Five-membered heterocydes

Table 34 Operating Conditions for GLC Separation of Five-membered Heterocydes with More Than One Heteroatom ...

Dipolar cydoadditions are one of the most useful synthetic methods to make stereochemically defined five-membered heterocydes. Although a variety of dia-stereoselective 1,3-dipolar cydoadditions have been well developed, enantioselec-tive versions are still limited [29]. Nitrones are important 1,3-dipoles that have been the target of catalyzed enantioselective reactions [66]. Three different approaches to catalyzed enantioselective reactions have been taken (1) activation of electron-defident alkenes by a chiral Lewis acid [23-26, 32-34, 67], (2) activation of nitrones in the reaction with ketene acetals [30, 31], and (3) coordination of both nitrones and allylic alcohols on a chiral catalyst [20]. Among these approaches, the dipole/HOMO-controlled reactions of electron-deficient alkenes are especially promising because a variety of combinations between chiral Lewis acids and electron-deficient alkenes have been well investigated in the study of catalyzed enantioselective Diels-Alder reactions. Enantioselectivities in catalyzed nitrone cydoadditions sometimes exceed 90% ee, but the efficiency of catalytic loading remains insufficient. 

An important area of progress in zirconacyclopentadiene chemistry has been the heteroatom transfer developed by Fagan and Nugent, leading to five-membered heterocydes (Eq. 2.19) [26],... 

Formation of Four-membered from Five-membered Heterocydes... 

The aromatic five-membered heterocyde imidazoie is important in many biological processes. One of its nitrogen atoms is pyridine-like in that it contributes one w electron to the aromatic sextet, and the other nitrogen is pyrrole-like in that it contributes two IT electrons. Draw an orbital picture of imidazole, and account for its aromaticity. Which atom is pyridine-like and which is pyrrole-like ... 

DHA gave a blue color with pyrrole, 3,4-dimethylpyrrole, and 2,2 -bipyrrole (69MI1 70MI2). On the other hand, pyrrole having substituents at the 2- or 2.5-positions, or other five-membered heterocydes such as furan, thiophene, or pyrrolidene, failed to give such a blue color when they were substituted for pyrrole. Although other attempts to isolate the reaction product failed, the use of the 6-benzoyl derivative of DHA instead of DHA did allow isolation. Based on IR spectroscopy and elemental analysis, it was concluded that the blue compound possesses an indophe-nine structure. 

Tactics for the synthesis of five-membered heterocydes are to disconnect both C-X bonds and to identify the electrophilic carbon fragment needed to add to the nucleophilic heteroatom. Cyclic sulphide (20) requires ds -dihalide (21) which comes from m-butenediol (22) (Chapter 16). 

One of the most studied heterocyclic rearrangement in the series of five-membered heterocydes is the Boulton—Katritzky rearrangement (BKR) of 1,2,4-oxadiazoles. This type of ring transformation can occur under a variety of conditions and with different types of participating side-chains, as shown in Scheme 6. Novel mechanistic studies have recently been carried out, including studies in micellar environments (2012JCIS67, 2014EJ07006). 

Five-Membered Heterocydes with More than Two Heteroatoms... 

To test the effect of a heteroatom, Starokon et al. [175] studied three five-membered heterocydes with a similar molecular structure, containing the oxygen (2,5-dihy-drofuran), nitrogen (3-pyrrole) and sulfur (butadiene sulfone). Only the oxygen-containing cyde was carboxidized selectively, while the others showed a strong tendency towards side reactions resulting in a set of unidentified products. 

In this large group of heterocycles, ring strain is of little or no importance. Ring-opening reactions are, therefore, rarer than in three- and four-membered heterocydes. The crudal consideration is rather whether a compound can be regarded as a heteroarene or whether it has to be classified as a heterocycloalkene (see p. 2). Various aromatidty criteria apply to heteroarenes, and, as a consequence, different opinions have been expressed on this matter [1]. As will be shown by means of examples of the various systems, the nature and number of heteroatoms are the critical factors. The parent compound of the five-membered heterocydes with one oxygen atom is furan. 

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