, 74, 3616–3619
10.1021/jo9005238 CCC: $40.75 2009 American Chemical Society
Published on Web 03/31/2009

SCHEME 2. Proposed Mechanism for (Cp2TiCl)2/
M-Mediated Coupling of 1
single-electron transfer from the reductive metal to the coor-
dinated carbonyl group, and (ii) as a template responsible for
the stereoselectivity observed. The Lewis acid character of
titanocene(III) and the ability of titanium to exert template
effects are well documented,3d,8b,22 and in fact, a high dl
stereoselection has been associated with metal-bridged inter-
mediates such as 6.15 To the best of our knowledge, however,
this is the first evidence reported to date suggesting that a
titanocene(III) can facilitate an outer sphere electron transfer
from an heterogeneous metal and a coordinated ketone.
Based on these encouraging results, we extended the stereo-
selective Ti(III)/M(0)-mediated homocoupling pinacol reaction
to other aromatic and R,ꢀ-unsaturated ketones (Table 1, entries
1-4).23
As expected, we obtained the homocoupling pinacol products
of different aromatic ketones (entries 1-3) and mesityl oxide
(entry 4) in good to moderate yields maintaining the dl
stereoselectivity. Although the effect of the substituents has not
been studied in depth it does not seem to affect substantially
the stereoselectivity.
Zn dust, we obtained closely related results.13 What is more,
when we used a substoichiometric proportion of (Cp2TiCl)2 (0.3
equiv) and Mn or Zn dust, both good yields (74-82%) and
stereoselectivities (dl/meso ) 15/1) were retained. Finally, after
control experiments with Mn or Zn, in the absence of titanium,
pinacol coupling products were not detected and ketone 1 was
recovered unchanged.13 The high stereoselection obtained
suggests that a bulky titanocene(III) complex is directly involved
in the pinacol coupling process.14,15 It is worth noting that there
are few examples of pinacol couplings of acetophenone deriva-
tives with high stereoselection.16
Moreover, intermediate species 5 would have nucleophilic
character, thus achieving the “umpolung” of the intrinsically
electrophilic ketone like 1, and can be used to carry out inter-
and intramolecular cross-coupling reactions.
Although it has been described that (Cp2TiCl)2 promotes the
pinacolization of aromatic and R,ꢀ-unsaturated aldehydes9 via
an inner-sphere electron transfer generating the corresponding
titanoxy radicals, our experimental results suggest that in this
case a smooth reducing agent such as (Cp2TiCl)2 (E0 for
Cp2TiCl2/Cp2TiCl is -0.8 V vs Fc+/Fc)11a,17 is not acting as a
simple single electron donor. Mn dust, a stronger reducing
agent18 present in the reaction media, was also unable to promote
the pinacolization reaction of 1. Nevertheless, it is known that
metals with Lewis acid character are able to decrease the E0
values in the electrochemical reduction of carbonyl com-
pounds.19 Moreover, it is known that mixtures of Zn/ZnCl2 are
able to pinacolize acetophenone in 50% aqueous THF at 70
°C, although without significant stereoselection.20
Therefore, we checked the ability of titanocene(III) to promote
pinacol coupling between dissimilar ketones. Initially, we stirred
acetophenone 1 with Cp2TiCl (1.1 mmol) in THF/acetone during
1 h at room temperature. In this manner, we obtained the
intermolecular cross-coupling product, 2,3-dihydroxy-2-methyl-
3-phenylbutane 19 (entry 5), isolated by flash chromatography
at an 83% yield. This result showed that in our reaction
conditions ketone-derived ketyl radicals can attack an aliphatic
ketone to give an unsymmetrical diol. An intramolecular version
of this reaction would lead to cyclic vicinal diols. Bearing this
idea in mind, we prepared substrates 12-14,13 and they were
submitted to the standard reaction conditions. We obtained in
moderate isolated yields (50-80%) the intramolecular cross-
coupling products 20-22, definitively confirming the first
presumption of our hypothesis.
