Four-membered carbocycles cycloaddition

Four-membered carbocyclic ring systems are commonly formed by cycloaddition of electrophilic alkenes, ketenes and arynes to enamines. Since cycloaddition reactions of enamines are dealt with in Chapter 18 these reactions will only be mentioned briefly here. 

The procedure described here illustrates a practical and convenient method for the generation of thio-substituted ketenes which participate in surprisingly facile cycloadditions with both activated and unactivated alkenes, alkynes, and imines to form four-membered carbocycles and heterocycles. As... 

The results of these model studies have shown that transition metal catalyzed [2+21-cycloadditions of methylenecyclopropanes are — at least at the moment — not very useful for the controlled formation of four-membered carbocycles. 

Four-membered carbocycles Compounds with sufficiently electron-rich olefinic double bonds react with TCNE to yield tetracyanocyclobutyl derivatives by [2 + 2] cycloadditions. Thus 1-vinylpyrazoles 369" as well as 4-vinyl-pyrazoles 371" react to yield the corresponding substituted tetracyanocyclobutanes 370 and 372, respectively. The same reaction has been observed with 1-vinylindazoles". ... 

All these Ni(0) catalyzed [2- -2]-cycloadditions proceed through nickelacyclopentane derivatives as intermediates. This has been supported by the isolation of model complexes and the study of their reactivity The results of these model studies have shown that transition metal catalyzed [2 -)- 2]-cycloadditions of methylenecyclopropanes are — at least at the moment — not very useful for the controlled formation of four-membered carbocycles. 

Cyclobutanes are important building blocks, primarily resulting from their ring-expansion chemistry, which derives from substantial strain energy. In addition, the four-membered carbocycle is frequently found in numerous natural products and synthetically derived bioactive substances. Recently, asymmetric preparation of cyclobutanones 184 by [2 -I- 2] cycloaddition of dichloroketene 183 to chiral enol ethers 182 was reported (Scheme 16.27). The cycloaddition provides not only chiral cyclobutane... 

Lately a third type of transition state has been favored for [2 + 2] cycloadditions forming carbocyclic and heterocyclic four-membered rings. The experimental data on the addition of diarylketenes to arylethylenes are well accommodated by the [ 2s + 2s + 2s] process proposed by Baldwin (70JA4874). The steric effects on the cycloaddition of allenes to ketenes also favor this mechanism (76JA7698). 

Although a number of multistep procedures are available for the introduction of five-membered carbocycles, their direct formation in a thermal cycloaddition is rare.6 Interest in the potential application of such a three-carbon + two-carbon cyclopentane cycloaddition has been derived from the expectation that such a process could prove to be an effective complement to the four-carbon + two-carbon Diels-Alder reaction which is used extensively in the regio- and stereocontrol led preparation of functionalized six-membered carbocycles. 

Tetramethoxyethyiene readily undergoes 2 + 2 cycloadditions with electrophiles to give carbocyclic and heterocyclic four-membered rings.4 Thus it reacts at 0° with... 

In Scheme 10, examples of eaiantioseleetive cycloadditions with formation of three-, four-, five-, and six-membered carbocyclic or heterocyclic rings are presented, to demonstrate the use of Ti-TADDOLates as Lewis acids. The Diels-Alder reaction has, so far, been studied most extensively, and many protocols have been proposed for the preparation of the Ti catalyst, of which as little as 5 mol-% and as much as several equivalents were employed (more often than not, Lewis acids bind strongly to the products of reactions they have mediated cf. the classical Friedel-Crafts acylation with AICI3 ). 

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