Silane reduction of 5-hydroxy-6-methyl-pyridine-3,4-dicarboxylic acid diethyl ester: Synthesis of vitamin B6

Article abstract of DOI:10.3390/81200873

Alternative methods for the synthesis of pyridoxine have been investigated. The key intermediate, 5-hydroxy-6-methyl-pyridine-3,4-dicarboxylic acid diethyl ester (5), was reduced with either a silane monomer (MeSiH(OEt)₂) or a polysiloxane (polymethylhydrosiloxane, PMHS) to afford crude pyridoxine. An isolation technique utilizing a commercially available resin was devised, affording the desired product, vitamin B₆, in an overall yield of 38-54% and a purity of 76%.

Full text of DOI:10.3390/81200873

Molecules 2003, 8, 873-881
molecules
ISSN 1420-3049
http://www.mdpi.org
Silane Reduction of 5-Hydroxy-6-methyl-pyridine-3,4-
dicarboxylic Acid Diethyl Ester: Synthesis of Vitamin B6
Yves René Dumond and Andrew G. Gum*
DSM Nutritional Products§ R&D Chemical Process Technology, P.O. Box 3255, Bldg. 214/0.61, CH-
4002 Basel, Switzerland, Tel. (+41) 61 687 3293, Fax (+41) 61 687 2117.
* Author to whom correspondence should be addressed; email: andrew.gum@dsm.com.
§ registered as Roche Vitamins Ltd., Grenzacherstrasse 124, CH-4070 Basel, Switzerland
Received: 31 October 2003; in revised form: 1 December 2003 / Accepted: 10 December 2003/
Published: 31 December 2003
Abstract: Alternative methods for the synthesis of pyridoxine have been investigated. The
key intermediate, 5-hydroxy-6-methyl-pyridine-3,4-dicarboxylic acid diethyl ester (5), was
reduced with either
a
silane monomer (MeSiH(OEt)2) or
a
polysiloxane
(polymethylhydrosiloxane, PMHS) to afford crude pyridoxine. An isolation technique
utilizing a commercially available resin was devised, affording the desired product, vitamin
B6, in an overall yield of 38-54 % and a purity of 76%.
Keywords: Polymethylhydrosiloxane (PMHS), silanes, ester reduction, pyridoxine, vitamin
B6
Introduction
Vitamin B6 is a water-soluble vitamin that is manufactured in bulk as pyridoxine hydrochloride.
Vitamin B6 is an important nutrient and plays an essential role in the body's amino acid biochemical
pathways. As a consequence, it is found in a variety of vitamin preparations and is a common food
additive. Because of its importance, the synthesis and commercial production of vitamin B6 have been
the subject of intense research for many years [1-2]. Currently, the preferred industrial synthesis of
vitamin B6 uses the Kondrat’eva approach [3-6], which combines a Diels-Alder reaction with a
subsequent aromatization as the key step in forming the hydroxypyridine ring. Typically, the Diels-

Molecules 2003, 8
874
Alder precursors are an oxazole diene and a dienophile, usually derived from 2-butene-1,4-diol.
Derivatives of maleic and fumaric acids [7-16] are also good dienophiles for this reaction. A major
disadvantage of using the unsaturated succinic acid approach is their cost. Excess equivalents of
hydride reagents are required to reduce the two carboxylic groups, resulting in unacceptably large
waste streams of inorganic salts. As a result no commercial process is based on this strategy.