We only detected the cis isomer of cyclic diol 20, but five-
and six-membered rings were formed as mixtures of cis/trans
diastereomers (21, 1:1; 22, 3:1). The preference for cis-
cyclohexanediol 22-cis has synthetic value because it is
complementary to the trans-selectivity observed in pinacol
coupling of 1,6-dials catalyzed by bulky Cp2TiPh.24 Thus,
titanocene chemistry becomes a versatile tool for the synthesis
of 1,2-cyclohexanediols with reagent control on the stereo-
chemistry. It should be noted that other synthetic methods
recently reported can only provide trans isomers.25
Based on these precedents, the experimental results can be
easily rationalized if the mechanism depicted in Scheme 2 is
accepted.21 In this mechanism titanium plays a double role: (i)
as a Lewis acid to coordinate with ketone 1, facilitating the
(13) For more details, including experimental ones, see the Supporting
Information.
(14) For a helpful discussion about the stereoselectivity in TiIII-mediated
pinacolizations, see: Enemærke, R. J.; Larsen, J.; Hjollund, G. H.; Skrydstrup,
T.; Daasbjerg, K. Organometallics 2005, 24, 1252–1262.
(15) For a recent review of stereoselective pinacol coupling reactions, see:
Chatterjee, A.; Joshi, N. N. Tetrahedron 2006, 62, 12137–12158.
(16) (a) Nishiyama, Y.; Shinomiya, E.; Kimura, S.; Itoh, K.; Sonoda, N.
Tetrahedron Lett. 1998, 39, 3705–3708. (b) Ogawa, A.; Takeuchi, H.; Hirao, T.
Tetrahedron Lett. 1999, 40, 7113–7114. (c) Arai, S.; Sudo, Y.; Nishida, A. Chem.
Pharm. Bull. 2004, 52, 287–288. (d) Aspinall, H. C.; Greeve, N.; Valla, C. Org.
Lett. 2005, 7, 1919–1922.
(17) Cyclic voltammograms of different titanocene(III) complexes determined
in THF indicated potential values considerably less negative than that of SmI2,
one of the most commonly used single-electron-transfer reagents; see: Enemærke,
R. J.; Daasbjerg, K.; Skrydstrup, T. Chem. Commun. 1999, 343–344.
(18) The described E0 value for Mn2+/Mn is-1.18 vs hydrogen electrode:
Handbook of Chemistry and Physics, 85th ed.; Lide, D. R., Ed.; CRC Press:
Boca Raton, 2004; pp 8-25-8-26.
(19) (a) Douch, J.; Mousset, G. Can. J. Chem. 1987, 65, 549–556. (b)
Fournier, F.; Fournier, M. Can. J. Chem. 1986, 64, 881–890.
(20) Tanaka, K.; Kishigami, S.; Toda, F. J. Org. Chem. 1990, 55, 2981–
2983.
(21) Together with the nucleophilic-coupling mechanism depicted in Scheme
2, the conventional bimolecular radical-radical pinacol coupling mechanism9
possibly coexists, but especially under the conditions with substoichiometric
proportions of titanium, the former probably prevails.
The cis-stereoselectivity observed for TiIII/M-promoted cy-
clizations of diketones 12 and 14 can be rationalized by the
closed transition-state models 25 and 26, respectively (Figure
1). In the intermediate 25, the geometry of the cyclobutane ring
imposes a cis configuration which leads to the cis diol 20. In
transition state 26-cis, only one of the bulky substituents (phenyl
(22) Sato, F.; Iida, K.; Ijima, S.; Moriya, H.; Sato, M. Chem. Commun. 1981,
1140–1141.
(23) Aliphatic ketones were inert under these reaction conditions.
(24) Yamamoto, Y.; Hattori, R.; Miwa, T.; Nakagai, Y.-i.; Kubota, T.;
Yamamoto, C.; Okamoto, Y.; Itoh, K J. Org. Chem. 2001, 66, 3865–3870.
