Metal Darzens condensation

Metal-based asymmetric phase-transfer catalysts have mainly been used to catalyze two carbon-carbon bond-forming reactions (1) the asymmetric alkylation of amino acid-derived enolates and (2) Darzens condensations [5]. The alkylation ofprochiral glycine or alanine derivatives [3] is a popular and successful strategy for the preparation of acyclic a-amino acids and a-methyl-a-amino acids respectively (Scheme 8.1). In order to facilitate the generation of these enolates and to protect the amine substituent, an imine moiety is used to increase the acidity of the a-hydrogens, and therefore allow the use of relatively mild bases (such as metal hydroxides) to achieve the alkylation. In the case of a prochiral glycine-derived imine (Scheme 8.1 R3 = H), if monoalkylation is desired, the new chiral methine group... 

Metal(salen) Complexes as Catalysts for Darzens Condensations... 

Very recently, Belokon and North have extended the use of square planar metal-salen complexes as asymmetric phase-transfer catalysts to the Darzens condensation. These authors first studied the uncatalyzed addition of amides 43a-c to aldehydes under heterogeneous (solid base in organic solvent) reaction conditions, as shown in Scheme 8.19 [47]. It was found that the relative configuration of the epoxyamides 44a,b could be controlled by choice of the appropriate leaving group within substrate 43a-c, base and solvent. Thus, the use of chloro-amide 43a with sodium hydroxide in DCM gave predominantly or exclusively the trans-epoxide 44a this was consistent with the reaction proceeding via a thermodynamically controlled aldol condensation... 

The Darzens synthesis of glycidic esters by condensation of carbonyl compounds with a-haloesters is an important and useful method" that has been extended in phosphorus chemistry. Unquestionably, the most general and perhaps most widely employed method for the synthesis of dialkyl 1,2-epoxyalkylphosphonates involves the reaction of dialkyl chloromethylphosphonates with carbonyl compounds. These synthetically useful phosphonates are readily obtained by standard alcoholysis of chloromethylphosphonic dichloride under anhydrous conditions. The latter is obtained in up to 67% yield from phosphorus trichloride and paraformaldehyde at 250°C. Several variations on the preparation of dialkyl 1,2-epoxyalkylphosphonates from dialkyl chloromethylphosphonates and different carbonyl partners have been reported. The conditions for generating the a-metallated dialkyl chloromethylphosphonates were found to be critical because of their notorious instability. 

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