Copper catalysts benzylic amination

The reactivities of alkyl halides are in the sequence RI > RBr > RCl and MeX > EtX > PrX. Benzyl hahde reactions with tin do not require catalysts (equation 2). For less reactive halides, the catalysts and promoters employed include metals (sodium, magnesium, zinc, or copper), Lewis bases (amines, triorganophosphines and -stibines, alcohols, or ethers), iodides, and onium salts (R4MX). The use of tin-sodimn alloys can result in tri- or tetraorganotin products. Electrochemical synthesis has also been reported, e.g. the formation of R2SnX2 from the oxidation of anodic tin by RX in benzene solution and the formation of ILtSn from RI (R = Me or NCCH2CH2) and cathodic tin. 

Copper catalysts offer several advantages over protic acids in hydrolysis reactions. They are mild, non-acidic, and can control regioselectivity by chelation. An example of the latter is shown by the hydrolysis of the bis benzyl ester 13. Complexation with the amine activates the adjacent carboxylate selectively to afford 14 as the sole hydrolysis product (Sch. 4) [11]. 

Amination. Copper(II) triflate is a good catalyst for amination of alkenes (using chloramine-T to give aziridines) and at benzylic and allylic positions (using t-BuOOCONHTs). ... 

Studies reporting substituent effects on the palladium- and copper-catalysed Sonogashira coupling reaction between an aryl iodide and an alkyne the 5 2 allylic substitution reactions between benzyl amine and racemic allyl carbonates substituted with a j -X-Ph- group on C(l) in the presence of a Rh(15,15, 2/ ,2/ -tangphos)(COD)Bp4 catalyst the stereoselective 5 2 reactions between a-substituted linear 0-ketoesters and meta- and /Jura-substituted cinnamyl carbonates generating vicinal quaternary and tertiary stereocenters in the presence of an Ir-V-arylphosphoramidite catalyst, TBD, and LiOBu-t identity vinyl halide reactions the S N... 

This new disilver system was found to be more active in intramolecular amidation reactivity compared to the original [Ag2(t-Bu3tpy)2] catalyst, showing both increased yields and decreased temperature (from 82 to 50°C). More importantly, this system was able to catalyze the intermolecular amination reaction of both benzylic and inert aliphatic C—Hbonds.Asimilar copper system reported similar activity however, it was only able to aminate benzylic C—H bonds (Table I). In the silver case, it was found that substitutions on the 2 and 9 positions of the phenanthroline shut down the reactivity of the catalyst, suggesting the importance of keeping a disilver core structure. 

Although the most common method of preparing ylids involves proton abstraction from a quaternary ammonium salt, another method which has been used in ylid synthesis involves the reaction of carbenes with tertiary amines. Bamford and Stevens 8> reported that the reaction of diazofluorene, 47, with benzyldimethylamine at 150 °C in the absence of solvent gives 9-benzyl-9-dimethylaminofluorene in 30% yield (48). Later, Wittig and Schlosser 177> noted that if copper II was used as a catalyst, the reaction could be carried out at a lower temperature in THF to give a 21% yield of the same product. 

When CoCl2 is used as a co-catalyst, the CDC reactions of allylic sp3 C—H and 1,3-dicarbonyl compounds smoothly afford Trost—Tsuji-type products, which are traditionally prepared from allyl halides or acetates (Equation 11.4) [14]. Moreover, when NBS is used instead of TBHP, selective C—H cleavage of tertiary aliphatic amines is possible (Equation 11.5) [15]. For benzylic C—H bonds, direct C—C bond formation can be achieved using copper perchlorate (Equation 11.6) [16]. 

Treatment of benzyl dimethyl amine with the diazo carbonyl compoimd 19 in the presence of a catalytic amount of copper afforded a-trifluoromethyl phenylalanine 20 via a [1,2]-Stevens rearrangement. The reaction time was reduced significantly to 1-2 h when dirhodium tetraacetate was used as catalyst. 

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