Methyl 2- propenoate, Michael

An excellent method for the diastereoselective synthesis of substituted amino acids is based on optically active bislactim ethers of cyclodipeptides as Michael donors (Schollkopf method, see Section 1.5.2.4.2.2.4.). Thus, the lithium enolates of bislactim ethers, from amino acids add in a 1,4-fashion to various a,/i-unsaturated esters with high diastereofacial selectivity (syn/anti ratios > 99.3 0.7-99.5 0.5). For example, the enolate of the lactim ether derivative 6, prepared from (S)-valine and glycine, adds in a highly stereoselective manner to methyl ( )-3-phenyl-propenoate a cis/trans ratio of 99.6 0.4 and a syn/anti ratio of 91 9, with respect to the two new stereogenic centers, in the product 7 are found105, los. 

Using 3-substituted cyclohexanones the /rans-diastereoselective synthesis of decalones and octahydro-1 //-indenones may be achieved 164 169. This method has been applied, for instance, in the synthesis of 19-norsteroids. In a related Michael addition the lithium enolate of (R)-5-trimethylsilyl-2-cyclohexenone reacts with methyl 2-propenoate selectively tram to the trimethylsilyl substituent. Subsequent intramolecular ring closure provides a single enantiomer of the bicyclo[2.2.2]octane170 (see also Section 1.5.2.4.4.). 

Similar additions may be performed with the enamine 13. However, with 3-buten-2-one or methyl 2-propenoate Lewis acid catalysis is needed to activate the Michael acceptor chloro-trimethylsilane proved to be best suited for this purpose. A remarkable solvent effect is seen in these reactions. A change from THF to HMPA/toluene (1 1) results in a reversal of the absolute configuration of the product 14, presumably due to a ligand effect of HMPA235. 

Michael addition of methyl 3-mercaptopropanoate to methyl 3-methylbut-2-enoate and Dieckmann cyclization of the resulting diester yields 2,2-dimethyltetrahydrothiopyran-4-one 539 (Scheme 220) <2005HCA1922>. Similarly, diethyl thiodipropanoate, accessible from ethyl propenoate by treatment with NaSH in methanol, cyclizes to ethyl 4-oxotetrahydrothiopyran-3-carboxylate under basic conditions. The carbon skeleton has also been provided by 1,4-pentadienones <1995JOC1665> and H2S in ethanol has been used as an alternative source of the heteroatom (Scheme 221) <1999SL735>. 

In the Michael reaction, an enolate acts as a nucleophile and adds 1,4 to an a,P-unsaturated carbonyl compound (Section 22.12). 1,3-Dicarbonyl compounds firequently provide the enolate, called the Michael donor. Three a,p-unsaturated carbonyl compounds are commonly used as Michael acceptors 3-buten-2-one (methyl vinyl ketone), 2-propenal (acrolein), and methyl 2-propenoate (methyl acrylate). For example, dimethyl malonate reacts with 3-buten-2-one in a base-catalyzed reaction. 

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