Asymmetric Hetero-Michael Additions

Besides the successful development of asymmetric syntheses with carbon-carbon bond formation, methods for carbon-heteroatom bond formation were also investigated intensively. In this context we developed several practical protocols for carbon-nitrogen, carbon-oxygen, and carbon-phosphorus bond formation. 

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In the eyes of a synthetic chemist this might be called a nitrogen-Michael-ad-dition to the a,P-unsaturated acid moiety as the 1,4-acceptor. Thus, it occurred to us that our favourite auxiliary, the hydrazine SAMP, might be used as a chiral ammonia equivalent in asymmetric hetero Michael additions to enoates. 

Other applications of oxazolines have also been discovered. Anomeric oxazolines have now emerged as useful glycosyl acceptors in the glycosylation of sugars. 2-Alkenyloxazolines have been found to undergo asymmetric Michael addition and hetero-Diels-Alder reactions. Further explorations in these areas of oxazoline chemistry will undoubtedly continue and the list of new applications will grow. 

In contrast to the extensive use of nitroolefins in asymmetric Michael additions [10], the vinylogous analogues, nitrodienes and nitroenynes, are less frequently utilized in the conjugate addition of enolate equivalents, despite the significant synthetic utility of the resulting products which possess carbonyl, nitro, and olefin functionalities. Likewise, studies on the hetero-Michael reaction with these acceptors have been very limited, possibly because of apprehension of the site-selectivity issue [11]. 

Cyclic (hetero- and carbocyclic) vinyl sulfoxides have been prepared by a tandem Michael addition/Homer olefination reaction of a-phosphorylvinyl sulfoxides and carbonyl compounds bearing a nucleophilic center. Using optically active a-phosphorylvinyl sulfoxides a series of enantiomeric cyclic vinyl sulfoxides in which the chiral sulfinyl group is bonded to a chromene, pyrrazolyne, quinoline or cyclopen-tene ring, has been obtained. The H-W-E reaction of aldehydes with sulfinimine-derived 3-oxo pyrrolidine phosphonates (228) represents a new method for the asymmetric synthesis of ring-functionalized cw-2,5-disubstituted 3-oxo pyrrolidines (229) (Scheme 90). ... 

In the presence of thiourea catalyst 122, the authors converted various (hetero) aromatic and aliphatic trons-P-nitroalkenes with dimethyl malonate to the desired (S)-configured Michael adducts 1-8. The reaction occurred at low 122-loading (2-5 mol%) in toluene at -20 to 20 °C and furnished very good yields (88-95%) and ee values (75-99%) for the respective products (Scheme 6.120). The dependency of the catalytic efficiency and selectivity on both the presence of the (thio) urea functionality and the relative stereochemistry at the key stereogenic centers C8/C9 suggested bifunctional catalysis, that is, a quinuclidine-moiety-assisted generation of the deprotonated malonate nucleophile and its asymmetric addition to the (thio)urea-bound nitroalkene Michael acceptor [279]. 

Hetero-Diels-Alder reactions of l-oxa-l,3-butadienes with vinyl ethers, which lead to 3,4-dihydro-2H-pyran derivatives, are synthetically equivalent to Michael type conjugate additions. Wada and coworkers presented the first examples of a catalytic asymmetric intermolecular hetero-Diels-Alder reaction by the use of ( )-2-oxo-l-phenylsulfonyl-3-alkenes 25 and vinyl ethers 26 (Table 3) [25]. 

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