Ring-closure reactions cycloaddition

A ring-closure reaction to the bicyclic triazolopyridine system implying intramolecular 1,3-dipolar cycloaddition was published by Couty et al. <2004TL3725>. The reaction pathway started from an /V-propargylaruinoalcohol 398, which was treated first with thionyl chloride followed by sodium azide to give the intermediate 399, which underwent the desired cyclization to afford the final product 400. Although in other related cases (cf. Chapter 11.15 for tetrazolopyrazines) the yields were acceptable, this nitrogen positional derivative was obtained only in 20% yield. 

This section is devoted to cyclizations and cycloadditions of ion-radicals. It is common knowledge that cyclization is an intramolecular reaction in which one new bond is generated. Cycloaddition consists of the generation of two new bonds and can proceed either intra- or intermolecularly. For instance, the transformation of 1,5-hexadiene cation-radical into 1,4-cyclohexadienyl cation-radical (Guo et al. 1988) is a cyclization reaction, whereas Diels-Alder reaction is a cycloaddition reaction. In line with the consideration within this book, ring closure reactions are divided according to their cation- or anion-radical mechanisms. 

Electrocyclic ring closure reactions of phenyl ketenimides 331 allow the construction of the quinazolone ring (Scheme 73). For instance, quina-zolones 332 were synthesized some years ago in 4-85% yield by heating 331 (R2 = Ph) in addition, dimerization through a [4 + 2] cycloaddition leading to 333 (30-73% yield) was observed (78S760). Compound 331 (R1 = CF3) has been employed for the preparation of the trifluoromethy-lated quinazolone 334 (71% yield) [90TL(31 )2717]. 

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. 

Figures 15.45 and 15.46 illustrate impressively that the significance of 1,3-dipolar cycloadditions extends beyond the synthesis of five-membered heterocycles. In fact, these reactions can provide a valuable tool in the approach to entirely different synthetic targets. In the cases at hand, one can view the 1,3-dipolar cycloaddition of nitrile oxides to alkenes as a ring-closure reaction and more specifically, as a means of generating interestingly functionalized five- and six-membered rings in a stereochemically defined fashion.

Tranylcypromine contains a cyclopropane ring and construction of this unit must be the overriding consideration in planning a synthesis for the compound. On the basis of the constitution given for the compound a ring closure reaction appears to be rather impracticable. Consequently, cycloaddition reactions must be considered for which three possibilities exist as shown by the disconnections a, b, or c in the formula below. 

Direct irradiation of myrcene (100) gives the cyclobutane derivative 101 by an electrocyclic ring-closure reaction, together with )3-pinene (102) formed in a [2 + 2] cycloaddition process. The sensitized reaction, however, yields the bicyclic compound 103. 

In copyrolytic reactions of the aminosilylenes with unsaturated ketones or imines (heterodienes) we mainly obtained isomeric mixtures. The chemo- and regioselectivity of main- and byproducts can be explained with multistep-cycloadditions. We assume a primary Lewis acid-base interaction between the lone electron pair of the heteroatom (oxygen or nitrogen) and the electron gap at silylene, which is followed by a [2+l]-cycloaddition and a radical ring-opening ring-closure reaction. 

Scheme 6 The redox non-innocent 2,6-diiminepyridine ligand acts as an electron reservoir in Fe-catalyzed [2 + 2] cycloaddition ring-closure reactions...

By Ring-Closure and Cycloaddition Reactions 5-Aroyl-3,6-diaryl-4A/-1,2,4-oxadiazines... 

Intramolecular nitrilimine cycloadditions gave new pyrazolo[4,3-c]pyrrolizines 50 <04H(63)1423>. The syntheses of 5-substituted ethyl 3-oxo-2/7-pyrazolo[4,3-c]pyridlne-7-carboxylates 51 <04H(63)609> and 5//-pyrazolo[4,3-c]quinolines 52 <04H(63)1883> have been described. Ring-closure reactions of 3-arylhydrazonoalkyl-quinolin-2-ones gave rise to 1-aryl-pyrazolo[4,3-c]quinolin-2-ones <04JHC681>. 

A mixture of a tetrasubstituted thiophene and the ruby-red 1,2-dithiin (59) is formed when thiobenzophenone reacts with tetracyanoethylene in refluxing benzene. It is considered that initial [2-i-2]-cycloadditions involving the C=S and nitrile groups are followed by electrocyclic ring opening and ring closure reactions <97LA1677>. 

Abstract Rings in a target structure are to be made from acyclic precursors by intramolecular one-bond formation (ring closure reaction) or by two-bond formation in a cycloaddition reaction. BicycUc and polycyclic target structures are approached in the same way, whereby two-bond disconnections or multi-bond disconnections in reaction cascades are preferred. Multi-bond disconnections may be advantageous, even when a surplus extra bond is generated in the forward synthesis. 

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