Cycloaddition with unactivated olefins

Intramolecular regioselective cycloadditions with unactivated olefins have been described by Sammes and Watt. Thermolysis of the pyridine betaine (254) at... 

Harano and colleagues [48] found that the reactivity of the Diels-Alder reaction of cyclopentadienones with unactivated olefins is enhanced in phenolic solvents. Scheme 6.28 gives some examples of the cycloadditions of 2,5-bis-(methoxycar-bonyl)-3,4-diphenylcyclopentadienone 45 with styrene and cyclohexene in p-chlorophenol (PCP). Notice the result of the cycloaddition of cyclohexene which is known to be a very unreactive dienophile in PCP at 80 °C the reaction works, while no Diels-Alder adduct was obtained in benzene. PCP also favors the decarbonylation of the adduct, generating a new conjugated dienic system, and therefore a subsequent Diels-Alder reaction is possible. Thus, the thermolysis at 170 °C for 10 h of Diels-Alder adduct 47, which comes from the cycloaddition of 45 with 1,5-octadiene 46 (Scheme 6.29), gives the multiple Diels-Alder adduct 49 via decarbonylated adduct 48. In PCP, the reaction occurs at a temperature about 50 °C lower than when performed without solvent, and product 49 is obtained by a one-pot procedure in good yield. 

Eschenmoser and coworkers achieved 1,4-cycloadditions by using a-chloro nitrones as precursors of 1,3-dipoles which react with unactivated olefins [4]. For example, the cycloadduct 7 is obtained by reaction of cyclohexene (5) and a-chloro nitrone 6... 

Examples of the application of this chemistry to the preparation of cyclobutanones, cyclobutenones, and P-lactams are presented in the Table. The mesityl thiol ester has proven to be particularly effective in reactions with less ketenophilic alkenes, although with the more reactive ketenophiles nearly identical results are obtained using either the mesityl a-diazo thiol ester or the more readily available thiophenyl ester. In the case of readily available ketenophiles, the reaction is best conducted using excess alkene, alkyne, or imine, but in other cases the cycloaddition can be carried out with excess diazo thiol ester. The efficiency of the reaction with unactivated alkenes is especially notable, and compares favorably with results obtained previously employing dichloroketene. For example, addition of dichloroketene to methylenecyclohexane is reported to proceed in 55% yield," while up to 81% of the desired [2-1-2] cycloadduct is produced in the reaction of (mesitylthio)ketene with this olefin under our conditions. 

CyelaaddiEoitt. Ordinarily, unactivated olefinic double bonds do not undergo Diels-Alder or 1,3-cycloaddition reactions. The outstanding property of a-chloro-nitrones is that, in the presence of silver ions, they undergo cycloaddition reactions with... 

Early extensive accounts of the 4v participation of a,/)-unsaturated carbonyl compounds in [4 + 2] cycloadditions detailed their reactions with electron-deficient dienophiles including a,/3-unsaturated nitriles, aldehydes, and ketones simple unactivated olefins including allylic alcohols and electron-rich dienophiles including enol ethers, enamines, vinyl carbamates, and vinyl ureas.23-25 31-33 Subsequent efforts have recognized the preferential participation of simple a,/3-unsaturated carbonyl compounds (a,/3-unsaturated aldehydes > ketones > esters) in inverse electron demand [4 + 2] cycloadditions and have further explored their [4 + 2]-cycloaddition reactions with enol ethers,34-48 acetylenic ethers,48 49 ke-tene acetals,36-50 enamines,4151-60-66 ynamines,61-63 ketene aminals,66 and selected simple olefins64-65 (Scheme 7-1). Additional examples may be found in Table 7-1. 

Similar studies of the regioselectivity in the HDA reaction between 2-substituted norbomadienes and unactivated terminal acetylenes catalyzed by a cobalt catalyst were also undertaken. Unfortunately, 2-sub-stituted norbomadienes are much less reactive with unactivated acetylenes in the cobalt-catalyzed HDA reaction than with electron-deficient olefins in the Ni-catalyzed HDA cycloadditions. When an electron-withdrawing group (Y = COOMe) or an electron-donating group (Y = OMe) is attached to the 2-position of the NBD, no desired [2 + 2 + 2] cycloadduct is observed with 1-hexyne, even in refluxing toluene for three days under the usual cobalt-catalyzed conditions (Scheme 12). Instead, some NBD dimers and acetylene trimers are detected. With a... 

Palladium-based catalysts also bring about cyclopropanations in high-yield. With palladium acetate/CHjNj, styrene , unactivated terminal olefins strained olefins , 1,3-dienesan enamine , as well as a,3-unsaturated carbonyl compounds have been cyclopropanated (Table 1). Contrary to an earlier report, the reaction also works well with cyclohexene if the conditions are chosen appropriately it seems that the notniyst is rapidly deactivated in the presence of this olefin >. Trisubstituted a,p-unsaturated carbonyl compounds were found to be unreactive, and the same is true for the double bonds in diethyl fumarate, maleic anhydride, coumarin and 1,3-dimethyluracil. Whereas the latter two were totally unreactive, [3-1-2] cycloaddition of diazomethane gave pyrazolines in the former two cases. The last entry of Table 1 shows that an allyl alcohol function can still be cyclopropanated, but methylene insertion into the O—H bond is a competing process. 

Transition metal-mediated cycloaddition and cyclization reactions have played a vital role in the advancement and applications of modem synthetic organic chemistry. Rhodium-catalyzed cycloadditions/cyclizations have attracted significant attention because of their versatility in the transformations of activated and unactivated acetylenes, olefins, allenes, etc. These reactions are particularly valuable because of their ability to increase molecular complexity through a convergent and highly selective combination of acyclic components. In addition, these reactions allow for the preparation of molecules with chemical, biological, and medicinal importance with greater atom economy. Recent developments in rhodium-catalyzed cycloaddition and cyclization reactions are described in this section. 

Wender s group has also developed rhodium-catalyzed intermolecular [5-1-2] cycloadditions. At first, they found the catalysis system of Rh(PPh3)3Cl for the intramolecular reactions was not effective at all for the intermolecular reactions. To effect the intermolecular [5-1-2] cycloadditions, [Rh(CO)2Cl]2 must be used and oxygen substitution of the cyclopropane was necessary (see (17)) [37-39]. Then they successfully expanded the substrate to unactivated vinylcyclopropanes by adjusting the substituents. For monosubstituted alkynes, the substitution on the olefin terminus directs the formation of single isomer that minimized steric hindrance (see (18)) [40]. The [5-1-2] cycloadditions can also be applied to VCPs with allenes (see (19)) [41]. It should be noted that the alkyne substituent did not interfere with the reaction, indicating that allenes as reaction partners were superior to alkyne in the [5-1-2] cycloadditions. Curiously, the authors didn t report the corresponding intermolecular [5-1-2] cycloadditions of VCPs with alkenes. 

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