(25) (a) Fujiwara, T.; Tsuruta, Y.; Arizono, K.; Takeda, T. Synlett 1997,
962–964. (b) Balskus, E. P.; Me´ndez-Andino, J.; Arbit, R. M.; Paquette, L. A.
J. Org. Chem. 2001, 66, 6695–6704.
J. Org. Chem. Vol. 74, No. 9, 2009 3617

TABLE 1. Cp2TiCl/M Dust C-C Bond-Forming Reactionsa
TABLE 2. Cp2TiCl/Mn Dust-Catalyzed Pinacol Reactions
entry
ketone
product (dl/meso)
yield (%)
1
2
3
4
5
1
8
9
10
11
2 (9:1)
83
75
71
60
75
15 (9:1)
16 (9:1)
17 (7:3)
18 (7:3)
of 14. The higher conformational flexibility of five-membered
rings would allow similar energies for both cis and trans
transition states, and thus, cis and trans isomers were formed
in similar proportions.
The ketyl radicals generated by this Ti/Mn dust mixture can
be also used in another interesting C-C bond-forming reaction
such as a Michael-type addition to R,ꢀ-unsaturated esters. These
reactions have been extensively carried out using SmI2 as
promoter of the ketyl radical.26 Nevertheless, SmI2 has some
drawbacks often associated with its chemoselectivity, its high
molecular weight, and its price.26 For this purpose, we use 20
equiv of methyl acrylate and methyl crotonate as trapping agents
for the initially formed ketyl radicals leading to lactones 23
(Table 1, entry 9) and 24 (Table 1, entry 10), respectively, in
acceptable yields. The 7:1 trans/cis stereochemistry obtained
for lactone 24 is almost correlated with the complete E
stereochemistry of starting methyl crotonate, showing that
minimal stereochemical information is lost during the addition
reaction.
More interestingly, the pinacol coupling reaction of acetophe-
none and related ketones can be carried out using only 0.2 mmol
of Cp2TiCl and 3.0 mmol of Mn dust with the aid of a
titanocene-regenerating agent (Table 2). In this case, the mixture
of trimethylsilyl chloride (1.5 mmol) and 2,4,6-collidine (3.0
mmol) developed in our laboratory was used,1c,27 giving, for
example, the corresponding coupling products of acetophenone,
2 and 3, in similar yield (83%) and stereoselectivity (9:1 dl/
meso) than in the stoichiometric conditions. Control experiments
showed that the mixture of Mn, trimethylsilyl chloride, and
2,4,6-collidine is unable to promote such pinacol couplings. We
also found that the molar relationship between the titanocene
and the trimethylsilyl chloride was critical in order to retain
the stereoselectivity. Thus, for example, an increase in the
amount of trimethylsilyl chloride (4 mmol) gave a 4:1 mixture
of dl/meso stereoisomers (73%), probably due to an early rupture
of the titanium-oxygen bond in species like 5 by the regenerat-
ing agent. It is also worth noting that to our knowledge it is the
first time that acetophenone and related compounds have been
pinacolized with high stereoselection using substoichiometric
amount of a metallic catalyst.28
a Carbonyl compound (1 mmol), Cp2TiCl2 (1.1 mmol), Mn (8 mmol).
b 100 equiv of acetone was added. c Zn was used instead of Mn. d 1:1
mixture of cis/trans stereoisomers. e 3:1 mixture of cis/trans
stereoisomers. f 20 equiv of methyl acrylate was added. g 20 equiv of
methyl crotonate was added. h 1:7 mixture of cis/trans stereoisomers.
In summary, we have demonstrated that, in contrast to the
low reactivity shown by (Cp2TiCl)2 alone, the combination of
Nugent’s reagent with a reductive metal (Mn or Zn) is capable
of promoting the pinacol coupling of conjugated ketones with
good yields and considerable stereoselectivity. This reaction has
mechanistic subtleties such as the role played by the carbonyl-
(26) For a recent review, see: Kagan, H. B. Tetrahedron 2003, 59, 10351–
10372.
