Organic compounds -- part of the class 532-570 series – Organic compounds – Heavy metal containing
Reexamination Certificate
1999-11-05
2002-07-02
Shaver, Paul F. (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Heavy metal containing
C585S024000, C536S018700, C536S022100
Reexamination Certificate
active
06414173
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention is in the field of synthetic organic chemistry. In particular, the invention relates to hypervalent silane and siloxane reagents (preformed or generated in situ) for transmetalation in palladium catalyzed reactions with derivatives of allylic alcohols, aryl halides, and aryl triflates derived from phenols and the like. The hypervalent silicon species used in this invention may be a preformed hypervalent silicon species, e.g. TBAT (tetrabutylammonium triphenyldifluorosilicate) and tetrasubstituted siloxane derivatives which form hypervalent silicon species in situ when an anion (e.g. TBAF (tetrabutylammonium fluoride)) is added.
2. Related Art
Palladium-catalyzed cross-coupling reactions are versatile methods for the synthesis of carbon-carbon bonds in both a catalytic and stoichiometric manner. One of the more general methods developed in this class of reaction is the Stille coupling (and its myriad of variants) in which an organopalladium complex is allowed to react with a tin (IV) reagent to afford the coupling product (Scheme 1).
(Trost, B. M., et al., “Organopalladium Compounds in Organic Synthesis and Catalysis,” in
Comprehensive Organometallic Chemistry,
Vol. 8, Wilkinson, G., et al., eds., Pergamon, Oxford, England (1982), pp. 799-938; Tamao, K., “Coupling Reaction Between sp
3
and sp
2
Carbon Centers,” in
Comprehensive Organic Synthesis,
Vol. 3, Trost, B. M., & Fleming, I., eds., Pergamon, Oxford, England (1991), pp. 435-480; Knight, D. W., “Coupling Reaction Between sp
2
Carbon Centers,” in
Comprehensive Organic Synthesis,
Vol. 3, Trost, B. M. & Fleming, I., eds., Pergamon, Oxford, England (1991), pp. 481-578; Miyaura, N. & Suzuki, A.,
Chem. Rev.
95:2457-2483 (1995); Andersson, P. G., et al.,
Tetrahedron
50:559-572 (1994); Stille, J. K.,
Angew. Chem.
98:504-519 (1986) and references cited therein: Tsuji, T.,
Palladium Reagents and Catalysis,
John Wiley & Sons, New York, N.Y. (1985); Stille, J. K., et al.,
Org. Synth
71:97-106 (1992) and references cited therein; Kalivretenos, A., et al.,
J. Org. Chem.
56:2883-2894(1991) and references cited therein; Gyorkos, A. C., et al.,
J. Amer. Chem. Soc.
112:8465-8472 (1990); Del Valle, L., et al.,
J. Org. Chem.
55:3019-3023 (1990); Stille, J. K. & Sweet, M. P.,
Tetrahedron Lett.
30:3645-3648 (1989); Echavarren, A. M. & Stille, J. K.,
J. Am. Chem. Soc.
109:5478-5486 (1987); Stille, J. K. & Tanaka, M.,
J. Am. Chem. Soc.
109:3785-3786 (1987); Stille, J. K. & Groh, B. L.,
J. Am. Chem. Soc.
109:813-817 (1987); Stille, J. K.,
Angew. Chem. Int. Ed. Engl.
25:508-524 (1986); Scott, W. J. & Stille, J. K.,
J. Am. Chem. Soc.
108:3033-3040 (1986); Stille, J. K.,
Pure Appl. Chem.
57:1771-1780 (1985); Labadie, J. W. & Stille, J. K.,
J. Am. Chem. Soc.
105:6129-6137 (1983); Godschalx, J. & Stille, J. K.,
Tetrahedron Lett.
21:2599-2602 (1980); Milstein, D. & Stille, J. K.,
J. Am. Chem. Soc.
101:4992-4998 (1979); Milstein, D. & Stille, J. K.,
J. Am. Chem. Soc.
100:3636-3638 (1978); Farina, V., et al.,
Org. React.
50:1-652 (1997); Farina, V.,
Pure Appl. Chem.
68:73-78 (1996); Farina, V. & Roth, G. P., in
Advances in Metal
-
Organic Chemistry,
Vol. 5, Liebeskind, L. S., ed., J. A. I., Greenwich, England (1995); Trost, B. M.,
Ace. Chem. Res.
13:385-393 (1980); Trost, B. M.,
Pure Appl. Chem.
51:787-800 (1979); Trost, B. M., et al.,
J. Am. Chem. Soc.
100:3930-3931 (1978); Trost, B. M.,
Tetrahedron
33:2615-2649 (1977);
Pd-Catalyzed Alkylation of Allylic Substrates: Class,
Y. J. & DeShong, P.,
Tetrahedron Lett
36:7631-7634 (1995); Curran, D. P. & Suh, Y. -G.,
Carbohydrate Res.
