Halides, aryl reaction with enamines

Allylic amines are coupled to halides giving either allylic amines or enamines depending on the reaction condition. Reaction of steroidal dienyl triflate with Boc-diprotected allylamine affords allylamine. Use of AcOK as a base is crucial for the clean coupling[102]. The tert-allylic amine 123 reacts with an aryl halide to give the enamine 125 in DMF and allylic amine 124 in nonpolar solvents[103]. 

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. 

The monoarylated enamine can then be acylated to form a mixture of 2-acyl-2-arylcyclohexanone and 2-aryl-6-acylcyclohexanone. This was held to indicate that arylation affords two enamines, 62 and 63, which differ only in the position of the double bond. The reaction involving acyl halides could be explained under the assumption that in the more probable enamine structure (with conjugation through the free electron pair on nitrogen, the double bond, and the aromatic ring) it is the hydrogen atom on C(6) which is more acidic. 

The scope of this reaction appeared to be limited to dialkylamides and electron-neutral aryl halides. For example, nitro-, acyl-, methoxy-, and dimethylamino-substituted aryl halides gave poor yields upon palladium-catalyzed reaction with tributyltin diethylamide. Further, aryl bromides were the only aryl halides to give any reaction product. Vinyl bromides gave modest yields of enamines in some cases. Only unhindered dialkyl tin amides gave substantial amounts of amination product. The mechanism did not appear to involve radicals or benzyne intermediates. 

Besides Michael additions the mild reaction conditions of CIR are also compatible with cycloadditions. Since chalcones can also be considered as heterodienes, Diels-Alder reactions with inverse electron demand are suitable elementary steps that are applicable for heterocycle synthesis. Therefore, after CIR of electron-deficient (hetero)aryl halides 11 and (hetero)aryl propargyl alcohols 12, (hetero) cyclic and acyclic morpholino enamines 98 are added and, finally, after adding... 

The method is quite useful for particularly active alkyl hahdes, such as allylic, benzyhc, and propargyhc halides, and for a-halo ethers and esters. Other primary and secondary halides can show sluggish reactivity. The react of enamines with benzotriazole derivatives has been reported. Tertiary hahdes do not give the reaction at all since, with respect to the halide, this is nucleophilic substitution and ehmination predominates. The reaction can also be applied to activated aryl halides (e.g., 2,4-dinitrochlorobenzene see Chapter 13), to epoxides, and to activated alkenes, such as acrylonitrile. The latter is a Michael-type reaction (15-24) with respect to the alkene. 

The initial success of the inverse electron demand [4 + 2]cycloaddition reaction of electron deficient, 1,2,4-triazine (61) with a-aryl enamine (60) to formulate the 4-arylpyridine forms the basis of a complementary approach to the CDE ring system of lavendamycin. In this strategy the oxidative insertion of aryl halide bond to provide the p-carboline derivative in the presence of palladium (0) was the notable feature. In a recently published article by Boger, a total synthesis of lavendamycin starting from the precursor 63 has been presented. The utility of... 

Various cyclic compounds can be prepared by the reaction of ketones with bifunctional aryl halides. The jS-naphthol derivative 52 was obtained by a-arylation of dibenzyl ketone (14) with o-bromobenzaldehyde derivative 51, followed by aldol condensation [38], Also the indole derivative 54 was synthesized by the reaction of cyclohexanone with 2-iodoaniline (53). Formation of 54 may be explained by enamine formation at first, followed by intramolecular Mizoroki-Heck reaction, rather than via a-arylation [39],... 

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