Cyclopropene ketal

In a third type of procedure,919 cyclopropene ketal 96 reacts with olefins bearing two... 

Enantioselective allylmetallation of chiral cyclopropene ketal is also possible [135] as well as allylmetallation of the achiral ketal but with the acid of chiral bisoxazoline (BOX) ligands [136] (Scheme 7-117). The chiral allylzinc reagents were much more reactive than the parent allylzinc bromide. 

Substituted cyclopropene ketals (R = Et, Ph) react much more selectively than the unsubstituted one (R = H), and surprisingly the facial choice of the addition is opposite to that for R = H. 

A comprehensive account of the chemistry of cyclopropene ketals, including their use as 1,3-dipoles in the preparation of... 

ROM-CM Sequence The ROM reaction of a cycloalkene engaged in the subsequent CM reaction with an olefinic partner provides the straightforward procedure for the synthesis of diene products having the isolated double bonds. This sequence is applicable not only to relatively strained cycloalkenes but also to unstrained compounds such as cyclohexene. The ROM-CM sequence of norbor-nene compounds or cyclopropene ketals with various olefins is reported for the preparations of natural products. 

Parrain and coworkers described an efficient cascade involving the ring opening of cyclopropene ketal of type 71 followed by CM with a variety of alkenes in the presence of catalyst [Ru]-I for the synthesis of protected divinyl ketones [42]. This sequence was employed by Kozmin and coworkers for the preparation of the linear center portion of bistramide A, a marine metabolite isolated from Lissodinum bistratum which exhibits potent cytotoxicity against several cell lines [43], as well as... 

Scheme 10.23 Cascade ROM/CM of cyclopropene ketal for the synthesis of routiennocin.

Reactions with cyclopropene.11 Lithium organocuprates react with the cyclo-propenone ketal 1 (12, 152-154) to form a copper species (a) that behaves as an enolate of a cyclopropanone. Thus it reacts with alkyl halides to form cis-2,3-disubstituted derivatives of 1. 

The high reactivity of the strained double bond in cyclopropenes has led to several other more recent developments especially involving cyclopropenone ketals as substrates97. 

Addition of cinnamyl(mesityl)zinc to the C2 symmetrical cyclopropenone ketal 133 led to excellent diastereoselectivities with respect to the newly formed carbon—carbon bond (de = 97%) and induction from the chiral ketal (de = 91%). Deuteriolysis afforded the cyclopropanone ketal 134 in which three stereocenters have been generated99,10°. A product-like transition state model was proposed, in which the cyclopropene underwent considerable rehybridization and the zinc became preferentially attached to the less hindered equatorial olefinic carbon from the face opposite to the axial ketal methyl group (equation 65). 

Besides the activation of the olefinic partner by a metal, the unfavorable thermodynamics associated with the addition of an enolate to a carbon—carbon multiple bond could be overwhelmed by using a strained alkene such as a cyclopropene derivative286. Indeed, Nakamura and workers demonstrated that the butylzinc enolate derived from A-methyl-5-valerolactam (447) smoothly reacted with the cyclopropenone ketal 78 and subsequent deuterolysis led to the -substituted cyclopropanone ketal 448, indicating that the carbometallation involved a syn addition process. Moreover, a high level of diastereoselectivity at the newly formed carbon—carbon bond was observed (de = 97%) (equation 191). The butylzinc enolates derived from other amides, lactams, esters and hydrazones also add successfully to the strained cyclopropenone ketal 78. Moreover, the cyclopropylzincs generated are stable and no rearrangements to the more stable zinc enolates occur after the addition. 

Cyclopropanecaiboxylic acid, 56, 70 Cyclopropanes, em-dihalo, 56, 32 Cyclopropanone ketals, 58, 40 Cyclopropenes, 58, 40 CYCLOPROPENONE, 57, 41 CYCLOUNDECANONE, 56, 107 Cycloundecanone, 2-hydroxy-, 56, 110 Cycloundecene, 1-caiboxy-, 56, 111 Cycloundecene, 1-methoxy-, 56, 111 1-Cycloundecene-l-carboxylic acid, methyl ester, 56, 108... 

