Stereoselective pinacol coupling in aqueous media

Full text of DOI:10.1021/ja9606485

5
484
J. Am. Chem. Soc. 1996, 118, 5484-5485
Stereoselective Pinacol Coupling in Aqueous Media
titanium complex is apparently sterically undemanding: the
pinacol” coupling of benzaldehyde using aqueous TiCl3 (pH
10-12) gives hydrobenzoin in good yield (88%) but with
“
)
Michael C. Barden and Jeffrey Schwartz*
3
o
poor diastereoselectivity (dl:meso ) 1.3:1). Inexpensive and
III
10
easy to prepare green titanocene chloride, [Cp2Ti Cl]2 (1),
Department of Chemistry, Princeton UniVersity
III
+
readily hydrolyzes to give blue [Cp2Ti (H2O)] (2) which is
stable in water in the absence of oxygen. Complex 1 is a
Princeton, New Jersey 08544-1009
1
1
12
good reducing agent, reacting with activated alkyl halides or
ReceiVed February 28, 1996
1
3
IV
epoxides by heteroatom abstraction to give Cp2Ti halide or
alkoxy complexes and alkyl radicals. We now report that 1
effectively reductively couples aromatic and R,â-unsaturated
aldehydes to give 1,2-diols in high yield under either anhydrous
or aqueous conditions. Perhaps because the metallocene moiety
Reductive coupling of aldehydes and ketones to glycols
1
(
pinacol coupling) is a standard reaction of organic synthesis,
2
3
4
and Mg metal or various low-valent complexes of Ti, Zr,
V, Nb,
5
5a,6
7
8
Sn, or Sm can be used for efficient synthesis of
1
4
inter- or intramolecular pinacol coupling, often with high
diastereoselectivity. However, most conventional reductive-
coupling methods are incompatible with aqueous conditions or
“Cp2Ti-X” is sterically demanding, pinacol coupling also
occurs with high diastereoselectivity.
1
5
In a general procedure, benzaldehyde (200 mg; 2 mmol)
dissolved in 20 mL of THF was added dropwise to a green
solution of 1 (462 mg; 1.1 mmol of the dimer; 1.1 equiv) in 20
mL of THF at -78 °C. The reaction mixture slowly turned
red-brown, and the reaction mixture was allowed to warm to
room temperature. After 1 h, hydrolysis (aqueous NaOH; Et2O
extraction) followed by chromatography gave 200 mg of
hydrobenzoin (95%; 98:2 dl:meso). When a similar procedure
was attempted in THF:H2O (4:1) but starting at 0 °C, the only
reaction noted was hydrolysis of 1. However, when NaCl (8
g; 62 equiv per Ti) was added, the reaction mixture rapidly
turned green. It was allowed to warm to room temperature,
and after 5 h, it had become red. Hydrolysis and gas
chromatographical analysis of an aliquot showed complete
consumption of the benzaldehyde. Workup was accomplished
by pouring the reaction mixture into 1 N NaOH followed by
extraction with Et2O to give hydrobenzoin. The crude residue
1
protic functionality, and reagents possessing aqueous stability
might not be stereoselective.3
n-p,9
For example, although
aqueous TiCl3 can be used for pinacol coupling of aromatic
ketones and aldehydes in basic solution, the intermediate aquo
(
1) For comprehensive reviews, see: (a) Wirth, T. Angew. Chem., Int.
Ed. Engl. 1996, 35, 61. (b) Dushin, R. G. In ComprehensiVe Organometallic
Chemistry II; Hegedus, L. S., Ed.; Pergamon: Oxford, 1995; Vol 12, pp
1
(
071-1095. (c) Furstner, A. Angew. Chem., Int. Ed. Engl. 1993, 32, 164.
d) Robertson, G. M. In ComprehensiVe Organic Synthesis; Trost, B. M.,
Ed.; Pergamon: New York, 1991; Vol. 3, pp 563-611. (e) McMurry, J. E.
