2-Cyclohexenone Cyclopropane

Chiral bicyclic lactams are excellent precursors to a wide variety of chiral, non-racemic carbocycles including cyclopentenones, cyclohexenones, cyclopropanes, indanones, naphthalenones, and asymmetric keto acids.3 Recently they have been applied to the synthesis of chiral, non-racemic pyrrolidines and pyrroiidinones,4 that are medicinally and synthetically important molecules.5 The three-step procedure described here provides an efficient route (overall yield 46%) to (S)-5-heptyl-2-pyrrolidinone of high enantiomeric purity. The scheme below illustrates this reaction. 

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°... 

Carbonylative [5 + l]-cycloaddition of allenylcydopropanes was successfully achieved by use of an Ir(I) catalyst to yield (2-alkylidene)cyclohexenones in good yields (Scheme 16.43) [43]. No carbonylative [5 + l]-cycloaddition was observed in the case of an allenylcyclopropane lacking substituents at the allenic terminus. It can be deduced that the metal is too distant to open the cyclopropane ring, probably owing to the preferred -coordination at the allenic Jt-bond distal to the cyclopropyl group. 

The transition metal-catalyzed reaction of diazoalkanes with acceptor-substituted alkenes is far more intricate than reaction with simple alkenes. With acceptor-substituted alkenes the diazoalkane can undergo (transition metal-catalyzed) 1,3-dipolar cycloaddition to the olefin [651-654]. The resulting 3//-pyrazolines can either be stable or can isomerize to l//-pyrazolines. 3//-Pyrazolines can also eliminate nitrogen and collapse to cyclopropanes, even at low temperatures. Despite these potential side-reactions, several examples of catalyzed cyclopropanations of acceptor-substituted alkenes with diazoalkanes have been reported [648,655]. Substituted 2-cyclohexenones or cinnamates [642,656] have been cyclopropanated in excellent yields by treatment with diazomethane/palladium(II) acetate. Maleates, fumarates, or acrylates [642,657], on the other hand, cannot, however, be cyclopropanated under these conditions. 

In early 1994, Padwa et al. (119) synthesized both mono- and bicyclic core skeletons of the illudins and ptaqualosins. By utilizing a 1,1-disubstituted cyclopropane as the core of the dipolar cycloaddition, Padwa was able to add a number of dipolarophiles including cyclopentenone and cyclohexenone to produce cycloadduct 233 amenable to subsequent transformations to form the illudins and ptaqualosins. The cycloaddition forms the bicyclic constrained ether in... 

Related to metal complexes are metal carbenoids such as those formed when zinc reacts with di-iodomethane. In early examples, such as the efficient cyclopropanation of cyclohexenone 54, the zinc was activated by some copper.13 The active reagent is the zinc a-complex 56. One might suppose an a-elimination 57 would occur to give the carbene, but this is apparently not so. The active reagent 56, nearly but not quite a carbene, is known as a carbenoid. 

Substrates 9 can be regarded as homoolefinic derivatives of 1. Here also the analogous vinyl cyclopropanes don t react similarly to 9, the allenic unit makes 9 more reactive [11]. In Ir1-catalyzed reactions with CO the six-membered analoges of 3, the cyclohexenones 11 [11], were formed in a [5+1] cycloaddition (Scheme 4). 

This transformation has found extensive use in converting cyclopentenone and cyclohexenone ring systems to the rearranged allylic alcohols during the course of the total syntheses of natural products. In the preparation of ( )-quadrone (Scheme 12), the tricyclic enone was epoxidized and the resulting a,P-epoxy ketone treated with hydrazine to afford the allylic alcohol. The cyclopropane-directed epoxidation shown in Scheme 13 gives an allylic alcohol that is taken on to (-)- and (+)-carenones. In the total syn-... 

This principle also allows generation of other very useful 1-hetero-substituted 1-lithio cyclopropanes, e.g. methoxy derivatives which, after treatment with carbonyl compounds and acid, afford 2-vinylcyclobutanones in excellent yields (equation 113). The latter have been expanded to cyclopentenones and cyclohexenones by various methods On the other hand, trimethylsilylcyclopropanes undergo a Peterson-type... 

Hydroxyphenylcyclohexanes Cyclohexanols—see Cahx[4]cyclohexanols Cyclohexanones—see Cahx [4] cyclohexanones Cyclohexenones—see Aryl-2-cyclohexenones 4-Cyclohexylphenol, formation of 613 Cyclopentadiene 5-carboxyUc acid 1057 Cyclopropanation, asymmetric 697 Cytochrome P-450 linked microsomal Papaver enzyme 1216 Cytotoxicity 654 CZE 971-974... 

Methyl 6 -Oxospiro(cyclopropane-l,8 -tricyclo[(3.2.].0 ]octane-l -carhoxylate) (ITa) " A solution of dienolate [prepared from cyclohexenone (0.22 g, 2.3 mmol) method A] in THF (20 mL) was treated with methyl 2-chloro-2-cyclopropylideneacetate (300 mg, 2.0 mmol) in THF (3mL) at — 40 C and then left to warm to 20"C for 1 h. After the usual workup the product was isolated by Kugelrohr distillation yield 140 mg (34%) bp 130X/0.02Torr. 

Vinylcyclopropanes can react with pentacarbonyliron to give two different types of addition products i) (diene)tricarbonyliron 7r-complexes as the result of ring opening, hydrogen shift, and complexation ii) cyclohexenones by photoinduced carbonyl insertions across the vinyl-cyclopropane system. 

The ketocyclopropane (40) photochemically rearranges into the cyclo-octadiene (41) which itself is photoconverted into the isomeric compound (42). The formation of the cyclo-octadiene involves the ring opening of the cyclohexenone and the cyclopropane moieties to afford the ketene (43). ... 

The unusual cyclopropane 551 was isolated [probably as the (5)-isomer] from Pistacia vera, together with the hydrated analog 552 551 was synthesized by Grignard reaction of cyclopropylmagnesium bromide with 4-methyl-3-cyclohexenone, and the diol 552 by lithium aluminum reduction of the epoxide of 551. ... 

Note that this reagent has a greater tendency to form a cyclopropane derivative than dimethylsulfonium methylide, which reacts with 2-cyclohexenone to give only the oxirane. 

Alkylation of lithiated l-(l-ethoxyprop-2-enyl)benzotriazole leads to enones after hydrolytic removal of the heterocycle addition of the lithiated species to cyclohexenone then hydrolytic cleavage of the heterocycle prodnces an nnsaturated l,4-diketone. ° Addition of the same anion to methyl but-2-enoate generates an anion in which the benzotriazole is displaced intramolecularly and a cyclopropane resnlts. ... 

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