Synthetic efficiency

Trost, B. (1991) The Atom Economy - a Search for Synthetic Efficiency. Science, 254, 1471-1477. 

For synthetic efficiency, it is useful to add MgBr2, which accelerates the equilibration. 

Synthetic efficiency. In many organic syntheses, it may be possible to eliminate the need for the protection and deprotection of functional groups, and save many synthetic steps. Water-soluble substrates can be used directly. This will be especially useful in carbohydrate and protein chemistry. 

Cyclopentadienylindium(I) has been shown to be effective in the reaction with aldehydes or electron-deficient alkenes to form highly functionalized cyclopentadienes in aqueous media (See Section 8.4.3).101 This reaction with the appropriate substrates can be followed by an intramolecular Diels-Alder reaction in the same pot to provide complex tricyclic structures in a synthetically efficient manner (Scheme 12.4). 

Since most synthetic applications require enzymes catalyzing nonnatural substrates, their properties often have to be improved. One way to achieve this is to optimize reaction conditions such as pH, temperature, solvents, additives, etc. [6-9]. Another way is to modulate the substrates without compromising the synthetic efficiency of the overall reaction [10]. In most cases for commercial manufacturing, however, the protein sequences have to be altered to enhance reactivity, stereoselectivity and stability. It was estimated that over 30 commercial enzymes worldwide have been engineered for industrial applications [11]. Precise prediction of which amino acids to mutate is difficult to achieve. Since the mid 1990s, directed evolution... 

The increasing current interest in processes that are able to generate complex molecular architectures in one pot has stimulated the development of domino-like procedures that create three bonds in one synthetic operation, with considerable advantages in terms of synthetic efficiency and environmental friendliness. This section describes some examples of the application of these concepts to the preparation of quinolizidine compounds. 

The scope and efficiency of [4+2] cycloaddition reactions used for the synthesis of pyridines continue to improve. Recently, the collection of dienes participating in aza-Diels Alder reactions has expanded to include 3-phosphinyl-l-aza-l,3-butadienes, 3-azatrienes, and l,3-bis(trimethylsiloxy)buta-l, 3-dienes (1,3-bis silyl enol ethers), which form phosphorylated, vinyl-substituted, and 2-(arylsulfonyl)-4-hydroxypyridines, respectively <06T1095 06T7661 06S2551>. In addition, efforts to improve the synthetic efficiency have been notable, as illustrated with the use of microwave technology. As shown below, a synthesis of highly functionalized pyridine 14 from 3-siloxy-l-aza-1,3-butadiene 15 (conveniently prepared from p-keto oxime 16) and electron-deficient acetylenes utilizes microwave irradiation to reduce reaction times and improve yields <06T5454>. 

Another important principle is related to the synthetic efficiency. The ligand derivatization and tethering should be achieved with the minimal modification of the total synthesis of the parent ligand. 

B. M. Trost, Atom Economy A Search for Synthetic Efficiency. , Science 1991,254,1471. 

A general way to improve synthetic efficiency and also address the mentioned criteria as well as give access to a multitude of diversified molecules is the development of domino processes.113 14 31 This methodology allows the formation of complex... 

While the convergent strategy, as described above, has been exceptionally successful, a considerable amount of effort has been devoted to improving its speed and synthetic efficiency. The remainder of this chapter reviews the major methodological developments and improvements in the accelerated, covalent, convergent synthesis of dendrimers. Dendrimers constructed via self-assembly and noncovalent interactions, as well as inorganic dendrimers [25], are beyond the scope of this brief chapter. 

The coupling of two molecules of aldehydes into esters (Tishchenko reaction) has been used as an efficient method for the industrial preparation of dimeric esters. Although a number of systems for such reactions using transition-metal catalysts have been reported [73], there is stiU great room for improvement of the synthetic efficiency. 

Piperazines and derivatives are archaetypical scaffolds and can be considered as efficient, however, structurally simple peptidomimics. The scaffolds combine conformational rigidity with peptide-like spacial placement of amino acid side chains or isosteres thereof. Moreover, piperazines can be used to confine compounds with beneficial properties such as water solubihty. Piperazines are therefore in the center of synthetic interest and many different synthetic pathways have been designed [16-19]. A preferred way to synthesize different piperazine scaffolds with plenty of variabihty provides MCR chemistry. Several piperazine scaffolds are currently only accessible by isocyanide-based MCR. Likely they could be assembled by sequential synthesis as well however, the synthetic efficiency, the diversity, and the size of the alternative chemical space will be inferior. The application of... 

Bienayme H, Huhne C, Oddon G et al (2000) Maximizing synthetic efficiency multi-component transformations lead the way. Chem Eur J 6(18) 3321-3329 Syamala M (2005) A decade of advances in three-component reactions. A review. Org Prep Proced Int 37(2) 103-171... 

The synthetic efficiency compares favorably with existing methods that largely use quaternary ammonium halides and chlorohydrocarbon solvents (Arends et al 1997). Sato and co-workers (Sato et al., 1997) provide several tables of primary and secondary alcohols that were successfully oxidized with aqueous hydrogen peroxide. 

Current Work and Industrial Applications. Recent efforts have been directed primarily toward refining the original process by using standard o -(acylamino)acrylic acids as substrates. The synthetic efficiency (in-... 

R. Noyori, Tris(dialkylamino)sulfonium Enolates and Phenoxide, in W. Bart-mann and B. M. Trost, eds., Selectivity—A Goal for Synthetic Efficiency, p. 121, Verlag Chemie, Weinheim, 1984. 

G. Stork, in Current Trends in Organic Synthesis, ed. H. Nozaki, Pergamon Press, Oxford, 1983, p. 359 G. Stork, in Selectivity—A Goal For Synthetic Efficiency , ed. W. Bartmann and B. M. Trost, Springer Verlag, Florida, 1984, p. 281. 

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