Allylation reactions cyclopentanone

As the aUylated enamine has higher reactivity (i.e., lower ionization potential) the selective mono-aUylation of cyclohexanone required excess (2 equiv.) ketone reagent. Nevertheless 20 equivalents of cyclobutane were necessary for the selective reaction with cyclobutanone and only 2,5-bis-allylated cyclopentanone was obtained, as the second oxidation occurred immediately on the iminium intermediate prior to hydrolysis with this substrate. The allylation reaction was compatible with alkyl and heteroatom substituents at the P and y positions. When non-symmetrical heteroatom containing substrates were used, C(4) allylation occurred selectively in high yields (70-86%) and in high ee (80-99%) (Figure 39.2). 

The formation of an enamine from an a,a-disubstituted cyclopentanone and its reaction with methyl acrylate was used in a synthesis of clovene (JOS). In a synthetic route to aspidospermine, a cyclic enamine reacted with methyl acrylate to form an imonium salt, which regenerated a new cyclic enamine and allowed a subsequent internal enamine acylation reaction (309,310). The required cyclic enamine could not be obtained in this instance by base isomerization of the allylic amine precursor, but was obtained by mercuric acetate oxidation of its reduction product. Condensation of a dihydronaphthalene carboxylic ester with an enamine has also been reported (311). 

Extension of these studies to the more sterically demanding allylic sulfoxide anion derived from T(/e/7-butylsulfinyl)-l-(2-methylpropyl)-2-butene on reaction with 2-cyclopentenone gave three diastcrcomcric 1,4-adducts, 3-[3-(7( rt-butylsulfinyl)-l, 5-dime thy lhexyl]cyclopentanones, in a ratio of 31 26 4333. 

Friedel Crafts acetylation of butadiene complex 56 proceeds smoothly to give a mixture of 1-acetyldienes 58 and 59 via the cationic 7r-allyl complex 57 [16]. Intramolecular Friedel-Crafts acylation with the acid chloride of the diene complex 60, promoted by deactivated AICI3 at 0 °C, gave the cyclopentanones. The (Z)-dienone complex 61 was the major product and the ( )-dienone 62 the minor one [17]. Acetylation of the 1,3-cyclohexadiene phosphine complex 63 proceeded easily at —78°C to give the rearranged complex 65 in 85% yield. Without phosphine coordination, poor results were obtained [18,19], In this reaction, the acetyl group at first coordinates to Fe, and attacks at the terminal carbon of the diene from the same... 

Under the oxidative conditions, allylation of active methine or methylene groups can be carried out with allylic sulfide/Mn3+, Cu2+. Eq. 4.36 shows the reaction of a-ethoxycarbonyl cyclopentanone (99) and 2-methyl-2-propenyl t-butyl sulfide (100) in the presence of Mn(OAc)3 and Cu(OAc)2 in acetic acid to form a-allyl-a-ethoxycarbonyl cyclopentanone (101) in good yield. Allyl sulfides are more effective than allyl sulfones [106, 107]. 

The 1,2-addition of allyl iodide to cyclic and acyclic a,/ -unsaturated carbonyl compounds has been achieved by using indium and indium trichloride. The reactivities of a,/3-unsaturated carbonyl compounds depend upon their structure. The reaction of ketones smoothly undergoes in THF or DMF. In the case of cyclic ketones, however, the solvent plays a crucial role, where much improved yields have been obtained in DMF than in THF (Equation (49)).236 Indium-mediated 1,2-allylation of /3-bromoacrolein produces homoallylic alcohol derivatives (Equation (50)), which can be transformed to cyclopentanones by a Pd-catalyzed cyclization.237,238... 

Further reaction of Aese species with carbonyl compounds and hydrolysis of the resulting alkoxide leads to p-oxidoalkyl selenoxides which have been transformed into allyl alcohols on thermal decomposition (Schemes 51, 52 and 54, entry a see Section 2.6.4.4) or reduced to p-hydroxyalkyl selenides or to alkenes (Scheme 53). P-Oxidoalkyl selenoxides derived from cyclobutanones react in a different way since Aey rearrange to cyclopentanones upon heating (Scheme 54, b. Schemes 120 and 121 and Section 2.6.4.5.3). 

