Reactions Stork

Many of the reactions already discussed for the preparation of bis-oxygenated pregnanes can also be used for the synthesis of 17,20,21-tris-oxygenated pregnanes by proper choice of substrate. Thus, reaction of a 17-vinyl-17-hydroxy steroid or a A -21-hydroxypregnene with osmium tetroxide will give the 17,20,21-triol, and the Stork reaction can be applied to 17a-hydroxy-20-keto steroids. 

In general the Stork reaction gives moderate yields with simple alkyl halides better yields of alkylated product are obtained with more electrophilic reactants such like allylic, benzylic or propargylic halides or an a-halo ether, a-halo ester or a-halo ketone. An example is the reaction of 1-pyrrolidino-l-cyclohexene 6 with allyl bromide, followed by aqueous acidic workup, to yield 2-allylcyclohexanone ... 

Carbonyl Condensations with Enamines The Stork Reaction... 

Enamines behave in much 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 aqQ-unsaturated carbonyl acceptor in a Michael-like process. The initial product is then hydrolyzed by aqueous acid (Section 19.8) to yield a 1,5-dicarbonyi compound. The overall reaction is thus a three-step sequence of (11 enamine formation from a ketone, (2) Michael addition to an a,j3-unsaturated carbonyl compound, and (3) enamine hydrolysis back to a ketone. 

The net effect of the Stork reaction is the Michael addition of a ketone to an cn/3-unsaturated carbonyl compound. For example, cyclohexanone reacts with the. cyclic amine pyrrolidine to yield an enamine further reaction with an enone such as 3-buten-2-one yields a Michael adduct and aqueous hydrolysis completes the sequence to provide a 1,5-diketone (Figure 23.8). 

Figure 23.8 The Stork reaction between cyclohexanone and 3-buten-2-one. Cyclohexanone is first converted into an enamine, the enamine adds to the a -unsaturated ketone in a Michael reaction, and the conjugate addition product is hydrolyzed to yield a 1,5-diketone.

Carbonyl condensations with enamines (Stork reaction Section 23.11) i o... 

Stork reaction (Section 23.11) A carbonyl condensation between an enamine and an a,/3-unsaturated acceptor in a Michael-like reaction to yield a 1.5-dicarbonyl product. 

Iminium ions (2) would be expected to undergo hydrolysis quite readily, since there is a contributing form with a positive charge on the carbon. Indeed, they react with water at room temperature." Acid-catalyzed hydrolysis of enamines (the last step of the Stork reaction, 12-18) involves conversion to iminium ions " ... 

The Stork reaction between methylvinyl ketone and enamine (130) derived from (S)-proline derivatives (131) is of particular interest since chiral cyclohexenones can be obtained. These are useful in many natural product syntheses. Optical yields of 20-50% have been reported 147>. 

The first examples of a Michael-Stork enamine addition to allenyl esters and ketones R1CH=C=C(R2)COX (X = alkyl, alkoxyl) has been reported. Mechanistic investigation revealed that 2 equiv. of enamine are required for optimum yields. In the case of an allenyl methyl ketone, cyclopentyl enamine addition afforded 8-oxobicyclo[3.2.1]octane, providing evidence for the in situ formation of an enamine intermediate following the initial Michael-Stork reaction.187... 

Arylation of enamines234 represents an analogy of the Stork reaction.236 Reactive aryl halides usually cause C-arylation. Treatment of 2,4-dinitrochlorobenzene with 1 -pyrrolidino-1 -cyclohexene affords 2-(2,4-dinitrophenyl)cyclohexanone (64) in very good yield. As... 

The enamine alkylation procedure is sometimes called the Stork reaction, after its inventor, Gilbert Stork of Columbia University. The Stork reaction can alkylate or acylate the a position of a ketone, using a variety of reactive alkyl and acyl halides. Some halides that react well with enamines to give alkylated and acylated ketone derivatives are the following ... 

The diversity of possible synthetic applications of the Stork reaction is therefore immediately apparent. The course of the reaction is often critically dependent on the... 

The Stork reaction of methyl vinyl ketones and enamines (e.g. 74) is a complementary procedure to the Robinson annulation method (equation 14)49. With this procedure, products from attack of the most reactive less substituted form of the enamine to the... 

A ketone that has been converted to an enamine can act as a Michael donor in a reaction known as the Stork reaction. 

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