Organic chemists have always been fascinated by the cyclopropane subunit.1 The smallest cycloalkane is found as a basic structural element in a wide range of naturally occurring compounds.2 Moreover, many cyclopropane-containing unnatural products have been prepared to test the bonding features of this class of highly strained cycloalkanes3 and to study enzyme mechanism or inhibition.4 Cyclopropanes have also been used as versatile synthetic intermediates in the synthesis of more functionalized cycloalkanes5,6 and acyclic compounds.7 In recent years, most of the synthetic efforts have focused on the enantioselective synthesis of cyclopropanes.8 This has remained a challenge ever since it was found that the members of the pyrethroid class of compounds were effective insecticides.9 New and more efficient methods for the preparation of these entities in enantiomerically pure form are still evolving, and this review will focus mainly on the new methods that have appeared in the literature since 1989. It will elaborate on only three types of stereoselective cyclopropanation reactions from olefins: the halomethylmetal-mediated cyclopropanation reactions (eq 1), the transition metal-catalyzed decomposition of diazo compounds (eq 2), and the nucleophilic addition-ring closure sequence (eqs 3 and 4). These three processes will be examined in the context of diastereoand enantiocontrol. In the last section of the review, other methods commonly used to make chiral, nonracemic cyclopropanes will be briefly outlined.

Stereoselective Cyclopropanation Reactions

Nitrile anion cyclizations

1-azaallylic anions in heterocyclic chemistry.

The regioselective conversion of propargylic alcohols into previously unreported α,α-diiodo-β-hydroxyketones was achieved by treatment with N-iodosuccinimide in the presence of a gold catalyst. The corresponding α,α-dichloro-β-hydroxyketones were obtained by treatment with trichloroisocyanuric acid in the absence of a catalyst. The latter reaction can be extended to other alkynols. These transformations can be used to prepare potentially useful halogenated building blocks. Preliminary mechanistic studies suggest that the reaction involves participation of the acetonitrile solvent in the formation of a 5-halo-1,3-oxazine intermediate.

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Regioselective dihalohydration reactions of propargylic alcohols: gold-catalyzed and noncatalyzed reactions.

ConspectusThe alkylation of enolates is one of the backbones of ketone chemistry, yet in practice it suffers from numerous limitations due to problems of regiochemistry (including O- versus C-alkylation), multiple alkylations, self-condensation, competing elimination, and incompatibility with many polar groups that have to be protected. Over the years, various solutions have been devised to overcome these difficulties, such as the employment of auxiliary ester or sulfone groups to modify the pKa of the enolizable hydrogens, the passage by the corresponding hydrazones, the use of transition-metal-catalyzed redox systems to formally alkylate ketones with alcohols, etc. Most of these hurdles disappear upon switching to α-ketonyl radicals. Radicals are tolerant of most polar functions, and radical additions to flat sp2 centers are generally easier to accomplish than enolate substitution at tetrahedral sp3 carbons. The main stumbling block, however, has been a lack of generally applicable methods for the gener...

The Xanthate Route to Ketones: When the Radical Is Better than the Enolate.

The favorskii rearrangement of dichlorinated methylketones

A new synthesis of 1, 1-dichloromethylketones is described. Methylketones are converted into cyclohexylketimines, which by N-chlorosuccinimide are chlorinated specifically to 1,1-dichloromethylketimines. Hydrolysis yields 1, 1-dichloromethylketones, containing less than 5% isomers. Overall yields normally are around 50%.

A New Synthesis of 1,1‐Dichloromethylketones

N-(2,2-Dichloro-1-phenylalkylidene)isopropylamines were synthesized by deprotonation of N-(2,2-dichloro-1-phenylethylidene)isopropylamine by lithium diisopropylamide and reaction of the resulting 3,3-dichloro-1-azaallylic anion with alkyl bromides or iodides. Acidic hydrolysis provides an easy access to 2,2-dichloro-1-phenyl-1-alkanones

A Convenient Synthesis of 2,2-Dichloro-1-phenyl-1-alkanones and the Corresponding Imines

Syntheses and reactions of 1-amino-2,2-dialkylcyclopropane-1-carbonitriles and -carboxamides - Potential precursors of ACC derivatives

Aldimines were selectively α-monochlorinated without any interference of α,α-dichlorinated derivatives, by a sequence of reactions involving α-trimethylsilylation of preformed 1-azaenolates, α-chlorination using N-chlorosuccinimide and desilylation in methanol. Upon acidic hydrolysis, these α-monochloroimines provide an easy access to α-monochloroaldehydes.

W. Coppens

Papers

The favorskii rearrangement of dichlorinated methylketones

A New Synthesis of 1,1‐Dichloromethylketones

A Convenient Synthesis of 2,2-Dichloro-1-phenyl-1-alkanones and the Corresponding Imines

Syntheses and reactions of 1-amino-2,2-dialkylcyclopropane-1-carbonitriles and -carboxamides - Potential precursors of ACC derivatives

A Facile Method for the α‐Monochlorination of Aldimines and Aldehydes