FIGURE 1. Closed transition-state models 25 and 26.
(27) For other regenerating agents, see: (a) Reference 1b. (b) Gansa¨uer, A.;
Bluhm, H.; Rinker, B.; Narayan, S.; Schick, M.; Lauterbach, T.; Pierobon, M.
Chem.sEur. J. 2003, 9, 531–542. (c) Gansa¨uer, A.; Lauterbach, T.; Narayan,
S. Angew. Chem., Int. Ed. 2003, 42, 5556–5573. (d) Fuse, S.; Hanochi, M.;
Doi, T.; Takahashi, T. Tetrahedron Lett. 2004, 45, 1961–1963.
(28) For a related titanium(III)-based system, see: Hirao, T.; Hatano, B.;
Asahara, M.; Muguruma, Y.; Ogawa, A. Tetrahedron Lett. 1998, 39, 5247–
5248.
or methyl) is in an axial position, thus minimizing the unfavor-
able 1,3-diaxial interactions. In the hypothetical intermediate
26-trans, however, both phenyl and methyl groups would be
in an axial disposition, thus raising the activation energy and
consequently lowering the reaction rate toward the trans isomer
3618 J. Org. Chem. Vol. 74, No. 9, 2009

dust (8.0 mmol) under Ar atmosphere, and the suspension was
stirred at room temperature until it turned green (about 15 min). A
solution of carbonyl compound (1.0 mmol), 2,4,6-collidine (3.0
mmol), and Me3SiCl (1.5 mmol) in THF (2 mL) was then added.
The mixture was stirred for 16 h and then diluted with EtOAc,
washed with 10% aqueous HCl solution and brine, and dried over
anhydrous MgSO4 and the solvent removed. The residue was
submitted to flash chromatography (EtOAc/hexane mixtures) to give
the corresponding products.
coordinated titanocene(III) in the initial electron transfer from
the heterogeneous metal. The nucleophilic intermediate thus
generated can be exploited for intramolecular cross-coupling
(cyclization) of diketones. At this time, we are engaged in the
development of an enantioselective version of this process.
Experimental Section
General Methods. For the reactions using titanocene all solvents
and additives were rigorously deoxygenated prior to use. The
following known compounds were isolated as pure samples and
showed NMR spectra identical to reported data: 2,29 12,30 13,31
14,32 16,33 18,34 19,35 20,36 21,36 22,36 23,37 and 24.38
General Procedure for Ti(III)/M(0)-Mediated Reaction. Rig-
orously deoxygenated THF (20 mL) was added to a mixture of
Cp2TiCl2 (1.1 mmol) and Mn or Zn dust (8.0 mmol) under Ar
atmosphere, and the suspension was stirred at room temperature
until it turned green (about 5 min). A solution of carbonyl compound
(1.0 mmol), and additive if required, in THF (2 mL) was then added.
The mixture was stirred for 1 h (Scheme 1, Table 1, entries 1-4)
or 16 h (Table 1, entries 5-10) and then diluted with EtOAc,
washed with brine, and dried over anhydrous MgSO4 and the solvent
removed. The residue was submitted to flash chromatography
(EtOAc/hexane mixtures) to give the corresponding products.
Compound 15: yellowish oil; (dl) 1H NMR (300 MHz, CDCl3)
δ 7.10-7.14 (m, 4H), 6.85-6.95 (m, 4H), 2.45 (s, 2H), 1.48 (s,
6H); 13C NMR (75 MHz, CDCl3, DEPT) δ 162.1 (d, 1JC-F ) 245.0
3
2
Hz, C), 139.3 (C), 129.3 (d, JC-F ) 7.0 Hz, CH), 114.0 (d, JC-F
) 21.0 Hz, CH), 78.8 (C), 25.1 (CH3); (meso) 1H NMR (300 MHz,
CDCl3) δ 7.19-7.21 (m, 4H), 1.56 (s, 6H); 13C NMR (75 MHz,
3
CDCl3, DEPT) δ (only distinctive signals) 128.9 (d, JC-F ) 7.0
Hz, CH), 78.6 (C), 25.3 (CH3); ESHRMS calcd for C16H16O2F2Na
m/z 301.1010, found m/z 301.1020).
