Vinyl halides reaction scope

Free-radical-mediated four-component coupling reactions are rare. However, when an allyltin-mediated radical carbonylation is conducted in the presence of electron-deficient alkenes, four-component coupling reactions take place efficiently to give good yields of p-functionalized <5,fi-unsaturated ketones [40]. The wide scope of this four-component coupling reaction is noteworthy Primary, secondary, and tertiary alkyl bromides and iodides can be used as well as aromatic and vinylic halides. A variety of electron-deficient alkenes, such as methyl vinyl ketone, ethyl acrylate, acrolein, acrylonitrile, and vinyl sulfone, can be used as the acyl radical trap (Scheme 6.23). Fluorous allyltin compounds can also be used in four-component coupling reactions [41]. 

Vinyl halides represent yet another important class of intermediates in the conversion of ketones to alkenes. The most widely applied conditions for the conversion of ketones into vinyl halides are those developed by Barton et a/. ° for the conversion of 3p-acetoxyandrost-5-ene-17-one into 3P-hydroxyandrosta-5,16-diene (Scheme 44). These conditions of vinyl halide formation and subsequent reduction have been useful in a number of steroid systems for the introduction of a A -carbon-carbon double bond and have been shown to be compatible with such functional groups as alcohols, isolated double bonds and acetals. The scope of vinyl iodide formation from hydrazones has been studied by Pross and Stemhell, and recently the original reaction conditions were improved by using sterically hindered guanidine bases rather than triethylamine. Haloalkenes have also been prepared from the corresponding ketones by treatment with iodoform and chromium chloride or with phosphorous penta-halides. ... 

In the presence of ethanol, butanolides 149 or 150 undergo mild cleavage with tri-methylsilyl iodide to form the iodohydrin 159 in good yield. Cyclization of 159 to epoxide 160 under basic conditions (e.g., sodium carbonate) leads to isomerization within 5 min, but use of silver oxide affords 160 with no racemization. Opening the epoxide with cuprates furnishes j -hydroxyesters 161 with >99% ee (Scheme 21) [57]. The scope of this reaction can be extended to include cuprates derived from substituted vinyl halides. 

D. SCOPE OF THE REACTION D.i. Vinyl Halides and Related Compounds... 

The original cross-coupling reactions of aryl and vinyl halides with boronic acid coupling partners have been extensively developed since their inception. Over the past few years several interesting adaptions have expanded the scope of the original coupling protocol, below are just a few recent examples of systems that have harnessed the Suzuki-Miyaura protocol to access enantio-enriched coupling products. 

Having screened many different conditions for the palladium-catalysed cyanation of P-bromostyrene (148), the optimised conditions were apphed to a number of other vinyl halides in order to explore the scope of the reaction. The results are outlined in Table 7.7. 

The optimised reaction conditions, namely one-portion addition of 145 (1.1 equivalents), Pd2(dba)3 (5 mol%), DPPP (15 mol%), Na2C03 (1.1 equivalents), Et20 DMAc 2 l, 100 °C, were then applied to a number of vinyl halides in order to investigate the substrate scope. 

In his initial review on the scope of the reaction, Heck reported the use of a variety of relatively simple aryl, heteroaryl and vinyl halides. For example, exposure of bromopyridine 48 to alcohol 49 gave ketone 51 in good yield, following tautomerization of the initial Heck adduct 50. 

In 1982, JnUa s group showed that vinyl snUones react with Grignard reagents in the presence of iron salts to afford moderate yields of conpling product (Scheme 25). The reaction is stereoselective but its scope is limited. Thus, with secondary alkylmagnesium halides, only the reduction product is formed. 

Members of the she same compound class, arylethenylpurines, can also be prepared in a two step sequence. The cross-coupling of a halopurine with vinyl-tributylstannane leads to the formation of a vinylpurine, which in turn can undergo palladium catalyzed Heck reaction with a series of aryl halides (8.20.),28 The two step procedure is of particular interest, since the alternate approach, the Heck reaction of halopurines and arylethenes is of very limited scope. 

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. 

The traditional scope for this reaction involved coupling alkenyl or aryl iodides or bromides with aryl, alkenyl, or alkynylzinc halides. However, recent modifications have allowed the scope to be extended to include additional electrophiles see Electrophile) such as aryl and vinyl chlorides, sulfonate esters, aryl ethers, and substrates with... 

The original procedure involved the coupling of aryl bromides with secondary amines. However, since then the scope has been expanded to include substrates such as aryl iodides, chlorides, fluorides, triflates, tosylates, nonaflates, iodonium salts, and even boronic acids. While the reaction has not been extensively utilized with vinyl or alkynyl substrates, it can be performed with various heteroaryl halides. Similarly, numerous types of nitrogen-containing coupling partners, including primary amines, imines, various azoles, lactams, and simple amides, can now be used in this reaction. 

By extension to cross-coupling with vinyl and aryl triflates, the scope of the Stille reaction has been expanded greatly. Almost all functional groups are tolerated without the need for protection. The reactivity order of organic halides is I>Br>OTf>>Cl, but the order between Br and OTf can be reversed by addition of LiCl. By addition of LiCl (2 or 3 equiv) to provide a more reactive Pd-intermediate (vinyl-PdCIl versus vinyl-PdOTfL ) [25] and/or stable tin by-product (RjSnCl versus R3SnOTf), the reaction proceeds smoothly at ambient temperature. 

Blaser and Spencer used aroyl halides in place of aryl halides, with aroyl chlorides being of specific interest as ubiquitous, relatively cheap compounds ( Blaser reaction ) [24], This latter reaction is normally conducted in aromatic solvents phosphines are not used here as catalyst ligands since they fully inhibit the reaction. In the same way, benzoic acid anhydrides can be used as the aryl source in combination with PdCl2 and catalytic amounts of NaBr [79]. In this reaction, one of the arenes is used in the coupling reaction by elimination of CO, whereas the other benzoate serves as the base. The benzoic acid thus formed can easily be recycled into the anhydride. The use of aryl and vinyl triflates according to Cacchi [25] and Stille [26] extends the scope of the Heck coupling to carbonyl compounds phenol derivatives act via triflate functionalization as synthetic equivalents of the aryl halides. The arylation of cyclic alkenes [27], electron-rich vinyl ethers [28], and allylic alcohols [29] is accessible through Heck reactions. Allylic alcohols yield C-C-saturated carbonyl compounds (aldehydes) for mechanistic reasons (y9-H elimination), as exemplified in eq. (6). 

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