Meso-heterocycles

Enantioselective desymmetrization of achiral or meso compounds with formation of enantiomerically enriched products, among them heterocycles 99JCS(P1)1765. 

The reaction of benzyl radicals wdth several heterocyclic compounds W as more extensively studied by Waters and Watson, " - who generated benzyl radicals by decomposing di-tert-butyl peroxide in boiling toluene. The products of the reaction with acridine, 5-phenyl-acridine, 1 2- and 3 4-benzacridine, and phenazine were studied. Acridine gives a mixture of 9-benzylacridine (17%) (28) and 5,10-dibenzylacridan (18%) (29) but ho biacridan, w hereas anthracene gives a mixture of 9,10-dibenzyl-9,10-dihydroanthracene and 9,9 -dibenzyl-9,9, 10,10 -tetrahydrobianthryl. This indicates that initial addition must occur at the meso-carbon and not at the nitrogen atom. (Similar conclusions were reached on the basis of methylations discussed in Section III,C.) That this is the position of attack is further supported by the fact that the reaction of benzyl radicals with 5-... 

HaiC77 Haigh, C. W. The combinatorial enumeration of meso-ionic heterocyclic annulenes. MATCH 3 (1977) 87-96. 

The new heterocyclic derivative 130 has been shown to be an efficient chiral auxilliary for asymmetric desymmetrization of cyclic meso-l,2-diols via diastereoselective acetal cleavage . 

Ag(ll) can be stabilized by nitrogen-containing heterocycles such as py, polypyridyls and macrocycles. In fact, Ag(I) disproportionates in the presence of the 14-membered tetraaza macrocycle meso-Me5[14]aneN4(M)... 

Ogawa, C. Azoulay, S. Kobayashi, S. (2005) Bismuth triflate-chiral bipyridine complex catalyzed asymmetric ring opening reactions of meso-epoxide in water., Heterocycles, 66 201-206. 

Lastly, Antilla has disclosed a novel asymmetric desymmetrization of a wide range of aliphatic, aromatic, and heterocyclic meso-aziridines with TMS-N3 promoted by 11 and related 12 (Scheme 5.31) [56]. Uniquely, this is one of only several reports of electrophilic activation of nonimine substrates by a chiral phosphoric acid. Mechanistic studies suggest that silylation of 11 or 12 by displacement of azide generates the active catalytic species A. Consequently, the aziridine is activated through coordination of it carbonyl with chiral silane A to produce intermediate B. Nucleophilic ring opening by azide furnishes the desymmetrized product and regenerates 11 or 12. 

III. The Two Types of Five-Meratered Meso-ionic Heterocycles... 

IV. Five-Memb ed Meso-ionic Heterocycles of Type A V. Five-Membered Meso-ionic Heterocycles of Type B... 

The review is based on two lectures given by one of us (W.D.O.) a Plenary Lecture entitled Meso-ionic Heterocycles—Fact and Fiction given at the Chemical Society Autumn Meeting (September 26, 1972) and the Second Ronald Slack Memorial Lecture, entitled Meso-ionic Heterocycles—Serendipity and Systematic Investigation (February 8, 1974). 

The purpose of the present review is to provide a general survey of meso-ionic heterocycles described up to September 1974. Some more recent references are also included, but in view of the extensive current activity in this area of heterocyclic chemistry, it is necessary to be selective rather than comprehensive. No attempt has been made to discuss the chemistry of meso-ionic heterocycles in detail. Our main objective is to present a summary of the presently known types of meso-ionic heterocycles, which can then be considered in relation to the total number of possibilities associated with certain structural conditions. 

It is now evident that it is desirable to divide five-membered meso-ionic heterocycles into two general classes type A and type B. This review is mainly concerned with the presently known 44 members of type A (Table I) and eight members of type B (Table II). Brief reference is made at the end of the review to various six-membered heterocycles and polycyclic systems that have been described as meso-ionic, but it is now firmly proposed that this practice should be discontinued. 