Results and Discussion
Using the method reported by Firestone and Harris [8], a neat mixture of 5-ethoxy-4-
methyloxazole (1) and excess diethyl maleate (2) underwent a Diels-Alder cycloaddition to afford a
mixture of bridged intermediates -endo (5R,6S)- and exo (5S,6R)-4-ethoxy-3-methyl-7-oxa-2-
azabicyclo[2.2.1]-hept-2-ene-5,6-dicarbocyclic acid diethyl esters (rac-3 and rac-4). Although not
necessary for the synthesis of the desired diester 5, the rac-3 endo and rac-4 exo adducts could be
separated by column chromatography and were characterized by NMR for the first time. The
bridgehead proton of the rac-3 endo isomer was observed as a doublet (J= 4Hz) at 5.80 ppm, which
supports a dihedral angle of 45° with the adjacent proton. In the model of the rac-4 exo isomer, this
angle changes to approximately 90°, thus no splitting of the bridgehead proton is expected and indeed
none was observed. In a typical reaction, the crude bicyclic adducts were not isolated, but instead were
treated with HCl to facilitate aromatization. After a final treatment with sodium bicarbonate, a single
achiral product, 5-hydroxy-6-methyl-pyridine-3,4-dicarboxylic acid diethyl ester (5), was isolated
(Scheme 1).
Scheme 1: Synthesis of hydroxypyridine diester 5 using the Diels-Alder reaction
OH
OH
OEt
OEt
O
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
100° C
HCl in EtOH
O
+
N
N
N
CO2Et
Diels-Alder Adducts
1
2
5
OEt
OEt
O
O
H
CO2Et
CO2Et
H
+
N
H
CO2Et
CO2Et
N
H
H
H
δ 5.80, d, J= 4 Hz
δ 6.10, s
4 exo (5S, 6R)
3 endo (5R, 6S)

Molecules 2003, 8
875
The reduction of hydroxypyridine diester (5) with stoichiometric metal hydride reagents like
lithium aluminum hydride [17], sodium aluminum hydride [18], alkaline earth metal borohydrides [19]
and lithium borohydride [20] is known. Thus, focus was placed on using silane reagents as an
alternative approach for the complete reduction of the ester functional groups to the desired primary
alcohols. These hydride reagents have not previously been applied in a synthesis of vitamin B6.
The catalyzed-hydrosilylation / reduction was considered based on several recent publications in
journals and patents. The use of inexpensive silanes such as polymethylhydrosiloxane, PMHS, which
is a by-product of the silicon industry, or alkoxysilanes, which can be synthesized from inexpensive
chlorosilanes [21-27], was examined. A variety of catalysts can be used to activate the hydrosilylation:
transition metals (especially Ti [28-31] and Zn [32-36]) or nucleophiles (especially metal hydroxides /
alkoxides [37-41], and fluoride salts [42-55]). Because fluoride salts were reported to catalyze ester
reductions at room temperature, this mild hydrosilylation / reduction method was investigated for the
synthesis of vitamin B6.
In a model experiment, diethyl phthalate (6) was easily reduced using Lawrence’s conditions [50]
(THF, 6 equiv. PMHS, 10 mol% n-Bu4NF, 22 °C) to afford 1,2-benzenedimethanol (7) in 47% isolated
yield (Scheme 2). The isolated yield was increased to 64% when 12 equiv. of PMHS were used.
Replacing PMHS by 12 equiv. of the monomer silane, MeSiH(OEt)2, afforded a comparable isolated
yield of 62%. The model system was advantageous because the diol product (7) could be extracted into
an organic solvent, and thus readily isolated. With this positive result, the conditions were then applied
to the more challenging hydroxypyridine diester derivative (5).
Scheme 2: Reduction of a model compound, diethyl phthalate (6)
6-12 equiv. PMHS
12 equiv. MeSiH(OEt)2
or
CO2Et
CO2Et
OH
OH
10 mol % Bu4NF
THF, 22 °C
6
7
Initially, the 5-hydroxy-6-methyl-pyridine-3,4-dicarboxylic acid diethyl ester (5) was not reduced
under the mild conditions (either 8 equiv. PMHS or 7.5 equiv. MeSiH(OEt)2 -10 mol%Bu4NF in THF,
22 °C, 24 h; Table 1, entries 1 and 2). Additionally, under the PMHS conditions, large amounts of
solids formed during the reaction. Reduction did occur at 22 °C when large excesses of the monomeric
reducing reagent MeSiH(OEt)2 (18-30 equiv.) and stoichiometric amounts of Bu4NF (1.2 equiv.) were
used (Scheme 3). No vitamin B6 was isolated from the PMHS reactions and little or no starting
material (5) was observed following the reaction. The desired vitamin B6 product as a free base can
serve as a multi-dentate ligand, capable of cross coupling with the polymeric backbone of PMHS and
thus producing the observed solids. Such solidification was also observed by Mimoun and coworkers
during reduction attempts on lactones [36], further supporting the claims of polymeric cross coupling.

