Activation cyclobutenes

Finally, it is important to mention that there are other related publications in which porphyrin macrocycles are not directly used as dipolarophiles but are transformed into new derivatives that can react with carbonyl ylides via ACE (alkene cyclobutene epoxide) reactions. This idea arose in 1997, when Russell and co-workers found that fused ester-activated cyclobutene epoxides 86 can be ring-opened to give carbonyl ylides 87, and that these can be trapped stereospecifically by ring-strained alicyclic dipolarophiles, such as 2,5-norbomadiene, to form hetero-bridged norbomanes 88 in good yields, through ACE transformations (Scheme 31) <97CC1023>. 

Addition of benzyl azide 56 to ester-activated cyclobutenes can be achieved under thermal conditions (no solvent, RT, several days) or better still under high-pressure (8-15 kbar, RT, DCMorTHF). 

Displayed in Scheme 17 is another case of pure EGB behavior of superoxide anion. The base-catalyzed sulfone anion expulsion giving a previously unknown activated cyclobutene is not catalytic in EGB [44]. 

The reverse reaction, closure of butadiene to cyclobutene, has also been explored computationally, using CAS-SCF calculations. The distrotatory pathway is found to be favored, although the interpretation is somewhat more complex than the simplest Woodward-Hoffinann formulation. It is found that as disrotatory motion occurs, the singly excited state crosses the doubly excited state, which eventually leads to the ground state via a conical intersection. A conrotatory pathway also exists, but it requires an activation energy. 

A more conventional cycloaddition occurs with activated acetylenes, however, the intermediate cyclobutene adducts undergo rearrangement to give insertion of two carbon atoms into the enamine chain (55). Thus the enamine (16) reacted with methyl propiolate to give the dienamino ester (73), presumably via the cycloaddition product (65a). 

Although the orbital-symmetry rules predict the stereochemical results in almost all cases, it is necessary to recall (p. 1070) that they only say what is allowed and what is forbidden, but the fact that a reaction is allowed does not necessarily mean that the reaction takes place, and if an allowed reaction does take place, it does not necessarily follow that a concerted pathway is involved, since other pathways of lower energy may be available.Furthermore, a forbidden reaction might still be made to go, if a method of achieving its high activation energy can be found. This was, in fact, done for the cyclobutene butadiene interconversion (cis-3,4-dichloro-cyclobutene gave the forbidden cis.cis- and rran.y, ra i -l,4-dichloro-1,3-butadienes,... 

The series of wide-bite-angle, bulky ligands derived from a cyclobutene scaffold gave Pd complexes (117) showing appreciable activity in the cross-coupling of reactive aryl bromides with trimethylsilylacetylene. A considerable shift of electron density to the phosphorus atoms, probably arising from alternative aromatic canonical structures, may account for the ligand properties.422... 

Cycloaddition of the carbene chromium complexes 97 with CO incorporation provides a versatile method for naphthol synthesis, in which the metallacy-clic intermediates 99 are involved [47]. An alternative entry to 101 is achieved by metal carbonyl-catalyzed rearrangement of the cyclopropenes 98 via the same metalla-cyclobutenes 99 and vinylketene complexes 100 [52], Mo(CO)6 shows a higher activity than Cr(CO)6 and W(CO)6. The vinylketene complex 103 is formed by the regioselective ring cleavage of 1,3,3-trimethylcyelopropene 102 with an excess of Fe2(CO)9 [53]. (Scheme 35 and 36)... 

This process is quite unexpected for another reason. The cyclobutene ring is highly strained, making this monomer one of the most easily polymerized of all the cycloolefins. Thus, the variety of catalysts effective for cyclobutene polymerization is much broader than that effective for metathesis of low-strained cycloolefins and acyclic olefins (73). Therefore, the recovery of monomeric cyclobutene rather than its respective polymer is remarkable and indicates the lack of substantial metathesis activity in the above retrocarbenation system. 

If the alkenes and acetylenes that are subjected to the reaction mediated by 1 have a leaving group at an appropriate position, as already described in Eq. 9.16, the resulting titanacycles undergo an elimination (path A) as shown in Eq. 9.58 [36], As the resulting vinyltitaniums can be trapped by electrophiles such as aldehydes, this reaction can be viewed as an alternative to stoichiometric metallo-ene reactions via allylic lithium, magnesium, or zinc complexes (path B). Preparations of optically active N-heterocycles [103], which enabled the synthesis of (—)-a-kainic acid (Eq. 9.59) [104,105], of cross-conjugated trienes useful for the diene-transmissive Diels—Alder reaction [106], and of exocyclic bis(allene)s and cyclobutene derivatives [107] have all been reported based on this method. 

