Allylic with aniline nucleophiles

In addition to isolating complex 5, Markovic and Hartwig performed kinetic studies on the amination of methyl cinnamyl carbonate with aniline. The proposed mechanism involves reversible dissociation of product, reversible, endothermic oxidative addition of the allylic carbonate to form a 7i-allyliridium species, and irreversible nucleophilic attack on the 7i-allyliridium intermediate, as depicted in... 

A variety of rhodium complexes, including [Rh(CO)2Cl]2 and [Rh(COD)Cl]2 when used in combination with a variety of bisphosphine ligands, will catalyze the ring opening of vinyl epoxides in the presence of aniline nucleophiles [19, 20]. These reactions occur under very mild and neutral conditions (at room temperature or with mild heating) and are highly regio- and stereoselective. In all cases, nucleophilic attack occurs at the allylic epoxide carbon atom and proceeds with inversion of stereochemistry (Scheme 9.11). 

The relative importance of N-substituted arylamines for the construction of biologically significant molecules, particularly pharmaceuticals and agrochemicals, prompted the extension of rhodium-catalyzed allylic amination to aniline nucleophiles (Tab. 10.6) [41, 42]. The N-arylsulfonyl-protected anihnes were again optimal for high selectivity, analogous to that observed with the N-toluenesulfonyl-N-aLkylamines. 

Knochel and co-workers have carried out a series of nucleophilic substitution reacion on ( )-allyl bromide using thiolate ions. The reaction between bromide 326 and lithium phenylthiolate yielded the ( )-sulfide 327 exclusively. However, treatment of ( )-sulfide 327 with the more nucleophilic reagent sodium methyl thiolate led to a 20 80 mixture of 327 and ( )-methyl sulfide 328. They proposed that either a S- 2 mechanism is operative, or two S- 2 substitutions eventually resulted in the thermodynamically more stable sulfide (ii)-methyl sulfide 328. A similar reaction of 326 with aniline in excess or its chloromagnesium amide gave a mixture of 5 n2 and 5 n2 products 329 and 330 which slowly equilibrate to give S-f 2 product 329 in 78% yield (Scheme 3.143). 

The same group developed an interesting intermolecular palladium-catalyzed alienation of aryliodide with N-tosyl o-iodoanilines with nucleophiles in combination with two palladium-coupling reactions [69]. In this reaction, the N-allyl(2-iodopalladium)aniline intermediate 52 underwent an intramolecular Heck reaction followed by a cross-coupling reaction with phenyl boronic acid to give the 3,3-disubstituted indoline 53 in 78% yield (Scheme 8.27). 

Anilines with strongly electron-withdrawing groups or diarylamines [38] are only weak nucleophiles, and might require deprotonation to react with electrophiles at acceptable rates (Scheme 6.8). These anilines can also be allylated by allyl palladium complexes [34], Electron-deficient anilines are electrophiles themselves, and can transfer the aryl group to other nucleophiles by aromatic nucleophilic substitution [39]. 

The direct catalytic reaction of nucleophiles such as amines with 1,3-dienes to give allylic amines is difficult to achieve. A high-throughput assay was used to screen catalysts for the 1 1 hydroamination of aniline to 1,3-cyclohexadiene (equation 44). ... 

The reaction between alkyl hahdes and ammonia or primary amines is not usually a feasible method for the preparation of primary or secondary amines, since they are stronger bases than ammonia and preferentially attack the substrate. However, the reaction is very useful for the preparation of tertiary amines and quaternary ammonium salts. If ammonia is the nucleophile, the three or four alkyl groups on the nitrogen of the product must be identical. If a primary, secondary, or tertiary amine is used, then different alkyl groups can be placed on the same nitrogen atom. The conversion of tertiary amines to quaternary salts is called the Menshutkin reaction It is sometimes possible to use this method for the preparation of a primary amine by the use of a large excess of ammonia or a secondary amine by the use of a large excess of primary amine. The use of ammonia in methanol with microwave irradiation has also been effective. Microwave irradiation has also been used in reactions of aniline with allyl iodides. A base other than the amine... 

The nucleophilic substitution reactions of anilines at arylmethyl (ArCH2—), arylethyl (ArCH2CH2—), allyl (CH2=CHCH2—) and alkynylmethyl (CH=CCH2—) carbon centers take place by a direct displacement (SN2) mechanism with Bronsted coefficients, fix, in the range 0.3-0.8 as can be seen in Table 229-48... 

Cross-coupling reactions leading to the formation of C-X (X = heteroatom) bonds catalyzed by Pd(dba)2 have been reported. Aniline derivatives have been prepared via reaction of amine nucleophiles with aryl halides in the presence of Pd(dba)2 and phosphines, especially P( Bu)3. Likewise, diaryl and aryl alkyl ethers are produced from aryl halides (Cl, Br, I) and sodium aryloxides and alkoxides under similar conditions. Conditions effective for the coupling of aryl chlorides with amines, boronic acids, and ketone enolates using an easily prepared phosphine chloride as a ligand have recently been uncovered (eq 22). The preparation of aryl siloxanes and allyl boronates via Pd(dba)2-catalyzed C-Si and C-B coupling have been reported as well. 

Cyanide addition to the lactamic carbonyl group has been described in a reaction in which the cyanide ion acts as a catalyst (Fig. 14).The intermediate acyl cyanide can be attacked by an added nucleophile (allylic, propargylic, benzylic alcohols, aniline, benzylmercaptan). Comparative experiments were carried out using more classical procedures, such as under catalysis by potassium cyanide with stirring at room temperature, and with sodium alkoxides at -78 C. This last method provides the highest yields, up to 95% in most of the cases tested, but the sonochemical method proceeds under less basic conditions. Both methods preserve the integrity of the asymmetric center. 

In this reaction, the tethered alkene functionality of the aniline derivatives form a Tr-allyl complex with the Pd(II) catalyst, and then the cyclization takes place via intramolecular nucleophilic attack by the N to form another Pd-complex, which reacts with CO as the electrophilic carbon source in the presence of MeOH to afford substituted bicy-clic pyrrolidine derivatives. However, these products were not stereoselective in nature. A similar type of Pd-catalyzed nonstereoselective cyclizations were also reported by Weinreb et al. and by Larock and Yang for the construction of bicyclic and bridged aza-cycles." ... 

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