Reactions of Allylic Amines

The facile cyclopalladation of allylamine proceeds due to the chelating effect of the nitrogen. Carbopalladation of allylamine with malonate affords the chelating complex 203, which undergoes insertion of methyl vinyl ketone to form the amino enone 204 [124]. Homoallylamines and allyl sulfides behave similarly [125], 

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An in situ method for capturing nitrones too unstable for isolation involved reaction of allylic amines such as proline derivative 33 with A -methylhydroxylamine in basic formalin solution to give, in this instance, chiral oxadiazinane 34 (Equation 7) <1997TL8545>. 

Figure 7.8 Directed Mizoroki-Heck reaction of allylic amines.

Mechanistic smdies of Pd(MeCN)2Cl2-catalysed hydroalkylation reactions of allylic amine derivatives by n-BuZnBr in the presence of Zn(OTf)2, benzoquinone, and DMA suggested a reversible )3-hydride elimination/hydride insertion process leading to the primary Pd-alkyl intermediate, which underwent trans-metalation followed... 

Some nucleophiles other than carbon nucleophiles are allylated. Amines are good nucleophiles. Diethylamine is allylated with allyl alcohol[7]. Allylammes are formed by the reaction of allyl alcohol with ammonia by using dppb as a ligand. Di- and triallylamines are produced commercially from allyl alcohol and ammonia[l74]. 

Electron transfer to vinylaziridines results in ring-opening reactions, yielding allyl amines. Treatment of 268 with SmI2/DMEA (N,N-dimethylethanolamine) provided allyl amine 269 as a 2 1 mixture of olefmic isomers in 88% yield (Scheme 2.66) [97]. 

The formation of telomers rests on Tjhallylic intermediates, and the ratio of formation of 1 1 vs. 1 2 telomers stems from the reaction of the amine on a C4-allylic complex vs. a Cg-allyhc complex, an excess of phosphine and the presence of an acidic (Bronsted or Lewis) co-catalyst favoring the qhcrotyl complex (Scheme 4-5) [178, 180, 189-196]. 

This allows for easy reuse of the catalyst in the reaction of allylation of secondary amines like piperidine or morpholine for several runs. The leaching of palladium was less than 0.001% of the initial amount. 

The selectivity in the Heck reaction of allylic alcohol 111 is interesting, and the factors that lead to the observed preference for (3-hydride elimination toward nitrogen in this system are unclear, although a combination of steric effects and stereoelectronic factors (i.e., alignment of C-H and C-Pd bonds, nN a c H interactions) is likely involved. Examination of related examples from the literature (Scheme 4.20) reveals no clear trend. Rawal and Michoud examined substrate 115, which lacks the influence of both the amine and hydroxyl substituents and also seems to favor (3-hydride elimination within the six-membered ring over formation of the exocyclic olefin under standard Heck conditions [18a]. However, under... 

Silylated primary allylic amines, e.g. CH2=CHCH2N(SiMe3)2, are produced from allylic chlorides and the mixed reagent AgI/LiN(SiMe3)2205. The formation of allylic amines from olefins by the ene reaction is shown in equation 77. The ene adducts 205 from bis(2,2,2-trichloroethyl) azodicarboxylate are converted into 206 by zinc dust in acetone/acetic acid206. 

Substitution reactions of allylic nitro compounds often lead to rearranged products, as in palladium(0)-catalysed aminations and alkylations. Thus treatment of the nitro ester 419 with piperidine in the presence of tetrakis(triphenylphosphine)palladium yields a mixture of the unrearranged and rearranged amines 420 (R = piperidin-l-yl) and 421... 

Reactions of allylic electrophiles with stabilized carbon nucleophiles were shown by Helmchen and coworkers to occur in the presence of iridium-phosphoramidite catalysts containing LI (Scheme 10) [66,69], but alkylations of linear allylic acetates with salts of dimethylmalonate occurred with variable yield, branched-to-linear selectivity, and enantioselectivity. Although selectivities were improved by the addition of lithium chloride, enantioselectivities still ranged from 82-94%, and branched selectivities from 55-91%. Reactions catalyzed by complexes of phosphoramidite ligands derived from primary amines resulted in the formation of alkylation products with higher branched-to-linear ratios but lower enantioselectivities. These selectivities were improved by the development of metalacyclic iridium catalysts discussed in the next section and salt-free reaction conditions described later in this chapter. 

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. 

For Rh(I)/BINAP-catalyzed isomerizations of allylic amines, the mechanistic scheme outlined in Eq. (2) has been proposed. The available data are consistent with the notion that Rh(I)/PF-P(o-Tol)2-catalyzed isomerizations of allylic alcohols follow a related pathway [11]. For example, the only deuterium-containing product of the reaction depicted in Eq. (9) is the l,3-dideuterated aldehyde, which estabhshes that the isomerization involves a clean intramolecular 1,3-migration. The data illustrated in Eqs. (10) and (11) reveal that the catalyst selectively abstracts one of the enantiotopic hydrogens/ deuteriums alpha to the hydroxyl group. 

One of the landmark achievements in the area of enantioselective catalysis has been the development of a large-scale commercial application of the Rh(I)/BINAP-catalyzed asymmetric isomerization of allylic amines to enamines. Unfortunately, methods for the isomerization of other families of olefins have not yet reached a comparable level of sophistication. However, since the early 1990s promising catalyst systems have been described for enantioselective isomerizations of allylic alcohols and aUylic ethers. In view of the utility of catalytic asymmetric olefin isomerization reactions, I have no doubt that the coming years will witness additional exciting progress in the development of highly effective catalysts for these and related substrates. 

Rhodium-Catalyzed Nucleophilic Ring Cleaving Reactions of Allylic Ethers and Amines... 

A synthesis of optically active citronellal uses myrcene (7), which is produced from P-pinene. Reaction of diethyl amine with myrcene gives AyV-diethylgeranyl- and nerylamines. Treatment of the allylic amines with a homogeneous chiral rhodium catalyst causes isomerization and also induces asymmetry to give the chiral enamines, which can be readily hydrolyzed to (H-)-citronellal (151). 

Protection of primary amines cf. 8, 437). I.aguzza and Ganem- recommend the diallyl derivatives for protection of primary amines. These compounds are prepared by reaction of the amine with allyl bromide and cthyldiisopropylaminc. Dc-protcction is accomplished by isomerization of the allyl groups to propenyl groups by Wilkinson s catalyst (5. 736) in refluxing aqueous acetonitrile. Under these conditions the resulting cnaminc is hydrolyzed with evolution of propionaldchyde, and llte amine is obtained in 65 90", yield. 

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