The activation energy 180 K J mole"1 is much higher than for opening of simple cyclobutenes. 

The very low value of the energy of activation for this isomerization is of considerable interest. Comparison with the decomposition of cyclobutane shows a reduction of 30 kcal mole caused by the presence of the double bond. If a similar transition state were involved in both reactions, then this difference would be a measure of the extra strain energy of the cyclobutene. This is quite unrealistically high. Thus we eliminate the possibility that the reaction path is as shown below ... 

A transition complex which is consistent with the low energy of activation of the isomerization involves the simultaneous deformation (twisting) of the cyclobutene ring with the stretching of the carbon-carbon bond opposite the double bond ... 

The optimum catalyst for a given reaction depends primarily on (a) the energetics of the reaction and (b) the functional groups present in the substrate. If, for instance, a strained cycloalkene such as norbomene or cyclobutene is to be polymerized, a catalyst of low activity will be sufficient to attain acceptable reaction rates. RCM... 

The retro-Diels-Alder reaction has been reviewed.A fully concerted cyclic transition state has been proposed for conrotatory opening of cyclobutenes, in order to account for the low activation entropy and unexpected activation volume of ca —2 to —3cm mol . ... 

Fig. 12.1 Representative biological activities of the 3-cyclobutene-l, 2-dione scaffold.

The fact that the lowest two orbitals of the reactants, which are those occupied by the four 7t electrons of the reactant, do not correlate to the lowest two orbitals of the products, which are the orbitals occupied by the two o and two 7t electrons of the products, will be shown later in Chapter 12 to be the origin of the activation barrier for the thermal disrotatory rearrangement (in which the four active electrons occupy these lowest two orbitals) of 1,3-butadiene to produce cyclobutene. 

FIGURE 25. Transition structures for the epoxidation of cyclopropene, cyclobutene and cyclopen-tene with peroxyformic acid (PFA), optimized at the B3LYP/6-31+G(d,p) level of theory. The classical activation barriers are given at B3LYP/6-311+G(3df,2p)//B3LYP/6-31+G(d,p). Dihedral angles (deviation from an ideal spiro approach (c n, is 90°) of the HO group in PFA onto the C=C bond of the alkene... 

Nonacarbonyldiiron in the presence of activated zinc as well as disodium tetracarbonylferrate have both been utilized to dechlorinate dimethyl cispransjransA,2,3,4-tetrachlorocyclobutane-1,2-dicarboxylate (41), which leads to [dimethyl l,2,3,4- 7-l,3-cyclobutadiene-l,2-dicarboxy-latejiron tricarbonyl (42) in 1 and 35-40% yield, respectively.15 As a result of the better leaving tendency of the bromide anion, the yield of 42 can be improved to 70% by reaction of the analogous dibromide with nonacarbonyldiiron in dimethylformamide.16 In another experiment, debromination with activated zinc in tetrahydrofuran converts cyclobutane-1,2-di-carboxylate 43 to cyclobutene-1,2-dicarboxylate 44 in 58% yield.15... 

In the area of reaction energetics. Baker, Muir, and Andzehn have compared six levels of theory for the enthalpies of forward activation and reaction for 12 organic reactions the unimolecular rearrangements vinyl alcohol -> acetaldehyde, cyclobutene -> s-trans butadiene, s-cis butadiene s-trans butadiene, and cyclopropyl radical allyl radical the unimolecular decompositions tetrazine -> 2HCN -F N2 and trifluoromethanol -> carbonyl difluoride -F HF the bimolecular condensation reactions butadiene -F ethylene -> cyclohexene (the Diels-Alder reaction), methyl radical -F ethylene -> propyl radical, and methyl radical -F formaldehyde -> ethoxyl radical and the bimolecular exchange reactions FO -F H2 FOH -F H, HO -F H2 H2O -F H, and H -F acetylene H2 -F HC2. Their results are summarized in Table 8.3 (Reaction Set 1). One feature noted by these authors is... 

Cyclobutenes. This derivative of ketene undergoes [2 + 2]cycloaddition with ethyl propiolate in refluxing methylene chloride to produce the cyclobutene 1 in 65% yield. The ester group activates 1 sufficiently for Diels-Alder addition with the silyl enol ether 2 to give the I I adduct 3 under mild conditions. Hydrolysis of 3 can... 

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