Strategies for synthesis

It is not surprising that multistep synthesis of challenging and complex target molecules is an engine for the discovery of new synthetic principles and novel methodology which may have very broad application. Just as each component of structural complexity can signal a strategy for synthesis, each obstacle to the realization of a chemical synthesis presents an opportunity for scientific discovery. 

Eda and Kurth applied a similar solid-phase combinatorial strategy for synthesis of pyridinium, tetrahydropyridine, and piperidine frameworks as potential inhibitors of vesicular acetylcholine transporter. One member of the small library produced was prepared from amino-functionalized trityl resin reacting with a 4-phenyl Zincke salt to give resin-bound product 62 (Scheme 8.4.21). After ion exchange and cleavage from the resin, pyridinium 63 was isolated. Alternatively, borohydride reduction of 62 led to the 1,2,3,6-tetrahydropyridine 64, which could be hydrogenated to the corresponding piperidine 65. 

Mardn and coworkers have used this strategy for synthesis of ct- and fi-ll,6 -linked C-thsaccharides lEq. 5.40. ... 

The Batcho indole synthesis involves the conversion of an o-nitrotolnene to a fi-dialkyl-amino-o-nitrostyrene v/ith dimethylformairude acetM, followed by redncdve cychzadon to indoles. This provides a nsefid strategy for synthesis of snbsdtuted indoles fEq. 10.49. ... 

The macrolide carbonolide B contains six stereogenic centers at sp3 carbons. Devise a strategy for synthesis of cabonolide B and in particular for establishing the stereochemistry of the C(l)-C(8) segment of the molecule. 

Dipolar addition to nitroalkenes provides a useful strategy for synthesis of various heterocycles. The [3+2] reaction of azomethine ylides and alkenes is one of the most useful methods for the preparation of pyrolines. Stereocontrolled synthesis of highly substituted proline esters via [3+2] cycloaddition between IV-methylated azomethine ylides and nitroalkenes has been reported.147 The stereochemistry of 1,3-dipolar cycloaddition of azomethine ylides derived from aromatic aldehydes and L-proline alkyl esters with various nitroalkenes has been reported. Cyclic and acyclic nitroalkenes add to the anti form of the ylide in a highly regioselective manner to give pyrrolizidine derivatives.148... 

RG. 66. Commercially available dendrimer scaffolds commonly used for glycodendrimer syntheses, and general synthetic strategies for synthesis of glycodendrimers. 

Abstract In this chapter, recent progress in the synthesis, crystal structures and physical properties of monomeric phthalocyanines (Pcs) is summarized and analysed. The strategies for synthesis and modification of Pcs include axial coordination of central metal ions, peripheral substitution of Pc rings and the ionization of Pcs. The crystal structures of various typical Pcs, especially the effects of different synthetic and modification strategies on the supramolecular assemblies of Pcs via %—% interactions between Pc rings, are discussed in detail. Finally, the UV-vis spectroscopic, conducting, magnetic and catalytic properties of some Pcs with crystal structures are presented briefly, and the correlations between various properties and the molecular structure discussed. 

In some cases, silylation of AN and their derivatives produces nitroso acetals containing the N -siloxy fragment or cyclic ethers of oximes (predominantly substituted 5.6-dihydro-4f/-oxazines). To use these products in strategies for synthesis, it is worthwhile to develop convenient procedures for selective reductions of the above derivatives to the corresponding amines. 

The asymmetric Birch reduction and reduction-alkylation strategies for synthesis of natural products... 

Our strategy for synthesis of the oligosaccharide chains,27.28 calls for 2,6-dideoxyhexoses or the corresponding glycals to serve as precursors for both a- and p-glycosidation reactions. It a selective p-glycosidation protocol can be developed, then in principle any structural isomer or analogue of the natural product can be assembled from a common set of monosaccharide precursors.29... 

Determining strategies for synthesis problems Figuring out a one-step synthesis... 

Intramolecular carbene addition reactions have a special importance in the synthesis of strained ring compounds. Because of the high reactivity of carbene or carbenoid species, the formation of highly strained bonds is possible. The strategy for synthesis is to construct a potential carbene precursor, such as diazo compounds or di- or trihalo compounds, which can undergo intramolecular addition to the desired structure. Section E of Scheme 10.5 gives some representative examples. 

The use of mixed anhydrides derived from Al-acyl-a-amino acids has become an interesting strategy for synthesis of saturated 5(4//)-oxazolones 101 (Scheme 7.26). For example, reaction of Al-acyl-a-amino acids with methyl chloroformate in the presence of Al-methylmorpholine affords racemic 5(47/)-oxazolones. 

M. C. McIntosh and S. M. Weinreb, A strategy for synthesis of conduritols and related cyclitols via stereodivergent vinylsilane-aldehyde cyclizations, J. Org. Chem. 56 5010 (1991). 

Chapters 21-23 are for the neophyte trying to determine which technique can be useful for unraveling a mechanism and/or preparing a strategy for synthesis. The virtues of the key techniques described in Chapter 3 are illustrated here with specific chemical examples. 

Aakeroy and coworkers used the seven new cocrystals of 1,4-diiodotetrafluorobenzene they discovered to critically discuss the progress made in the field, and to comment on challenges that remain unsolved [22]. The goal of the work was to match the desired supramo-lecular outcome with a strategy for synthesis of the intended system, and the investigators were able to obtain the anticipated intermolecular interactions in several cases. The crystallization of one intended system was complicated by the production of a solvated crystal form, and it was concluded that the serendipitous inclusion of solvent molecules in a crystal lattice was not always predictable, and the outcome not always favorable. 

Vorosmarty C.J. Hinzman L.D. Peterson B.J. Bromwich D.H. Hamilton L.C. Morison J. Romanovsky V.E. Sturm M. and Webb R.S. (2001). The Hydrological Cycle and Its Role in Arctic and Global Environmental Change A Rationale and Strategy for Synthesis Study. Arctic Research Consortium of the U.S., Fairbanks, AL, 84 pp. 

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