Stereoselectivity Darzens synthesis

A very interesting organocatalyzed one-pot Michael addition/aldol condensation/Darzens condensation has been reported for the asymmetric synthesis of epoxy-ketones <06JA5475>. An initial asymmetric Michael condensation between 16 and 17 is catalyzed by proline derivative 18. Intermediate 19 then undergoes an aldol condensation followed by a stereoselective Darzens condensation to provide epoxy-ketone 20 in moderate yield and with surprisingly good enantiomeric excess. 

Darzens reaction can be used to efficiently complete the stereoselective synthesis of a"-substituted epoxy ketones. As an example, Enders and Hett reported a technique for the asymmetric synthesis of a"-silylated a,P-epoxy ketones. Thus, optically active a -silyl a-bromoketone 38 was treated with LDA followed by the addition of benzaldehyde to give a"-silyl epoxyketone 40 in 66% yield with good... 

The synthesis of vinylaziridines through reactions between allylic carbenoid reagents and imines (i.e., Darzen-type reactions) was first reported by Mauze in 1980 [13]. Treatment of aldimines or ketimines 16 with gem-chloro(methyl)allyllithium (17) afforded N-substituted vinylaziridines 18 (Scheme 2.6). Similarly, 2,3-trans-N-diphenylphosphinyl-2-vinylaziridines 21 were prepared with good stereoselectivities (trans cis= 10 1 Scheme 2.7) by treatment of a-bromoallyllithium (20) with N-diphenylphosphinyl aldimines 19 in the presence of zinc chloride [14]. 

The use of quininium salts can add to the high stereoselectivity (65-80% ee) that can be achieved under phase-transfer catalytic conditions in the synthesis of oxiranes by the Darzens reaction (Section 12.1) from chloromethylsulphones and aromatic aldehydes [6],... 

Shibata, I., Yamasaki, H., Baba, A., Matsuda, H. Stereoselective synthesis of a,P-epoxy ketones by the Darzen s reaction with methyl N-ethyl-N-(tributylstannyl)carbamate. Syrr/etf 1990, 490-492. 

In addition to alkenes, imines are tremendously popular aziridine precursors via an aza-Darzens approach. For example, a stereoselective synthesis of C-sulfonylated aziridines was reported via an aza-Darzens approach employing bromomethyl phenyl sulfbne, NaHMDS, and a series of N-tert-butanesulfinyl imines (14MI969). Likewise as shown below, chiral tert-butane- and mesitylsulfinimines were subjected to an aza-Darzens reaction with substituted 2-bromoesters to provide a host of aziridines in good yield with excellent stereocontrol (14OL6920). In turn, these aziridines could be subsequently converted to chiral A/-H aziridines in a total of three steps starting with a wide range of commercially available aldehydes. 

Stereoselective synthesis of 2,3-di- and 2,2, 3-tri-substituted aziridines in good yields and excellent diastereo-selectivities (>98% de) is achieved through aza-Darzens... 

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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