Allyl complexes amines

Allylic acetoxy groups can be substituted by amines in the presence of Pd(0) catalysts. At substituted cyclohexene derivatives the diastereoselectivity depends largely on the structure of the palladium catalyst. Polymer-bound palladium often leads to amination at the same face as the aoetoxy leaving group with regioselective attack at the sterically less hindered site of the intermediate ri -allyl complex (B.M. Trost, 1978). 

Typical nucleophiles known to react with coordinated alkenes are water, alcohols, carboxylic acids, ammonia, amines, enamines, and active methylene compounds 11.12]. The intramolecular version is particularly useful for syntheses of various heterocyclic compounds[l 3,14]. CO and aromatics also react with alkenes. The oxidation reactions of alkenes can be classified further based on these attacking species. Under certain conditions, especially in the presence of bases, the rr-alkene complex 4 is converted into the 7r-allylic complex 5. Various stoichiometric reactions of alkenes via 7r-allylic complex 5 are treated in Section 4. 

Allylic amine is a less reactive leaving group[7], but the allylic ammonium salts 214 (quaternary ammonium salts) can be used for allylalion(l30,131]. Allylic sulfonium salts are also used for the allylation[130]. The allylic nitrile in the cyclic aminonitrile 215 can be displaced probably via x-allylic complex formation. The possibility of the formation of the dihydropyridinium salts 216 and subsequent conjugate addition are less likelyfl 32],... 

There appear to be few examples of the formation of azetidin-2-ones by closure of the C(2) —C(3) bond. One reaction which fits into this category involves reaction of the iron carbonyl lactone complexes (144) with an amine to give the allyl complexes (145) which on oxidation are converted in high yield to 3-vinyl-/3-lactams (146) (80CC297). 

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]. 

Another easily available palladium compound is PdCl2 however, it has low or no activity. The chloride ion in the coordination sphere of palladium seems to inhibit the coordination of two moles of butadiene to form the bis-77-allylic complex. However, PdCl2 can be used in the presence of an excess of bases, such as KOH, NaOH, sodium phenoxide, sodium acetate, potassium acetate, sodium methoxide, or tertiary amines. These bases deprive the chloride ion from the coordination sphere of palladium to form the active species. Thus, very stable and easily prepared... 

Allylation of amines with allyiic alcohols in the presence of reducible nickel complexes easily occurs at 80°C (example 4, Table X). 

The Pd-catalyzed reaction of 5-vinyl-l,3-oxazolidin-2-ones 260 at 65-70°C and 65 atm of CO in ethanol gave 5-lactams 263 in fairly good to high yields (Scheme 38).As Scheme 38 illustrates, this decarboxylative carbonylation reaction is likely to involve (i) the cleavage of the allylic C-O bond of 260 to form tr-allyl-Pd complex syn-2(A, (ii) isomerization to anti-2(A, (iii) decarboxylation forming 7r-allyl-Pd-amine complex 262, and (iv) CO insertion to 262 followed by aminolysis to yield 5-lactam 263. 

The bridging chlorine atoms in these ir-allylicpalladium complexes are readily replaced by bromine, iodine, or the thiocyanate group by treatment with the corresponding alkali metal salt in a suitable solvent such as acetone 105, 194). The chlorine bridge is split by amines for example, the ir-allyl complex [PdCl(7r-CsH6)]2, with p-toluidine, gives [PdCl(7r-C3H6) (p-tolui-dine)] as stable, pale yellow crystals (105). 

The development of methods to effect nucleophilic addition to carbon-carbon double bonds by prior activation with metal cations has been applied, at least in a preliminary way, as a method of pyrrole ring closure. The conversion of butadienes to N-substituted pyrroles can be accomplished in two stages. In acetic add, 1,4-dienes react with PdnCl2 to give tr-allyl complexes with introduction of acetate at C-4. The ir-allyl complexes then react with amines to give a l-amino-4-acetoxy-2-butene (equation 70). When the addition of the amine is carried out in the presence of a silver salt and triphenylphosphine, a pyrrole is isolated, probably by cyclization of the amino-substituted allyl-Pd complex (equation 71) (81CC59). Although this procedure is attractive in terms of the simplicity of the... 