Compound 17: colorless oil; (dl) H NMR (300 MHz, CDCl3)
1
δ 7.36 (bs, 2H), 6.36 (bs, 2H), 6.24 (bs, 2H), 1.48 (s, 6H); 13C
NMR (75 MHz, CDCl3, DEPT) δ 156.8 (C), 141.8 (CH), 110.5(CH),
107.3(CH), 76.7(C), 22.6(CH3); (meso) 1H NMR (300 MHz, CDCl3)
δ 7.36 (bs, 2H), 6.24 (bs, 2H), 6.04 (bs, 2H), 1.60 (s, 6H); 13C
NMR (75 MHz, CDCl3, DEPT) δ 156.9 (C), 141.6 (CH), 110.3
(CH), 106.5 (CH), 76.6 (C), 21.7 (CH3); ESHRMS calcd for
C12H14O4Na m/z 245.0784, found m/z 245.0788.
General
Procedure
for
Ti(III)/Mn(0)-Catalyzed
Homocoupling Pinacol Reaction. Rigorously deoxygenated THF
Acknowledgment. To the Spanish Ministry of Sciences and
Innovation (projects CTQ2005-08402 and CTQ2008-06790) and
the “Junta de Andalucia” (projects P05-FQM-1111, P06-FQM-
01726, and aids to the group FQM339) for financial support.
M.P. thanks the “Junta de Andalucia” for his grant. A.G.C.,
R.E.E., and T.J. thank the Spanish Ministry of Sciences and
Innovation for their grants. L.A.C. thanks the University of
Granada for a postdoctoral contract.
(15 mL) was added to a mixture of Cp2TiCl2 (0.2 mmol) and Mn
(29) (a) Fu¨rstner, A.; Csuk, R.; Rohrer, C.; Weidmann, H. J. Chem. Soc.,
Perkin Trans. 1 1988, 1729–1734. (b) Seebach, D.; Oie, H. A.; Daum, H. Chem.
Ber. 1977, 110, 2316–2333.
(30) Goossen, L. J.; Ghosh, K. Eur. J. Org. Chem. 2002, 3254–3267.
(31) Li, L.-Z.; Xiao, B.; Guo, Q.-Z.; Xue, S. Tetrahedron 2006, 62, 7762–
7771.
(32) Balskus, E. P.; Me´ndez-Andino, J.; Arbit, R. M.; Paquette, L. A. J.
Org. Chem. 2001, 66, 6695–6704.
(33) Balu, N.; Nayak, S. K.; Banerji, A. J. Am. Chem. Soc. 1996, 118, 5932–
5937.
(34) Pons, J.-M.; Santelli, M. J. Org. Chem. 1989, 54, 877–884.
(35) Kobayashi, S.; Endo, M.; Nagayama, S. J. Am. Chem. Soc. 1999, 121,
11229–11230.
(36) Kise, N.; Shiozawa, Y.; Ueda, N. Tetrahedron 2007, 63, 3415–5426.
(37) Garnier, J. M.; Robin, S.; Rousseau, G. Eur. J. Org. Chem. 2007, 3281–
3291.
Supporting Information Available: . Experimental data for
control experiments and the synthesis of compounds 12-14.
Spectroscopic data and copies of NMR spectra for products
described. This material is available free of charge via the
Internet at http://pubs.acs.org.
(38) Fang, J.-M.; Hong, B.-C.; Liao, L.-F. J. Org. Chem. 1987, 52, 855–
861.
JO9005238
J. Org. Chem. Vol. 74, No. 9, 2009 3619