Nitrogen nucleophiles allylation

Carbamates are allylated in the presenee of strong bases in DMSO or HMPA[197], Phthalimide (320) and succimide are allylated with the allyl-isoureu 321 at room temperature or the allylic acetate 322 at 100 C[I98.I99], Di-/-butyl iminodicarbonate is used as a nitrogen nucleophile[200]. 

Kinetic data on acetate displacement from C-3 using a number of sulfur and nitrogen nucleophiles in aqueous solution at near neutral pH demonstrate that the reaction proceeds by an 5 1 mechanism (B-72MI51004). The intermediate in this reaction is depicted as a dipolar allylic carbonium ion (9) with significant charge delocalization. Of particular significance in this regard is the observation that the free carboxylate at C-4 is required since... 

Aregioselective catalytic system for the allylic substitution of non-symmetric allyl carbonates by carbon and nitrogen nucleophiles based on [ Bu N][Fe(NO)(CO)3] and PPhj was developed (Scheme 2.26). The high regioselectivity was ascribed to the slow a-allyl- to Jt-aUyl-isomerisation relative to the rate of substitution. However, the use of high excess of the pro-nucleophile and DMF solvent are drawbacks on the atom efficiency and functional group tolerance of the system. 

Complexes derived from the oxazolinylpyridine ligand Ph-Pybox and [Ir(COD)Cl]2 catalyze allylic substitution reactions of several oxygen and nitrogen nucleophiles... 

As previously discussed, activation of the iridium-phosphoramidite catalyst before addition of the reagents allows less basic nitrogen nucleophiles to be used in iridium-catalyzed allylic substitution reactions [70, 88]. Arylamines, which do not react with allylic carbonates in the presence of the combination of LI and [Ir(COD)Cl]2 as catalyst, form allylic amination products in excellent yields and selectivities when catalyzed by complex la generated in sim (Scheme 15). The scope of the reactions of aromatic amines is broad. Electron-rich and electron-neutral aromatic amines react with allylic carbonates to form allylic amines in high yields and excellent regio- and enantioselectivities as do hindered orlAo-substituted aromatic amines. Electron-poor aromatic amines require higher catalyst loadings, and the products from reactions of these substrates are formed with lower yields and selectivities. 

Evans and co-workers demonstrated that rhodium-catalyzed allylic amination of enantiomerically enriched acyclic unsymmetrical allylic carbonates occurs with excellent regio- and enantiospedfidty (Tab. 10.5) [35]. Interestingly, while the classical nitrogen nucleophiles furnished allylic amination products in poor yield and with modest regioselectivity, the lithium anion of N-toluenesulfonyl-N-alkylamines proved optimal, in terms of nucleophilicity and basicity. 

Cyclizations with nitrogen nucleophiles involving alkynes and allenes have received little attention until recently. The cyclizations of several a-aminoallenes to 3-pyrrolines with silver tetrafluoroborate was reported by Claesson and coworkers (equation 133).264 A similar cyclization to form A -carba-penems has been reported (equation 134).265 Diastereomeric allenes (R1 R2) were shown to cyclize with complete stereocontrol. Cyclization with palladium chloride in the presence of allyl bromide or electrophilic alkenes allowed for the intermediate vinylpalladium species to be trapped by the electrophile.2651 A related product was obtained by cyclization of an alkynic substrate (equation 13S).265 Other examples of 5-endo cyclization of p-aminoalkynes50 include the formation of indoles by cyclization of 2-alkynylanilines with mercury salts200 or palladium chloride,266a,266b,266c formation of 1-pyrrolines with catalytic palladium chloride (equation 136)198 and formation of pyrroles by cyclization of hydroxy-substituted p-aminoalkynes.198,2666... 

Anodic oxidation of allylsilanes in the presence of nucleophiles results in replacement of a trimethylsilyl group by a nucleophile which is introduced into the allylic carbon. Various oxygen and nitrogen nucleophiles such as alcohols, water, caboxylic acids, p-toluenesulfonic acid, carbamates or a sulfonamide can be employed in this reaction (equations 9—11)11 —13. 

The second approach for the nucleophilic animation reactions to be considered here will be reactions of allyl halides and allyl acetates leading to allyl amines. Allyl halides are normally very reactive in SN2 reactions, but the direct coupling of allyl halides with nitrogen nucleophiles has been performed with limited success [4], as di- and trialkylated by products often predominate. The application of the Gabriel synthesis can to a certain extent eliminate the problem with polyalkylation of amines using, e.g., the stabilized phthalimide anion 19 as the nucleophile. The allyl amine 20... 

In principle, allylic sulfoximines can be used as substrates for the allylation of an external nucleophile (Nu) if that nucleophile can compete with the sulfinamide anion C for the palladium(0) complex B or if the formation of D is reversible. In 1997 Pyne and co-workers99 reported that stabilized carbon and nitrogen nucleophiles can be efficiently allylated in a regioselective manner using allylic sulfoximines and palladium(O) catalysis (Eq. 5). 

In this sense Organ and coworkers [80] have developed intriguing syntheses of polysubstituted olefins based upon consecutive intermolecular reactions such as allylic and allylic-vinylic halide coupling sequences. Therefore, l-acetoxy-4-chloro but-2-ene can be readily submitted as a template for Pd-catalyzed allylic substitutions with two different carbon or nitrogen nucleophiles, leading to unsymmetrically substituted butene derivatives 66-70 in good yields (Scheme 22). Mechanistically, the chloro substituent is replaced... 

The stereochemistry of Pd -catalyzed allylic alkylation is net retention (equation 62). This arises from sequential inversion steps. Initially, the Pd approaches from the face of the C3 unit opposite the leaving group, to form the jt-allyl complex. Subsequently, the nucleophile adds to the face of the TT-allyl opposite palladium. If a bulky or umeactive nucleophile is used with allylic acetates, the acetoxy group can add again to the complex. Ultimately, this results in the production of a mixture of stereoisomers upon nucleophihc addition. As an example of the range of allylic substrates that react, nitrogen nucleophiles, in particular primary and secondary amines, undergo palladium-catalyzed substimtion with aUyhc alcohols, acetates, and ethers (equation 63). 

This section focuses on those reactions of nitrogen nucleophiles with rr-allylpalladium complexes which proceed by stereoselective C-N bond formation. For the sake of brevity, the rr-allyl-palladium complexes involved as reactive intermediates in catalytic processes arc omitted in the diagrams and tables. If not explicitly mentioned otherwise, the depicted structures represent racemic mixtures. 

The dimeric 7r-allylpalladium complex 1 prepared by stoichiometric methoxypalladation of 1,3-cyclohexadiene is aminated with clean inversion of configuration to cis-212. Electron-withdrawing substituents flanking the re-allyl complex generally direct nitrogen nucleophiles to the distal carbon. A similar stereo- and regioselective reaction is seen for the monodentate re-olefin complex 31 Under the conditions used, the intermediate dimethylamino analog of 1 is immediately converted into 4 by attack of excess amine. 

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