Molecules 2003, 8
876
Scheme 3: Reduction of 5-hydroxy-6-methyl-pyridine-3,4-dicarboxylic acid diethyl ester (5) at 22 °C
OH
OH
CO2Et
CO2Et
18-30 eq MeSiH(OEt)2
OH
OH
N
N
1.2 eq n-Bu4NF, THF, 22 °C
5
8 51% isolated yield
Not only was the desired product vitamin B6 (8) covalently trapped on the polymer, but also
mixtures of the partially reduced intermediates lactone (9) and mono reduced ester (10) (Figure 1). The
trapping of these intermediates also contributed to the solidification of the reaction mixture.
Figure 1: Some partially reduced Vitamin B6 intermediates
OH
OH
OH
O
N
N
CO2Et
O
9
10
Use of the additive Si(OEt)4 afforded a nearly homogeneous solution. It was proposed that the
Si(OEt)4 allowed for an exchange between the alkoxy groups of the vitamin B6 free base (8) and the
different silicon sites. Thus, a reduction in the amount of cross-coupled polymer was observed.
However, use of this additive provided only modest yields under the PMHS conditions. A further
disadvantage with the starting material, hydroxypyridine diester (5), was that the phenolic hydroxyl
group also acted as a nucleophile and readily attached to the polysiloxane surface, further complicating
the isolation of fully and partially reduced products.
A variety of conditions were screened and the results are reported in Table 1. The best conditions
found for complete reduction utilized 10-15 equiv. MeSiH(OEt)2, either neat or in dioxane, 10 mol%
Bu4NF and 100 °C for circa 24 h (Table 1, exp. 10 and 13). These conditions afforded at best a 50-
54% isolated yield of vitamin B6 free base and up to 18% of the intermediates. These partially reduced
products were either characterized by comparison to known compounds, lactone (9) [56], or observed
in GC/MS experiments, mono reduced (10) (Figure 1). Based on another publication [57], Bu4NF was
replaced by the combination of 10 mol% CsF and 20 mol% 18-crown-6 ether. It was proposed that this
would increase the nucleophilicity of the fluoride as a “naked” anion and improve the reaction.
However, under these modifications the reaction still required 24 h at 100 °C for completion and
afforded a similar LC yield of 52% (Table 1, Exp. 14).

Molecules 2003, 8
877
As stated previously, several difficulties were encountered in the isolation of vitamin B6 after the
silane reduction. An isolation method had to be developed in order to efficiently remove vitamin B6
free base from the crude reaction mixture. The best purification approach consisted of adding EtOH to
the reaction mixture in order to allow for fluoride-catalyzed exchange [50] between vitamin B6 and
EtOH on the silicon sites. The resulting reaction mixture was filtered over the strongly acidic resin
Dowex 50-WX8, which retained vitamin B6. The siloxanes and other by-products were easily eluted
with EtOH. Then the desired product, vitamin B6 free base (8), was eluted from the resin using a
gradient of water and NH4OH. Concentration of the combined fractions afforded vitamin B6 as the free
pyridoxine in an overall yield of 54% and a HPLC purity of 75.9 w/w% (weight/weight%, calibrated
HPLC; Table 1, Exp. 13).
Table 1: Reduction of 5-hydroxy-6-methyl-pyridine-3,4-dicarboxylic acid diethyl ester (5).
Overall yielda Purity
Conditions (silane reagent-catalyst, solvent, temperature, time)
Exp.