Cyclopropanes Cyclopropene 1,3-propane-diyl ketal. Trimethylstannylmethyllithium. 

A final example of a rDA cycloreversion of a cycloadduct that acts as a protected butadiene illustrates the generation of extended conjugation in a non-aromatic cyclic system. Equation (65) shows that the addition of cyclopropene (147) to (146) can yield either (148) or (149), and both adducts undergo rDA extrusion of carbon dioxide to produce a triene. Hydrolysis of the triene ketals gives access to substituted tropones (150). 

Finally, the carbometallation reaction of spirocyclic cyclopropenes with a chiral ketal attached to the substrate was described. Thus, carbocupration of the chiral cyclopropene 96 proceeded with 96% diastereoselectivity with a higher-order organocuprate [134] (Scheme 7-114). 

The pressure-promoted [4 + 2]-cycloaddition of 2-pyrone 318 with cyclo-propenone ketal 377 (25 C, 6.2 kbar) affords a mixture of reaction products exo-adduct 378a, cycloheptatrienone ketal 379, and cycloheptatrienone 380 (resulting from Si02 hydrolysis of 379), each representing the product derived from the Diels-Alder reaction of 2-pyrone 318 with cyclopropen-one ketal 377 (86JA6695). The mdo-adduct 378b loses carbon dioxide upon depressurization, while the exo-adduct 378a is thermally stable. 3-... 

Cyclopropanes, 101, 267 Cyclopropanone ketals, 315-316 Cyclopropene, 113 Cyclopropenone, 519 Cyclopropenones, 27, 399 Cyclopropylacetylene, 401 Cyclopropyl azides, 323 Cyclopropylcarbinyl compounds, 53 Cyclopropyldiphenylsulfonium fluoroborate, 211,213-214... 

Some thermally unstable cyclopropenes are known, which react with olefines at or below ambient temperature by ring-opening to give vinylcyclopropanes (Eq. 10)65). Cyclopropenone ketals react with electron deficient olefines in the same manner, but here an ionic mechanism is more likely 65e). 

The carbocupration of cyclopropenes has been especially investigated with cyclopropenone ketals as reactants. The cuprio cyclopropanes formed can serve as a synthon for the cyclo-propanone enolate. " Achiral ketals with an unsubstituted cyclopropene double bond 15 undergo instantaneous reaction with lithium dimethylcuprate at — 78 C to give the methyl derivative 17 (R = Me) in 96% yield after quenching with methanol. Similar reactions, with a deuterium oxide or iodomethane quench, indicate that the carbocupration takes place in a cis fashion. 

The addition of cyclopropenone 1,3-propanediyl ketal to electron deficient olefins produces cyclopentanone ketals 4,4,5-trisubstituted 3,3-[l,3-propanediylbis(oxy)]cyclopentenes 1 in 42-86 % yield with high regioselectivitv. Presumably diradicals or zwitterions are not involved as reactive intermediates, and the reaction starts with nucleophilic attack of the strained cyclopropene olefin onto the electron-deficient olefin2. 

Cycloheptatriene.—Synthesis. Details have been published on the preparation of specifically substituted cycloheptatrienes by the cycloadditon of cyclopropenes to thiophene-1,1-dioxides followed by expulsion of S02. Substituted tropones have been obtained from the furan adducts of bromo-oxyallyl cations e.g. treatment of l,l,3,3-tetrabromo-4-methylpentan-2-one with di-iron nonacarbonyl in the presence of furan gave adduct (141) which was converted into a-thujaplicin (142). Acid hydrolysis of the norbornyl ketal (143) followed by warming to 70 "C gave 7,7-dimethyl-cycloheptatriene. ... 

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