Enamines halogenation

The most extensive use of enamine halogenations has, hctwever, been in the attachment of fluorine to the steroid skeleton (499-503). The formation of a ]6-fluoro-17-ketosteroid by the reaction of perchlorofluoride with a 17-enamide has also been reported (504). 

Aryl halides with a halogen activated by electron-withdrawing groups react with pyrrolidine enamines of cyclic ketones (68) to give the a-arylated ketones after hydrolysis. The enamine (28) with 2,4-dinitrochlorobenzene gave an excellent yield of 2(2,4-dinitrophenyl)cyclohexanone (88). The... 

The halogenation of enamines is formally analogous to protonation with salt formation. Thus the steroidal enamine (164) undergoes bromination (7/5) to give the j8-bromo iminium bromide (165), which is readily hydrolyzed to the /5-bromo aldehyde (166). 

Nitrilimines can be produced by treating halogenated hydrazones with a base such as triethylamine. These nitrilimines undergo 1,3 cycloaddition with enamines to form pyrazoles (181-183). This is shown by the reaction of the pyrrolidine enamine of cyclohexanone with diphenyinitrilimine to... 

Grignard reagents do not add directly to enamines, but their reactions with the corresponding imonium salts readily furnish tertiary amines (225,526). The reductive removal of halogen has been observed in the addition of Grignard reagents to a-bromoimonium salts (527). 

Kim and coworkers introduced silyl radical mediated addition of alkyl radical to silyloxy enamine 76. The silyloxy enamine moiety is readily accessible from a variety of functionalities. The mechanistic concept is illustrated in the Scheme 12 and involves the addition of R radical to 76 to give the radical adduct 77 and the subsequent homolytic cleavage of N-O bond to yield the desired product 78 and a silyloxy radical 79. The latter undergoes 1,2-phenyl migration to give the silyl radical 80 that abstracts halogen from the alkyl halide to regenerate the R radical. 

Such functional groups as OR, OH, NH2, SMe, halogen, and COOR may be present in the molecule," but not groups that are reducible by borane. Hydroboration of enamines with 9-BBN provides an indirect method for reducing an aldehyde or ketone to an alkene, for example. 

Instead of direct halogenation of ketones, reactions with more reactive derivatives such as silyl enol ethers and enamines have advantages in certain cases. 

Reactions of Halogenation and Nitrosation Nitrones with protons in the a-alkyl group can occur in tautomeric nitrone-hydroxylamine equilibrium (Scheme 2.117) similar to keto-enol and imine-enamine tautomerisms. 

Another example of halogen-atom transfer by CPO is the vinylic halogenation of cyclic enaminones and enamines (Eq. 10, Table 11). 

Enantioselective -Functionalization of Aldehydes and Ketones The direct and enantiosective functionalization of enolates or enolate equivalents with carbon-, nitrogen-, oxygen-, sulfur- or halogen-centered electrophiles represents a powerful transformation of chemical synthesis and of fundamental importance to modem practitioners of asymmetric molecule constmction. Independent studies from List, J0rgensen, Cordova, Hayashi, and MacMiUan have demonstrated the power of enamine catalysis, developing catalytic enantioselective reactions such as... 

Type B enamine catalysts have been developed more recently. They include the diarylprolinol ethers (developed by the Hayashi and Jprgensen groups, e.g. 47 and its derivatives) [71-75] as well as the MacMillan imidazolidinone catalysts (e.g. 46) [76-78]. They excel in reactions where hydrogen bonding assistance is either not required or is not essential, such as a-halogenation reactions as well as some conjugate addition reactions (Scheme 12). 

A range of nitrogen, phosphorus, chalcogen (O, S, Se) and halogen electrophiles react with enamines, resulting in a net a-functionalization of the carbonyl compound. In the past five years, all of these reaction variants have been subjected to asymmetric enamine catalysis, with excellent results. 

Fig. 4 a-Halogenations with elemental chlorine Perhaps the next bold step in enamine catalysis... 

Direct /3-metalation of a tetrahydropyridine has not been achieved, but as with exocyclic enamine systems (Section V,A,2), halogen-metal exchange has been performed successfully. Thus, 2-aryl-3-bromo-l-methyltetrahydropyridines have been metalated with either n-BuLi or t-BuLi, in a procedure that starts with bromination of the parent system to give an a-bromoiminium salt, which can then be deprotonated to give the desired /3-bromoenamine (Scheme 147) [77JA8356 82BSF(2)297]. If the... 

Halogenation of enamines to give stable halo enamines [162]. 

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