[LC yield] %
%
8 equiv. PMHS-10 mol% Bu4NF in THF, 22 °C, 24 h
7.5 equiv. MeSiH(OEt)2-10 mol% Bu4NF in THF, 22 °C, 24 h
12 equiv. Si(OEt)4-30 equiv. PMHS, 1.2 equiv. Bu4NF in THF,
22 °C, 24 h
1
2
3
0
0b
38
5.1
9.2
30 equiv. MeSiH(OEt)2-1.2 equiv. Bu4NF in THF, 22 °C, 24 h
8 equiv. MeSiH(OEt)2-10 mol% Bu4NF in THF, reflux, 2 h
8 equiv. MeSiH(OEt)2-10 mol% Bu4NF in THF, reflux, 96 h
4
5
6
51
0b
[21]b
[11]b,c
[9]d
16 equiv. PMHS-8 equiv. Si(OEt)4-10 mol% Bu4NF in DMF, 150 °C, 24 h 7
8 equiv. Si(OEt)4-8 equiv. PMHS-10 mol% Bu4NF, 160 °C, 24 h
16 equiv. MeSiH(OEt)2-1.2 equiv. Bu4NF in THF, 22 °C, 24 h
10 equiv. MeSiH(OEt)2-10 mol% Bu4NF, no solvent, 100 °C, 21 h*
15 equiv. MeSiH(OEt)2-10 mol% Bu4NF, no solvent, 100 °C, 21 h
15 equiv. MeSiH(OEt)2-20 mol% Bu4NF, no solvent, 100 °C, 26 h
15 equiv. MeSiH(OEt)2-10 mol% Bu4NF in dioxane,100 °C, 24 h*
15 equiv. MeSiH(OEt)2,10 mol% CsF, 20 mol% 18-crown-6 ether,
8
9
[60]b
51 [60]b
42 [60]b
46 [65]b
54
10
11
12
13
14
55.8e
65.2f
64.8f
75.9
[52]b
dioxane, 100 °C, 24 h
a
b
*Best conditions (highlighted in blue); Weight yield x Purity; incomplete reaction: partially
c
reduced product(s) detected; partially reduced product characterized as 5-hydroxy-pyridine
d
lactone (9) (cyclization during work-up); no change after 1 h, either decomposition of Si-H or
e
f
not enough reagent; partially reduced products (9) and (10) observed (18%); partially reduced
products (<6%)

Molecules 2003, 8
878
Conclusions
5-Hydroxy-6-methyl-pyridine-3,4-dicarboxylic acid diethyl ester (5) was successfully reduced with
silane reducing reagents. Cross-linking problems with PMHS made this reagent less attractive for the
synthesis of vitamin B6. Alkoxysilanes, when used in a fluoride-catalyzed hydrosilylation, allowed for
the isolation of the desired fully reduced product. The isolation of free vitamin B6 from the reaction
mixture was best accomplished by using the resin Dowex 50-WX8.
Even though the fluoride-catalyzed hydrosilylation / reduction was possible, large excesses of the
silane reducing reagent were required to yield reasonable amounts of fully reduced vitamin B6.
Although the yields were significantly lower than the classical hydride reduction methods, the
described examples provide the first successful use of silanes for the reduction of a hydroxypyridine
diester to the pyridoxine free base. Thus, the use of these reagents offers an alternative route to vitamin
B6. Further reduction of the required amount of silane, final product isolation techniques, as well as a
recovery strategy for the silane waste stream still need to be further addressed. Additionally, recovery
and full conversion of the partially reduced products to vitamin B6 free base needs to be further
developed in order to consider this methodology as a potential large scale production process.
Investigations continue and will be reported in due course.
Acknowledgements
The authors would like to especially thank G. Schiefer and J. Kleissner for the analytical support,
as well as J. Fischesser, D. Burdick, R. Karge, T. Netscher, W. Bonrath and M. Breuninger for
discussions during this project.
Experimental
General
All chemical reagents were purchased from Fluka. The reactions were monitored by GC (Perkin
Elmer Auto System XL, RESTEK Rtx-5SilMS 30 m, 0.28 micron column) and HPLC (Hewlett
Packard 1050, YMC Hydroxphere-C18, HS-303 column). The known partially reduced products
7-hydroxy-6-methyl-1H-furo[3,4-c]pyridine-3-one (9) and 4-hydroxymethyl-2.5-dimethylpyridin-3-ol
(10) were observed by HPLC/MS (Hewlett Packard 1100MSD) and their structures confirmed by
1H-NMR (Bruker Avance 400 MHz) for comparison to the literature data.
