Unsaturated Cyclobutanes

Other unsaturated cyclobutanes have also been studied for details reference should be made to Frey s review . 

Unsaturated sulfoncs (314,315) and nitroolcfins (303,315-317) also give alkylation products with enamines. In the latter reactions the formation of nitroethyl or cyclobutane derivatives has been found (316) to depend on the reaction medium as well as steric and electronic parameters which determine the fate of zwitterionic intermediates. Thus no enamine products could... 

Cyclobutanes are cleaved less readily than are cyclopropanes, but, nonetheless, hssion occurs without difficulty if the ring has additional strain UI3,I74b,I76), adjacent unsaturation 72b,J53a), or aromatic substituents... 

A low ion pair yield of products resulting from hydride transfer reactions is also noted when the additive molecules are unsaturated. Table I indicates, however, that hydride transfer reactions between alkyl ions and olefins do occur to some extent. The reduced yield can be accounted for by the occurrence of two additional reactions between alkyl ions and unsaturated hydrocarbon molecules—namely, proton transfer and condensation reactions, both of which will be discussed later. The total reaction rate of an ion with an olefin is much higher than reaction with a saturated molecule of comparable size. For example, the propyl ion reacts with cyclopentene and cyclohexene at rates which are, respectively, 3.05 and 3.07 times greater than the rate of hydride transfer with cyclobutane. This observation can probably be accounted for by a higher collision cross-section and /or a transmission coefficient for reaction which is close to unity. 

Many interesting examples of photodimerizations and photocycloadditions of a,/ -unsaturated carbonyls and acid derivatives yielding cyclobutanes have been reported. In this section, as in Section 10.1, we will first discuss photodimerizations and then photocycloadditions. 

One of the first examples of photodimerization of an a,/3-unsaturated carbonyl was that of dibenzylideneacetone reported by Ciamician and Silber. Direct irradiation of this compound in ethanol or in isopropanol/benzene solution yields cyclobutane (66), although irradiation in the presence of uranyl chloride as sensitizer results in (67)(81) ... 

Some years ago we began a program to explore the scope of the palladium-catalyzed annulation of alkenes, dienes and alkynes by functionally-substituted aryl and vinylic halides or triflates as a convenient approach to a wide variety of heterocycles and carbocycles. We subsequently reported annulations involving 1,2-, 1,3- and 1,4-dienes unsaturated cyclopropanes and cyclobutanes cyclic and bicyclic alkenes and alkynes, much of which was reviewed in 1999 (Scheme l).1 In recent days our work has concentrated on the annulation of alkynes. Recent developments in this area will be reviewed and some novel palladium migration processes that have been discovered during the course of this work will be discussed. 

The reaction of ethylene with steroidal a,/ -unsaturated ketones yields both cis and trans cyclobutane derivatives as illustrated in Eq. 55. 145)... 

Several other types of photochemical reactions involving unsaturated carbohydrates have been reported. One of these is38 photochemical, E -Z isomerization of the groups attached to a double bond (see Scheme 5). A second is the internal cycloaddition between two double bonds connected by a carbohydrate chain.39-41 Although the carbohydrate portion of the molecule is not directly involved in this cycloaddition, its presence induces optical activity in the cyclobutane derivatives produced photochemically. Finally, a group of acid-catalyzed addition-reactions has been observed for which the catalyst appears to arise from photochemical decomposition of a noncarbohydrate reactant.42-44... 

Many other ion-molecule reactions involving highly unsaturated hydrocarbon ions and neutral olefins or the equivalent strained cycloalkanes have been studied by mass spectrometry98. For example, we may mention here the addition of ionized cyclopropane and cyclobutane to benzene radical cations giving the respective n-alkylbenzene ions but also isomeric cyclodiene ions such as ionized 8,9-dihydroindane and 9,10-dihydrotetralin, respectively. Extensive studies have been performed on the dimerization product of charged and neutral styrene4. 

Cycloparaffins (cycloalkanes single bonds) / C. /C C H2 - no double bonds Cyclopropane, cyclobutane, cyclopentane Compounds are unsaturated since ring can be broken C H2 + H, —> C H2 +2... 

The irradiation of , 3-unsaturated carbonyl compounds in the presence of olefins does not usually lead to oxetanes. In some cases, however, a photocycloaddition reaction takes place, yielding a cyclobutane ring. This has proved to be a useful reaction which has warranted recent review.71 These carbonyl compounds typically are not reduced upon irradiation in isopropanol, nor do they show any phosphorescence emission. The mechanism of this reaction has been discussed 72,73 however, the nature of the excited state involved (n,n or 7r,7r singlet or triplet) is still in question. 