Scheme 190) and cyclopentanones (Schemes 54b and 121), respectively, rather than produce the corresponding allyl alcoholates via the well-established seleninic acid elimination (Section 2.6.4.4). The latter reaction, however, becomes inq>ortant with oxaspiropentanes where the oxirane ring is trialkyl substituted (Scheme 191). ... 

The use of -fhio- and -silylacryloylsilanes switches the reaction mode from [2-1-1] to ]3-i-2] armulation to form cyclopentanone silyl enolates (Scheme 10.226) [588]. The annulation wifh /i-lhioacryloylsilaries might proceed via the delocahzed allylic carbanion 159 whereas a reaction pathway through 1,3-sigmatropic rearrangement of the vinylcyclopropane intermediate 160 has been proposed for/fsilylacryloylsilaries [589]. 

Control over the geometry of the allylic ether portion of the starting material is easy - just use the appropriate allylic alcohol. Control over the vinyl ether is more difficult as that alkene is created in the exchange reaction. If the vinyl ether is cyclic, the problem disappears. The allyl vinyl ether 165, made from cyclopentanone and the allylic alcohol but-2-en-l-ol 8 rearranges with catalysis by 2,6-dimethylphenol into one diastereoisomer of the allylated product32 168. The stereoselectivity is easily predicted by the chair transition state 167. 

Tetracarbonylnickel and other nickel(O) compounds, as well as palladium complexes, catalyze the [2 + 2 + 1] cycloaddition of allylic systems with alkenes or alkynes and carbon monoxide to form cyclopentanones or cyclopentenones. This reaction type resembles stoichiometric zirconium- and cobalt-mediated [2 + 2 + 1] cycloadditions (vide supra), mechanistically, however, it proceeds via transition metal 7r-allyl complexes. 

Another synthetically useful carbon bond-forming reaction involves reaction of diiron nonacarbonyl with halo-carbonyl compounds. Noyori found that a,a -dibromoketones (498) react with diiron nonacarbonyl [Fe2(CO)9] to give an iron stabilized alkoxy zwitterion (499). The intermediate Jt-allyl iron species reacts with alkenes in a stepwise manner (initially producing 500) to give cyclic ketones such as 501, 23 and the product is equivalent to the product of a [3-t2]-cycloaddition with an alkene (sec. 11.11). This cyclization method is now known as Noyori annulation. This reaction is related to the Nazarov cyclization previously discussed in Section 12.3.C. Enamines can react with 498, but the initially formed enamino ketone product eliminates the amino group to form cyclopentanone derivatives. Intermediates such as 499 may actually exist as cations hound to a metal rather than as the alkoxide-iron structures shown.323b-d noted that Zn/B(OEt)3 is... 

Cascade reactions of substituted 1,2,4-triazines are of great interest as simple ways to a dramatic increase in molecular complexity, from planar 1,2,4-triazine unit into a polycyclic system. Indeed, in this multistep process, the diallylamine and cyclopentanone react first in situ to give the corresponding enamine, which undergoes an inverse electron demand cycloaddition reaction with 1,2,4-triazine to give an intermediate dihydropyridine compound. A spontaneous intramolecular Diels-Alder reaction between the allyl moiety and the dihydropyridine gives the tetracyclic compound (Scheme 99) <2004JA12260>. 

Michael addition, followed by an intramolecular aldol condensation to provide the seven-membered ring. Subsequent retro-Dieckmann reaction, dehydration, and ester saponification provide the bicyclic product in 98% yield. A related cascade reaction was recently reported by the same research group in which the reactions of various allylic halides with cyclopentanone derivatives provide seven-membered rings. ... 

To a solution of 1 mmol allyl phosphonamide in 10 mL THF was added 1.2 mmol of n-BuLi (1.6 or 2.5 M solution in hexane) at —78°Cunder argon. A solution of 1.2 mmol a,fi-unsaturated-cyclopentanone in 5 mL THF at -78°C was added immediately via cannula. The reaction mixture was stirred at —78°C for 30 min, slowly quenched with saturated aqueous NH4CI (or with Mel (10 eq.), with BnBr (5 eq.), and with allyl bromide (5 eq.)) to form further alkylated products and allowed to warm to ambient temperature. The mixture was diluted with 50 mL EtOAc and washed with 20 mL brine and 20 mL water. The organic layer was separated, dried over MgS04, and concentrated in vacuo. The resulting crude product was purified by column chromatography (EtOAc/MeOH) to give 88% of 1,4-addition product, with R S ratio of 93 7. 

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