Isolation of Diels-Alder adducts endo (5R,6S)-4-ethoxy-3-methyl-7-oxa-2-aza-bicyclo[2.2.1]hept-2-
ene-5,6-dicarbocyclic acid diethyl ester (3) and exo (5S,6R)-4-ethoxy-3-methyl-7-oxa-2-aza-
bicyclo[2.2.1]hept-2-ene-5,6-dicarbocyclic acid diethyl ester (4).

Molecules 2003, 8
879
5-Ethoxy-4-methyloxazole (1, 0.64 g, 5 mmol) and diethyl maleate (2, 1.72 g, 10 mmol) were
heated neat in a round bottom flask under argon in an oil bath at 110 °C for 3 h. Chromatography of
the crude Diels-Alder adducts on silica gel (EtOAc/hexane, 1:1) afforded 620 mg of the endo isomer
rac-3 (41%) and 360 mg of exo isomer rac- 4 (24%).
Spectral and Analytical Data
1
rac-3: H-NMR (CDCl3, SiMe4) δ 5.80 (d, J = 4 Hz, 1 H), 4.05-4.1 (m, 4 H), 3.75-3.9 (m, 2 H), 3.73
13
(dd, J = 10 Hz, J = 4 Hz, 1 H), 3.19 (d, J = 10 Hz, 1 H), 2.32 (s, 3 H), 1.2-1.35 (m, 9 H); C-NMR
(CDCl3) δ 179.33, 169.02, 167.84, 113.32, 88.14, 63.30, 61.17, 60.99, 51.15, 46.42, 16.91, 15.51,
14.21, 14.05. Analysis: Found C, 55.85; H, 6.75; N, 4.64; C14H21HO6 requires C, 56.17; H, 7.07; N,
4.68.
1
rac-4: H-NMR (CDCl3, SiMe4) δ 6.10 (s, 1 H), 4.1-4.25 (m, 4 H), 3.8-3.9 (m, 1 H), 3.65-3.75 (m, 1
13
H), 2.8-2.9 (m, 2 H), 2.14 (s, 3 H), 1.2-1.35 (m, 9 H); C-NMR (CDCl3) δ 177.89, 169.92, 168.74,
113.17, 89.42, 64.52, 61.69 (2 C), 50.89, 45.57, 15.67, 14.95, 14.57, 14.39. Analysis: Found C, 56.01;
H, 6.80; N, 4.77; C14H21HO6 requires C, 56.17; H, 7.07; N, 4.68.
Hydrosilylation/reduction of hydroxypyridine diester (5) to vitamin B6
To a solution of 5-hydroxy-6-methyl-pyridine-3,4-dicarboxylic acid diethyl ester (5, 506 mg, 2
mmol) and diethoxymethylsilane (4.03 g, 30 mmol) in dioxane (1 mL) was added a solution of
tetrabutylammonium fluoride (0.2 ml, 1 M, 0.2 mmol) in THF. The reaction mixture was heated in an
oil bath at 100 °C for 24 h. The flask was removed from the oil bath and to the reaction mixture was
added EtOH (100 mL). The mixture was allowed to cool and to further stir overnight. A glass-fritted
filter (pore 2) was filled with Dowex 50-WX8, pre-washed three times with concentrated aqueous HCl
and water to a pH of 6. The ethanolic crude reaction solution was filtered through the resin and the
resin was rinsed successively with EtOH (100 mL), water (200 mL), 1% NH4OH (200 mL), 4%
NH4OH (200 mL) and 25% NH4OH (200 mL). Only the fraction obtained from the 4% NH4OH elution
contained vitamin B6 free base. Concentration of the 4% NH4OH fraction afforded 240 mg of crude
vitamin B6 (8) free base (HPLC purity 75.9 w/w%, isolated yield 54%).
