Section 3-4 Ring formation reactions

Section III contains a discussion of the electrolytic reactions in which a heterocyclic system is formed the reactions will be treated under the following headings ring formation reactions, ring contractions, and ring expansions. 

In this section, ring formation of silicon-containing metallacycles is described and classified according to the heteroatom involved in the reaction. Therefore, various syntheses of disilacyclopentanes, disilacyclopentenes, silaboracyclopentanes, azasilacyclopentanes, oxasilacyclopentanes, and finally thiasilacyclopentanes are described. 

Ring-opening polymerization is another reaction that can be used to form polyamides and it can be contrasted with the ring-formation reactions described in Section 2.1.3. An important example is the polymerization of caprolactam to give nylon 6 which takes place at 520 K and is catalysed by water. 

Pyrazolines can be prepared from the reaction between a hydrazine and two carbonyl compounds, one of them having at least one hydrogen atom a to the carbonyl group. Formally, these reactions correspond to the [NN + C + CC] class. However, if one considers the different steps in the ring formation, they more properly belong to the [CNN + CC] (Section 4.04.3.1.2(ii)), the [CCNN + C] (Section 4.04.3.1.2(i)), or the formation of one bond (Section 4.04.3.1.1) classes. 

Some examples of alkylation reactions involving relatively acidic carbon acids are shown in Scheme 1.3. Entries 1 to 4 are typical examples using sodium ethoxide as the base. Entry 5 is similar, but employs sodium hydride as the base. The synthesis of diethyl cyclobutanedicarboxylate in Entry 6 illustrates ring formation by intramolecular alkylation reactions. Additional examples of intramolecular alkylation are considered in Section 1.2.5. Note also the stereoselectivity in Entry 7, where the existing branched substituent leads to a trans orientation of the methyl group. 

Entry 6 involves formation of a stabilized benzylic carbocation and results in a very efficient closure of a six-membered ring. Entry 7 involves an activated ring. The reaction was done using enantiomerically pure alcohol, but, as expected for a carbocation intermediate, the product was nearly racemic (6% e.e.). This cyclization was done enantiospecifically by first forming the Cr(CO)3 complex (see Section 8.5). 

The final cyclization manifold has been realized with a different ruthenium catalyst (Scheme 22). The cationic [Cp Ru(MeCN)3]PF6 induces exclusive endo-dig cyclization of both homopropargylic and bis-homopropargylic alcohols.29 73 The clean reaction to form a seven-membered ring is noteworthy for several reasons intramolecular exo-dig cyclization with bis-homopropargylic alcohols is not well established, the platinum-catalyzed case has been reported to be problematic,80 and the selectivity for seven-membered ring formation over the exo-dig cyclization to form a six-membered ring is likely not thermodynamic. The endo-dig cyclization manifold was thus significant evidence that a re-examination of alkyne hydrosilylation mechanisms is necessary (see Section 10.17.2). 

The asymmetric oxidation of organic compounds, especially the epoxidation, dihydroxylation, aminohydroxylation, aziridination, and related reactions have been extensively studied and found widespread applications in the asymmetric synthesis of many important compounds. Like many other asymmetric reactions discussed in other chapters of this book, oxidation systems have been developed and extended steadily over the years in order to attain high stereoselectivity. This chapter on oxidation is organized into several key topics. The first section covers the formation of epoxides from allylic alcohols or their derivatives and the corresponding ring-opening reactions of the thus formed 2,3-epoxy alcohols. The second part deals with dihydroxylation reactions, which can provide diols from olefins. The third section delineates the recently discovered aminohydroxylation of olefins. The fourth topic involves the oxidation of unfunc-tionalized olefins. The chapter ends with a discussion of the oxidation of eno-lates and asymmetric aziridination reactions. 

The same type of ring-closure reaction that leads to the [3,2- ]-fused 50 can also result, in principle, in formation of a [3,4- ]-fused ring system (see Sections 11.16.5.2 and 11.16.7). This case has been found when an amino group was present in the triazole ring, and formation of 51 has been supported by X-ray diffraction. The crystalline structure... 

Finally, three ring-enlargement reactions should be referenced in this section. Gerecke et al. reported <1994H(39)693> that treatment of the 5-chloromethyl-substituted triazolo[4,3-c]quinazoline compound 141 with sodium hydroxide results in the formation of a seven-membered diazepine ring 142 in good yield. 

Novel ring opening reactions of the 1,3-thiazinone moiety of triazolo[5,l- ][l,3]thiazines (13) have been studied Britsun et al. <2005CHE1334>. The experienced transformations are reminiscent of formation of 81 from 79 (Section 11.16.5.1.1). In the frame of this research activity, ring contraction of the thiazine moiety to a thiazole was also observed by the same team <2005CHE782>. 

All synthetic works belonging to this section relate, with one exception, to the preparation of tetrazolo[l,5-A -[l,2,4]triazines. Although the final outcome of this outstanding work as published by Chupakhin et al. <2005IZV713> is also formation of this ring system, the reaction pathway actually involves a ring transformation reaction. The interesting result is summarized in Scheme 10. 

As mentioned in Section 4.10.6.5, substituents on C(2) and C(5) are strongly activated and control the reactivity of the thiadiazole molecule as a whole. The amino group is by far the most popular substituent for further modifications, due to its nucleophilicity and ease of ring formation with the annular N(3). To a somewhat lesser extent, the thiol group has also been utilized in further derivatizing, with the carbon and halogen substituents being the least amenable to further reactions. 

Deoxyhalogeno sugars are susceptible to nucleophilic attack, leading either to displacement, elimination, or anhydro-ring formation. The ease of displacement decreases in the order I > Br> Cl > F the iodo and bromo derivatives have, therefore, been especially utilized in such reactions, although several reactions with chlorodeoxy sugars have now been reported as a result of the increased availability of these compounds. The approach delineated in Section 11,1 (see p. 227) for predicting the reactivity of sulfonic esters can be expected also to be applicable, in an approximate and qualitative way,... 

The formation of alicyclics by electrocyclic and cycloaddition reactions (Section 9.4) proceeds by one-step cyclic transition states having little or no ionic or free-radical character. Such pericyclic (ring closure) reactions are interpreted by the Woodward-Hoffmann rules in the reactions, the new a bonds of the ring are formed from the head-to-head overlap of p orbitals of the unsaturated reactants. 

Reference to Scheme 1 reveals that there are six possible patterns for formation of pyrrole rings in reactions which close two bonds. These can be further subdivided into the [4 + 1] processes (llab, IIac and IIbe) and the [3 + 2] processes (Ilac, Had and Ylbd). In this section we will consider first the [4+1] processes and then the [3 + 2] processes. 

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