Cyclopropylketones

A high yield approach to the hexahydropyrrolo[3,2-e [l,4]diazepine-2,5-diones, 105 and their tetrahydrofuro analogues, 106, based on rearrangements of cyclopropylketimines and the cyclopropylketones, derived by acid hydrolysis, have been described. Thermolysis followed by DDQ oxidation of the unstable dihydro intermediates then gave compounds 105 (eg. R1 = Me, R2 = i-Bu) and 106 (eg. R = 4-Cl(C6H4)CH2) . 

Triethylamine as the electron donor was also used by Mattay and co-workers in tandem fragmentation cyclization reactions of a-cyclopropylketones. The initial electron transfer on the ketone moiety is followed by the fast cyclopropyl-carbinyl-homoallyl rearrangement, yielding a distonic radical anion. With an appropriate unsaturated side chain within the molecule both annealated and spi-rocyclic ring systems are accessable in moderate yields (Scheme 41) [62]. 

Fagnoni, M., Schmoldt, P., Kirschberg, T., and Mattay, J. (1998) Reductive cyclization of ot-cyclopropylketones with alkynyl- and aryl-tethered substituents. Tetrahedron, 54, 6427-6444. 

Resolved P-hydroxy sulfoximines derived from cyclic enones undergo dias-tereoselective Simmons-Smith cyclopropanation reactions to give, after thermolysis, cyclopropylketones in high enantiomeric purity (94-98%). Cyclopropanation occurs syn to the hydroxyl group of the P-hydroxy sulfoximine. This method is less diastereoselective for acyclic enones.73... 

In recent years, Seebach et al. have elaborated synthetic applications of ot-halo-lithiocyclopropanes, for instance, insertion of a CO-group between the two vinylic carbon atoms of an olefin (Eq. (43) 48)), annulations of four-membered rings and of lactones (Eq. (44) 9y), preparation of cyclopropylketones from olefins (Eq. (45) 49>), and, by using the same cyclopropylbromohydrins, bromovinylations S0) and synthesis of methyleneeyclopropanes from olefins, bromoform and aldehydes (Eq. (46)51)). 

The preparation of other cyclopropylketone derivatives by ring closure of the 4-chlorobutyryl group is provided (4). 

Unprecedented high ann-selectivities are obtained when E-substituted chiral allylic alcohols are treated with bis(iodomethyl)zinc and the dioxaborolane ligand (eq 8). In contrast, the ryn-isomer is obtained if the substrate is treated with the zinc reagent in the absence of the chiral ligand. The method complements that involving the direct reduction of cyclopropylketones with LiAlH4 or DIBAL-H. z... 

CLOKE WILSON Cyclopropylketone Rearrangemervi Reafrangement of cyclopropyl ketones or mines to dihydrofurans or dihydropyrroles, thermally, photochemically, or by Lewis adds... 

Tandem fragmentation-cyclization of bicyclic ketones connected to unsaturated side chains have been used to construct hi-, tri-, and spirocyclic ketones [334], Cossy et al. have shown that depending upon the substitution pattern, ketyl radical anions obtained from photochemically induced electron transfer from amines to cyclopropylketones lead either to the formation of 3-substituted cycloalkanones or to ring expanded products (Scheme 78) [335],... 

Similarly, 2-methoxy cyclopropylketones form y-ketoaldehydes and ethyl alkoxycy-clopropanecarboxylates lead to y-oxoesters after treatment with strong acid " the corresponding cyclopropanecarboxylic acids afford y-oxoacids by heating in... 

The rearrangement of heterocyclic analogs of vinylcyclopropanes are well-known and have been compiled in several recent reviews. Only a few selected cases dealing with the rearrangements of vinylaziridines, cyclopropylimines, vinyloxiranes and cyclopropylketones are covered in the following section. 

Direct and sensitized irradiation of the cyclopropylketone (102) leads to the formation of the cyj isomer (103) and the two rearrangement products (104) and (105). The trans-cis isomerization is a normal event by ring opening of the cyclopropane ring followed by rebonding. The formation of the rearrangement products is thought to wise via the biradical (106) as illustrated in Scheme 5. ... 

Chromium trioxide-3,5-dimethylpyrazole is a mild and selective reagent for oxidation of a-methylenecyclopropanes into cyclopropylketones <93CC954>. 

Fig. 22. Haller-Bauer reaction with unsaturated- and cyclopropylketones.

The reaction of diphenylsulfonium 2-propcnylide with ( )-l,3-diphenyl-2-propenone provides the ethenvl-substituted cyclopropylketone 18 with moderate simple diastereoselectivity13. The S-ylide intermediate 17 is generated by deprotonation of the corresponding sulfonium salt. 

Scheme 8). Base treatment of (44) under appropriate conditions also provides routes to cyclopropylketones (46) and hydroxyketones (47). p-Hydroxyalkylphosphine oxides (49) can also be prepared directly from the corresponding epoxyalkyl phosphine oxide (48) by reaction with lithai.26... 

When photodeconjugation leads to only one asymmetric carbon, photocyclization of a-aminocyclohexanone, involving a y-H abstraction equally in the photochemical step allows the formation of a bicyclic molecule with three new asymmetric centers. Similarly, in the photorearrangement of prochiral cyclohexenones, two new asymmetric carbons are created in the corresponding cyclopropylketone. During the di-II-methane rearrangement of prochiral dibenzobarrelenes, four asymmetric carbons are created, while up to four new asymmetric centers can be obtained in the 2-1-2 photocycloaddition of molecules as simple as 2-cyclopentenone and cyclopentene. 

Cyclic ethylenehalides from cyclopropylketones Stereospecific conversion... 

Phenalenone (20 R = H) did not give the expected cyclopropylketone (21 R = H) on reaction with dimethylsulphoxonium methylide, attack at the 9-position instead generating the betaine (22X which collapsed to 9-methylphenalenone (20 R = Me). However, treatment of the latter gave the cyclopropane (21 R = Me). 

Thermolysis of the cyclopropylketones (544) and (545) also proceeds by a cyclic H-abstraction mechanism, and this provides a useful route to functionalized seven-membered rings/... 

More specific cycfizations are shown in Scheme 56. Carbonate of hydroxyacetone is not an allyl carbonate, but it can give rise to an 17 -l-oxaallylpalladium complex, which reacts with rigid olefins to afford cyclopropylketones.f ° Monocarbonate of cis-butene-l,4"di i forms a zwitterionic r/ -allylpalladium complex, which reacts as a dipole with Ceo to afford a vinyltetrahydrofuran derivative of fullerene. A... 

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