Cyclopropanation enones

This protective group was used to direct the selective cyclopropanation of a variety of enones. Hydrolysis (HCl, MeOH, H2O, it, 94% yield) affords optically active cyclopropyl ketones. 

The key step in this sequence, achieved by exposure of 46 lo a mixture of sulfuric acid and acetic anhydride, involves opening of the cyclopropane ring by migration of a sigma bond from the quaternary center to one terminus of the former cyclo-l>ropane. This complex rearrangement, rather reminiscent of the i enone-phenol reaction, serves to both build the proper carbon. keleton and to provide ring C in the proper oxidation state. 

Key features of the cyclopropanation include the ylide acting as a mild base to isomerize the 1,2-dioxines into cis-y-hydroxy enones, followed by Michael addition of the ylide and last by cyclization of the intermediate enolate [35]. It must be noted that the trans-y-hydroxyenones do not give the cyclopropanation. 

Chemo- and stereoselective reduction of (56) to (55) is achieved In highest yield by sodium borohydride in ethanol. The isolated ketone is reduced more rapidly than the enone and (55) is the equatorial alcohol. Protection moves the double bond out of conjugation and even the distant OH group in (54) successfully controls the stereochemistry of the Simmons-Smith reaction. No cyclopropanation occurred unless the OH group was there. Synthesis ... 

Replacing the epoxide by a cyclopropane, also available from an enone as in the preparation of 99 (Eq. 114), also possesses in excess of 209 kJ/mole (50 kcal/mole)... 

Cyclopropanation of enones.1 Reaction of an enone with tris(phenylthio)-methyllithium and then with CuOTf (1 equiv.) results in a bis(phenylthio)-cyclopropane (equation I). 

Cyclopropanation of enones. The adduct (a) of 1 to cyclohexenone can be metallated at - 45° by sec-BuLi to give a dianion b, which when quenched at 0°... 

In a single case, thermal treatment of enone 36 induced a 1,3-sigmatropic silyl shift which led to the formation of the rearranged product 37 (Eq. 8.3) [40], So far, only one example of a ring-opening reaction of a cyclopropane 38 has been reported which furnished tetramethoxy-substituted allene 39 (Eq. 8.4) [41],... 

Vaska s complex catalyzed the transformahon of aUenylcyclopropane into 2-alkenylidenecyclohex-3-enone under conditions of pressurized CO (Scheme 11.25) [38]. In this reaction, the jr-coordination to internal oleflnic moiety of the aUene brings the metal closer to the cyclopropane ring. Release of the cyclopropane ring strain then facilitates the oxidative addition of vinylcyclopropane moiety along with C-C bond cleavage, such that metallacyclohexene is obtained a subsequent carbonyl insertion and reductive elimination then provides the product Hence, the reaction can be recognized as a [5+1] cycloaddition of vinylcyclopropane and CO. 

Synthesis of enones and cyclopropanes from bis(oxoalkyl)tellurium dichlorides... 

The sequential treatment of bis(2-oxomethyl)tellurium dichlorides with 2 equiv of LDA in THF at -78°C and 2 equiv of an aldehyde, followed by heating at 25°C, affords the enones with E geometry in good yields. The same reaction performed with methyl vinyl ketone gives rise to the cyclopropane. ... 

A useful and practical version of the above protocol involves a catalytic process in which the enone, a bromoallyl silane, cesium carbonate and diisobutyl teUuride react in a one-pot procedure to give the desired cyclopropanes with a high cw-stereoselectivity. 

A weak base such as glycine added to [HMIMjPFg has also been reported to catalyze a Knoevenagel reaction of malononitrile and benzaldehyde 110). A KOH-treated [BMIMjPFg also provides a suitable medium for the Corey-Chaykovsky epoxidation of enones and cyclopropanation of aldehydes using trimethyl sulfonium iodide (///). 

Ikegami s successful synthesis of racemic 720 materialized by initial conversion of 701 to 725 via a 1,2-carbonyl transposition sequence (Scheme LXXVIII) Treatment of 725 with methoxycarbene, deprotection, and oxidation provided 72 6. Acid-promoted cyclopropane ring cleavage and added functional group manipulation led to 727 which could be allylated stereoselectively. The tricyclic enone 724 was subsequently produced conventionally. 

Starting from optically active 1-chlorovinyl p-tolyl sulfoxide derived from 2-cyclohex-enone, the asymmetric synthesis of cyclopropane derivative (85) was realized (equation 23) . Addition reaction of lithium enolate of tert-butyl acetate to 83 gave the adduct (84) in 96% yield with over 99% ee. Treatment of the latter with i-PrMgCl in a similar way as described above afforded optically pure (15,6/ )-bicyclo[4.1.0]hept-2-ene (85) in 90% yield. 

Next to the cyclopropane formation, elimination represents the simplest type of a carbon-carbon bond formation in the homoenolates. Transition metal homoenolates readily eliminate a metal hydride unit to give a,p-unsaturated carbonyl compounds. Treatment of a mercurio ketone with palladium (II) chloride results in the formation of the enone presumably via a 3-palladio ketone (Eq. (24), Table 3) [8], The reaction can be carried out with catalytic amounts of palladium (II) by using CuCl2 as an oxidant. Isomerization of the initial exomethylene derivative to the more stable endo-olefin can efficiently be retarded by addition of triethylamine to the reaction mixture. 

Bicyclo[3.2.0]heptan-6-ones 10 were obtained by transformation of 2-methoxycyclohex-2-enones 8 to l-methoxybicyclo[4.1.0]heptan-2-ols 9 and subsequent rearrangement (Table 13).155 161 For the synthesis of the requisite precursors, a sequence of reduction and cyclopropanation 8 - 9, eventually followed by oxidation and an addition to the carbonyl group 9 — 11 — 12, proved most effective. 

Notes This reagent finds use in epoxidation of carbonyl groups. Can also cyclopropanate enone... 

---