Saturated five-membered nitrogen heterocycles

Synthesis of Saturated Five-Membered Nitrogen Heterocycles... 

As discussed in Chapter 6, nitro compounds are converted into amines, oximes, or carbonyl compounds. They serve as usefid starting materials for the preparation of various heterocyclic compounds. Especially, five-membered nitrogen heterocycles, such as pyrroles, indoles, ind pyrrolidines, are frequently prepared from nitro compounds. Syntheses of heterocyclic compounds using nitro compounds are described partially in Chapters 4, 6 and 9. This chapter focuses on synthesis of hetero-aromadcs fmainly pyrroles ind indolesi ind saturated nitrogen heterocycles such as pyrrolidines ind their derivadves. 

In a study of synthetic routes to the phorbol class of compounds, Lautens cyclised the stannane 307 (with 5 equiv MeLi, to avoid stannane reincorporation) to the 7,5-fused ring system 3 0 8.138 This reaction also works in the synthesis of analogous saturated five-membered nitrogen and sulfur heterocycles (see below). 

An alternative to the bis-lactim ether approach is based on condensations of saturated five-membered heterocycles such as imidazolidinone (532) which can now be obtained in an optically pure state by a straightforward classical resolution/ The related oxazolidinone (533) has been obtained from methionine and used to prepare (R)-amino-acids [cf. (528) ] as well as the vinyl substituted derivatives(534) by oxidation and elimination of the sulphur group." Yet more general routes to chiral amino—acids have been reported using a variety of asymmetrically substituted ester enolate equivalents (535) in combination with the electrophilic nitrogen source di-t-butyl... 

This chapter is one of the first attempts of systematic review of the synthetic methods and chemistry of nonaromatic saturated and unsaturated perfluorinated heterocycles. It summarizes data on the synthesis and chemical transformation of perfluorinated six- and to some extent five- membered nonaromatic heterocyclic compounds containing oxygen, nitrogen, sulfur, selenium, and phosphorous. It should be pointed out that the review is not all-inclusive one, but it is an attempt to provide representative examples of synthetic methods and chemistry of perfluorinated nonaromatic hetero-cychc materials. 

Saturated and Partially Saturated Systems with Bridge-head Nitrogen Atoms and Saturated Five- and Six-membered Ring Heterocyclic Compounds , T. A. Crabb, in MTP International Review of Science, Organic Chemistry Series One , ed. D. H. Hey, Butterworth, London, 1973, vol. 4, pp. 291-317. 

Condensed heterocyclo[n,m-n, b, or cjquinazolines. 52, I Condensed 4-thiazolidinones, 49, I Condensed thiophene systems, tetra- and pentacyclic, 32, 127 Condensed 1,2,4-triazines I. Fused to heterocycles with three-, four-, and five-membered rings, 59, 39 Condensed l,2,4-triazolo[3,4-z) heterocycles, synthesis, 49, 277 Conformational equilibria in nitrogen-containing saturated six-membered rings, 36, I... 

Among other methods, leading to the formation of saturated perfluorinated five-and six-membered oxygen and nitrogen heterocycles, having limited application, but... 

The fact that the lone pair on sulfur contributes to the aromaticity is seen in the lower dipole moment of thiophene as compared to its saturated analogue tetrahydrothiophene (0.52 D vs 1.90 D) <72JA8854>. In thiophene, as in most of the other five-membered heterocycles and their saturated analogues, the dipole is directed from the ring towards the heteroatom. The only exceptions to this are pyrrole and iV-alkylpyrroles where the nitrogen atom is the positive end of the dipole. 

Hydrolysis of imidazolylidenes has been studied by DFT calculations and NMR experiments. The outcome of the reaction has been shown to be highly dependent on the amount of water involved in the reaction, and an equilibrium between the carbene and hydroxide ion has been identified. Related to this study, the pAT s of a range of NHCs have been determined via deuterium exchange experiments monitored by H NMR and found to increase markedly with electron donation from nitrogen substituents. Saturation was found to have only minor influence on the acidity of the flve-membered heterocycles. In contrast, the ring size has a major influence (moving from five- to six-membered heterocycles raised the pAT by up to 5 units). 

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