Three-membered ring synthesis

Diazoacetic esters <27) are available from diazotisation of glycine esters (26) and provide carbenes for three-membered ring synthesis. 

The alkylpalladium intermediate 198 cyclizes on to an aromatic ring, rather than forming a three-membered ring by alkene insertion[161], Spirocyclic compounds are easily prepared[l62]. Various spiroindolines such as 200 were prepared. In this synthesis, the second ring formation involves attack of an alkylpalladium species 199 on an aromatic ring, including electron-rich or -poor heteroaromatic rings[l6.5]. 

The chemical inertness of the three-membered ring permitted many conversions of functional groups in diazirines. Esterifications, cleavage of esters and acetals, synthesis of acid chlorides, oxidation of hydroxy groups to carboxyl groups as well as Hofmann alkenation all left the three-membered ring intact (79AHC(24)63). 

SYNTHESIS OF THREE-MEMBERED RINGS WITH TWO HETEROATOMS... 

Since syntheses of three-membered rings with two heteroatoms almost always proceed under mild conditions with good yields and from simple starting materials, they are useful intermediates in synthesis. The easy formation of N—O and N—N bonds offers synthetic potentialities. Furthermore, the three-membered ring may serve as a protecting group during additional operations of substitution. 

This chapter will deal exclusively with three-membered rings containing the hetero atoms O, S and N, and fused to the steroid skeleton. Because of the conformational requirements in steroids, not all of the usual methods of synthesis of three-membered rings are applicable to the fused ring system. For the synthesis of steroids to which an aziridine, oxirane or thiirane is attached either in the side chain or at a ring position but not directly fused to the nucleus, the methods discussed in this chapter, as well as others, are applicable. 

Iodine isocyanate was used to synthesize the first steroidal aziridine, 2, 3 -iminocholestane (95). from 5a-cholest-2-ene (91). This reaction sequence which is believed to proceed through a three-membered ring iodonium ion (92) illustrates the limitation of pseudohalogen additions for the synthesis of -aziridines. The iodonium complex forms from the least hindered side (usually alpha) and is opened tmK5-diaxially to give a -oriented nitrogen function. The 3a-iodo-2 -isocyanate (93) is converted by treatment with... 

D. The Synthesis of Three-membered Ring Sulfones and Sulfoxides.. . ... 

The cydopropanation reaction of an unsaturated substrate is one of the most important strategies to access three-membered ring derivatives. The use of Fischer carbene complexes to perform this kind of cyclisation has become an important tool in organic synthesis [4]. In the next few sections the most significant features of this chemistry are briefly described. 

Most thiirene dioxides (and oxides) have been prepared through a modified Ramberg-Backlund reaction as the last crucial cyclization step, as illustrated in equation 40 for the benzylic series . Synthesis of thiirene dioxides requires two major modifications of the originally employed reaction first, the inorganic base has to be replaced by the less basic and less nucleophilic triethylamine - and second, the aqueous media has to be substituted by an aprotic organic solvent (e.g. methylene chloride). Under these mild reaction conditions the isolation of aryl-substituted thiirene dioxides (and oxides) is feasible . In fact, this is the most convenient way for the preparation of the aryl-disubstituted three-membered ring sulfones and sulfoxides. ... 

Heterocycles can be employed as precursors for the synthesis of pyrazoles. Pyrazoles can be synthesized by three-membered ring substrates. For example, allyl amines 12 and pyrazoles 13 could be obtained by hydrazinolysis of 2-ketoaziridines 11 <06TL255>. Regioselective ring opening of 3-aryl-2-benzoyl-l,l-cyclopropanedicarbonitriles 14 with hydrazine provided a new process for the synthesis of 5-aryl-3-phenylpyrazoles 15 <06JHC495>. 

Taking 1,2-disubstituted cyclopropane as an example, retro synthesis analysis shows that there are three possible ways to disconnect the three-membered ring—a, b, and c as shown in Figure 5-11. Route a involves the addition of methylene across a double bond, and this is often a stereospecific conversion or Simmons-Smith reaction.92 One can clearly see that route b or c will encounter the issue of cis/trans-product formation. 

The three-membered ring in metal-ketyl anion-radicals can be readily opened. In steroid synthesis, this reaction is a classic procedure for introducing angular methyl groups (Dauben and Deviny 1966 Scheme 7.45). 

In the synthesis of cyclohexene oxide from cyclohexene shown, this does implicate the less favourable diaxial conformer in the epoxide-forming step. Cyclohexene oxide contains a c/s-fused ring system, the only arrangement possible, since the three-membered ring is necessarily planar (see Section 3.5.2). 

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