Alkenyl halides reactions with ketones

Terminal attack occurs with water, methyl iodide, and trimethylchlorosilane, whereas central attack was preferred with alkenyl halides, aldehydes, and ketones at low temperatures under kinetic control [Eq. (5)]. The Et3SiO group is readily removed from 6 by potassium fluoride in isopropanol to give the vinyl ether RCH2CH2COCH=CH2 (61). Some of these reactions have also been used in elegant syntheses of terpenes (99-102). 

Aldehydes may be converted to ( )-alkenyl halides by the reaction of CrCh with a haloform in THF. The highest overall yields for the conversion were with iodoform, but somewhat higher (E) (Z) ratios were observed with bromoform or chloroform. Other low-valent metals, such as tin, zinc, manganese and vanadium, were ineffective. As the examples in Table 19 indicate, the reaction is selective for the ( )-isomer, except in the case of an a,3-unsaturated aldehyde. In addition, the reaction with ketones is sufficiently slow for chemoselectivity to be observed for mixed substrates. 

Tin enolates of ketones can be generated by the reaction of the enol acetate 733 with tributyltin methoxide[60i] and they react with alkenyl halides via transmetallation to give 734. This reaction offers a useful method for the introduction of an aryl or alkenyl group at the o-carbon of ketones[602]. Tin enolates are also generated by the reaction of siiyl enol ethers with tributyltin fluoride and used for coupling with halides[603]. 

E-Alkenyl halides.1 Iodoform in combination with CrCl2 reacts with an aldehyde at 0° to form an (E)-alkenyl iodide in 75-90% yield. Replacement of CHI, by CHC13 and use of higher temperatures results in (E)-alkenyl chlorides. (E)-Alkenyl bromides can be obtained by use of CHBr3 and CrBr2. The E/Z ratio increases in the order I < Br < Cl, but the rate is in the order I > Br > Cl. Ketones undergo this reaction very slowly. 

Radical carbonylation reaction serves as a powerful tool for the synthesis of a range of carbonyl compounds. Radical carbonylation has been successfully applied to the synthesis of functionalized ketones from alkyl, aryl, and alkenyl halides.The radical aminocarbonylation reaction of alkynes and azaenynes provided efficient routes to 2-substituted acrylamides, lactams, and pyrrolidinones. For example, the aminocarbonylation of 4-pentyn-l-yl acetate 318 initiated by tributyltin hydride (Bu"3SnH) (30mol%) with AIBN (20mol%) gave acrylamide 325 in 92% yield (Scheme 43).A proposed mechanism starts from the addition of tributyltin radical 319 to alkyne... 

Aromatic carboxylic acids, a,/f-unsaturated carboxylic acids, their esters, amides, aldehydes and ketones, are prepared by the carbonylation of aryl halides and alkenyl halides. Pd, Rh, Fe, Ni and Co catalysts are used under different conditions. Among them, the Pd-catalysed carbonylations proceed conveniently under mild conditions in the presence of bases such as K2CO3 and Et3N. The extremely high toxicity of Ni(CO)4 almost prohibits the use of Ni catalysts in laboratories. The Pd-catalysed carbonylations are summarized in Scheme 3.9 [215], The reaction is explained by the oxidative addition of halides, and insertion of CO to form acylpalladium halides 440. Acids, esters, and amides are formed by the nucleophilic attack of water, alcohols and amines to 440. Transmetallation with hydrides and reductive elimination afford aldehydes 441. Ketones 442 are produced by transmetallation with alkylmetal reagents and reductive elimination. 

The Reformatsky reagents, i.e. zinc enolates of esters, undergo Ni catalysed cross-coupling with aryl halides.53 The Ni catalysed reaction of arylzincs with a-bromoacetates also permits a-arylation of esters54 (Scheme 11.13). However, a-alkenylation of enolates of ketones, aldehydes, and esters has been less satisfactory. Its further development is clearly desirable. Alternatively, a-alkenylation of a-iodoenones in conjunction with conjugate reduction discussed earlier should be considered. 

The insight that zinc ester enolates can be prepared prior to the addition of the electrophile has largely expanded the scope of the Reformatsky reaction.1-3 Substrates such as azomethines that quaternize in the presence of a-halo-esters do react without incident under these two-step conditions.23 The same holds true for acyl halides which readily decompose on exposure to zinc dust, but react properly with preformed zinc ester enolates in the presence of catalytic amounts of Pd(0) complexes.24 Alkylations of Reformatsky reagents are usually difficult to achieve and proceed only with the most reactive agents such as methyl iodide or benzyl halides.25 However, zinc ester enolates can be cross-coupled with aryl- and alkenyl halides or -triflates, respectively, in the presence of transition metal catalysts in a Negishi-type reaction.26 Table 14.2 compiles a few selected examples of Reformatsky reactions with electrophiles other than aldehydes or ketones.27... 

The palladium-catalyzed carbonylative coupling reaction of alkenyl halides with organoboron compounds in the presence of carbon monoxide is a valuable procedure for the synthesis of unsymmetrical ketones. " ... 

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