Unsaturated halides, synthesis

Significant synthetic applications of the nickel-salen catalysts are the formation of cycloalkanes by reduction of <>, -a-dihaloalkanes255,256 and unsaturated halides,257,258 the conversion of benzal chloride (C6H5CHC12) into a variety of dimeric products 259 the synthesis of 1,4-butanediol from 2-bromo- and 2-iodoethanol260 or the reduction of acylhalides to aldehydes261 and carboxylic acids.262... 

Carbohydrates.—The acid (87), an intermediate in the synthesis of oxaprostaglandin derivatives from D-ribofuranose sugars,84 is obtained from the aldehyde (88) and the sodium salt of (79). The condensation of 2,5-anhydro-D-allose derivatives with (89) gave the expected products (90).85 Similarly, 1,4-furanoses (91) afford (92).86 These unsaturated halides are useful intermediates for further modifications. 

An important reaction for synthesis of alkyl and dialkylethanoic acids (RX and R X are primary or secondary alkyl halides) dicarboxylic acids (RX = haloester) unsaturated acids (RX = an unsaturated halide, best for allylic halides) /3-keto acids (R = acyl chloride) (see Sections 18-8C and 18-8D). 

Based on this concept, Whitby and co-workers [110] reported an interesting palladium-catalyzed three-component synthesis of aromatic and heteroaromatic amidines 133 starting from unsaturated halides, amines, and t-butylisocyanide (Scheme 8.53). The catalytic cycle for this iminocarbonylative coupling reaction is analogous to the reactions incorporating carbon monoxide-isoelectronic with isocyanides-as the third partner [111]. 

The synthesis of a,ft--unsaturated halides has been realized via new dephosphorylation reactions of ,/l-clhylcnic and acetylenic phosphonic acid monoesters with (biscollidine)iodine(I) or (biscollidine)bromine(I) hexafluorophosphate (Scheme 6)23... 

Allylic chlorides, e.g., allyl, methallyl, and crotyl chlorides, are very reactive and are employed in the synthesis of unsaturaled ethers Besides the usual coupling of the sodium alcoholate and halide in alcohol solutions other conditions have been described, including reaction of the alcohol and unsaturated halide in the presence of potassium carbonate or sodium hydroxide in acetone or water. The combination of anhydrous potassium carbonate and acetone is widely used in the preparation of allyl aryl ethers the reaction is aided by the addition of finely powdered potassium iodide. ... 

An impressive alternate approach to the synthesis of furans beginning with alkynols was developed by Balme [160, 161] and subsequently applied in a total synthesis by Morimoto [162]. Balme discovered that a three-component coupling reaction between a propargylic alkoxide, a conjugate addition acceptor, and an unsaturated halide yields a variety of di- and trisubstituted furans. In one example, propargyl alcohol, diethyl ethoxymethylene malonate (193), and iodobenzene combine to furnish disubstituted furan 194 in... 

Heterocyclization of unsaturated S-containing compounds 86KGS291. Hydrazidoyl halides, synthesis of N,S-heterocycles from 83H(20)2239 ... 

The reaction products are the A -unprotected 2-stannylindoles 27, which are available for further manipulation through the Stille palladium-mediated coupling with aromatic or unsaturated halides or triflates. Since a very wide variety of functional groups are known to tolerate both radical and palladium-mediated reactions, this synthesis was an interesting innovation for the construction of 3- or... 

Coupling reactions of alkyl boranes, formed by hydroboration of alkenes, with unsaturated halides (or triflates or phosphonates) is possible, and this reaction is finding increasing use in synthesis. For example, coupling of the alkyl borane derived from hydroboration (with 9-borobicyclo[3.3.1]nonane, 9-BBN) of the alkene 200 with the alkenyl iodide 201 gave the substituted cyclopentene 202, used in a synthesis of prostaglandin Ei (1.205). This type of B-alkyl Suzuki coupling reaction is very useful for the synthesis of substituted alkenes. 

In the presence of palladium(O), organoboranes undergo coupling reactions with unsaturated halides (or inflates). This type of S-alkyl Suzuki reaction is a useful method for the synthesis of substituted alkenes (see Section 1.2.4, Scheme 1.205). For example, hydroboration of the alkene 22 and coupling with the alkenyl iodide 23 was used in a synthesis of the alkaloid halichlorine (5.36). 

