Versatile synthons in heterocyclic synthesis

Although this review is by no means exhaustive, it should present an impression of the importance of iminophosphoranes as versatile synthons in heterocyclic synthesis. Much attention was paid to the aza-Wittig reaction, which enables the preparation of a wide range of simple and complex heterocyclic systems. 

Wamhoff, H., Heterocyclic f-Enamino Esters, Versatile Synthons in Heterocyclic Synthesis, 38, 299. 

Heterocyclic /3-enaminoesters, versatile synthons in heterocyclic synthesis , WamhofT, H., Adv. Heterocycl. Chem., 1985, 3S, 299. 

Besides the use of stereoselective nitrile-converting enzymes as described above, useful chiral building blocks have also been obtained by stereoselective nitrile-forming enzymes. The main product class of nitrile-forming enzymes are cyanohydrins (a-hydroxynitriles, 1-cyanoalkanols), which are versatile synthons in organic synthesis that are readily convertible to a-hydroxy acids [90], a-hydroxy aldehydes [91], ethanolamines [92], amino alcohols, pyrethroid insecticides [93], imidazoles, and heterocycles [94]. Examples of valuable bioactive products derived from chiral cyanohydrins are (i )-adrenaline, L-ephedrin, and (5)-amphetamines [95]. For the synthesis of chiral cyanohydrins, stereoselective enzymes from both plant and bacterial sources have been used. 

Species with CN = 2 comprise phospholide anions 4 and 2H- and. 4//-phospholes 5 and 6, respectively. The chemistry of these compounds has experienced an extraordinary development in the last 10 years. Nowadays, they are key synthons for the synthesis of phosphole derivatives with CN = 3 or for a range of other P-heterocycles. Furthermore, phospholide anions 4 are versatile 7] -ligands affording a variety of phosphametallocene complexes such as mono- and di-phospho-ferrocenes 7 and 8. Chiral derivatives based on monophosphoferrocene units are powerful ligands in asymmetric catalysis. 

The reagents used for the completion of the purine heterocycle are essentially the same as those used for the Traubc synthesis. The purine ring is formed by condensation with derivatives of formic acid or other carboxylic acids. Alternatively, formylation of the amino group is accomplished by a mixture of formic acid and acetic anhydride followed by cyclization. Alkyl esters or trialkyl ortho esters are also versatile synthons for ring closure. Moreover, heating in formamide or cyclization with urea or thiourea provides a satisfactory route. Condensations with isothiocyanates show unusual versatility leading to 2-sulfanylpurin-6-ols. From carbonic acid derivatives, cyclization is reported with chlorocarbonic esters, diethyl carbonate or carbon disulfide. 

Abstract Anhydro sugars have proved to be versatile chiral synthons for the synthesis of chiral heterocycles including pyradazines, oxazines, triazines, chiral morpholines, tetrahydroquinoxalines, benzodioxins, oxazolidinones, episulfides, thiazolines, and cyclic trithiocarbonates. Selected examples are described in this chapter. 

We next explored the applications of liquid-phase synthesis of benzofused heterocycles from a common building block PEG-bound nitro-activated aryl fluoride (Fig. 8). In these synthetic strategies, we created multiple accesses to the structurally diverse core molecules based on a fundamental scaffold 10. We focused on the construction of a variety of benzimidazole libraries starting from a versatile synthon 4-fluoro-3-nitrobenzoic acid via liquid-phase nucleo-... 

The use of temporary tethers in synthesis represents a powerful approach to the coupling of two advanced structures en route to more advanced synthons. RCM plays a key role in the construction of sultone and phosphate heterocycles providing effective methods where both sulfur and phosphorus serve as temporary tethers mediating several selective transformations. The use of sultones to construct 1,3-dienols possessing an internal Z-olefin has been utilized in the synthesis of the originally proposed structure of ( )-mycothiazole and has the potential of expanding to other biologically active natural products. Phosphate tethers have served a central role in the construction of asymmetric 1,3-antt-diol subunits, which have been demonstrated in the construction of both the C1-C14 and C15-C30 subunits of dolabeHde C [7]. Additional uses of these versatile heterocycles are in order and will be reported in future studies. 

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