Cyclobutane chlorination

Methane ethane and cyclobutane share the common feature that each one can give only a single monochloro derivative All the hydrogens of cyclobutane for example are equivalent and substitution of any one gives the same product as substitution of any other Chlorination of alkanes m which the hydrogens are not all equivalent is more com plicated m that a mixture of every possible monochloro derivative is formed as the chlo rmation of butane illustrates... 

The cyclohexasilane ring of trans-lfl has a chair form and both chlorine atoms occupy axial positions. The cyclotetrasilane ring has a folded structure with the fold angles of 33.0 and 33.6°. The structure of the silicon framework of trans-lfl resembles that of bicyclo[4.2.0]octane, in which the cyclohexane ring has a chair form and the cyclobutane ring has a folded structure.67... 

Thus, to achieve mirror-symmetric or centrosymmetric cyclobutane derivatives, one would start with monomers that are substituted with dichloro groups or amide functions, respectively. Both the chlorines and the amide groups can subsequently be removed readily, without affecting the stereochemistry of the ring. 

Of the wide array of platinum derivatives, carboplatin is the only compound except cisplatin that is used in medical practice, and it differs from cisplatin in the replacement of two chlorine atoms with a cyclobutan-l,l-dicarboxylic acid fragment. Like cisplatin, carboplatin also reacts with DNA to form both internal and external cross-bonds. The range and indications of use are practically analogous to cisplatin. Synonyms of this drug are paraplatin and others. 

The use of sulfuryl chloride for free radical chlorination of aliphatic carboxylic acids gives mixtures of positional isomers.7 However, with the cyclobutane ring, the attack is much more selective. The present method provides a procedure for free radical halogenation of a cyclobutane ring. 

The preferred conformation of intermediates appears to be decisive in selecting which cyclobutane bond will be broken.4 In many cases the iodo compounds gave better results than the 3-bromopropyl derivatives.5 If the substrates contained iodo or bromo as well as chloro substituents, the halogen atoms reacted selectively. With one equivalent of tin hydride only the iodo or bromo substituent was removed, with an excess of tin hydride the chlorine atoms were also substituted by hydrogen atoms. 

Scheme 6.12) [39]. Cyclobutane 33 was formed with perfect stereocontrol over the two stereogenic centers in a- and [3-position to the carbonyl group. The concave shape of the substrate forces a highly selective approach of the olefin. The relative and absolute configuration at the chlorine-bearing carbon atoms was not relevant, as chlorine was subsequently eliminated under reductive conditions. Compound 33 was further elaborated into (i)-sterpurene (34). 

Stepwise reactions by way of diradical intermediates are also possible, as in the coupling of the halogenated alkene 6.102 with butadiene 6.103. As we saw in Chapter 2 (see pages 67-68), any group, C, Z or X, stabilises a radical. Both radical centres in the intermediate 6.104 are stabilised, the one at the top by the o-chlorines and the /3-fluorines, and the one below because it is allylic. These combine rapidly 6.104 (arrow on the upper drawing) to give the cyclobutane 6.105. 

Copolymers X and XI were random-amorphous copolymers with Tg s of 92°C and 95°C, respectively. They were soluble in chlorinated solvents, cyclohexanone, and DMF. It should be noted that the relative quantum yield of cyclobutane formation in the solid state (films) for the polyvinylalcohol (PVA)-p-methoxycinnamate film was about 25% greater than for the amorphous PVA-cinnamate polymer film previously investigated (101. Consequently, the relative quantum yield of dimerization for an amorphous p-methoxycinnamate containing polymer film would be approximately 5%. 

In addition to the 3,4-dimethylcyclobutene case discussed in Section 10.5.1, there are many other examples of electrocyclic ring opening of cyclobutanes, and cis- and fra 5-3,4-dichlorocyclobutene have been examined carefully. The products are those expected for conrotation. In the case of the franx-isomer, the product results from outward rotation of both chlorine atoms, in agreement with the calculated substituent effect. The c/x-isomer, in which one of the chlorines must rotate inward, has a substantially higher E. ... 

The cis or trans relation of the chlorine atoms in reactions (c) and (d) is reported to be retained in the corresponding cyclobutane adducts by Schenck et These authors favour a mechanism involving a biradical complex of sensitiser and anhydride as the actual entity attacking the olefin. 

The cyclobutane intermediate is not an irreversible sink for the catalyst, but remains reversibly linked to the catalytic cycle. In this mechanistic scenario, the enantioselectivity of the reaction does not depend on the difference of the activation energies for the electrophilic attack on the two diastereotopic faces of the enamine intermediate and is controlled, according to the Curtin—Hammett principle, by the relative stability and reactivity of the diastereomeric intermediates (cyclobutane and enamine of the Michael adduct) downstream in the catalytic cycle [58, 60]. A very recent detailed mechanistic study of another reaction catalyzed by diarylproUnol sdyl ethers, the a-chlorination of aldehydes by iV-chlorosuccinimide, also suggests that the stereochemical outcome of this process is not determined by the transition state of the electrophilic attack to the enamine, but instead is correlated with the relative stability and reactivity of the diastereomeric 1,2-addition products from the resulting iminium intermediate [60]. 

Cyclopropane derivatives can be prepared by several methods. Michael addition of the enolate of ethyl chloroacetate to ethyl acrylate generated the cyclopropane ring in 7.223 via addition to form a carbanion and internal expulsion of the chlorine moietyl Manipulation of functional groups allowed selective reduction to 7.224 and conversion to 7.225 (as a mixture of cis- and trans-isomers). Rearrangement and hydrolysis led to c/s-2-(2-amino-l-cyclopropyl)ethanoic acid, 7,226. The analogous cyclobutane derivatives were also prepared by a similar route. 

Chlorination reactions of certain alkanes can be used for laboratory preparations. Examples are the preparation of chlorocyclopropane from cyclopropane and chlorocyclobutane from cyclobutane. 

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