The betaine-type formula (6) has not been found to be acceptable for the general representation of meso-ionic heterocycles, but in view of the recent advocacy of the symbolism depicted in formula 7 some further comment is necessary. Although we originally used this symbolism in the representation of the sydnones, we subsequently recommended its replacement by 5 because this is in accord with current practice. Our present view is that the use of a special symbol (7) is not justified it is too vague to be useful, and in any case it can cause misunderstanding if formulas of type 8 with e=f are used as well as those of type 7 with e—f. The general formula 5 has much to commend it for discussion of type A and type B five-membered meso-ionic heterocycles and for the correlation of corresponding structural features of these two types (Tables I and II). 

For the five-membered heterocycles (Fig. 1), it is important that the term meso-ionic is reserved for members of the general types 19 and 20. This point needs to be emphasized because recently several structures have been described as meso-ionic although they were in fact ylides 17 and 18. Petersen and Heitzer" have referred to Ae intermediate isolated... 

Having emphasized the need to discriminate between the ylides 17 and 18 and the five-membered meso-ionic heterocycles 19 and 20, it is... 

IV. Five-Membered Meso-ionic Heterocycles of Type A... 

Forty-four five-membered heterocycles of type A (13, 19) have been described (Table I). If the atoms or groups a, b, c, d, e, and f are selected from suitably substituted carbon, nitrogen, oxygen, and sulfur atoms, then with these conditions it can be shown that 144 structural possibilities are provided by the general formula 19. The number of structural possibilities can be deduced in various ways, but a very useful approach is to regard type A meso-ionic molecules (19) as being derived by the union (-<—u— ) of 1,3-dipoles (34) and heterocumulenes (35). 

The relation between the structures of the 44 known five-membered meso-ionic heterocycles (Table I) and the 1,3-dipoles (36—44) from which they can be formally derived by union is as foUows ... 

This list shows that the five-membered meso-ionic heterocycles related to the azomethine imine 1,3-dipole (43) comprise the largest group and that meso-ionic compounds related to the nitrosoimines (39), thionitrosoimines (41), and carbonyl imines (42) are not yet known. Clearly synthetic challenges still exist in the field of meso-ionic compounds. 

This second class of five-membered heterocyclic meso-ionic compounds is represented by the type formula 14 20. So far, only eight representatives (Table II) of type B have been described, whereas acceptable combinations of the groupings a, b, c, d, e, and f derived from suitably substituted carbon, nitrogen, oxygen, or sulfur atoms lead, in principle, to 84 possibilities. However, not all these 84 possible structures are necess y well based because valence tautomerism (see Section VI) might well be associated with thermodynamic preference for the acyclic covalent valence isomer (46) rather than the cyclic meso-ionic alternative (20). 

This possibility can be depicted generally by the situations 19 45 for type A and 20 46 for type B five-membered meso-ionic heterocycles. 

For the type A meso-ionic heterocycles the valence tautomerism 19 45 is now considered. Examples include the possibility that the sydnones (1) could be associated with a valence tautomerism involving the nitrosoketene isomer (47). Similarly, the relation between the isosydnones (48) and their acylaminoisocyanate isomers (49) have been... 

A similar 1,3-dipolar cycloaddition occurs with diethyl azodicarboxylate, and the intermediate 1,3-cycloadduct was isolated. Amidines (101) and halogenoacetonitriles (XCHjCN) yield 4-amino-1,3-diazolium salts (102) directly. These salts (102) could not be transformed into the corresponding meso-ionic heterocycles (98) with base ... 

Most of the known 1,3-dipolar cycloaddition reactions of meso-ionic heterocycles have been concerned with those types in which the exo-... 

R> = Me, R = R3 = Ph, K = H, R = N=CHAr), which with ammonia in chloroform solution give novel derivatives (224) of meso-ionic l,2,4-triazol-3-imines (216). These compounds are of interest in that they belong to a new type of meso-ionic heterocycle in which the exocyclic substituent f (see Table I) is a stabilized carbanionoid residue,... 

These heterocycles (240) are the first representatives of meso-ionic compounds to be S3mthesized in which the raocyclic subsfituent f. Table I) is a stabilized carbanionoid group [-C(CN)C02Me or -CfChOi]-Their synthesis d involves the reaction between (i) JV-aminoamidines (23 ) and bis(methylthio)acrylonitriles (241), (ii) iV-thioacylhydrazines (232), and 3-alkylamino-3-methylthioacrylonitriles (242), and (iii) 1,2,4-triazolium iodides (234, R = Me, X = I) and malononitrile. 

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