Carbon cycloaddition

PREPARATION AND THREE-CARBON + TWO-CARBON CYCLOADDITION OF A CYCLOPROPENONE KETAL CYCLOPROPENONE 1,3-PR0PANEDI0L KETAL... 

Cydopropenone ketals, of which cyclopropenone 1,3-propanediol ketal (1) is a representative and unusually stable example, have proven to be useful equivalents of the 1,3-dipole (1) 1n a regiospeclfic three-carbon + two-carbon cycloaddition with electron-deficient olefins, (eq 1). Table I shows representative results of a study of this reaction.7... 

An excellent asymmetric induction has also been observed by Snider et al. [164] in a hetero Diels-Alder reaction with the N-crotonyl oxazolidinone 2-172 which had already been used by Evans for the all carbon cycloaddition [ 164b]. Reaction of isobutene with 2-172 in the presence of Me2AlCl for 40 h at -30 °C in CH2C12 provided a mixture of the alcohol 2-174 and the lactone 2-175 via the primarily formed cycloadduct 2-173. Treatment of the mixture with sodium carbonate gave the lactone 2-175 as a pure enantiomer (Fig. 2-48). 

Boger DL, Brotherton CE. Thermal, four-carbon + three-carbon cycloaddition reaction of cyclopropenone ketals. Total synthesis of deacetamidocolchiceine formal total synthesis of colchicine. J. Org. Chem. 1985 50(18) 3425-3427. 

Chemoselectivity in the cycloaddition of 2-methylenecycloheptenone (174) changes on addition of In(acac)3. The allylic carbonate 175 reacts with the ketone 174 in the presence of In(acac)3 to give the methylenetetrahydrofuran 176, and the methylenecyclopentane 177 is obtained in its absence[l 13], The cycloaddition of ynones to produce the methylenetetrahydrofuran proceeds smoothly only in the presence of In(acac)3 (10 mol%)[114]. 

The TT-allylpalladium complexes 241 formed from the ally carbonates 240 bearing an anion-stabilizing EWG are converted into the Pd complexes of TMM (trimethylenemethane) as reactive, dipolar intermediates 242 by intramolecular deprotonation with the alkoxide anion, and undergo [3 + 2] cycloaddition to give five-membered ring compounds 244 by Michael addition to an electron-deficient double bond and subsequent intramolecular allylation of the generated carbanion 243. This cycloaddition proceeds under neutral conditions, yielding the functionalized methylenecyclopentanes 244[148], The syn-... 

Cycloadditions of benzonitril-4-nitrobenzylide to a variety of carbon to heteroatom multiple bonds including methyl dithiobenzoate and dimethyl trithiocarbonate (Scheme 148), X = MeS or Ph, have been examined in detail by Huisgen et al. (757). 

The Diels-Alder cycloaddition is one example of a pencyclic reaction, which is a one step reaction that proceeds through a cyclic transition state Bond formation occurs at both ends of the diene system and the Diels-Alder transition state involves a cyclic array of six carbons and six tt electrons The diene must adopt the s cis conformation m the transition state... 

Let us now examine the Diels-Alder cycloaddition from a molecular orbital perspective Chemical experience such as the observation that the substituents that increase the reac tivity of a dienophile tend to be those that attract electrons suggests that electrons flow from the diene to the dienophile during the reaction Thus the orbitals to be considered are the HOMO of the diene and the LUMO of the dienophile As shown m Figure 10 11 for the case of ethylene and 1 3 butadiene the symmetry properties of the HOMO of the diene and the LUMO of the dienophile permit bond formation between the ends of the diene system and the two carbons of the dienophile double bond because the necessary orbitals overlap m phase with each other Cycloaddition of a diene and an alkene is said to be a symmetry allowed reaction... 

Figure 10 12 shows the interaction between the HOMO of one ethylene molecule and the LUMO of another In particular notice that two of the carbons that are to become ct bonded to each other m the product experience an antibondmg interaction during the cycloaddition process This raises the activation energy for cycloaddition and leads the reaction to be classified as a symmetry forbidden reaction Reaction were it to occur would take place slowly and by a mechanism m which the two new ct bonds are formed m separate steps rather than by way of a concerted process involving a sm gle transition state... 

The chemistry of ketenes is dominated by their high reactivity most of them are not stable under normal conditions, many exist only as transient Species. Nucleophilic attack at the j -carbon, [2 + 2] cycloadditions, and ketene iasertion iato single bonds are the most important and widely used reactions of such compounds. 

