Formation of five membered heterocycles

As shown in Scheme 2, two heteroatom-carbon bonds are constructed in such a way that one component provides both heteroatoms for the resultant heterocycle. By variation of X and Z entry is readily obtained into thiazoles, oxazoles, imidazoles, etc. and by the use of the appropriate oxidation level in the carbonyl-containing component, further oxidized derivatives of these ring systems result. These processes are analogous to those utilized in the formation of five-membered heterocycles containing one heteroatom, involving cyclocondensation utilizing enols, enamines, etc. 

Table 11 Formation of five-membered heterocycles containing three oxygen or sulfur atoms in the 1,2,4-positions by ring interconversions.

The transition metal catalysed formation of five membered heterocycles through the insertion of a triple bond has also been explored. o-Halophenyl-alkynylamines, propargylamines and propargyl-ethers have been subjected to ring closure reactions. These processes, however also require the presence of a second, anionic reagent, which converts the palladium complex formed in the insertion step to the product. 

A significant part of the examples of transition metal catalyzed formation of five membered heterocycles utilizes a carbon-heteroatom bond forming reaction as the concluding step. The palladium or copper promoted addition of amines or alcohols onto unsaturated bonds (acetylene, olefin, allene or allyl moieties) is a prime example. This chapter summarises all those catalytic transformations, where the five membered ring is formed in the intramolecular connection of a carbon atom and a heteroatom, except for annulation reactions, involving the formation of a carbon-heteroatom bond, which are discussed in Chapter 3.4. 

Besides ring closure reactions proceeding through C-H activation, a major part of this chapter is devoted to the formation of five membered heterocycles in annulation reactions. 

Although the following reactions (3.88.-3.93.) show certain superficial similarity in involving the formation of five membered heterocycles starting from unsaturated carbon-carbon and/or carbon heteroatom bonds, they all have a complex, and sometimes strikingly different mechanism. 

The straightforward formation of five-membered heterocycles with three or four heteroatoms and at least one group III or IV metal is unknown. 

Formation of five-membered heterocycles through radical methodologies has been investigated extensively. Inter-, intramolecular, and cascade reactions have been reported for the synthesis of heterocycles. In the case of intramolecular cyclizations, 5-exo pathway is the preferred mode of reactivity. Rate constant for the formation of pyrrolidine by radical ring closure has been reported [95AJC2047],... 

The reactions of l,l-bis(trifluoromethyl)-2-fluoroethylene with compounds having two nucleophilic centers leads to the formation of five-membered heterocycles (90IZY2583, 88S194). 

This synthetic route has been useful for the formation of six-membered Sn heterocyclic dienes (see Section II, B, 2) but evidently has not been studied for formation of five-membered heterocycles by other metalloids that are known to undergo hydride addition to multiple bonds. 

Formation of five-membered heterocycles from hetera-l,3,5-hexatrienes ... 

Ketoesters react with methylhydrazine with formation of five-membered heterocycles (93JHC49) (Scheme 85). 

The reaction of 16 with 1,2-dithioglycol and 2-mercaptoethanol proceeds with predominant formation of five-membered heterocycles 116 and 118 along with fluorinated thiepines 117 and 119 (Fig. 10.45). However, both 117 and 119 were isolated by preparative GC, fully characterized and conformational behavior of these materials was smdied using variable temperature F NMR spectroscopy. ... 

REACTIONS LEADING TO THE FORMATION OF FIVE-MEMBERED HETEROCYCLES... 

Formation of five-membered heterocyclic rings under radical cyclization conditions 05T10603. 

Cyclic structures form on polymer backbones through 1,3-dipolar additions to caibon-to-caibon or carbon-to-nitrogen double bonds. Because many 1,3-dipoles are heteroatoms, such additions can lead to formations of five-membered heterocyclic rings. An example is addition of nitrilimine to an unsaturated polyesters ... 

A large class of organic reactions that lead to the formation of five-membered heterocyclic molecules, have been designated as 1,3 dipolar cycloaddition reactions °. Huisgen has defined the 1,3 dipole to be a species which is represented by zwitterionic resonance structures (i.e. the standmd Lewis octet structures) and which undergoes 1,3 cycloadditions to a multiple bond system, the dipolarophile , as in structures (18) and (19). 

Formation of five-membered heterocycles via a met-aUa-Diels-Alder reaction... 

Formation of Five-Membered Heterocycles via a Metalla-Diels-Alder Reaction... 

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