Small ring compounds cycloaddition reactions

Keywords Absolute configuration. Amino acids, Bicyclopropylidene, Coupling reactions. Cycloadditions, Cyclopropanation, Cyclopropanes, Organolithium derivatives. Palladium catalysis. Radical reactions. Small ring polycycles, Spiro compounds. Strain energy. Sulfides... 

Cyclopropanones act as three-carbon sources in [4 + 3] cycloadditions. However, these small-ring compounds are impractical for preparative scale experiments, because they are generally inaccessible and also must be handled with special precautions, in contrast to other oxyallyl species. One of the early descriptions of the synthesis of cyclopropanones appeared in 1932. NeverAeless, the development of the chemistry of cyclopropanones proceeded at quite a slow pace until the late 1960s when Turro reported their utilization in [4 -i- 3] cycloaddition reactions. 2,2-Dimethylcyclopropanone (14) adds to furan, cyclopentadiene, 6,6-dimethylfulvene and the relatively nucleophilic N-methylpyrrole to give the corresponding cycloproducts, but fails to react with anthracene and 1,3-butadiene. Parent cyclopropan-one cannot be used. 

There are so many different examples of photochemical dimerizations and cross-cycloadditions 8-11,13-17) 0f olefinic compounds that one is not surprised to find several variations of mechanistic patterns. Simple olefins, including dienes and strained small ring, bicyclic olefins and styrene derivatives form a class of compounds that undergo such reactions sensitized by triplet energy donors. Some examples axe given in Eqs. 19—23, where only cyclobutane products are depicted. Theory... 

Only a few papers on the formation of compounds with small rings have been published. One example is the [2 + 2]-cycloaddition of electron-rich enamines to Schiff bases under high pressure (1.4 GPa) (87JOC365). The reaction leads to substituted azetidines (1). Four-membered ring heterocycles, thietane derivatives (4), are formed by interaction of sulfene (2) with enamines (3) (86CB257 93JOC3429). 

The various approaches to forming heterocyclic ring systems by intramolecular cyclizations were discussed in Chapter 4 and by cycloaddition reactions in Chapter 5. In Chapters 6 and 7, numerous reactions of heterocyclics were described. We will now reexamine some of this material from a different standpoint, taking a particular heterocyclic family and considering some of the methods that are useful for the construction of the family. In addition, some information on the synthesis of important heterocycles not yet considered will be presented. As was discussed in Chapter 8, great numbers of new heterocyclic compounds have been, and continue to be, synthesized in the research laboratories of the pharmaceutical industry in their search for new materials of value in medicine, and the many accomplishments from this work provide a multitude of examples that can be used to illustrate the practical application of heterocycMc chemistry. However, the presentation must be limited to a small number of examples for more in-depth discussions of important syntheses, two works by... 

Since the isolation of the first molecular compound with an Si-Si double bond in 1981 [1] the chemistry of the disilenes has experienced an almost explosive development, as is reflected in numerous review articles [2]. Addition or cycloaddition reactions to this double bond provide an entry to a series of three- and four-membered ring compounds that are hardly accessible by other routes. Of particular interest among these systems are the disilaoxiranes and disiladioxetanes, both of which open up new questions about the bonding situation in small rings made up of main group elements. 

Since genuine [4-1-2] cycloaddition products had previously not been prepared, it was surprising to find that the action of sulfur on 24 resulted in a formal [4-I-1] cycloaddition to furnish the first ftve-membered ring with an endocyclic silicon-silicon double bond 25. The heavier chalcogens selenium and tellurium did not react with 24. However, in the presence of small amounts of triethylphosphane smooth reactions with these elements did occur to furnish two further ftve-membered ring compounds 26, 27, each with an endocyclic silicon-silicon double bond (Eq. 8) [14]. 

Click chemistry is a chemical concept enunciated by Barry Sharpless, Scripps Research Institute, USA, in 2001, which highlights the importance of using a set of powerful, highly reliable, selective reactions under simple reaction conditions to join small molecular units together quickly for the rapid synthesis of new compounds via heteroatom links and create molecular diversity. Several types of reactions have been identified that fulfill the criteria- thermodynamically favored reactions that lead specifically to one product such as nucleophilic ring opening reactions of epoxides and aziridines, nonaldol type carbonyl reactions, additions to carbon-carbon multiple bonds, Michael additions, and cycloaddition reactions. The best-known cHck reactions are the copper-catalyzed reaction of azides and alkynes or the so-called CuAAC reaction and the thiol-ene reaction. 

The Diels-Alder cycloaddition is the best-known organic reaction that is widely used to construct, in a regio- and stereo-controlled way, a six-membered ring with up to four stereogenic centers. With the potential of forming carbon-carbon, carbon-heteroatom and heteroatom-heteroatom bonds, the reaction is a versatile synthetic tool for constructing simple and complex molecules [1], Scheme 1.1 illustrates two examples the synthesis of a small molecule such as the tricyclic compound 1 by intermolecular Diels-Alder reaction [2] and the construction of a complex compound, like 2, which is the key intermediate in the synthesis of (-)chlorothricolide 3, by a combination of an intermolecular and an intramolecular Diels-Alder cycloaddition [3]. 

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