There are some cases where both types of photocycloaddition take place. For example, cinnamaldehyde and crotonaldehyde yield, upon irradiation with 2-methyl-2-butene, both the oxetane and the cyclobutane products.26 In marked contrast, mesityl oxide, as similar as it would appear to be to crotonaldehyde (Table I), is stable to irradiation in the presence of both isobutylene and isopropanol.37,74 These differences in reactivity of a,/9-unsaturated carbonyl compounds have been attributed to conformational (that is, s-cis or s-trans) differences.74... 

Cyclic allenes undergo head-to-head cyclodimerization to give tricyclic 1,2-alkylidenccyclobu-tanes. Unsaturated cyclic allenes represent molecules with increased strain and often dimerize spontaneously. Whereas cyclonona-1,2-diene (28) requires heating of a neat sample to 138°C,38 the tetraene 31 has a half-life of 10 minutes at 0°C.39 The more strained cycloocta-l,2,4,6-te-traene (34) could not be isolated and only the dimeric cyclobutane 35 was formed on thermolysis of the tosylhydrazone precursor 33.40... 

Cyclobutane formation via light-induced [2 + 2] cycloaddition is probably one of the best studied photochemical reactions and has been reviewed thoroughly up to 1972 (Houben-Weyl, Vols. 4/5 a and 4/5 b). The most important types of C —C double-bond chromophores undergoing such reactions arc alkenes, 1,3-dienes, styrenes, stilbenes, arenes, hetarenes, cycloalk-2-enones, cyclohexa-2,4(and 2,5)-dienones, 1,4-benzoquinones, and heteroanalogs of these cyclic unsaturated carbonyl compounds. For p notocyciodimerizations see Houben-Weyl, Vol. 4/5 a, p 278 and for mixed [2 + 2] photocycloadditions of these same chromophores to alkenes see Section 1.3.2.3. 

Enol ethers 23 and 26 readily undergo cycloadditions with 2,/f-unsaturaled esters such as dimethyl fumarate (24) and methyl tran.v-but-2-enoate (27) giving cyclobutanes, 25 and 28 + 29, respectively, under mild conditions.8 It is interesting to note that the stereochemical integrity of the acyclic alkene is maintained in the cycloadducts. 

Other examples of the synthesis of cyclobutanes with abstraction of an allylic hydrogen are the photochemical formation of tricyclo[4.1.0.03,7]heptan-5-ones (e.g., 5) from norborn-5-en-2-ones33 and of bicyclo[4.2.0]octenes (e.g., 7) from doubly unsaturated ketones.34... 

Many thermal and photochemical valence isomerizations leading to cyclobutanes have been investigated with regard to mechanistic aspects. However, preparative applications also exist, especially when eight-membered unsaturated compounds are used as substrates. 

Intramolecular [2 + 2 + 2] cycloadditions belong to the same type of valence isomerization as those of 1,5-unsaturated compounds to cyclobutanes.70 The cobalt-mediated cyclization of l-en-5-ynes stereoselectively converts enediynes directly to bicyclo[4.2.0]hexa-l,3-dienes, as single diastereomers, when a stoichiometric amount of dicarbonyl(cyclopentadienyl)cobalt is used. This cyclization90 has a high efficiency (92%). An example is the synthesis of the protoilludane framework 23 from the enediyne precursor 22.71... 

In a similar manner, from the unsaturated tetracyclic outside 4-bromobenzenesulfonate 12 the major products were two epimeric tetracyclic acetates 13 when the saturated inside 4-bro-mobenzenesulfonate was the substrate, the corresponding tetracyclic cyclobutane derivatives were formed in only 5% yield.83 ... 

Ring contraction of cyclopentenone and cyclohexenone derivatives to cyclobutanes was observed during direct irradiation of various j5,y-unsaturated cyclohexenones. By way of a Nor-rish type I cleavage in n,7i excited singlet (5t) and n,7t excited triplet (T2) states, an acyl/allyl diradical is formed which recombines in the allyl position to form the product of a 1,3-acyl migration,102 while sensitized irradiation leads mainly to oxa-di-rr-methane rearrangement (see Section 4.2.3.). 

Exocyclic unsaturation can stabilize small ring heterocycles. In three-membered rings it is difficult to separate the contributions from increased angle strain and from electronic interactions between the unsaturation and the heteroatom. In four-membered rings such separation has been done (74PMH(6)199, p. 235). The CRSEs change "from oxetane (106 kJ mol-1) by -11 kJ mol-1 to oxelan-2-one (95 kJ mol-1) (corrected for electronic effects) and 4-methyleneoxetan-2-one (95 kJ mol" ). In contrast, an increase of 10 kJ mol 1 over the value for cyclobutane (111 kJ mol-1) is observed on going to both methylenecyclobutane and l,3-bis(methylene)cyclobutane. 

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