Heteroatom nucleophiles conjugate addition

Conjugate Addition of Heteroatom Nucleophiles and Subsequent Nef Reaction... 

The chemical behavior of heteroatom-substituted vinylcarbene complexes is similar to that of a,(3-unsaturated carbonyl compounds (Figure 2.17) [206]. It is possible to perform Michael additions [217,230], 1,4-addition of cuprates [151], additions of nucleophilic radicals [231], 1,3-dipolar cycloadditions [232,233], inter-[234-241] or intramolecular [220,242] Diels-Alder reactions, as well as Simmons-Smith- [243], sulfur ylide- [244] or diazomethane-mediated [151] cyclopropanati-ons of the vinylcarbene C-C double bond. The treatment of arylcarbene complexes with organolithium reagents ean lead via conjugate addition to substituted 1,4-cyclohexadien-6-ylidene complexes [245]. 

The conjugate addition of heteronucleophiles to activated alkenes has been used very often in organic synthesis to prepare compounds with heteroatoms [3 to various activating functional groups, e.g. ketones, esters, nitriles, sulfones, sulfoxides and nitro groups. As in the Michael reaction, a catalytic amount of a weak base is usually used in these reactions (with amines as nucleophiles, no additional base is added). 

The nucleophilic reagent will depend on the heteroatom. If X=0 or S, base will probably be necessary, but if X=N, the amine itself should be nucleophilic enough to do conjugate addition. An example would be the amino ester 13. Numbering the carbon atoms 13a reveals the 1,3-relationship and C-N disconnection gives the secondary amine 14 and ethyl acrylate as reagents. 

L. Miginiac, Nucleophilic Additions to Conjugated Carbon-Heteroatom Multiple Bonds O, S, N, in Handbook of Grignard Reagents (G. S. Silverman, P. E. Rakita, Eds.), Marcel Dekker Inc., New York, 1996, 391-396... 

On the other hand, protecting groups can be used to thwart heteroatom-assisted delivery. Reaction of the a,f -unsaturated sulfone 51.1 with trimethylsilylethynyl-lithium resulted in intramolecular delivery of the nucleophile to afford adduct 51.2 with a dr = 100 1 [Scheme 1.51].88 When the hydroxy group was protected as its trivnethylsilyl ether, conjugate addition took place from the opposite face to give the diastereoisomeric adduct 51.4, again with a dr = 100 l. 

Nucleophilic Addition to Conjugated Carbon-Heteroatom Multiple Bonds O, S, N... 

This commoner type of reaction involves the attack of carbon or heteroatom nucleophiles onto carbonyl compounds, by direct or conjugate addition, and onto imines. Because we have just dealt with boranes we shall start with the reaction of allylic boron compounds with such electrophiles. You might strictly not call this nucleophilic attack. 

The term Michael addition has been used to describe 1,4- (conjugate) additions of a variety of nucleophiles including organometallics, heteroatom nucleophiles such as sulfides and amines, enolates, and allylic organometals to so-called Michael acceptors such as a,p-unsaturated aldehydes, ketones, esters, nitriles, sulfoxides, and nitro compounds. Here, the term is restricted to the classical Michael reaction, which employs resonance-stabilized anions such as enolates and azaenolates, but a few examples of enamines are also included because of the close mechanistic similarities. 

---