Copper catalysis halogenation

Sulfur dioxide (see above) as well as S02, SO , and SOj have been used as building blocks in three-component sulfone syntheses. It has long been known that aromatic sulfinic acids are easily available from diazonium salts and sulfur dioxide under copper catalysis . Mechanistically, aryl radicals as reactive intermediates add to sulfur dioxide generating arenesulfonyl radicals, which either take up an electron (or hydrogen) yielding a sulfinic acid or add to an olefinic double bond yielding final y -halogenated alkyl aryl sulfones (equation 78). 

The metal-catalyzed copolymerization from carbon-halogen bonds in the main chain can be employed widely for graft polymer synthesis. A combination of nitroxide-mediated and copper-catalyzed living radical polymerizations, for example, gives graft copolymers G-6, where the main chain is prepared by the former.432 The chlorobenzyl unit in the copolymer is not active during the polymerization but, upon copper catalysis, it can initiate living radical polymerizations of styrene and methacrylates. 

Some halogen sources, such as LiCl, NCS, and NIS, also couple with aromatic C-H bonds to form the corresponding C-halogen bonds under appropriate copper catalysis [7, 74-78]. Some representative examples are illustrated in Eqs. (43) to (45). 

Transition-Metal Catalyzed Cyclizations. o-Halogenated anilines and anilides can serve as indole precursors in a group of reactions which are typically cataly2ed by transition metals. Several catalysts have been developed which convert o-haloanilines or anilides to indoles by reaction with acetylenes. An early procedure involved coupling to a copper acetyUde with o-iodoaniline. A more versatile procedure involves palladium catalysis of the reaction of an o-bromo- or o-trifluoromethylsulfonyloxyanihde with a triaLkylstaimylalkyne. The reaction is conducted in two stages, first with a Pd(0) and then a Pd(II) catalyst (29). 

Classical catalysis of the addition by a redox system utilizes iron or copper salts. The usual catalyst is copper(I) chloride which is slowly oxidized by moist air to yield a green mixture of copper(I) and copper(II) salts. The example of the addition of 1,2-dibromo-l-chloro-l,2,2-trifluoroethane to oct-l-eiie to give 5 shows selective carbon-halogen homolytic cleavage." " ... 

The transformation of aryl diazonium salts by aryl iodides does not require catalysis by copper or its salts (see Sections 1.7.2.5 and 1.7.3.5). A drawback is unwanted reduction with removal of functionality (equation 34). Diazo ketones are reduced to ketones with HI and do not give halogenated products (Scheme 29). O ... 

Intramolecular displacement of an orf/to-halogen can be achieved at high temperature or with copper(I)-catalysis. " Palladium-catalysed aminations of halide can be used to form either the N-C-2 or N-C-7a links, or both, for example in the double displacement shown below. ... 

In contrast, Cu(I) catalysis makes possible the efficient synthesis of 3,5-disubsti-tuted isoxazoles 57 from aromatic or aliphatic aldehydes and alkynes. Stable nitrile oxides can be isolated and subsequently submitted to the reaction [21] in isolated form and submitted to the reaction in one-pot, three-step process [131]. Here, nitrile oxide intermediates 56 are generated in situ via the corresponding aldoxime and halogenation/deprotonation by Chloramine-T [132]. Capture of the intermediate nitrile oxide by copper(I) acetylides occurs presumably before dimerization. In this case, the Cu catalyst was obtained from copper metal and copper(II) sulfate, and the products were isolated by simple filtration or aqueous work-up. Trace amounts of toluenesulfonamide and unreacted acetylene are easily removed by recrystallization or by passing the product through a short plug of silica gel. 

The metallacycles can also be used for carbon-carbon bond-forming reactions (Scheme 5.67). Transmet-allation with cuprates, or the use of catalysis by copper(I) salts allows reaction with a variety of electrophiles. With an acid chloride, reaction occurs at one of the carbon-zirconium bonds of the metallacycle 5.234. This leaves the second carbon-zirconium bond of the acylated product 5.235 available for further chemistry by, for instance, halogenation, or back attack onto the ketone. More elaborate multiple component couplings can also be achieved (Scheme 5.68). ... 

Copper Cyclization via aminohalogenation of (195), affording pyrrolidine derivatives (196) at <93% ee, has been reported to proceed upon catalysis with [(7 ,7 )-Ph-box]Cu(OTf)2 in the presence of Pr X (X = I, Br, Cl) as the source of the halogen atom and Mn02. The reaction is believed to proceed via iyn-aminocupration, followed by atom transfer, to form the C-X bond. ... 

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