Chemical Properties. The chemistry of ketenes is dominated by the strongly electrophilic j/)-hybridi2ed carbon atom and alow energy lowest unoccupied molecular orbital (LUMO). Therefore, ketenes are especially prone to nucleophilic attack at Cl and to [2 + 2] cycloadditions. Less frequent reactions are the so-called ketene iasertion, a special case of addition to substances with strongly polarized or polarizable single bonds (37), and the addition of electrophiles at C2. For a review of addition reactions of ketenes see Reference 8. 

Ozonation ofAlkenes. The most common ozone reaction involves the cleavage of olefinic carbon—carbon double bonds. Electrophilic attack by ozone on carbon—carbon double bonds is concerted and stereospecific (54). The modified three-step Criegee mechanism involves a 1,3-dipolar cycloaddition of ozone to an olefinic double bond via a transitory TT-complex (3) to form an initial unstable ozonide, a 1,2,3-trioxolane or molozonide (4), where R is hydrogen or alkyl. The molozonide rearranges via a 1,3-cycloreversion to a carbonyl fragment (5) and a peroxidic dipolar ion or zwitterion (6). 

Polyimides have been synthesized by Diels-Alder cycloaddition of bismaleimides and substituted biscydopentadienones (81,82). The iatermediate tricychc ketone stmcture spontaneously expeU carbon monoxide to form dihydrophthalimide rings, which are readily oxidized to imides ia the presence of nitrobenzene. 

The ring opening of 2//-azirines to yield vinylnitrenes on thermolysis, or nitrile ylides on photolysis, also leads to pyrrole formation (B-82MI30301). Some examples proceeding via nitrile ylides are shown in Scheme 92. The consequences of attempts to carry out such reactions in an intramolecular fashion depend not only upon the spatial relationship of the double bond and the nitrile ylide, but also upon the substituents of the azirine moiety since these can determine whether the resulting ylide is linear or bent. The HOMO and second LUMO of a bent nitrile ylide bear a strong resemblance to the HOMO and LUMO of a singlet carbene so that 1,1-cycloadditions occur to carbon-carbon double bonds rather than the 1,3-cycloadditions needed for pyrrole formation. The examples in Scheme 93 provide an indication of the sensitivity of these reactions to structural variations. 

Dipolarophiles utilized in these cycloadditions leading to five-membered heterocycles contain either double or triple bonds between two carbon atoms, a carbon atom and a heteroatom, or two heteroatoms. These are shown in Scheme 9 listed in approximate order of decreasing activity from left to right. Small rings containing a double bond (either C=C or C=N) are also effective dipolarophiles, but these result in six- and seven-membered ring systems. 

When the chain between the azirine ring and the alkene end is extended to three carbon atoms, the normal mode of 1,3-intramolecular dipolar cycloaddition occurs. For example, irradiation of azirine (73) gives A -pyrroline (74) in quantitative yield 77JA1871). In this case the methylene chain is sufficiently long to allow the dipole and alkenic portions to approach each other in parallel planes. 

The 27T-electrons of the carbon-nitrogen double bond of 1-azirines can participate in thermal symmetry-allowed [4 + 2] cycloadditions with a variety of substrates such as cyclo-pentadienones, isobenzofurans, triazines and tetrazines 71AHC(13)45). Cycloadditions also occur with heterocumulenes such as ketenes, ketenimines, isocyanates and carbon disulfide. It is also possible for the 27r-electrons of 1-azirines to participate in ene reactions 73HCA1351). 

Azirine, trans-2-methyl-3-phenyl-racemization, 7, 33, 34 1-Azirine, 2-phenyl-reactions, 7, 69 with carbon disulfide, S, 153 1-Azirine, 3-vinyl-rearrangements, 7, 67 Azirines, 7, 47-93 cycloaddition reactions, 7, 26 fused ring derivatives, 7, 47-93 imidazole synthesis from, 5, 487-488 photochemical addition reactions to carbonyl compounds, 7, 56 photolysis, 5, 780, 7, 28 protonated... 

In general, reaction of diazomethane with a, -unsaturated carbonyl compounds affords pyrazolines in which the nucleophilic methylene group is attached to the carbon atom of the carbonyl compound. According to Huisgen, the reactions belong to the general class of 1,3-dipolar cycloadditions. 

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