Heterocyclic compounds four-membered ring opening

Five-membered heterocycles 206-209, in which two 1-adamantyl groups occupy cis positions, were synthesized from 175 (98BCJ1181).The reaction of tosyl azide with 175 gave 210, which has no tendency to cyclize to 211. These results, together with the fact that compound 173 exists in the ring-opened form, led to the conclusion that, when four-membered rings are constituted by a combination of one S—X (X = N, O, S) and one C—C double bonds, 1,2-dithietes are probably the only species that can adopt a ring-closed structure as the predominant isomeric form. 

The ease of ring formation helped us to make five-membered cyclic acetals from ketones and a seven-membered heterocyclic compound (see Chapter 6). In this chapter we have seen how three-membered epoxides are formed. Ring formation is generally preferred to bimolecular reactions forming open chain compounds providing that the ring is three-, five-, six-, or seven-membered. Four-membered ring are a special case discussed in Chapter 29 where all these points are developed more fully. 

In four-membered heterocycles, the ring strain is less than in the corresponding three-membered compounds and is approximately equal to that found in cyclobutane. Nevertheless, ring-opening reactions forming acyclic products predominate. At the same time, analogy with the reactivity of the corresponding aliphatic compounds (ethers, thioethers, secondary and tertiary amines, imines) becomes more evident. 

With 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 heterocycles. The crucial consideration is rather whether a compound can be regarded as a heteroarene or whether it has to be classified as a heterocycloalkane or heterocycloalkene (see p 2). Various aromaticity 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 heterocycles with one oxygen atom is furan. 

The simplest stable singlet carbene derived from a cyclic precursor is cyclo-propylidene. Like other carbocyclic carbenes, it does not contain a heteroatom within the ring and is therefore not further discussed here. The first cyclic carbene based on a four-membered heterocycle was described in 2004. Deprotonation of iminium salt 87a with KHMDS gave carbene dimer 88a=88a while the same reaction with 87b, bearing even bulkier N,N -substituents, led to the isolation of 88b (Scheme 1.11). Attempts to deprotonate 87a with KOt-Bu resulted in the opening of an endocyclic P-N bond, demonstrating the electrophilic character of the phosphorus atom in this compound. 

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