References and Notes
1. Coffen, D. L. “Vitamins (B6)”, in Kirk-Othmer: Encyclopedia of Chemical Technology, 3rd
Edition; John Wiley & Sons, Inc.: New York, 1984; vol. 24, pp. 94-107.
2. Pauling H.; Weimann, B. J. “Vitamin B6” in Ullmann’s Encyclopedia of Industrial Chemistry;
VCH Verlagsgesellschaft mbH: Weinheim, Germany, 1996; vol. A27, pp. 530-540.
3. Kondrat’eva, G. Y. Khim. Nauk Prom. 1957, 2, 666.

Molecules 2003, 8
880
4. Kondrat’eva, G. Y. Izv. Akad. Nauk SSSR, Ser. Khim. 1959, 484.
5. Kondrat’eva, G. Y. Dokl. Akad. Nauk SSSR 1961, 141, 628, 861 [Proc. Acad. Sci. USSR, Chem.
Sect. 1961, 1169, 1221].
6. Huang C. H.; Kondrat’eva, G. Y. Izv. Akad. Nauk SSSR, Otd. Khim. Nauk 1962, 525.
7. Harris, E. E.; Firestone, R. A.; Pfister, K.; Boettcher, R. R.; Cross, F. J.; Currie, R. B.; Monaco,
M.; Peterson, E. R.; Reuter, W. J. Org. Chem. 1962, 27, 2705.
8. Firestone, R. A.; Harris, E. E.; Reuter, W. Tetrahedron 1967, 23, 943.
9. Pfister III, K.; Harris, E.; Firestone, R. A. Merck & Co., US 3,227,722, 4 Jan. 1966.
10. Naito, T.; Yoshikawa, T. Chem. Pharm. Bull. 1966, 14, 921.
11. Doktorova, N. D.; Ionova, L. V.; Karpeisky, M. Y.; Padyukova, N. S.; Turchin, K. F.; Florentiev,
V. L. Tetrahedron, 1969, 25, 3527.
12. Itov Z. I.; Gunar, V. I. Chem. Pharm. J. (Engl. Transl.) 1988, 2, 151.
13. Kreher, R. Houben-Weyl Methoden der Organischen Chemie; Georg Thieme Verlag: Stuttgart-
New York, 1992; Band E7b Hetearene II Teil 2, Chap 4.2.1.3.4, pp. 532-539.
14. Karpeiskii, M. Y.; Florent’ev, V. L. Russ. Chem. Rev. 1969, 38, 540 and references therein.
15. Turchi, I. J.; Dewar, M. J. S. Chem. Rev. 1975, 75, 389 and references therein.
16. Boger, D. A. Chem. Rev. 1986, 86, 781.
17. Jones R. G.; Kornfeld, E.C. J. Am. Chem. Soc. 1951, 73, 107.
18. Lutz, A. H.; F. Hoffmann La Roche & Co., CH 408914, Switzerland, 1966.
19. Merck & Co., Inc., GB 1,116,118 [US 3,410,862], London, UK, 6 June 1968.
20. Jones, R. G. E. Lilly & Co., US 2,744,114, 1 May 1952.
21. Okawara, R.; Sakiyama, M. Bull. Chem. Soc. Jpn. 1956, 29, 236.
22. Koerner, G. Th. Goldschmidt A. G., DE 1,162,365, 5 May 1962.
23. Sagami Chemical Research Center, GB 1,401,948, 28 Feb. 1974.
24. Nagai, Y.; Ojima, I.; Inaba, S. Sagami Chemical Research Center, US 3,910,980, 7 Oct. 1975.
25. Kötzsch, H. J.; Seiler, C. D.; Vahlensieck, H. J. Dynamit Nobel A. G., US 4,228,092, 14 Oct.
1980.
26. Boyer, J.; Corriu, R. J. P.; Perz , R.; Reye, C. Tetrahedron 1981, 37, 2165.
27. Chuit, C.; Corriu, R. J. P.; Perz, R.; Reye, C. Synthesis 1981, 981.
28. Berk, S. C.; Buchwald, S. L. J. Org. Chem. 1992, 57, 3751.
29. Berk, S. C.; Buchwald, S. L. J. Org. Chem. 1993, 58, 3221.
30. Buchwald, S. L.; Gutierrez, A.; Berk, S. C.; Kreutzer, K. A. Massachusetts Institute of
Technology, US 5,220,020, 15 Jun. 1993.
