Heterocycles From Cycloadditions

Scheme 2.7 Formation of heterocycles from cycloaddition reactions of R2Si=SiR2-...

Recently, much attention has been paid to hetero Diels-Alder reactions as powerful tools for the construction of heterocyclic compounds. For example, cycloaddition of 2,3-dimethylbuta-l,3-diene 41a with 1,2-thiazinylium salt 95, in acetonitrile at room temperature, resulted in the exclusive formation of product 76a resulting from cycloaddition across the C—S1 bond (see entry 1 in Table 15 and Equation 26) <1999TL1505>. Similarly, isoprene 41b and... 

As shown in Scheme 2.21 Id, starting with N-allyl carbohydrate-nitrones (469), a series of chiral six- (470) and seven-membered(471) TV-heterocycles were synthesized (Scheme 2.227). A very interesting and useful aspect of this cycloaddition is the control of regioselectivity by the substitution at the nitrogen atom. Therefore, it is possible to direct reactions towards the syntheses of preferred six- or seven-membered heterocycles from carbohydrate derivatives (722). 

Discovery of New Enantioselective Dipolar Cycloadditions from Small Ring Heterocycles (from Johnson, 2003)... 

Further examples of intramolecular 1,3-dipolar cycloadditions (cf. Section 10.21.9.2.2(ii)) include the synthesis of an isoxazolidine from nitrone 193 (Equation 128) <1997J(P1)1805>, and a pyrazolo heterocycle from the nitrile oxide generated in situ from the oxime 194 (Equation 129) <1999TL3535>. 

The reaction of 2- and 3-vinylindoles with dienophile 214 constitutes the first example of an asymmetric Diels-Alder reaction of vinyl heterocycles. From 3-vinylindoles, enantiomerically pure carbazoles 215a-c were obtained, whereas from the vinylindole 197 together with 215d, diastereomer 216 was obtained as a minor product. Conversely, 2-vinylindoles provided inseparable mixtures of diasteromeric carbazoles. On the other hand, the cycloaddition reactions of 3-vinylindoles with 217 furnish the tetrahy-drocarbazoles 218 with endo-diastereoselectivity (93T2863). 

The nitrene 28 is not produced from the azide precursor, but from heterocycles via photolysis and thermolysis as shown in Sch. 11 [20]. Iminoacyl nitrenes react intramolecularly giving benzimidazoles with good yields (Sch. 11), and, dependending on the precursor used and the reaction conditions, varying amounts of carbodiimides are obtained. The reactivity of the acyl nitrenes is influenced by the substituent connected to the acyl group (see Sch. 10), however all acyl nitrenes are quite reactive and therefore rather unselective. Apart from cycloaddition reactions with Tt-bonds, insertion reactions into a-bonds, additions to lone pair electrons of... 

This reactivity of N-acylenamines 1 has opened up new possibilities for the use of enamides. in photochemical rearrangements2 as well as in acid-catalyzed cyclizations3,4, which lead to a variety of complex nitrogen-containing heterocycles from readily available simple precursors. These reactions have also been used to form a wide variety of natural products and polyfunctional compounds. Enamides can be also used as electrophilic reagents for amidoalkylation5,6, which can occur under certain conditions as a [4 + 2] cycloaddition to form 1,3-oxazinium heterocycles7. 

A wide variety of main group heteroatom-containing ring systems are formed by the reaction of appropriate reagents with metallacycles derived from cycloaddition of Cp2Zr with alkynes, diynes, dienes, enynes or alkynenitriles. This is an exceptionally general process of considerable potential, especially for the synthesis of less-common types of heterocycles (Schemes IS and 16). ... 

It is intended that the heterocyclic compounds that are collected here should derive from products of process (1). Those of interest are variations of equation (1) which lead to cyclic products in at least two steps rather than from cycloadditions. As was evident in the last section, both acyclic and cyclic examples are often conveniently discussed together. Only a few representatives of the possible structures, i.e. with different combination of atoms of oxygen, sulphur, nitrogen, etc., can be mentioned. 

A special case occurs in compounds with a C=Z bond (Z = P, Si) arising from a [l,2]-shift to a carbene center (Scheme 17). The formation of heterocycles from these compounds occurs via [2 + 2]- and [4 + 2]-cycloaddition reactions. 

Cycloaddition of isocyanates with formation of N-heterocycles 86ZC117. Cycloaddition of nitrones in synthesis of N-heterocycles 85OPP23. Dioxopyrrolidines, synthesis of N-heterocycles from 84YGK340. 

Iminyl radicals, formation of N-heterocycles from 78YGK368. Intramolecular cycloaddition of o-quinodimethanes in synthesis of bi- and... 

Scheme 15. Synthesis of Heterocycles from 1,6-Dienes, Enynes, and Diynes via (a) Cycloisomerization, (b) Tandem Addition—Cyclization, and (c) Cycloaddition...

Azomethine ylides have been successfully used for rapid synthesis of dispiro-heterocycles by cycloaddition to 9-azylidenefluorene 162 dipolarophile in a 3-component solvent-free micro vave reaction either neat or in the presence K-10 montmorillonite (Scheme 11.40) [3k, 102]. Although extremely sterically demanding, these reactions were performed successfully, reducing reaction times from 5-8 h under conventional conditions (methanol reflux) to only few minutes under the action of microwaves. The reactions were clean and products 165 were obtained in high yields (78-92%) compared with the conventional conditions (3-60%). 

Sarkar N, Banerjee A et al (2008) [4 + 2] Cycloadditions of A(-alkenyl iminium ions Structurally complex heterocycles from a three-component Diels-Alder reaction sequence. J Am Chem Soc 130 9222-9223... 

S.2.2.7. Fused Heterocycles from Cyclic Dipolarophiles. Furan provides a useful example of a diene acting instead as a dipolarophile. As will be discussed in Chapter 6, this molecule has the lowest aromaticity of the 5-membered heterocycles. It is also useful as a diene in Diels-Alder cycloadditions, but here we will observe that one double bond can react with a 1,3-dipole (Scheme 5.34). 

Heterocycles by Cycloadditions of Carbonyl Ylides Generated from Diazo Ketones... 

The formal acetals of ketene 2, e.g. (diethoxyvinyhdene)triphenylpho-sphorane 4, are highly reactive and, hke 2, add all sorts of H-X compoimds such as carboxylic acids, alcohols, amines, 1,3-dicarbonyls etc. across their C=C bond. Heterocycles result from cycloadditions of these yhdes to heteroallenes [17]. 

Sodium carbonate Transannular cycloaddition Bridged heterocyclics from cyclohepta-2,6-dienones... 

Treatment of acyl chlorides with pyridine and trifluoroacetic anhydride (TFAA) was assumed to involve generation of ketenes which can be subjected to electrophiUc attack by TFAA to afford jd-trifluoroacetylacetic acid derivatives 484. Quenching of the reactions with dienophiles resulted in construction of heterocycles 485 that clearly result from cycloaddition reactions of intermediate acylketenes generated by ehmination from 484 (Scheme 155) (1992TL1285, 1995T2573, 1995T2585). 

The higher-order cycloaddition of azomethine ylides has emerged as a powerful and efficient tool for the convergent enantioselective synthesis of various mediumsized heterocycles from simple precursors. As a consequence, much attention has been paid into this research area in recent years. 

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