Darzens-like reaction

The addition of halomethyl metal reagents provides another Darzens-like route to aziridines <06JOC9373>. Reaction of ICH2C1 with MeLi generates a chloromethyllithium reagent, which then adds to the inline 74. A subsequent intramolecular /V-alkylation provides the aziridine 75. The isolation of a chloromethyl ketone byproduct demonstrated that the chloromethyllithium reagent is operative as opposed to a carbene. 

Imines can readily serve as aziridine precursors via an aza-Darzens or Darzens-like approach. Vinyl aziridines were synthesized in 57 to 77% yield by reacting ylides generated from substituted allyltetrahydrothiphenium salts with V-(dimethylsulfamoyl)phenyl imine <07SL2879>. Aziridines carrying two or three heteroaryl groups were synthesized on the basis of the Darzens reaction between imines and a-chloroalkyl heterocycles <07EJO5926>. 

An interesting Darzens-like formal cycloaddition of azirines has also been reported <2004EJ02421>. While this is not a true cycloaddition reaction, two bonds are formed in the same reaction sequence. Reaction of sulfone 114 with lithium diisopropylamide (LDA) generates a carbanion which then adds to the azirine to generate intermediate 115. Cyclization of this intermediate with the allyl halide provides the product aziridine 116. This reaction proceeds in only 13% yield but is nonetheless an interesting route to fused-ring aziridines (Equation 27). 

The basic route to the synthesis of epoxides and, in general, vicinal bifunctional derivatives is a non-isohypsic (oxidative) transformation of alkenes (to be discussed below), Epoxides can also be formed directly as a result of certain C-C bond-forming reactions such as the Darzens reaction (modification of a classical aldol-like reaction with a-chloro esters 130 as a methylene component)... 

The Darzens condensation is an aldol-like reaction in which the aldolate product closes to give an epoxy ketone. The reaction has been achieved with moderate... 

The usual Darzen s reaction consists of the reaction of aldehydes or ketones with a-haloester or a-halonitriles in presence of a base like potassium tertiarybutoxide to give glycidic esters or nitriles, respectively (Scheme 20). 

It is a yellow liquid with a powerful, green, cucumber-like and melon odor. It can be prepared by Darzens reaction of 6-methyl-5-hepten-2-one with ethyl chloroacetate. The intermediate glycidate is saponified and decarboxylated to yield the title compound. 

The unexpected products come from variations in this mechanism. para-Methoxy-benzaldeh- is conjugated and unreactive so that the chloroketone ignores it and does a Darzens reaction itself, rather like the self-condensations we met in Chapter 21. 

The first use of carbonyl ylides as dipoles in intramolecular cycloadditions has been published and has led to a stereoselective synthesis of oxygen heterocycles. On heating above 170 °C the ene-oxiran (70), readily available by a Darzens reaction, isomerized to the intramolecular cycloadducts (71) and (72). The reaction is most likely initiated by conrotatory opening of the oxiran ring to a carbonyl ylide, and the product then depends on the conformation of the alkenyloxy-group leading to trans-(71) or c/s-(72) annelation (Scheme 8). 

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