Cyclobutane cleavage Reaction

It is well known that the [2+2] photodimerization of diolefinic compounds is allowed to occur photochemically but not thermally, whereas the cyclobutane cleavage reaction occurs both photochemically and thermally. The cleavage reaction occurs with irradiating light of shorter wavelength... 

The following cleavage reactions depict the importance of these hetereoatom substituted cyclobutanes in organic synthesis. 

That the situation is different for photochemical reactions is indicated by a particularly interesting recent study of some dialkylketones (239). In solution, 5-nonanone, 152, reacts photochemically to yield the cyclobutanol 153 and its isomer 154 in comparable amounts. Within the urea clathrate, however, 153 is the dominant product, with only traces of 154 being formed. The cyclobutanols analogous to 153, that is, having methyl and hydroxyl cis, also predominate in the urea-clathrate-mediated photocyclization of 2-hexanone and 2-undecanone. It might be expected that the bulky cyclobutane derivatives, which almost certainly cannot be crystallized in a urea clathrate, would also not be formed in such a clathrate. There are decomposition pathways (cleavage reaction 0 of the diradical intermediate that occur both in the clathrate and in solution. Nevertheless, the ring closure is a major pathway of reaction even in the clathrate. 

A great deal is already known about the pyrolysis of pinenes," which constitutes a perfect case for the study of cyclobutane cycloreversion reactions. In practice, this avenue was first explored with the hope of obtaining products with commercial value.99 Unfortunately, the application of these reactions to organic synthesis is somewhat restricted, because complex product mixtures cause complications. For the sake of clarity Table 6100 110 outlines only the cycloreversion products and their straightforward secondary derivatives nevertheless, it demonstrates some of the synthetic uses of these thermal cleavage reactions. 

Figure 16. Femtosecond dynamics of addition/cleavage reaction of the cyclobutane-ethylene system. Bottom Experimental observation of the intermediate diradical by mass spectrometry. Top The PES showing the nonconcerted nature of the reaction, together with three snapshots of the structures at to (initial), tj (diradical) and (/ (final). The parent precursor is also shown.

Narasaka s chiral titanium catalyst, prepared from (Pr 0)2TiCl2 and a tartrate-derived (2R,3R)-l,l,4,4-tetraphenyl-2,3-0-(l-phenylethylidene)-l,2,3,4-butanetetrol, is utilized for the asymmetric [2+2] cycloaddition of A-acyl oxazolidinones to 1,2-propadienyl sulfides possessing a-substituents, which afford methylenecyclobutane derivatives with high enantiomeric purity. These chiral adducts are readily transformed to seven- and eight-membered carbocycles with chiral side chains by the ring-cleavage reaction and subsequent cationic cyclization of the chiral cyclobutane derivative [68] (Eq. 8A.44). 

Both of these reactions were expected to profit from relief of strain in the starting material and from a strain-free heterocycle in the product. Owing to the polar nature of the ylide it was desirable, however, to introduce at least 1 heteroatom into the cyclobutane ring in order to facilitate heterolytic cleavage of the system. The silacyclobutanes seemed to be an excellent choice, and, consequently, a project on ylide cleavage reaction of mono-and disilacyclobutanes was initiated. Although no stable cyclic pentaalkylphosphorane was obtained, it was possible to confirm the appearance of... 

From a preparative point of view the heteroatom in P-position has an influence because important latent cyclobutane cleavage pathways exist in the product. The prototypical reaction of this type is the [2 + 2]-photocycloaddition/retro-aldol reaction sequence (de Mayo reaction) [55-57], the course of which is illustrated for substrate A3 (Q = O, PG = protecting group) in the reaction with ethylene as a generic olefin. 

Similar to other strained ring compounds, cleavage reactions of cyclobutanes have also been described [79-81]. Recent examples of this topic and its implications may be found in the comprehensive review article by Mattay [10b]. 

Most of the polymers are easily depolymerized photochemically and thermally in solution to the corresponding monomers, as is expected from the ring cleavage reaction of a number of cyclobutane derivatives yielding two olefins. For example, poly-DSP in solution is depolymerized to DSP nearly quantitatively upon photoirradiation for a relatively short period36 or by heating at above 200°C70). 

The type of pictorial, back-of-the-envelope, application of theory exemplified by the 4n + 2 rule would soon be applied toward understanding a wide range of no-mechanism reactions. The Diels-Alder reaction (see chapter 3) is one example. The reverse reaction ( retro-Diels-Alder ) also occurs readily. In one step (one transition state), three n bonds are broken and two new o bonds and one n bond are created. The simultaneous cleavage and formation of all bonds in one step is referred to as concerted and such reactions often occur under mild conditions and form specific stereoisomers. Since the bonds made and broken form a continuous cycle in the transition state, the Diels-Alder is an example of an electrocyclic reaction. In contrast to the Diels-Alder reaction, dimerizations of two alkene molecules (R2C=CR2) to cyclobutanes typically fail (as do the reverse thermal decompositions of cyclobutanes). These reactions often succeed when ultraviolet light (photochemistry) is used in place of heat (thermal chemistry). 

The biradical pathway for the cyclobutane cleavage and geometric isomerization was first pursued by Walters with cis- and ran -l,2-dimethylcyclobutane which interconvert roughly one-fifth as fast as they undergo cleavage to propylene at 400°C (Scheme 5.23). There is also 5-10% ethylene and 2-butene formed in the reaction, and, further, there is some preservation of stereochemistry at Cl and C2. The ratio of cis- to trans-2-buionQ formed from the trans compound is 0.125 while that from the cis compound is 2 at low conversions. ... 

A system analogous to the taxanes has been prepared by using the intramolecular de Mayo reaction of vinylogous esters. Irradiation of the mixture of diastereomers 223 results in cycloaddition of one diastereomer to give adduct 225 and recovery of the other isomer 224. The tetrahydrofuran is oxidized with RUO4 to the lactone, which is saponified with concomitant cyclobutane cleavage to the diketo acid 227. 

In a recent total synthesis of the novel neurotrophic agent merrilactone A (22, Scheme 4) by Inoue and Hirama [24], key intermediate 21 with the cis-bicyclo[3.3.0] octane framework embedded within the caged pentacycle 22 was elaborated from cyclobutane 18 by a sequence of RCM and immediate cleavage of the resulting bicyclic vicinal diol 19 to raeso-diketone 20. Cyclooctenedione 20 then underwent regioselective transannular aldol reaction at low temperature (LHMDS, THF, -100 °C) to produce a 3 1 mixture of isomers in 85% combined yield. The major isomer 21 with the required stereochemistry was then converted into the racemic natural compound ( )-22 in 19 steps. 

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