Ketones, synthesis from epoxides

In recent years, dioxiranes have become workhorses for a variety of selective transformations in organic synthesis, from epoxidation of alkenes to the conversion of alcohols into fee corresponding ketones <99CJC308>. Dioxirane-mediated epoxidation continues to be the method of choice for complex substrates wife acid-sensitive functionality. Thus, fee dimethyl-dioxirane (DMD)-mediated epoxidation of the silylated stilbene lactam 159 has been reported as a key step in fee synthesis of protoberberines <99JOC877>. 

Cyclopropyl ketones, e.g. (1), can be made from 7-halo ketones (2), whose synthesis from epoxides and activated ketones was discussed in Chapter 23. 

N,O-acetal intermediate 172, y,<5-unsaturated amide 171. It is important to note that there is a correspondence between the stereochemistry at C-41 of the allylic alcohol substrate 173 and at C-37 of the amide product 171. Provided that the configuration of the hydroxyl-bearing carbon in 173 can be established as shown, then the subsequent suprafacial [3,3] sigmatropic rearrangement would ensure the stereospecific introduction of the C-37 side chain during the course of the Eschenmoser-Claisen rearrangement, stereochemistry is transferred from C-41 to C-37. Ketone 174, a potential intermediate for a synthesis of 173, could conceivably be fashioned in short order from epoxide 175. 

Historically, the asymmetric synthesis of epoxides derived from electron-poor alkenes, for example a, (3-unsaturated ketones, has not received as much attention as the equivalent reaction for electron-rich alkenes (vide supra). However, a recent flurry of research activity in this area has uncovered several... 

POLYHYDROGEN FLUORIDE REAGENT 1-FLUORO-ADAMANTANE. Dichloroalkane synthesis is shown in cis-DI-CHLOROALKANES FROM EPOXIDES cis-1,2-DICHLORO-CYCLOHEXANE. Nitrile functionality can be introduced from a ketone, as in NITRILES FROM KETONES CYCLOHEXANENITRILE, or from a reactive diene, as shown in 2,3-DICYANOBUTADIENE AS A REACTIVE INTERMEDIATE BY in situ GENERATION FROM 1,2-DICYANO CYCLOBUTENE 2,3-DICYANO-1,4,4a,9a -TETRAHYDRO-FLUORENE. 

A novel approach to the asymmetric synthesis of epoxides, allylic alcohols, a-amino ketones, and a-amino aldehydes from carbonyl compounds through a,/i-epoxy sulfoxides using the optically active p-tolylsulfmyl group to induce chirality./. Org. Chem. 1989, 54, 3130-3136. 

Mechanism of Shi epoxidation was probed for synthesis of (+)-(R,R) epoxide 20 in the reaction of frans-2-methylstyrene 18 with peroxymonosulphate (Oxone) in the presence of catalyst 19, chiral ketone derived from fructose (Scheme 5).74... 

Sello et al. have reviewed recent developments in oxirane preparation including metal- and ketone-mediated methods, the synthesis of epoxides from carbonyls, and enzymatic reactions <2006CSY457>. 

Ylides derived from the salts obtained by A. A -dialkylation of sulfoximines and anions derived from A -tosylsulfoximines are useful reagents for the synthesis of epoxides or cyclopropanes from aldehydes and ketones or enones. ... 

The Darzens-type products from a-halo sulfoxides and carbonyl compounds undergo reductive desulfurization by the action of butyllithium. This is a useful synthetic route to various epoxides. Yamakawa and coworkers disclosed a novel asymmetric synthesis of epoxides (109) using optically active 1-chlo-roalkyl p-tolyl sulfoxide (107). This method is most effective when the starting ketones are symmetrical, because only one diastereomer is then formed in the Darzens-type condensation (equation 26). 

Hydroxyalkylphosphonates have been prepared by reduction of the corresponding ketones. These include phosphonomalate esters by highly diastereose-lective reduction of 3-phosphonopyruvates with NHs.BHa and both 2-hydroxyalkyl-phosphonates, e.g. 178, and thiophosphonates by asymmetric hydrogenation using chiral ruthenium catalysts. An enantioselective synthesis, from 179, of both enantiomers of phosphonothrixin 180 and their absolute stereochemistry have been reported.The epoxide 179 was prepared from 2-methy -3-hydroxymethyl-1,3-butadiene via a Sharpless epoxidation. 

Lithium derivatives of these sulfones can be alkylated with alkyl halides or epoxides,28 and acylated with esters to give the ketones 95 from which the sulfonyl group can be removed with aluminium amalgam Deprotection and cyclisation provides a synthesis of cyclopentenones 98 (cf. chapter 6).26... 

One of the obvious alternatives to butyrolactone synthesis from ester enolates and epoxides is to use nucleophilic attack by ester homo-enolates (vide supra) onto aldehydes and ketones. Two further versions of this latter method are condensations between ketones and methyl 3-bromopropionate using a lanthanum metal to provide the... 

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