STORK Enamine alkylation

STORK Enamine alkylation 369 STORK Cyanohydnn alkylation 370 STORK Radical cyeteation 371... 

Muller s group developed a one-pot three-step four-component process for the construction of dihydropyrindines and tetrahydroquino-lines [96]. Through a coupling-isomerization-Stork-enamine alkylation-cyclocondensation sequence of an electron poor (hetero)aryl halide, a... 

Among other methods for the preparation of alkylated ketones are (1) the Stork enamine reaction (12-18), (2) the acetoacetic ester synthesis (10-104), (3) alkylation of p-keto sulfones or sulfoxides (10-104), (4) acylation of CH3SOCH2 followed by reductive cleavage (10-119), (5) treatment of a-halo ketones with lithium dialkyl-copper reagents (10-94), and (6) treatment of a-halo ketones with trialkylboranes (10-109). 

When enamines are treated with alkyl halides, an alkylation occurs that is analogous to the first step of 12-14. Hydrolysis of the imine salt gives a ketone. Since the enamine is normally formed from a ketone (16-12), the net result is alkylation of the ketone at the a position. The method, known as the Stork enamine reaction is an alternative to the ketone alkylation considered at 10-105. The Stork method has the advantage that it generally leads almost exclusively to monoalkylation of the ketone, while 10-105, when applied to ketones, is difficult to stop with the introduction of just one alkyl group. Alkylation usually takes place on the less substituted side of the original ketone. The most commonly used amines are the cyclic amines piperidine, morpholine, and pyrrolidine. 

Stork Enamine Synthesis A reaction leading to the formation of an a-alkyl or a-carbonyl compound from an alkyl or aryl halide reacting with an enamine. 

Spiroannelation Boron trifluoride etherate, 43 Triphenyltin hydride, 335 Stork-enamine reaction (see Alkylation reactions)... 

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... 

Initiated by Stork and co-workers,47 the scope and stereochemistry of enamine alkylations have been well explored. In general, good stereoselectivities can be obtained using bulky directing groups, polar aprotic solvents, and low temperatures. 

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 ... 

Enamines like enolates are alkylated when treated with reactive alkylating agent, a-Substituted enamines can be converted into aldehydes and ketones by acid-catalyzed hydrolysis. Thus, in the three-step process, alkylation of aldehydes and ketones may be carried out via enamines (Stork enamine synthesis) (Scheme 3.19). 

Nitrogen has an unshared electron pair so an enamine could function as an enolate ion. Many people had had this idea before, but nobody had done anything synthetically useful with it. We were extremely lucky because the kind of reaction we tried, the monoalkylation of a ketone enamine with an alkyl halide, is actually poor with enamines with one exception, and, by chance, it was that exception that we tried first and it worked very well. The particular molecule was a so-called -tetralon. These ketones give 90% yield by the enamine alkylation process. This was in the mid-1950s and we published a general review in 1963 [Stork, G. Brizzolara, A. H. Landesman, H. K. Szmuszkovicz, J. Terrell, R. The enamine alkylation and acylation of carbonyl compounds. /. Am. Chem. Soc. 1963,... 

When the nitrogen of the substrate contains a chiral R group, both the Stork enamine synthesis and the enamine salt method can be used to perform enantiose-lective syntheses. The use of A-proline can generate a chiral enamine in situ, thus allowing alkylation to occur, giving alkylated product with good enantioselec-tivity,. The reaction has been done intramolecularly. ... 

Stork enamine synthesis Alkylation of enamines with alkyl halides to afford a-alkylated aldehydes or ketones. 444... 

Prior to the discoveries that lithium and other less electropositive metal cations were valuable counterions for enolate alkylations, the Stork enamine reaction was introduced to overcome problems such as loss of regioselectivity and polyalkylation that plagued attempts to alkylate sodium or potassium enolates of ketones or aldehydes.Methods of synthesis of enamines by reactions of ketones and aldehydes with secondary amines have been thoroughly reviewed.Enamine alkylations are usually conducted in methanol, dioxane or acetonitrile. Enamines are ambident nucleophiles and C- and V-alkylations are usually competitive. Subsequent hydrolysis of the C-alkylated product (an iminium salt) yields an... 

Stork enamine reaction The reaction of an enamine with an alkyl halide that results in the alkylation of the (P-carbon. Usually followed by hydrolysis of the resultant imine salt to give a carbonyl functionality at the a-carbon. 

Stork enamine reaction. Synthesis of a-al-kyl or a-acyl carbonyl compounds from enamines and alkyl or acyl halides. 

Alkylation with simple alkyl halides is generally a poor reaction with enamines. Alkylation often takes place on nitrogen instead of carbon, and Stork and others7 have developed the aza-enolates to remedy this deficiency. A primary amine, usually cyclohexylamine, combines with an aldehyde to form an imine 42. Treatment with LDA 43 gives the lithium derivative, the analogue of a lithium enolate, known as an azaenolate 44. These intermediates are alkylated reliably at carbon 45 with most primary, and even with secondary alkyl halides, to give the alkylated aldehyde 47 after hydrolysis of the imine 46. 

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