Selected Applications in Synthesis

A series of review articles on the synthesis of biofunctional molecules have appeared and several of these describe extensive use of phosphorus-based olefination reactions, for example, in the synthesis of vitamin D, tetramic acids, polyene macrolide antibiotics and bioactive marine macrolides.  

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Miscellaneous Reactions Reactions of Phosphonate Anions Selected Applications in Synthesis... 

Selected Applications in Synthesis 4.1 Carotenoids, Retenoids and Pheromones.- Classical Wittig methods involving the ylide (146) and the dialdehyde (147) have been used to synthesize (148), a diastereoisomer of decaprenoxanthin.88 The retinonitrile (150) has been prepared as a mixture of four geometric isomers by phosphonate-based olefination of the 1-cis, 9-cis-Ci5-aldehyde (149). It was possible to separate the four isomers of (150) and reduce each of them to the corresponding retinal. 

Although the Paterno-Buchi reaction is of high synthetic potential, its use in organic synthesis is still not far developed. In recent years some promising applications in the synthesis of natural products have been reported. The scarce application in synthesis may be due to the non-selective formation of isomeric products that can be difficult to separate—e.g. 6 and 7—as well as to the formation of products by competitive side-reactions such as Norrish type-I- and type-II fragmentations. 

Aziridination remains less well developed than epoxidation. Nevertheless, high selectivity in inline aziridination has been achieved through the use of chiral sulfi-nimines as auxiliaries. Highly successful catalytic asymmetric aziridination reactions employing either sulfur ylides or diazo esters and chiral Lewis acids have been developed, although their scope and potential applications in synthesis have yet to be established. 

For a successful application in synthesis, several problems have to be solved regioselectivity, whether the C-C bond is formed with the 1- or 3-position in an unsymmetrical ambident anion, EjZ selectivity in the formation of the double bond, and simple diastereoselectivity, since two new stereogenic centers are created from prostereogenic compounds. Further, different types of induced stereoselectivity or enantioselectivity may be required. Allylmetals with a wide choice of substituents are accessible by various methods (Sections D. 1.3.3.3.1.-10.). 

The aim of this volume is to convince the reader that metal carbene complexes have made their way from organometallic curiosities to valuable - and in part unique - reagents for application in synthesis and catalysis. But it is for sure that this development over 4 decades is not the end of the story there is both a need and considerable potential for functional organometallics such as metal carbon multiple bond species which further offer exciting perspectives in selective synthesis and catalysis as well as in reactions applied to natural products and complex molecules required for chemical architectures and material science. 

The /lomo-Diels-Alder reaction is a [2 + 2 + 2] cycloaddition of a 1,4-diene with a dienophile which produces two new bonds and a cyclopropane ring. This reaction is an example of a multi-ring-forming reaction that to date has found few applications in synthesis, since the use of 1,4-dienes has been limited mainly to bridged cyclohexa-1,4-dienes and almost exclusively to norbornadiene. Lewis-acid catalysts accelerate /lowo-Diels-Alder reactions and increase the selectivity for the [2 + 2 + 2] vs. [2 + 2] cycloaddition. 

However, more significant modifications in selectivity, which have useful applications in synthesis, have been reported in a number of other reactions performed under the action of MW irradiation [9, 44, 70]. Many of these reactions were performed under heterogeneous and/or solvent-free conditions, and only those performed under homogeneous conditions will be discussed here. 

The cross-metathesis reaction has evolved extensively during the past few years, but there is still a considerable amount of work to be done before the full potential of this reaction is realised. The development of new metathesis catalysts, greater understanding and control of selectivity, and more extensive applications in synthesis that will surely follow in the near future, make this a particularly exciting time in the evolution of the alkene cross-metathesis reaction. 

Reetz et al. described the solid-phase enzymatic synthesis of oligonucleotides on Kieselguhr-PDMA-resins via T4 RNA ligase. Goncomitantly, they found that RNase A selectively cleaves the last bound nucleotide at the ribose sugar leaving a 3, 5 - diphosphorylated ohgomer on the resin, but application in synthesis has not yet been undertaken [22]. 

In a general sense, [1,2]-Wittig rearrangements have only a limited application in synthesis because yields and selectivities are frequently moderate at best. For example, the valuable stereoselective conversion of 117 to 118 (which also works with higher homologues) proceeds in only 14% yield.85 86... 

Thiazolylium quaternary salts show great reactivity toward nucleophiles. The unsubstituted 2-position of thiazolylium and benzothiazolylium cations is exceptionally reactive and its hydrogen atom is removed by bases affording an ylide which is particularly stabilized by the adjacent sulfur atom. This stabilization is for a large part responsible for the natural selection of thiazolylium, among other azolyliums, as the active part of vitamin Bi. 2-Alkylthiazolylium and benzothiazolylium quaternary salts are transformed by bases into exceptionally reactive anhydro bases which have wide application in synthesis. 

Aggarwal VK, Winn CL. Catalytic, asymmetric sulfur ylide-mediated epoxidation of carbonyl compounds scope, selectivity, and applications in synthesis. Acc. Chem. Res. 2004 37 611-620. Li A-H, Dai L-X, Aggarwal VK. Asymmetric ylide reactions epoxidation, cyclopropanation, aziridination, olefination, and rearrangement. Chem. Rev. 1997 97 2341-2372. 

The majority of published work on aza-ylides concerns their applications in synthesis, and here we report a selection of contributions from this area. The Staudinger reaction is a popular route to aza-ylides and has been used to prepare a series of perfluoroalkyl-tagged aza-Wittig reagents, e.g., (68), which were generated in situ (Scheme 22), and utilised in the synthesis of 3//-quinazolidine-4-ones in a fluorous biphasic system. A method for the preparation of aza-polycyclic compounds derived from pyrrolidine, indolizidine and indole has... 

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