The Stille reaction [41] is a general, selective, and multifaceted palladium-catalyzed reaction used to construct C—C bonds [42]. It proceeds via Pd-catalyzed coupling of organic electrophiles such as unsaturated halides, sulfonates, or triflates with functionalized organostannanes. Although it is nowadays considered a standard method in organic synthesis, recent modifications and variants of the Stille reaction have opened up a multitude of new and highly attractive synthetic possibilities. 

The Nozaki-Hiyama reactions are applied mainly to coupling reactions between aldehydes and unsaturated halides. For example, an intermediate of antibiotics rifamycin S synthesis is shown in eq. (13.54) [86,86a]. 

Higher dendralenes are accessible by double cross-coupling by including branched alkenes into the electrophile unit. For example, in their state-of-the-art synthesis of the parent dendralenes [23], Sherburn and coworkers prepared [6]dendralene (21) by the reaction between 2,3-dichloro-1,3-butadiene (20), and the Grignard reagent (9) prepared from chloroprene, another readily available unsaturated halide produced annually on a megaton scale (Scheme 1.4) [24]. The scope of this reaction in the synthesis of substituted higher dendralenes remains unexplored. 

The bromination of 4,5-j -dihydrocortisone acetate in buffered acetic acid does not proceed very cleanly (<70%) and, in an attempt to improve this step in the cortisone synthesis, Holysz ° investigated the use of dimethylformamide (DMF) as a solvent for bromination. Improved yields were obtained (although in retrospect the homogeneity and structural assignments of some products seem questionable.) It was also observed that the combination of certain metal halides, particularly lithium chloride and bromide in hot DMF was specially effective in dehydrobromination of 4-bromodihydrocortisone acetate. Other amide solvents such as dimethylacetamide (DMA) and A-formylpiperidine can be used in place of DMF. It became apparent later that this method of dehydrobromination is also prone to produce isomeric unsaturated ketones. When applied to 2,4-dibromo-3-ketones, a substantial amount of the A -isomer is formed. 

The behavior of such activated halides as alkylating agents under Friedel-Crafts conditions expands the scope of the synthesis. Aluminum chloride enhances the electrophilic character of the a,/S-unsaturated carbonyl system and permits the nucleophilic attachment of the aromatic addendum (Y ) to the carbon bearing the positive charge, with displacement of halogen [Eq. (5)]. Thus,... 

C ( propyl) N phenylmtrone to N phenylmaleimide, 46, 96 semicarbazide hydrochloride to ami noacetone hydiochlonde, 46,1 tetraphenylcyclopentadienone to diphenyl acetylene, 46, 44 Alcohols, synthesis of equatorial, 47, 19 Aldehydes, aromatic, synthesis of, 47, 1 /3-chloro a,0 unsaturated, from ke tones and dimethylformamide-phosphorus oxy chloride, 46, 20 from alky 1 halides, 47, 97 from oxidation of alcohols with dimethyl sulfoxide, dicyclohexyl carbodumide, and pyndimum tnfluoroacetate, 47, 27 Alkylation, of 2 carbomethoxycyclo pentanone with benzyl chloride 45,7... 

This method ensures the deposition of very reactive metal nanoparticles that require no activation steps before use. We shall review here the following examples of catalytic reactions that are of interest in line chemical synthesis (a) the hydrogenation of substituted arenes, (b) the selective hydrogenation of a, 3-unsaturated carbonyl compounds, (c) the arylation of alkenes with aryl halides (Heck reaction). The efficiency and selectivity of commercial catalysts and of differently prepared nanosized metal systems will be compared. 

Allylation of acyloyl-imidazoles and pyrazoles61 with allyl halide mediated by indium in aqueous media provides a facile regioselective synthesis of P, y-unsaturated ketones (Scheme 11.1), which has been applied to the synthesis of the monoterpene artemesia ketone. The same product can be obtained by indium-mediated allylation of acyl cyanide (Eq. 11.35).62 Samarium, gallium, and bismuth can be used as a mediator for the allylation of nitrones and hydrazones to give homoallylic hydroxylamine and hydrazides in aqueous media in the presence of Bu4NBr (Scheme 11.2).63 The reaction with gallium and bismuth can be increased dramatically under microwave activation. 

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