Hetero Michael Reaction

Soon thereafter, the Yamamoto group reported an extension of this work to the highly diastereo- and enantioselective synthesis of nitroso Diels-Alder-type bicycloketones using dienamines in the presence of the BINOL derivative 44 (Scheme 5.61) [115]. This reaction was thought to proceed through a sequential N-NA/ hetero-Michael reaction mechanism. Support for this mechanism was provided from an experiment employing bulkyl 4,4-diphenyl dienamine where the N-NA... 

Sharma and Degani have used 2-hydroxyethylammonium formate as a low cost alternative to imidazolium based ILs in hetero-Michael reactions. They have synthesized many Michael addition products containing C-N... 

The kinetic control approach to constructing the CD-spiroacetal segment envisaged a hetero-Michael cyclisation of the dihydropyrone 28 (derived from 26 by sequential oxidation to the P-diketone, PMB removal and cyclisation to provide the D-ring), where axial attack might be favoured (Scheme 7). In practice, treatment of 28 with DBU led to installation of the C-ring via hetero-Michael reaction, with a small preference (60 40) for formation of the desired spiroacetal 29 over 30. Despite the modest selectivity observed in this mode of spiroacetal formation, the endeavour highlighted an important new means for... 

For solid-phase synthesis of 26.4 (Figure 15.26), compound 26.1 was immobilized on the resin as for the previous example (loading 86%, 26.2). The free hydroxyl derivative obtained after the acetonide removal was subjected to crucial hetero-Michael reaction. The use of NaH as a base at room temperature provided the expected product 26.3. After cleavage from the support, the crude sample was purified giving product 26.4 (25% overall yield in four steps), which was further assigned by NMR. It was interesting to note that this unusual regio- and stereoselective hetero-Michael reaction worked in a similar manner as in solution synthesis. For comparison purposes, compound 26.5 was also synthesized in solution in a similar manner. 

Nagasawa, K., Georgieva, A., Takahashi, H. and Nakata, T. (2001) Acceleration of hetero-Michael reaction by symmetrical pentacyclic guanidines. Tetrahedron, 57, 8959-8964. 

The phospha-Michael reaction has been the last hetero-Michael reaction to be developed under iminium activation. In addition to the selectivity issues that have to be addressed, the identification of a suitable phosphorous nucleophile has been the most difficult task to overcome when developing the reaction because of the high tendency of phosphines toward oxidation in the presence of air. The first example was developed independently by Melchiorre and... 

In fact, the only example of a simple hetero-Michael reaction under PTC conditions which does not involve a cascade process consists of an intramolecular aza-Michael reaction of conveniently 2-substituted indole compounds incorporating an a,p-unsaturated ester moiety at the side chain (Scheme 5.35)." This methodology shows up as a very straightforward and efficient method for building up the l,2,3,4-tetrahydropyrazino[l,2-u]indole... 

Two examples of hetero-Michael reactions have been reported using these kinds of bis-cinchona alkaloid-based chiral Bronsted bases as catalysts. One of them refers to a sulfa-Michael reaction and the other is a case of an aza-Michael reaction. 

The other report regarding a base-catalyzed hetero-Michael reaction was a contribution from the group of Jorgensen regarding the conjugate addition of azide to nitroalkenes (Scheme 6.17). In this case, the authors carried out an intensive effort directed toward the identification of the best catalyst and reaction conditions which would provide high yields and enantioselectivities. However, while the reaction was found to proceed with a good efficiency level... 

Cascade Processes Initiated by Hetero-Michael Reactions... 

The mechanism was proposed to involve an enamine intermediate that could undergo a domino p-elimination, followed by a subsequent inter-molecular hetero-Michael reaction to access the p-anomer (Scheme 5.29). ... 

Organocatalytic Enantioselective Michael and Hetero-Michael Reactions Vicario, J.L. Badia, D. Carrillo, L. Synthesis 2007, 2065. 

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]. 

---