Allylamines addition reactions

Addition reactions to olefins can be used both for the construction and for the functionalization of molecules. Accordingly, chiral catalysts have been developed for many different types of reactions, often with very high enantioselectiv-ity. Unfortunately, most either have a narrow synthetic scope or are not yet developed for immediate industrial application due to insufficient activities and/ or productivities. These reactions include hydrocarbonylation [Ilf], hydrosilyla-tion [12 i], hydroboration [12j], hydrocyanation [12 k], Michael addition [11 g, 121, 12 m], Diels-Alder reaction [11 h, 12n] and the insertion of carbenes in C-H bonds [Hi, 12p, 12q, 38], Cyclopropanation [Hi, 12p, 12q] and the isomerization of allylamines [12 s] are already used commercially for the manufacture of Cilastatin (one of the first industrial processes) [12 r], and citronellol and menthol (presently the second largest enantioselective process) [12t] respectively. 

Radical addition. The adducts of S-(a-ketoalkyl) xanthatcs to allylamines (from reaction catalyzed by lauroyl peroxide) are useful precursors of piperidines. 

Michael additions of secondary allylamines to nitroalkenes followed by treatment with Me3SiCl and Et3N afford highly functionalized pyrrolidines via the stereoselective ISOC reaction (Eq. 8.86).137... 

Nucleophilic addition of primary o.-R -allylamine to nitrone followed by a reverse Cope cyclization and Meisenheimer rearrangement gives the oxadiazi-nanes (426a-h) (Scheme 2.198). These reactions have found use for the preparation of oxadiazines, vicinal aminohydroxylamines, and diamines the latter are of particular interest as chiral ligands (683, 684). 

Scheme 22. The rate equation for this mechanism is described in (1). The authors determined that the reaction is first-order in allylic carbonate, aniline and catalyst, and inverse first-order in allylamine product. These results are consistent with the proposed mechanism. Thus, iridium-catalyzed allylic substitution is inhibited by product. In addition, the formation of the allyliridium intermediate is disfavored.

When the secondary amine 33 was used instead of a primary amine, a different type of three-component coupling reaction took place with aldehyde 34 and 1-alkynes 35 to afford the corresponding allylamines (36 and 37) [22]. In this reaction, Ir-hydride generated by amine (33) with Ir, would be a key intermediate. The reaction may proceed by addition of the Ir-hydride to the enamine derived from amine 33 and alkyne 34, followed by insertion of aldehyde and dehydration to give the coupling product (36 and 37). 

Ring-closing metathesis seems particularly well suited to be combined with Passerini and Ugi reactions, due to the low reactivity of the needed additional olefin functions, which avoid any interference with the MCR reaction. However, some limitations are present. First of all, it is not easy to embed diversity into the two olefinic components, because this leads in most cases to chiral substrates whose obtainment in enantiomerically pure form may not be trivial. Second, some unsaturated substrates, such as enamines, acrolein and p,y-unsaturated aldehydes cannot be used as component for the IMCR, whereas a,p-unsaturated amides are not ideal for RCM processes. Finally, the introduction of the double bond into the isocyanide component is possible only if 9-membered or larger rings are to be synthesized (see below). The smallest ring that has been synthesized to date is the 6-membered one represented by dihydropyridones 167, obtained starting with allylamine and bute-noic acid [133] (Fig. 33). Note that, for the reasons explained earlier, compounds... 

The chiral a-cyano allylamines prepared from ( )-3-phenylpropenal, potassium cyanide and (L)-ephcdrinc [(17 ,2S )-2-methylamino-l-phenylpropanol] hydrochloride as a mixture (1 1) of C-l epimers, were deprotonated using 2 equivalents of LDA in THF to give the dilithio compound37. Alkylation at C-3 afforded regioselectively a mixture of (E)- and (Z)-enamines in variable amounts depending on reaction conditions. Diastereoselectivity varied from moderate to excellent. Addition of HMPA and especially lithium iodide improved the diastereoselectivity. De-aggregation is proposed to be the reason for the effect of these additives. 

The overall reaction is best viewed as intramolecular oxidative addition of the C(l)—H bond to the Rh(I) center, causing cyclometalation (25), followed by reductive elimination of an enamine from the Rh(III) intermediate accompanied by allylic transposition. Notably, the allylamine ligand in the initial Rh(I) complex as well as the Rh(III) intermediate has an s-trans conformation with respect to the N—C(l) and C(2)—C(3) bonds, allowing the overall suprafacial 1,3-hydrogen shift to produce the is-configured enamine product. 

The reaction of oxygen with cobalt(n) chloride and triphenylphosphine (L) in allylamine (AA) proceeds226 as shown in Scheme 4 [A] is probably a mixture of peroxidic species which dissolves on addition of BTH and precipitates an orange solid on irradiation. The same novel complex (48) is slowly deposited when solution [B] is allowed to stand in the dark oxidation of the PPh3 to OPPh3 has occurred under mild conditions. 

The scope aromatic C-N bond formation extends beyond simple amine substrates. For example, selected imines, sulfoximines, hydrazines, lactams, azoles, and carbamates give useful products from intermolecular aromatic C-N bond formation. Intramolecular formation of aryl amides has been reported. In addition, allylamine undergoes arylation, providing a readily cleaved amine alternative to the ammonia surrogates benzylamine, t-butylcarbamate, or benzophenone imine. Although it is an amine substrate, the reaction of this reagent is included here because of its special purpose. 

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