Chem. ReV. 1989, 89, 1513. (f) Kahn, B. E.; Rieke, R. D. Chem. ReV. 1988,
8
8, 733.
(2) (a) Furstner, A.; Csuk, R.; Rohrer, C.; Weidmann, H. J. Chem. Soc.,
Perkin Trans. 1 1988, 1729 and references therein. (b) Chan, T. H.; Vinokur,
E. Tetrahedron Lett. 1972, 1, 75.
(
3) (a) Swindell, C. S.; Fan, W.; Klimko, P. G. Tetrahedron Lett. 1994,
3
4
5, 4959. (b) McMurry, J. E.; Siemers, N. O. Tetrahedron Lett. 1994, 35,
505. (c) Nicolaou, K. C.; Yang, Z.; Sorenson, E. J.; Nakada, M. J. Chem.
Soc., Chem. Commun. 1993, 1024. (d) McMurry, J. E.; Siemers, N. O.
Tetrahedron Lett. 1993, 34, 7891. (e) Swindell, C. S.; Chandler, M. C.;
Heerding, J. M.; Klimko, P. G.; Rahman, L. T.; Raman, J. V.; Venkataraman,
H. Tetrahedron Lett. 1993, 34, 7005. (f) Davey, A. E.; Schaeffer, M. J.;
Taylor, R. J. J. Chem. Soc., Perkin Trans. 1 1992, 2657. (g) McMurry, J.
E.; Dushin, R. G. J. Am. Chem. Soc. 1990, 112, 6942. (h) McMurry, J. E.;
Rico, J. G.; Shih, Y.-N. Tetrahedron Lett. 1989, 30, 1173. (i) McMurry, J.
E.; Rico, J. G. Tetrahedron Lett. 1989, 30, 1169. (j) Pierrot, M.; Pons, J.-
M.; Santelli, M. Tetrahedron Lett. 1988, 29, 5925. (k) Handa, Y.; Inanaga,
J. Tetrahedron Lett. 1987, 28, 5717. (l) Suzuki, H.; Manabe, H.; Enokiya,
R.; Hanazaki, Y. Chem. Lett. 1986, 1339. (m) Raubenheimer, H. G.;
Seebach, D. Chimia 1986, 40, 12. (n) Clerici, A.; Porta, O. J. Org. Chem.
1
was analyzed by H NMR and GC of the corresponding
3i
acetonides to determine the product dl:meso distribution by
comparison with authentic materials. Results (84%; dl:meso
) 94:6) compare favorably with those reported for coupling
3,9,16
using simple reducing agents under aprotic conditions.
Other
examples of pinacol coupling in mixed solvent systems are given
in Table 1. It is especially interesting to note that methyl
glyoxylate and glyoxylic acid are easily converted to dimethyl
tartrate and tartaric acid, respectively, with no adverse partici-
pation of the carboxylic functionality. Also, even though
1
983, 48, 1690. (o) Clerici, A.; Porta, O. Tetrahedron Lett. 1982, 23, 3517.
(
p) Clerici, A.; Porta, O. Tetrahedron 1982, 38, 1293. (q) Trylik, S.
III
17
Wolochowicz, I. Bull. Chem. Soc. Fr. 1973, 2147. (r) Mukaiyama, T.; Sato,
T.; Hanna, J. Chem. Lett. 1973, 1041.
Cp2Ti can react with aryl halides, no reduction of that
functionality was noted for the case studied.
(
4) Askham, F. R.; Carroll, K. M. J. Org. Chem. 1993, 58, 7328.
5) (a) Kammermeier, B.; Beck, G.; Jacobi, D.; Jendralla, H. Angew.
