Applications of the Stille Reaction

Deshpande, M. S. Formation of Carbon-Carbon Bond on Solid Support Application of the Stille Reaction, Tetrahedron Lett. 1994, 35, 5613-5614. 

For a recent review for the application of the Stille reaction in the synthesis of complex natural products see M. Vinfcius and N. de Souza, Curr. Org. Synth. 2006, 3, 313. 

The most spectacular application of the Stille reaction is represented by the final step of Nicolaou s elegant total synthesis of rapamycin (2) (see Section III.B), in which a tandem Stille coupling is carried out on the fully functionalized skeleton. 

Recent reviews that can be used to complement the presentation in this chapter ought to be mentioned [1-3]. Farina et al. [la] have done invaluable work in reviewing the Stille reaction, and the article (with 865 references ) published in 1997 in the series Organic Reactions was republished in 1998 in book form [lb]. The intramolecular variant of the reaction is of great importance, particularly for the preparation of macrocycles, and has been reviewed recently by Duncton and Pattenden [lc,d]. Applications of the Stille reaction in organometallic chemistry were reviewed by Lo Sterzo [2a,b]. Mechanisitic aspects have recently been discussed by Espinet and Echavarren [3a,b]. 

A Stille coupling reaction always takes place between two sp carbon atoms. For example, treatment of vinyl or aryl halides or triflates with vinyl or aryl organostan-nanes would lead to the formation of diene (or higher polyene) systems. A more useful application of the Stille reaction is when the diene generated serves as a transient intermediate which will undergo additional reactions and participate in the cascade sequence. 

Bailey described the first application of the Stille coupling to pyrroles, and one of the earliest examples of any such reaction involving heterocycles [66]. Lithiation of IV-methylpyrrole and quenching with trimethylstannyl chloride gives 2-(trimethylstannyl)pyrrole (76), and palladium-catalyzed coupling with iodobenzene affords l-methyl-2-phenylpyrrole (46) in good yield. 

The next phase focused on the goal of elaboration of the side chain in the desired sense. The primary alcohol function at C7 was unveiled by hydrogenolysis (Pd(OH)2/EtOAc-MeOH). Oxidation of the resultant compound 13 with chromic oxide pyridine afforded aldehyde 14, which was now to be elongated through some variation of a Homer-Emmons type of reaction. Shortly before tiiese investigations were launched. Still had demonstrated the use of phosphonate 15 as a device to achieve the two-carbon extension of an aldehyde to a Z-enoate (12). Happily, application of the Still method to compound 14 afforded the desired 16, mp 120-121° C, in 80% yield as a 20 1 mixture of Z E enoates. 

Similar application of the oxo reaction, as described in Section VI,2, to tetra-0-acetyl-3-deoxy-a-D-threo-hex-2-enopyranose (61) afforded a complex mixture of branched-chain carbohydrates. The separation and characterization of these products are still under investigation. 

The imidazole, benzoxazole, and benzthiazole derivatives in Table 7-3 are rather moisture-sensitive.92 On the whole, however, the heteroarylstannanes show the same reactions that characterise the homoarylstannanes. With a palladium catalyst, they undergo coupling112 and cross-coupling reactions68 and indeed much of the recent interest in the heteroarylstannanes stems from their applications in the Stille reaction (see Section 22.2). One aspect of this is the synthesis of oligomers and polymers or copolymers, for example by the cross-coupling of 2,5-distannylthiophene with a 1,4-diiodo-arene.113,114... 

In this chapter we focus on applications of the Stille coupling reaction for the synthesis of complex natural products published in recent years (mainly the last 10 years). The chapter is organized by the type of bond being formed in the cross-coupling reaction. 

Considering this development and the variability of phenomena encountered It Is clear that organic photochemistry Is still In the period of youth and growth with respect to application of the discovered reactions and even more so regarding quantitative Interpretation. A few additions can be formulated complementing the three principles that served as a basis for a qualitative rationalization of phenomena and that In the course of more than 15 years have proved to be valuable guidelines In experimental exploration. The set of partly well-known effects and partly tentative working hypotheses now can be formulated as follows ... 

The use of the Stille reaction (cross coupling and carbonylative variation) has been the subject of numerous excellent reviews and books over the past few years and we will mention in this part only a few examples to illustrate the power and broad applicability of the method. 

The practical applicability of the HWE reaction and Still-Gennari varianted HWE olefination reaction is evident from its employment in the total-synthesis of numerous complex natural products. Macrolactin A, 68, is a 24-membered polyene macrolide. It displays strong cytotoxic activity in vitro on... 

Before the widespread availability of instrumental methods the major approach to structure determination relied on a battery of chemical reactions and tests The response of an unknown substance to various reagents and procedures provided a body of data from which the structure could be deduced Some of these procedures are still used to supple ment the information obtained by instrumental methods To better understand the scope and limitations of these tests a brief survey of the chemical reactions of carbohydrates is m order In many cases these reactions are simply applications of chemistry you have already learned Certain of the transformations however are unique to carbohydrates... 

For example, a UF-resin for particleboard at the end of the 1970s would have had a F/U molar ratio of approx. 1.6-1.8. To day a UF-resin for the same application has a molar ratio of between 1.02 and 1.08, but the requirements for the boards, as given in the quality standards, are still the same. The degree of crosslinking of the cured resins as well as the reactivity of the hardening reaction depends on the availability of free formaldehyde in the system. 

Solution A rigorous treatment of a reversible reaction with variable physical properties is fairly complicated. The present example involves just two ODEs one for composition and one for enthalpy. Pressure is a dependent variable. If the rate constants are accurate, the solution will give the actual reaction trajectory (temperature, pressure, and composition as a function of time). If ko and Tact are wrong, the long-time solution will still approach equilibrium. The solution is then an application of the method of false transients. 

Web in the life of the medicinal chemist. One may see the development of alerting services for the primary medicinal chemistry journals. The Web-based information search process could be replaced by a much more structured one based on metadata, derived by automated processing of the original full-text article. To discover new and potentially interesting articles, the user subscribes to the RSS feeds of relevant publishers and can simply search the latest items that appear automatically for keywords of interest. The article download is still necessary, but it may be possible for the client software to automatically invoke bibliographic tools to store the found references. Another application of the Chemical Semantic Web may be as alerting services for new additions to chemical databases where users get alerts for the new additions of structures or reactions. 

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