Sequential organic reactions

Metal-promoted reductive p-elimination reactions in 1,2-difunctionalized substrates have been one of the most important means of generating C=KZ bonds [9]. In the past few years, a number of reductive elimination reactions of 1,2-difunctionalized compounds have been reported under various organometallic reagents, such as Sml2 [10], Zn [11], or In [12], In addition, those low-valent organometallic species exhibit excellent properties for sequential organic reactions and several examples have been described in which a metal-promoted ehmination reaction occurs as a step of a sequential process [13],... 

Page et al. (see [298] and references therein) have shown that generally excellent stereocontrol in organic reactions can be obtained by using DITOX (1,3-dithiane-l-oxide) derivatives as chiral auxiliaries. The one-pot stereo-controlled cycloalkanone synthesis given here outlines some aspects of the chemistry worked out for efficient acylation-alkylations steps. Of note are the use of N-acyl imidazoles under mixed base (sodium hexamethyldisilazide/n-butyllithium) conditions to yield the lithium enolates of 2-acyl-l,3-dithiane-l-oxides) and the sequential alkylation-cyclization of the latter (steps (iv) and (v)). 

The purpose of this chapter is to provide an introduction to the scope and limitations of radical cyclization reactions. Emphasis will be placed on the reactivity profile of radicals with respect to chemo-, regio-and stereo-selectivity. Because most sequential radical reactions include at least one cyclization, they are also presented in this chapter. The organization of this chapter is similar to the previous chapter on radical additions. However, the basic principles of radical reactions, selectivity requirements, methods to conduct radical reactions (including experimental techniques), and mechanisms are extensively discussed in the previous chapter, and these aspects will be reiterated rather sparingly. A reader who is not familiar with the principles of radical reactions as applied to synthesis should read the addition chapter (Chapter 4.1, this volume) first. 

Corsico, E.F. and Rossi, R.A. (2002) Sequential photostimulated reactions of trimethylstannyl anions with aromatic compounds followed by palladium-catalyzed cross-coupling processes. Journal of Organic Chemistry, 67, 3311-3316. 

We can easily predict that cascade and sequential catalytic reactions will be the subject of important investigations not only by promoting the cooperation of several metal catalysts but also by organizing the tolerance and the cooperative work of metal and organo catalysts, and of metal and enzyme catalysts. This will be possible through a deep understanding of the mechanisms of each catalytic system, so as to organize their mutual tolerance. 

Radical reactions provide a powerful means for manipulating the structure of organic compounds. A vast range of radical transformations is available to the synthetic organic chemist, ranging from functional group interconversions to asymmetric reactions and complex, sequential cyclization reactions where molecular complexity can be increased spectacularly in a single step. Many of these processes are complementary to more traditional polar processes and are characterized by attractive features such as the mild, neutral reaction con-... 

The ubiquitinylation of proteins is a complex process, which involves three sequential enzymatic reactions performed by three types of enzymes, El, E2 and E3 (Fig. 2.9). The enzymatic conjugating cascade is organized in a hierarchical way There is one El enzyme, a limited number of E2 enzymes, each of which may serve several E3 enzymes, and a much larger number of E3 enzymes (Fig. 2.10). 

A wide range of taxonomically distinct organisms is able to degrade or transform xenobiotics, and reactions carried out under anaerobic conditions merit continued attention. Sequential transformations reactions carried out by different organisms may be necessary to accomplish degradation of the initial substrate, and attempts to mimic such situations in laboratory experiments have been illuminating. 

D. P. Curran, Radical Addition Reactions, and Radical Cyclization Reactions and Sequential Radical Reactions. In Comprehensive Organic Synthesis, B. M. Trost, I. Fleming, Eds. Pergamon Elmsford, NY, 1991 Vol. 4, Chapters 4.1 and 4.2. 

The sequential variations in the mineralogy of the carbonate cement reflect the compositional evolution of the interstitial pore waters during burial of the sediments. These variations may be ascribed to changes in the degree of dissolution of minerals, to mineral and organic reactions and to the authigenesis of minerals. The iron content of the carbonate cements of the intercalated argillaceous layers, e.g., increases frequently with depth of burial (Boles and Frank 1979 Irwin 1980 Matsumoto and Fijma 1981). It could be tied to the transformation of the clay minerals. 

Domino reduction/aldol cydization was applied for the synthesis of ( )-fredericamydn A 44, a potent antitumor and antibiotic agent, by Kelly et al. [18] in 1988 (Scheme 9.10). DIBAL-H (diisobutylaluminum hydride) reduction of lactone 45 afforded an intermediate 46 having both enolate and aldehyde. Subsequent cychzation via aldol reaction gave a diastereomeric mixture of spiro hydroxy ketone 47, which was further converted into ( )-fredericamycin A 44 by sequential organic transformations. A similar strategy was employed by Mehta et al. [19] for the synthesis of bicyclo[3.3.1]nonan-9-one core of hyperforin, an antidepressant. 

Observational studies Adverse reactions to amphotericin B deoxycholate have been studied in a retrospective analysis of 39 courses of treatments in 33 Chilean patients 1% On average, therapy lasted 12 (range 2-39) days and the cumulative dose was 600 (100-1950) mg. In 63% of cases 24-hour infusions were used and 36% received a 4-to 6-hour infusion. In addition, 37% received daily an infusion of saline before amphotericin. There were adverse reactions in 40% of treatments fever was the most common (25%). Nephrotoxicity was relatively infrequent (9.4%), and it affected only patients without previous renal disease and not requiring dialysis. Hypokalemia developed in 22% of treatments. In a multivariate analysis, age over 60 years was an independent factor for infusion-related adverse reactions and a Sequential Organ Failure Assessment (SOFA) score over 3 and glucocorticoid administration at the same time as amphotericin were independently associated with fatal outcomes. 

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