We believe that the mechanism of pinacol coupling involves
formation of an intermediate Cp2Ti(aldehyde)Cl complex, 3
(
Chem., Int. Ed. Engl. 1994, 33, 685. (b) Park, J.; Pederson, S. F. Tetrahedron
1
992, 48, 2069. (c) Kempf, D. J.; Sowin, T. J.; Doherty, E. M.; Hannick,
(
Scheme 1). A hydride complex analog has been analyzed by
S. M.; Codavoci, L.; Henry, R. F.; Green, B. E.; Spanton, S. G.; Norbeck,
D. W. J. Org. Chem. 1992, 57, 5692. (d) Annunziata, R.; Benaglia, M.;
Cinquini, M.; Cozzi, F.; Giaroni, P. J. Org. Chem. 1992, 57, 782. (e) Raw,
A. S.; Pederson, S. F. J. Org. Chem. 1991, 56, 830. (f) Park, J.; Pederson,
S. F. J. Org. Chem. 1990, 55, 5924. (g) Konradi, A. W.; Pederson, S. F. J.
Org. Chem. 1990, 55, 4506. (h) Annunziata, R.; Cinquini, M.; Cozzi, F.;
Giaroni, P. Tetrahedron: Assymetry 1990, 1, 355. (i) Takahara, P. M.;
Freudenberger, J. H.; Konradi, A. W.; Pederson, S. F. Tetrahedron Lett.
1
8
EPR, and 3 likely has significant unpaired electron density
on the carbonyl carbon atom, as shown in the ketyl complex
(10) Coutts, R. S. P.; Wailes, P. C.; Martin, R. L. J. Organomet. Chem.
1973, 47, 375.
(11) Wailes, P. C.; Coutts, R. S. P.; Wiegold, H. In Organometallic
Chemistry of Titanium, Zirconium, and Hafnium; Academic Press: New
York, 1974; Chapter VI, pp 206 and references therein.
(12) (a) Cavallaro, C. L.; Schwartz, J. J. Org. Chem. 1995, 60, 7055.
(b) Yanlong, Q.; Guisheng, L.; Huang, Y.-Z. J. Organomet. Chem. 1990,
381, 29.
1
989, 30, 7177. (j) Freudenberger, J. H.; Konradi, A. W.; Pederson, S. F.
J. Am. Chem. Soc. 1989, 111, 8014.
(6) (a) Szymoniak, J.; Besan c¸ on, J.; Moise, C. Tetrahedron 1994, 50,
2841. (b) Szymoniak, J.; Besan c¸ on, J.; Moise, C. Tetrahedron, 1992, 48,
3867.
(13) RajanBabu, T. V.; Nugent, W. A. J. Am. Chem. Soc. 1994, 116,
986.
(14) Jungst, R.; Sekutowski, D.; Davis, J.; Luly, M.; Stucky, G. Inorg.
Chem. 1977, 16, 1645.
(
7) Hays, D. S.; Fu, G. C. J. Am. Chem. Soc. 1995, 117, 3867.
(
8) For example, benzaldehyde reacts with SmI2 to yield hydrobenzoin
(95%), but stereoselectivity is poor (dl:meso ) 55:45). See: (a) Namy,
J.-L.; Souppe, J.; Kagan, H. B. Tetrahedron Lett. 1983, 24, 765. For other
examples, see: (b) Anies, C.; Pancrazi, A.; Lallemand, J.-Y.; Prange, T.
Tetrahedron Lett. 1994, 35, 7771. (c) Chiara, J. L.; Martin-Lomas, M.
Tetrahedron Lett. 1994, 35, 2969. (d) Lebrun, A.; Namy, J.-L.; Kagan, H.
B. Tetrahedron Lett. 1993, 34, 2311. (e) Arseniyadis, S.; Yashunsky, D.
V.; Freitas, R. P.; Dorado, M. M.; Toromanoff, E.; Potier, P. Tetrahedron
Lett. 1993, 34, 1137. (f) Uenishi, J.; Masuda, S.; Wakabayashi, S.
