Reactions on small rings

The enolates of these lactones can be made in the usual way with LDA at -78 °C and are stable at that temperature. 

The formation of the lithium enolate is straightforward but it might be expected to be unstable because of a simple elimination reaction. It is not possible to make open-chain lithium enolates with P oxygen substituents like this because they do undergo elimination. 

in the four-membered ring, the p orbitals of the enolate and the C-O single bond are orthogonal (see drawing in margin) so that no interaction between them, and no elimination, can occur. The enolate can be combined with electrophiles in the usual way (Chapters 26 and 27). 

If the (3-lactone has a substituent already then there maybe a choice as to which face of the enolate is attacked by an electrophile. Simple alkylation with a variety of alkyl halides gives essentially only one diastereoisomer of the product. 

The enolate, as we have seen, is planar, the phenyl group is in the plane (so it doesn t matter which of the two possible diastereo-isomers of the starting material is used), and the isopropyl group is the only thing out of the plane. The electrophile simply adds to the face of the enolate not blocked by the isopropyl group. This is a very simple case of a diastereoselective reaction. 

The smallest ring that we can conveniently work on is four-membered. Saturated four-membered rings have a slightly bent conformation but four-membered lactones are flat. —0 -78 °c. thf 

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Small amounts of salt-like addition products (85) formed by reaction on the ring nitrogen may be present in the medium. (Scheme 60) but. as the equilibrium is shifted by further reaction on the exocyclic nitrogen, the only observed products are exocyclic acylation products (87) (130. 243. 244). Challis (245) reviewed the general features of acylation reactions these are intervention of tetrahedral intermediates, general base catalysis, nucleophilic catalysis. Each of these features should operate in aminothiazoles reactivity. 

The reaction of small ring hydrocarbons with acids has been extensively studied. Although cyclopropane does not react with acetic acid, bicyclo[2.1.0]pentane (20) reacts rapidly to give cyclopentyl acetate. On the other hand, bicyclo[2.2.0]hexane (21) does not react. Other small ring hydrocarbons that react rapidly with acetic... 

There has been only a few reports on reactions of small rings with metal ynolates. Oxiranes are much less electrophilic than carbonyls and sometimes need activation by Lewis acids or Lewis-acidic organometals. The lithium-trimethylaluminum ate complex of i/ZyZ-substituted ynolate 105 reacts with the oxirane 106 to give the y-lactone 107 (equation 44), while lithium silyl-substituted ynolates are inert to oxiranes. There have been no reports using carbon-substituted metal ynolates. 

L. B. Sims, Kinetic Isotope Effects and Mechanism of Thermal Reactions of Small Ring Compounds, Report on Research No. 320-G, Michigan State University (1968). 

Synthesis of heterocycles by forming C—X bonds by radical reactions is not a generally applicable method, and seems not to be useful for making small rings. However, the attack of thiol radicals on double bonds can be a practical synthetic route, such as in the conversion of 1-hexene-7-thiol to thiepane (Section 5.17.3.3.1). 

The reversal of ring-closing metathesis, namely ring-opening metathesis, is also a synthetically useful reaction. With strained (small-ring) cycloalkenes, e.g. 12, the equilibrium of the reaction lies on the side of the open-chain product 13 ... 

Cyclic systems have frequently been used in studies of chemical bonding and reactivity, reaction mechanisms and a variety of other problems of interest to chemists3. Their utility depends on the changes in the carbon-carbon and the carbon-heteroatom bonds as well as on steric and electronic effects that result from the introduction of heteroatoms into the system. Indeed, the carbon-heteroatom bond length in small rings shows an effective increase with increasing heteroatom electronegativity4, in line with a... 

Thermal degradation below 300°C in inert atmospheres produces only small amounts of gaseous products. These are mostly unreacted monomers or water, which are by-products eliminated from condensation reactions between hydroxymethyl groups and reactive ortho or para positions on phenolic rings. A small... 

Since their development in 1974 ZSM-5 zeolites have had considerable commercial success. ZSM-5 has a 10-membered ring-pore aperture of 0.55 nm (hence the 5 in ZSM-5), which is an ideal dimension for carrying out selective transformations on small aromatic substrates. Being the feedstock for PET, / -xylene is the most useful of the xylene isomers. The Bronsted acid form of ZSM-5, H-ZSM-5, is used to produce p-xylene selectively through toluene alkylation with methanol, xylene isomerization and toluene disproportionation (Figure 4.4). This is an example of a product selective reaction in which the reactant (toluene) is small enough to enter the pore but some of the initial products formed (o and w-xylene) are too large to diffuse rapidly out of the pore. /7-Xylene can, however. 

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