Copper® chloride reaction scheme

Acylation reactions can also be greatly improved in this way, with t-alkyl- or sec-alkyl-manganese reagents reacting with acid chlorides in excellent yields [123]. The related addition-elimination to 3-ethoxy-2-cyclohexenone is also improved, resulting after acidic aqueous workup in 3-methyl-2-cyclohexenone [125]. The perilla-ketone 126 was prepared in an improved yield using copper(I) catalysis (Scheme 2.58) [129]. 

In a quest for a more environment-friendly process it has been found that reaction 8.4 can be catalyzed by Pd(II) complexes of various nitrogen-donor ligands (Scheme 8.1) under not too harsh conditions (100 °C, air) without the need of copper chlorides [10,11]. Of the investigated ligands, sulfonated batophenanthroline proved to be the best. Higher olefins, such as 1-hexene or cyclooctene were similarly transformed by this catalyst. Very importantly, there was no isomerization to internal olefins and 2-hexanone was formed with higher than 99 % selectivity. This outstanding selectivity is probably due to the absence of acid and Cu-chlorides. 

Different primary, secondary aryl or heteroaryl manganese bromides 519 were prepared by reaction of activated manganese [prepared form manganese dichloride, lithium and a catalytic amount (15%) of 2-phenylpyridine as electron carrier, in THF] with the corresponding brominated compounds 516. These intermediates react with different electrophiles in THF at 0°C with or without copper chloride, to yield the corresponding products 20 (Scheme 144). ... 

Addition of alkynes to imines generated in situ can lead to quinolines when the reaction is conducted in the presence of copper chloride [126] or montmorillonite clay doped with copper bromide [127]. In the latter case, the reaction was performed under solvent-free conditions and was microwave assisted (Scheme 8.57). 

A new copper-catalyzed reaction involving imines, acid chlorides, and alkynes has been applied to the synthesis of propargyl amides 160 in a single operation by Arndtsen and co-workers. The same method allows the synthesis of N-carbamate-protected propargylamines [149]. a-Substituted amides 161 may also be prepared under palladium catalysis by substituting alkynes for vinyltin (Scheme 8.71) [150]. 

Reaction of compounds 985 and 98R with copper chloride in aqueous THF139 led to the first synthesis of o.p. 965 and 96R oxisuran, respectively (Scheme 32). 

Ionic and free-radical reactions leading to the formation of ketonic products can occur simultaneously in the copper-catalyzed reaction of a Grignard reagent with a sterically hindered acid halide. These reactions have been studied by Dubois and co-workers 102-108, 194). Contrary to the report of Percival et al. 229), ferric chloride inhibits the catalytic role of copper and does not favor the formation of ketones 106, 108). The scheme depicted in Fig. 4 is proposed 103) to account for the products of the reaction. Similar radical reactions were suggested by Khar-asch et al. 169) to explain the role of cobalt chloride in like reactions. 

CIDNP studies have proven to be a valuable tool in investigating the mechanisms of decarbonylation and disproportionation reactions in micelles27 29). Since the mechamisms involve the formation of triplet radical pairs, nuclear polarization of the protons near the radical centers occurs and results in the observation of emission or enhanced absorption in the NMR spectra of products of the radical pairs. For example, the photolysis of di-t-butyl ketone (11) in HDTCI yields both decarbonylation and disproportionation products (Scheme VII)27,29). The CIDNP spectra (Fig. 12) taken at various concentrations of copper chloride (free radical scavenger) illustrates that the intramicellar product is isobutylene (72), while 2,2,4,4-tetramethylbutane (13) and 2-methyl-propane (14) are the extramicellar products. 

Dipheny[amine (7) is prepared industrially either by heating aniline with aniline hydrochloride at 140 °C under pressure, or by heating aniline with phenol at 260 °C in the presence of zinc chloride. The most convenient laboratory synthesis uses the Ullmann reaction (Scheme 8.9) (see Chapter 10), in which acetanilide is refluxed with bromobenzene in the presence of potassium carbonate and copper powder in nitrobenzene solvent. Triphenylamine is similarly prepared from diphenylamine and iodobenzene. 

DIBAL-H/n-butyllithium, in cyclic and acyclic systems with iron pentacarbonyl, in cyclodecanes with lithium dihydrodimethoxyaluminate(III)/copper(I) iodide, and in cyclohexane and cyclopentane systems with NaH/sodium r-butylpentyl/Ni(OAc)2. ° The monoreduction of 1,3-diketones can be carried out under similar conditions, as illustrated by the reaction of a substituted cyclohexane-1,3-dione with oxalyl chloride to give the corresponding 1-chlorocyclohexenone, which was subsequently reduced to the enone with zinc-silver couple (Scheme 45). Kropp et al. have reported the photolytic reduction of vinyl iodides in acyclic systems however, when an a-hydrogen is present, formation of the diene product is a limiting side reaction (Scheme 46). For a more extensive discussion of vinyl halide reductions, see the preceding chapter in this volume. 

Another methodology applied to the monosubstitution of diols is the use of copper complexation of dianions. The dianion is first formed by reaction of a diol with two equivalents of NaH. The copper complex is then formed by addition of a copper salt. Reaction of the copper complex with various electrophiles (alkyl halides, acyl chlorides) then gives the selectively protected products. As with the phase-transfer technique, very little disubstitution is observed. However, as illustrated in Scheme 3.16, the regioselectivity is reversed (i.e., 4,6-diols give mainly 4-substitution and 2,3-diols give mainly 3-substitution). Using this technique, both alkylations (benzylation, allylation) and acylations (acetylation, benzoylation, pivaloylation) have been carried out. As usual, the degree of selectivity depends on reaction conditions and structural factors [44]. 

Most of the above mentioned derivatives have been reduced ° by tributyltin hydride to methyl-3-ediylcyclohexanones. These have been produced with a stereochemical control often superior to that observed from the copper chloride catalyzed addition of ethylmagnesium bromide in ether to the same ketones (Scheme 149, b Scheme 131, a). Reaction of the C-1 and C-3 adducts with copper chloride (1... 

Copper chloride catalysts are used to operate at lower temperature, and to improve selectivity. Their action mechanism can be explained by the formation of a complex with ethylene, which is then capable of being converted to ethylene dichloride. In these conditions, the usual reaction scheme is as follows ... 

Ketene dithioacetals are deprotonated with LDA-HMPA and complexed with copper(l) iodide (Scheme 36). This reagent reacts with allylic halides exclusively at the y-position with allylic rearrangement (5n20. The reaction of the lithium reagent with simple alkylating reagents gives mostly a-attack. Ketene dithioacetals can be converted to esters by aqueous mercury(II) chloride. 

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