171:161-191 (1987); Dunkerton, L. V. & Serino, A. J.,
J. Org. Chem.
47:2812-2814 (1982); Baer, H. H. & Hanna, Z. S.,
Can. J. Chem.
59:889-906 (1981);
Asymmetric Pd-Catalyzed Alkylations:
Trost, B. M. & Bunt, R. C.,
Angew. Chem.
108:70-73 (1996); Rieck, H. & Heimchen, G.,
Angew Chem.
107:2881-2883 (1995); von Matt, P. & Pfaltz, A.,
Angew. Chem., Int. Ed. Engl.
32:566-568 (1993); Other Reactions of Tin Reagents: Michell, T. N.,
Synthesis
803-815 (1992); Kosugi, M., et al.,
Chem. Lett.
1423-1424 (1997); Kosugi, M., et al.,
Chem. Lett.
301-302 (1997); Kosugi, M., et al.,
J. Organomet. Chem.
129:C-36-C-38 (1977)).
This is an exceedingly versatile process because it is highly tolerant of functional groups, provides a good yield of the coupled product, and retains the geometry of the alkene substrates. Accordingly, this process has been employed widely by the synthetic community for the formation of carbon-carbon bonds in pharmaceuticals and new materials. However, there are two serious limitations of this process for large scale synthesis: (1) the use of highly toxic tin (IV) substrates, and subsequently, (2) the removal of tin by-products.
Several remedies to these problems with Stille coupling have been developed, although no comprehensive solution has been developed to date. One of the more novel and potentially efficient solutions has been developed by Curran who has demonstrated that fluorous-based tin reagents can be utilized in Stille couplings (Hashimoto, J., et al.,
J. Org. Chem.
67:8341-8349 (1997)). Based upon previous studies by Zhu and Horvath, Curran has demonstrated that by employing fluorinated tin compounds as reagents, the unused tin reagent and the tin by-products of the Stille coupling protocol were removed by extraction with fluorocarbon solvents. This is a novel solution to the particularly vexing problem of removal of tin residues from the coupling product. In a research lab where small quantities of material are synthesized, handling of small quantities of tin reagents does not pose a significant health hazard (assuming it is performed in a hood). Also, it may be possible to remove the last vestiges of the toxic tin compounds from the desired product by chromatography, usually HPLC. (For a discussion of the purification of tin (IV) derivatives see: Hashimoto, J., et al.,
J. Org. Chem.
67:8341-8349 (1997); Crich, D. & Sun, S. R.,
J. Org. Chem.
61:7200-7201 (1996); Vedejs, E., et al.,
J. Am. Chem. Soc.
114:6556-6558 (1992).) However, in process/production labs that are responsible for multi-kilo synthesis, the handling of reagents, removal of tin by-products and excess reagent, and waste disposal of kilos of tin compounds poses a serious hazard to workers and a serious financial burden to the company. The situation is further complicated by the need to employ excess tin reagent in Stille couplings.
The solution is to replace toxic tin reagents by environmentally benign hypervalent silicon compounds. This solution would rectify both of the major concerns with the Stille coupling outlined above in that it would eliminate the inclusion of toxic tin reagents/by-products from the reaction protocol altogether. Another environmental consideration, as noted below, the silicate reactions could be performed in tetrahydrofuran (THF), a Class 3 solvent, rather than DMF.
Shibata, K. et al.,
Chem. Commun.
1309-1310 (1997), disclose cross coupling reactions of aryltrialkoxysilanes with aryl bromides. The reaction was carried out in the presence of TBAF, THF-DMF mixed solvent or toluene, and a palladium catalyst (palladium acetate or tetrakis(triphenylphosphine)-palladium(0).
SUMMARY OF THE INVENTION
The invention relates to a method for the preparation of a compound of Formula I:
wherein R and R
1
are zero to three substituents, each of which is independently alkyl, alkenyl, aryl, alkanoyl, alkoxy or nitro comprising reacting a compound of Formula II:
where R is defined above and X is Cl, Br, I or triflate (OTf) with a compound of Formula II:
where R
1
is defined above and R
2
is an alkyl group,
wherein the reaction is carried out in the presence of a Pd catalyst, under conditions whereby said compound of Formula I is produced.
The invention also relates to a method for the preparation of a compound having Formula IV:
where R
3
is zero to three substituents, each of which is independently alkyl, alkenyl, aryl
Brescia Marc-Raleigh
DeShong Philip
Handy Christopher J.
Manoso Amy S.
Mowery Molly E.
Shaver Paul F.
University of Maryland
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