Cyclic ketones, condensation catalyzed

The 3.8-nonadienoate 91, obtained by dimerization-carbonylation, has been converted into several natural products. The synthesis of brevicomin is described in Chapter 3, Section 2.3. Another royal jelly acid [2-decenedioic acid (149)] was prepared by cobalt carbonyl-catalyzed carbonylation of the terminal double bond, followed by isomerization of the double bond to the conjugated position to afford 149[122], Hexadecane-2,15-dione (150) can be prepared by Pd-catalyzed oxidation of the terminal double bond, hydrogenation of the internal double bond, and coupling by Kolbe electrolysis. Aldol condensation mediated by an organoaluminum reagent gave the unsaturated cyclic ketone 151 in 65% yield. Finally, the reduction of 151 afforded muscone (152)[123]. n-Octanol is produced commercially as described beforc[32]. 

Thorpe reaction org chem The reaction by which, in presence of lithium amides, a,(rt-dinitriles undergo base-catalyzed condensation to cyclic iminonitriles, which can be hydrolyzed and decarboxylated to cyclic ketones. thorp re,ak-shan TMPC See tetrakis(hydroxymethyl)phosphonium chloride, thulia See thulium oxide. thu-le-a ... 

The synthesis of the required acids was effected as outlined below. Condensation of the cyclic ketone (XXVI) with- dimethylsulfonium methylide 10 ) afforded a mixture of exo and endo aldehydes (XXVIII and XIX) on acid work-up of the reaction. The very great ease with which the intermediate epoxide (XXVII) undergoes acid catalyzed isomerization is not surprising in view of the very great stability of a-ferrocenyl carbonium ions previously noted. 

Scheme 7.4 presents some representative examples of Claisen-Schmidt reactions. Entries 1 and 2 are typical base-catalyzed condensations at methyl groups. Entry 3 illustrates the use of a cyclic ketone, and reaction occurs at the methylene group, where dehydration is possible. The stereochemistry presumably places the furan ring trans to the carbonyl group for maximum conjugation. Entry 4 shows the use of phthalaldehyde to effect a cyclization. Entry 5 illustrates the preference for condensation at the more-substituted position under acidic conditions. 

The scope of the Friedlander condensation in the preparation of chiral alkyl-substituted 1,10-phenanthrolines was investigated. A range of chiral [x, y-fc]-cycloalkeno-condensed phenanthrolines 343 and 344 were prepared in one step from the chiral pool of steroidal 342 or other cyclic ketones and 302 via base-catalyzed conditions (Scheme 73) (00MI423, 01JOC400). In the case of the major product, aldol bond formation takes place from the sterically less hindered a-carbon (C2) 343 while the steri-cally more hindered a-carbon (C6) 344 reacts to form the minor product (Scheme 73). 

A particularly difficult situation arises when combining in the same reaction the use of these rather unreactive acceptors such as enones with the incorporation of ketones as Michael donors in which the formation of the intermediate enamine by condensation with the amine catalyst is much more difficult. For this reason, the organocatalytic Michael addition of ketones to enones still remains rather unexplored. An example has been outlined in Scheme 2.22, in which it has been shown that pyrrolidine-sulfonamide 3a could catalyze the Michael reaction between cyclic ketones and enones with remarkably good results, although the reaction scope was exclusively studied for the case of cyclic six-membered ring ketones as nucleophiles and 1,4-diaryl substituted enones as electrophiles. In this system the authors also pointed toward a mechanism involving exclusively enamine-type activation of the nucleophile, with no contribution of any intermediate iminium species which could eventually activate the electrophile. Surprisingly, the use of primary amines as catalysts in this transformation has not been already considered. 

Thus the reactions of cyclic or acyclic enamines with acrylic esters or acrylonitrile can be directed to the exclusive formation of monoalkylated ketones (3,294-301). The corresponding enolate anion alkylations lead preferentially to di- or higher-alkylation products. However, by proper choice of reaction conditions, enamines can also be used for the preferential formation of higher alkylation products, if these are desired. Such reactions are valuable in the a substitution of aldehydes, which undergo self-condensation in base-catalyzed reactions (117,118). Monoalkylation products are favored in nonhydroxylic solvents such as benzene or dioxane, whereas dialkylation products can be obtained in hydroxylic solvents such as methanol. The difference in products can be ascribed to the differing fates of an initially formed zwitterionic intermediate. Collapse to a cyclobutane takes place in a nonprotonic solvent, whereas protonation on the newly introduced substitutent and deprotonation of the imonium salt, in alcohol, leads to a new enamine available for further substitution. 

Alkyl A-(3-oxobuten-l-yl)-2-aminobenzyl ketones 9 (as their cyclic acetals), formed by condensation of alkyl 2-aminobenzyl ketones with 3-methoxybut-3-ene-2-one, undergo acid-catalyzed cyclization to give rare examples of A -unsubstituted 1H-1 -benzazepines 10 in high yields.81... 

Chiral oxazolidines 6, or mixtures with their corresponding imines 7, are obtained in quantitative yield from acid-catalyzed condensation of methyl ketones and ( + )- or ( )-2-amino-l-phcnylpropanol (norephedrine, 5) with azeotropic removal of water. Metalation of these chiral oxazolidines (or their imine mixtures) using lithium diisopropylamide generates lithioazaeno-lates which, upon treatment with tin(II) chloride, are converted to cyclic tin(II) azaenolates. After enantioselective reaction with a variety of aldehydes at 0°C and hydrolysis, ft-hydroxy ketones 8 are obtained in 58-86% op4. 

Diketones are readily transformed to cyclic derivatives, such as cyclopentanones and furans. In this manner, the fragrance dihydrojasmone (3-methyl-2-pentyl-2-cyclopenten-l-one) is prepared by the base-catalyzed aldol condensation of 2,5-undecanedione. 2,5-Undecanedione is itself prepared from heptanal and methyl vinyl ketone in the presence of thiazolium salts (329). cis-jasmone can be similarly prepared (330,331). 

Iodonium ylides of type 6 cannot be isolated, unless the carbanion center is substantially stabilized (83MI1, 92MI1, 97MI1, 02MI1). For example, although iodonium enolates 22 can be prepared by base-catalyzed condensations of DAIB or iodosylbenzene with /J-dicarbonyl compounds, they are not similarly available from unactivated ketones and esters. Indeed, cyclic and acyclic mono-ketones are converted to a-hydroxy dimethylketals 23 with DAIB (or 13) in KOH/MeOH (86ACR244, 99QR273). Other... 

NAP-MgO acts as a bifunctional heterogeneous catalyst for the Claisen-Schmidt condensation (CSC) of benzaldehydes with acetophenones to yield chalcones, followed by asymmetric epoxidation (AE) to afford chiral epoxy ketones in moderate to good yields and impressive enantioselectivities (ee s). NAP-MgO, in combination with the chiral auxiliary (11 ,21 )-(- -)-1,2-diphenyl-1,2-ethylenediamine (DPED), catalyzed the asymmetric Michael addition of malonates to cyclic and acyclic enones. 

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