Heterocyclic synthesis five-membered rings

Phosphorus heterocyclic compounds, 1, 493-538 five-membered ring systems, 1, 513-523 nomenclature, 1, 496 six-membered ring systems, 1, 497-513 Photoaromatization oxirenes from, 7, 125-126 Photobleaching chromenes in, 3, 880 Photochemical reactions heterocyclic compound synthesis from, 5, 159 reviews, 1, 56 heterocyclic compounds reviews, 1, 71, 72... 

Dipolar cycloaddUions. Interest in 1,3-dipolar cycloadditions increased dramatically during the past 20 years, largely because of the pioneering studies of Huisgen [7, 2] The versatility of this class of pericychc reactions in the synthesis of five-membered-ring heterocyclic compounds is comparable with that of the Diels-Alder reaction in the synthesis of six-membered-ring carbocyclic systems (equation 1)... 

Many versatile approaches to the construction of fused heterocyclic systems (6 5 6) with ring junction heteroatoms have been reported. More general reactions which can be used for synthesis of derivatives of several tricyclic systems, and transformations which have potential for use in the preparation of a series of substituted compounds, are discussed in this section. Formation of the five-membered ring is presented first because it is a conceptually simple approach. It should be noted, however, that the addition of a fused six-membered ring to a bicyclic component offers much more versatility in the construction of a (6 5 6) system. Each subsection below starts with intramolecular cyclization of an isolated intermediate product. Reactions which follow are one-pot intermolecular cyclizations. 

A general approach to the synthesis of (6 5 6) fused heterocyclic ring systems involves intramolecular cyclization of two substituents attached to a five-membered ring of the fused (6 5) system. A typical example is cyclization of 211 to... 

The concept of five-membered ring heterocyclic synthesis by transformation of the initial adduct of the ADC compound and substrate is not limited to cyclization of substitution products. l,3,4-Oxadiazol-2-ones (30, Scheme 3) result from heating the initial DEAZD-dichlorocarbene adduct.72 Treatment of the Diels Alder adducts 96 with zinc in acetic acid gives pyrroles in good yield (Eq. 17).151 The reaction has been extended to the synthesis of dipyrroles from the appropriate Diels-Alder adduct (96, R = pyrrol-2-yl). 

A lot of methods are available for the synthesis of this heterocycle, and most of them rely on the formation of the five-membered ring. In this section, only the methodologies of reasonable scope will be reported. The most classical method involves the cyclocondensation of 2-aminopyridine with an a-halo carbonyl compound. Due to the broad availability of the required substrates and the efficiency of this cyclocondensation, it continues to be the method of choice to prepare this heterocycle. New examples highlighting the generality of this reaction are collected in Table 14. 

The preparation of five-membered rings in solid-phase organic chemistry has been reported in several publications. Versatile syntheses of these heterocycles with different numbers and kinds of heteroatoms have been described. The synthesis of five-membered rings containing one nitrogen atom (Fig. 3.6) as pyrrolidines (231) [311-316] pyrroles (232) [317-320] pyrrolidinones (233) [321-323] pyr-rolinones (234) [324—326] 2,5-pyrrolidinediones (235) [327-329] 2,4-pyrrolidine-diones (236) [330-332] 2,5-pyrrolinediones (237) [333] or heterocycles with one oxygen or one sulfur atom like tetrahydrofurans (238) [334—336] 2,5-dihydrofurans (239) [337], furans (240) [338, 339], yS-lactones (241) [340-343], 2,5-dihydrofura-nones (242) [344] (Scheme 3.35) and thiophenes (243) [345, 346] can be accomplished on solid supports. 

The Sjv -cyclization is also suitable for the construction of enantioenriched heterocycles as demonstrated by the synthesis of the divinylpyrrolidine 333 (90% ee) from the dialkenylamine 331 (equation 88) ". The absolute configuration (3R,4R) (elucidated by anomalous X-ray diffraction) again results from stereoinversion at the metal-bearing C(l) atom in (S)-332 during the formation of the five-membered ring by S -substitution. 

This section provides a critical evaluation of synthetic methods available for the preparation of the most common compounds. Most heterocyclic systems included in this review are made by only one of the following protocols synthesis of the fused srx-membered ring (Section 10.13.9.1), synthesis of the fused five-membered ring (Section... 

The transition metal catalyzed synthesis of five membered heterocycles, particularly of condensed ring systems, has attracted considerable attention. The ease of the formation of five membered rings has been utilised both in intramolecular ring closure processes, and in the combination of two (three) fragments through the formation of a carbon-carbon and a carbon-heteroatom bond. This chapter is dedicated to examples, where the construction of the five membered heterocycle is achieved in a transition metal catalysed step. 

Synthesis of Six-membered Rings from Other Heterocycles 4.2.4.3.1 From five-membered rings... 

Despite the numerous studies devoted to the synthesis of five-membered ring heterocycles using enamines as synthons, most publications on the use of enamines in the synthesis of heterocycles deal with six-membered heterocyclic ring systems, especially pyridine, pyrimidine, and pyran derivatives. 

A number of other five-membered ring nitrogen heterocycles have been prepared by cyclative cleavage. The illustrative examples (Fig. 4) depict the synthesis of pyrazolones,12 succinimides and phthalimides,13 pyrrolo[3,4-h] pyridines,14 2-aminoimidazolones,15 imidazo[4,5-fr]pyridin-2-ones,16 and l,2,4-triazoline-3,5-diones.17... 

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