Tetrahedron Lett. 1991, 32, 5097. (g) Chiara, J. L.; Cabri, W.; Hanessian,
S. Tetrahedron Lett. 1991, 32, 1125. (h) Molander, G. A.; Kenny, C. J.
Am. Chem. Soc. 1989, 111, 8236. (i) Molander, G. A.; Kenny, C. J. Org.
Chem. 1988, 53, 2134.
(15) All manipulations were performed either using standard Schlenk
techniques or, for nonaqueous systems, in a glove box under a purified
nitrogen atmosphere. Except when mixed aqueous procedures were used,
THF was distilled from sodium/benzophenone ketyl. Deionized H2O was
thoroughly purged with argon to remove dissolved oxygen. Titanocene
chloride dimer, (Cp2TiCl)2, was prepared10 and stored in the dry box.
Aldehydes were distilled prior to use.
(16) So, J.-H.; Park, M.-K.; Boudjouk, P. J. J. Org. Chem. 1988, 53,
5871.
(17) Liu, Y.; Schwartz, J. Tetrahedron 1995, 51, 4471; J. Org. Chem.
1994, 59, 940.
(18) Barden, M. C.; Schwartz, J. J. Org. Chem. 1995, 60, 5963.
(9) Tanaka, K.; Kishigami, S.; Toda, F. J. Org. Chem. 1990, 55, 2981.
S0002-7863(96)00648-8 CCC: $12.00 © 1996 American Chemical Society

Communications to the Editor
J. Am. Chem. Soc., Vol. 118, No. 23, 1996 5485
Table 1. Reductive Coupling of Aldehydes by Cp
2
TiCl
Scheme 1
Ti-O bonding in a sterically crowded environment is the origin
of the pinacol diastereoselectivities observed. Cationic, hydrated
1
1
species 2 could coordinate an aldehyde to give [Cp2Ti(H2O)-
+
(
aldehyde)] (5) which is apparently unreactive for such
reductive coupling; no reductive coupling occurs in the absence
-
of added Cl or when noncoordinating triflate is used instead.
Simple chloride ion addition to 5 affords 3; it is reasonable that
-
replacement of H2O by Cl could favor transfer of electron
density from Ti to the coordinated carbonyl group. Studies to
elucidate the reaction mechanism and to expand the scope of
1
9
the coupling reaction are now in progress.
Acknowledgment. The authors thank the National Science Founda-
tion for support of this research.
JA9606485
a
All reactions were run in the presence of excess NaCl. b Initial
(
19) The complex (EBTHI)2TiCl was more stereoselective than was [Cp2-
temperature; final temperature was room temperature in all cases.
Combined yields for isolated dl and meso products. Determined by
H NMR (300 MHz) of the crude reaction mixtures following
hydrolysis. Requires 8 equiv of Cp
TiCl]2 for aldehyde reductive coupling. For example, benzaldehyde yielded
c
d
hydrobenzoin dl:meso ) 36:1 (95%) at 0 °C using [Cp2TiCl]2; dl:meso )
1
>
50:1 (92%) using (EBTHI)2TiCl. [Cp2TiCl]2 shows low reactivity toward
e
20
2
TiCl.
pinacol coupling of aromatic ketones or aliphatic aldehydes and ketones.
20) Workup was accomplished by quenching the reaction with 1 N
(
“
resonance structure” 4. Dimerization of 4 would give the
NaOH followed by filtration and washing with Et2O. The aqueous layer
was concentrated to ca. 5 mL, and saturated solution of BaCl2 was added.
The mixture was heated to 70 °C, and the Ba salt precipitated on standing.
See: Katsaros, N.; Vrachnou-Astra, E.; Konstantatos, J.; Stassinopoulou,
C. I. Tetrahedron Lett. 1979, 20, 4319.
glycolate. According to this hypothesis, strong bonding between
the carbonyl group oxygen and Ti is an a priori requirement
for glycolate formation; perhaps the requirement for strong