Enones alkylation

Certain catalysts promote the reduction of ketones with organosilanes. The reduction of acetophenone with Et3SiH is catalyzed by the diphosphine 65 and gives only a small amount of overreduction to ethylbenzene.377 Aryl alkyl enones and ynones are reduced to the corresponding alcohols with triethoxysilane and the titanium-based catalyst 66.378 Trichlorosilane reduces acetophenone in 90% yield with /V-formylpyrrolidinc catalysis.379... 

Ketone rac-13 was transformed into the corresponding silylenolether and by Pd(II)-mediated Saegusa oxidation [14] into a, -unsaturated ketone rac-14. By alkylative enone transposition comprising methyl lithium addition and pyridinium chlorochromate (PCC) oxidation [15], rac-14 was finally converted into the racemic photo cycloaddition precursor rac-6. In conclusion, the bicyclic irradiation precursor rac-6 was synthesized in a straightforward manner from simple 1,5-cyclooctadiene (11) in nine steps and with an overall yield of 21%. 

The introduction of the double bond of rac-14 was performed by conversion of rac-13 into its a-phenylselenide, subsequent peroxide oxidation, and elimination. Following the synthesis reported by Mehta and Srinivas, an alkylative enone transposition was used as the last step towards irradiation... 

Another approach to secondary amines has been reported (J. Am. Chem. Soc. 125 16178, 2003) by Masakafsu Shibasaki of the University of Tokyo. Addition of methoxyamine to a chalcone 7 (alkyl enones work in slightly lower ) gives the amine 8. The amine 8 can be reduced with high stereocontrol to the amino alcohol 9. K-Selectride gives the complementary diastereomer. 

Tagat et al. reported an approach to SDB as illustrated in Fig. (6). They used commercially available abietic acid 50 structurally similar to SDB especially at carbon 4, 5 and 10 as a starting material. Tricyclic enone 51 was prepared according to the method reported previously by Abad et al. [44] with slight modification. To construct D-ring, intramolecular alkylation of the homonuclear diene 52, readily accessible from 51, was carried out to afford g-alkylated enone 53. Methylation of the enone 53 with LDA/THF at -78°C and Mel followed by ozonolysis gave the 12-methyl enone 54. After selective reduction of the side chain of 54 with Na(OAc)3BH, the mesylate 56 obtained from alcohol 55 was converted to... 

Ketones. The reagent (1) is a propenoyl anion synthon. After alkylation, enones are released. On the other hand, the adducts undergo allylic displacement with Grignard reagents, and on hydrolytic workup, ketones are formed. The possibility of creating a-bromoalkyl ketones, 1,4-diketones, 2-ethoxy-2-cyclopentenones, and a-keto enamines bespeaks for the versatility of this synthesis. 

A highly enantioselective conjugate addition of nitromethane and nitroethane to acyclic enones has been recently achieved using chiral cyclohexanediamine-derived primary amine thiourea 48 (Scheme 2.57) [168], With respect to the electrophile, the reaction shows a broad substrate scope and not only 1-aryl- but also 1-alkyl enones afford the corresponding chiral y-nitroketones with good yields and excellent enantioselectivities (92-99% ee). 

As a 4-Alkyl Enone Scaffold. PhS02CHD-epoxide can be used as a template for the construction of enantiopure 4-alkyl cyclohex-2-enones (eq 4). Addition of alkyl groups in an exclusive trans-1,4-fashion effectively transfers chirality from the epoxide to the newly formed carbon-carbon bond etherification is quantitative. Isomerization of the //-methoxy vinyl sulfone to an aUyhc... 

Finally, Chong [49] has observed a high-temperature tolerance in asymmetric conjugate arylboration of enones catalyzed by a BlNOL-derivative (20mol%). At 120 °C the products were obtained with good yields (65-90%) and enantioselectivi-ties (80-98% ee), both for diaryl and aryl-alkyl enones (Scheme 21.21). 

Most enones are reduced to anion radicals by organo cuprates. It is likely, that this reaction is connected with the alkylation. Both the formation of anion radicals and of conjugate adducts are not observed, when the redox potential of the enone becomes too negative (H.O. House, 1976). 

An interesting case are the a,/i-unsaturated ketones, which form carbanions, in which the negative charge is delocalized in a 5-centre-6-electron system. Alkylation, however, only occurs at the central, most nucleophilic position. This regioselectivity has been utilized by Woodward (R.B. Woodward, 1957 B.F. Mundy, 1972) in the synthesis of 4-dialkylated steroids. This reaction has been carried out at high temperature in a protic solvent. Therefore it yields the product, which is formed from the most stable anion (thermodynamic control). In conjugated enones a proton adjacent to the carbonyl group, however, is removed much faster than a y-proton. If the same alkylation, therefore, is carried out in an aprotic solvent, which does not catalyze tautomerizations, and if the temperature is kept low, the steroid is mono- or dimethylated at C-2 in comparable yield (L. Nedelec, 1974). 

As first demonstrated by Stork,the metal enolate formed by metal-ammoni reduction of a conjugated enone or a ketol acetate can be alkylated in liquic ammonia. The reductive alkylation reaction is synthetically useful since ii permits alkylation of a ketone at the a-position other than the one at whicf thermodynamically controlled enolate salt formation occurs. Direct methyl-ation of 5a-androstan-17-ol-3-one occurs at C-2 whereas reductive methyl-... 

A useful alternate procedure which allows the generation and alkylation of the less stable enolate anion has been reported by Stork.This method takes advantage of the fact that the thermodynamically less stable enolate anion formed in the lithium ammonia reduction of a conjugated enone... 

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