Vinyl substitution occurs with conjugated dienes as well as with alkenes, employing aryl-, vinyl-, methyl-, alkoxycarbonyl- or benzyl-mercury reagents and lithium tetrachloropalladate(II), but the products are usually rr-allylpalladium complexes if the reactions are carried out under mild conditions (equation 8).24,25 The ir-allylic complexes may be decomposed thermally to substituted dienes26 or reacted with nucleophiles to form allylic derivatives of the nucleophile. Secondary amines, for example, react to give tertiary allylic amines in modest yields, along with dienes and reduced dienes (equation 9).25... 

In the presence of triethylamine, decomposition of the ir-allylic complexes to conjugated dienes may occur, particularly when electron-withdrawing substituents are present on a methyl group in the 1- or 3-position of the iT-allyl system.31 Cyclic alkenes and vinylpalladium chlorides also yield iT-allylic complexes in the absence of an amine. If a tertiary amine is present, however, l,4-dienes are obtained (equation 1l).32... 

Vinylation of dienes in the presence of piperidine or morpholine yields aminodienes as major products. Sometimes trienes are minor products. The reaction is believed to proceed by way of a ir-allylpal-ladium complex formed by addition of the vinylpalladium halide to the least-substituted diene double bond. Nucleophilic attack of the amine upon the ir-allylic complex gives the aminodienes, while hydridopalladium halide elimination yields trienes (Scheme 6).97... 

Vinyloxiranes are used for facile 7i-allyl complex formation [14], The -allylic ferralactone complex 41 was prepared by oxidative addition of Fe2(CO)9 to the functionalized vinyloxirane 40 and CO insertion. Treatment of the ferralactone complex 41 with optically active a-methylbenzylamine (42) in the presence of ZnCl2 gave the 7r-allylic ferralactam complex 45 via 44. In this case, as shown by 43, the amine attacks the terminal carbon of the allylic system and then the lactone carbonyl. Then, elimination of OH group generates the 7r-allylic ferralactam complex 45. Finally the /1-lactam 46 was obtained in 64% yield by oxidative decomplexation with Ce(TV) salt. The <5-lactam 47 was a minor product (24%). The precursor of the thienamycin 48 was prepared from 46 [15,16]. This mechanistic explanation is supported by the formation of both 7r-allyllactone and lactam complexes (49 and 51) from the allylic amino alcohol 50 [17]. 

Pd-catalysed allylation of amines proceeds smoothly. Allylamine (132) and di- and triallylamines are produced commercially by the Pd-catalysed reaction of ammonia with allyl alcohol using DPPB as a suitable ligand [69]. Allylic alcohols are rather unreactive substrates for 7r-allylpalladium complex formation under usual conditions. The intramolecular amination of 133 afforded the azaspiro ring 134 and the reaction was applied to the synthesis of perhydrohistrionicotoxin (135) [70]. Smooth Pd-catalyzed allylation of the purine base 136 gives 137, which is utilized for the synthesis of nucleosides [71]. 

Cyclic ethers and amines can be formed if the nucleophile is an intramolecular alcohol or amine. Stoichiometric palladium can be avoided by using benzoquinone as the stoichiometric oxidant with a catalytic amount of palladium. In this example intramolecular oxypalladation of a diene is followed by attack of an external nucleophile on a TC-allyl complex. 

Arguably the best, or at least the most versatile, allylic oxidation method is based on Pd [114]. Since the intermediates are palladium-allyl complexes rather than free radicals the number of by-products is limited compared to the preceding examples (Fig. 4.41). Furthermore, a large number of nucleophiles (amines, alcohols, stabilized carbanions, carboxylates or halides) may attack the palladium-allyl complex, giving a wide variety of products. 

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). 

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