Partially and Fully Reduced Rings

The fully saturated rings share with cyclohexane the property of being able to adopt one or more conformations which are virtually free of torsion or bond angle strain. 

Exceptionally the tetrathiane (72) prefers the twist form in the solid phase. In CS2 solution at 0°C chair and twist forms coexist with a free energy difference of ca. 3.5 kJ between them (67JA5978, 68JA2450). Strain energies for several thianes have been derived from heats of formation. 

Besides the shapes adopted by the rings, considerable attention has been paid to the conformational preferences of substituents, both on carbon and on the heteroatoms (nitrogen and sulfur)  

Hetero-substituted cyclohexenes, e.g. dihydropyrans, exist in half-chair conformations. 

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Some of the partially and fully reduced heterocyclic six-membered rings are sufficiently important to have trivial names with which the reader should be familiar. Thus hexahy-dropyridine (38) is known as piperidine, and tetrahydro-l,4-oxazine (39) is morpholine. Tetrahydropyridines are also sometimes referred to as piperideines, with the position of the double bond denoted by a A, but this system is obsolescent (at the least). 

There are numerous reactions reported in the literature that produce highly functionalized derivatives of the parent bicyclic compounds. Many of those reactions have been detailed in this chapter. For several of the bicyclic systems, general synthetic routes that lead to high product yields are unavailable. Many of the known synthetic routes lead to carbonyl derivatives of the ring systems. Within this chapter, these compounds have been treated in each section according to the ring substitution pattern. Likewise, syntheses of partially and fully reduced derivatives of the compounds are included with each parent compound. 

The situation with respect to the thiazolo[3,4-a]pyridines is rather different. Very little information was contained in the first edition, and only a handf ul of papers, all concerned with partially or fully reduced ring systems, have appeared in the period since then. Comment on the perhydro system was included in the above-mentioned review <90AHC(49)193>. 

Thiadiazole 1 was first prepared and characterized in 1955 but products containing this ring system were described as early as 1821. The 1,2,4-thiadiazole nucleus is numbered as in structure 1. The double bonds in the partially reduced rings are designated A2, A3, A4, respectively and these compounds are called thiadiazolines. The fully reduced ring is termed a thiadiazolidine. 

Most of the synthetic routes to the compounds start from a six-membered ring heterocycle. As found in the previous review <1996CHEC-II(7)167>, the focus of many of the studies has been on the pyridine series-pyrrolo-pyridines, furopyridines, and thienopyridines. Within each of these classes of compounds, the [2,3-3] isomers have, by far, received the most attention. Also, as found in the previous review, some of the ring systems have not been investigated at all. Since that time, there has been much interest in thienopyridines because of the wide variety of biologically active compounds that originate from derivatives of thienopyridines (see Section 10.06.12.3). Much of the chemistry of furopyrans involves partially or fully reduced derivatives. There are few literature references to the parent series listed in Figure 6 however, there has been considerable activity with the reduced derivatives. 

Individual functional groups attached to a partially or fully reduced pyran ring behave much as expected of their aliphatic equivalents but there is often a quantitative difference in their reactivity which enables selective reactions to be carried out on polysubstituted compounds. Many examples of this are known in the tocopherol series which are the most important members of the chroman family. Since they are known by trivial names, these are shown with their structures (674). The most important tocopherol is natural vitamin E or a-tocopherol the four natural tocopherols have 7 -configuration at each of their asymmetric centres at C-2, C-4 and C-8. ... 

Since the most direct evidence for specihc solvation of a carbene would be a spectroscopic signature distinct from that of the free carbene and also from that of a fully formed ylide, TRIR spectroscopy has been used to search for such car-bene-solvent interactions. Chlorophenylcarbene (32) and fluorophenylcarbene (33) were recently examined by TRIR spectroscopy in the absence and presence of tetrahydrofuran (THF) or benzene. These carbenes possess IR bands near 1225 cm that largely involve stretching of the partial double bond between the carbene carbon and the aromatic ring. It was anticipated that electron pair donation from a coordinating solvent such as THF or benzene into the empty carbene p-orbital might reduce the partial double bond character to the carbene center, shifting this vibrational frequency to a lower value. However, such shifts were not observed, perhaps because these halophenylcarbenes are so well stabilized that interactions with solvent are too weak to be observed. The bimolecular rate constant for the reaction of carbenes 32 and 33 with tetramethylethylene (TME) was also unaffected by THF or benzene, consistent with the lack of solvent coordination in these cases. °... 

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