Carbonyl Condensations with Enamines The Stork Reaction

I Carbonyl Condensations with Enamines The Stork Reaction 

In addition to enolate ions, other kinds of carbon nucleophiles also add to a, 8-unsaturated acceptors in Michael-like reactions. Among the most important such nucleophiles, particularly in biological chemistry, are enamines, 

As the following resonance structures indicate, enamines are electronically similar to enolate ions. Overlap of the nitrogen lone-pair orbital with the double-bond p orbitals leads to an increase in electron density on the a carbon atom, making that carbon nucleophilic. An electrostatic potential map of A/. Al-dimethylaminoethylene shows this shift of electron density (red) toward the a position. 

Enamines behave in mnch the same way as enolate ions and enter into many of the same kinds of reactions. In the Stork reaction, for example, an enamine adds to an a,/3-unsatnrated carhonyl acceptor in a Michael-like process. The initial product is then hydrolyzed hy aqueous acid (Section 14.7) to yield a 1,5-dicarbonyl compound. The overall reaction is thus a three-step sequence of (1) enamine formation from a ketone, (2) Michael addition to an a,j8-unsaturated carbonyl compound, and (3) enamine hydrolysis back to a ketone. 

CHAPTER 17 CARBONYL ALPHA-SUBSTITUTION AND CONDENSATION REACTIONS 

Gilbert Stork (1921-) was born on New Year s eve in Brussels, Belgium. He received his secondary education in France, his undergraduate degree at the University of Florida, and his Ph.D. with Samuel McElvain at the University of Wisconsin in 1945. Following a period on the faculty at Harvard University, he has been professor of chemistry at Columbia University since 1953. A world leader in the development of organic synthesis. Stork has devised many useful new synthetic procedures and has accomplished the laboratory synthesis of many complex molecules. 

Enamines behave in much the same wav as enolate ion.s and enter into 

The enamine-Michael reaction has two advantages over the enolate-ion-Michael reaction that makes it particularly useful in biological pathways. First, an enamine is neutral, easily prepared, and easily handled, while an enolate ion is charged, sometimes difficult to prepare, and must be handled with care. Second, an enamine from a monoketone can be used in the Michael addition, whereas enolate ions only from j8-dicarbonyl compounds can be used. 

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CARBONYL CONDENSATIONS WITH ENAMINES THE STORK REACTION... 

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