31. Breeden, S. W.; Lawrence, N. J. Synlett 1994, 833.
32. Mimoun, H. Firmenich, WO 96/12694, 2 May 1996.
33. Mimoun, H. Firmenich, WO 96/28497, 19 Sept. 1996.
34. Mimoun, H. Firmenich, WO 99/50211, 7 Oct. 1999.
35. Mimoun, H. J. Org. Chem. 1999, 64, 2582.

Molecules 2003, 8
881
36. Mimoun, H.; de Saint Laumer,J. Y.; Giannini, L.; Scopelliti, R.; Floriani, C. J. Am. Chem. Soc.
1999, 121, 6158.
37. Kohra, S.; Hayashida, H.; Tominaga, Y.; Hosomi, A. Tetrahedron Lett. 1988, 29, 89.
38. Hosomi, A. Chisso Corporation, JP 63,010,738, 18 Jan. 1988.
39. Hojo, M.; Murakami, C.; Fuji, A.; Hosomi, A. Tetrahedron Lett. 1999, 40, 911.
40. Corriu, R. J. P.; Guerin, C.; Henner, B.; Wang, Q. Organometallics 1991, 10, 2297.
41. Corriu, R. J. P.; Guerin, C.; Henner, B.; Wang, Q, Inorg. Chim. Acta 1992, 198-200, 705.
42. Deneux, M.; Akhrem, I. C.; Avetissian, D. V.; Myssoff, E. I.; Volp’in, M. E. Bull. Soc. Chim. Fr.
1973, 2638.
43. Akhrem, I. S.; M. Dene, M.; Volp’in, M. E. Izv. Akad. Nauk SSSR Ser. Khim. (Engl. Transl.)
1973, 897.
44. Boyer, J.; Corriu, R. J. P.; Poirier, M.; Reye, C. Synthesis 1981, 558.
45. Boyer, J.; Corriu, R. J. P.; Perz, R.; Reye, C. Tetrahedron 1981, 17, 2165.
46. Chuit, C.; Corriu, R. J. P.; Perz, R.; Reye, C. Synthesis 1982, 981.
47. Fujit, M.; T. Hiyama, T. J. Org. Chem. 1988, 53, 5405.
48. Furin, G. G.; Vyazankina, O. A; Gostevsky, B. A.; Vyazankin, N. S. Tetrahedron 1988, 44, 2675.
49. Goldberg, Y.; Abele, E.; Shymanska, M.; Lukevics, E. J. Organomet. Chem. 1991, 410, 127.
50. Drew, M. D.; Lawrence, N. J.; Fontaine, D.; Sehkri, L. Synlett 1997, 989.
51. Drew, M. D.; Lawrence, N. J. Tetrahedron Lett. 1997, 38, 5857.
52. Kobayashi, Y.; Takahisa, E.; Nakano, M.; Watani, K. Tetrahedron 1997, 53, 1627.
53. Kobayashi, Y. Shin-Etsu Chemical Industry Co., JP 10,087,530, 7 Apr. 1998.
54. Lawrence, N. J.; Drew, M. D.; Bushell, S. M. J. Chem. Soc., Perkin Trans. 1 1999, 3381.
55. Abele, E.; Lukevics, E. Main Group Met. Chem. 2001, 24, 315.
56. Asakawa, H.; Fukushima, Y.; Imamiya, E.; Kawamatsu, Y. Chem. Pharm. Bull. 1979, 27, 522.
57. Goldberg, Y.; Abele, E.; Shymanska, M.; Lukevics, E. J. Organomet. Chem. 1991, 410, 127.
Samples Availability: Starting materials, intermediates and final products are all known compounds.
Some are available from the author upon request.
© 2003 by MDPI (http://www.mdpi.org). Reproduction is permitted for noncommercial purposes.