Palladium catalysts allylic cyclization

In the presence of a palladium catalyst, allyl epoxides (113) react with nitrogen nucleophiles at the al-kenic carbon atom remote from the oxirane ring to give 1,4-adducts (114)." In the absence of a palladium catalyst, azide ion attacks the oxirane ring affording 1,2-adducts (115 Scheme 52 and Table 2)." Vinyl epoxide (116) gave 1,2- and 1,4-azido alcohol in a ratio of 1 1.5 irrespective of the reaction system. " Intramolecular cyclization of vinyl epoxide (117) in the presence of a palladium catalyst afforded isoquinuclidine (118 Scheme 52). ... 

Intramolecular cycloadditions of substrates with a cleavable tether have also been realized. Thus esters (37a-37d) provided the structurally interesting tricyclic lactones (38-43). It is interesting to note that the cyclododecenyl system (w = 7) proceeded at room temperature whereas all others required refluxing dioxane. In each case, the stereoselectivity with respect to the tether was excellent. As expected, the cyclohexenyl (n=l) and cycloheptenyl (n = 2) gave the syn adducts (38) and (39) almost exclusively. On the other hand, the cyclooctenyl (n = 3) and cyclododecenyl (n = 7) systems favored the anti adducts (41) and (42) instead. The formation of the endocyclic isomer (39, n=l) in the cyclohexenyl case can be explained by the isomerization of the initial adduct (44), which can not cyclize due to ring-strain, to the other 7t-allyl-Pd intermediate (45) which then ring-closes to (39) (Scheme 2.13) [20]. While the yields may not be spectacular, it is still remarkable that these reactions proceeded as well as they did since the substrates do contain another allylic ester moiety which is known to undergo ionization in the presence of the same palladium catalyst. 

Reduction of iV-(3-bromopropyl) imines gives a bromo-amine in situ, which cyclizes to the aziridine. Five-membered ring amines (pyrrolidines) can be prepared from alkenyl amines via treatment with N-chlorosuccinimide (NCS) and then BusSnH. " Internal addition of amine to allylic acetates, catalyzed by Pd(PPh3)4, leads to cyclic products via a Sn2 reaction. Acyclic amines can be prepared by a closely related reaction using palladium catalysts. Three-membered cyclic amines (aziridines)... 

The effect of the nature of the electrophile on the stereoselectivity of reactions with substrates containing a terminal alkene and an allylic substituent is dramatically illustrated by some recent results with palladium electrophiles.124 Cyclizations of 3-methyl- or 3-phenyl-5-hydroxyalkenes with palladium catalysts proceed with high selectivity (>9 1) for the 2,3-trans isomer (equation 41).50-124 It is suggested that the steric interactions of the palladium-alkene complex affects the stereochemistry of these cyclizations. In some related cyclizations to form tetrahydropyran products (equation 42 and Table 10), reaction with iodine in the presence of sodium bicarbonate gives a different major diastereomer from cyclization with mercury(II) trifluoroacetate or palladium chloride.123... 

All of these processes are of limited synthetic utility because of the requirement of the use of stoi chiometric amounts of palladium complexes. However, by judicious choice of reactants and condition the above-mentioned impediments to catalysis can be overcome. For example, an efficient palladium(II) catalyzed cyclization of o-allyl- and o-vinyl-anilines to indoles has been developed (equation 14).28 Be cause arylamines are -106 less basic than aliphatic amines, and because the cyclized product in thi system gave an enamine (indole) stabilized by aromatization, the problems of catalyst poisoning by sub strate or product were circumvented, and catalysis was successfully achieved. The system was quit tolerant of a variety of functional groups and was used to prepare indoloquinones in excellent yieli... 

Evidence based on product mixtures now suggests, at least in the cases of a-halocarbonyl and perhaloalkyl starting marterials, that these reactions are in fact atom transfer radical cyclizations (equation 166)324,325. In them, the palladium catalyst is proposed to have roles both as the radical initiator and as a trap for iodine, similar to the more commonly used hexabutylditin. Intramolecular allyl halide-alkyne cyclizations proceed with trans-addition to the triple bond this is evidence that a still different mechanism may be operating in these cases (equation 167)1,326. 

As will be highlighted in the following examples, the most interesting feature of this strategy lies in the possibility of generating the dipole component in situ under mild, neutral conditions by simple exposure of a properly designed allylic substrate to a suitable palladium catalyst (for an updated, general review of Pd-catalyzed cyclizations of allylic compounds, see [17]). 

While simple unactivated cyclopropanes have yet to be used for [3 + 2] cycloaddition, Tsuji and coworkers have developed a palladium-catalyzed cycloaddition reaction using electron-deficient vinylcy-clopropanes. Thus, vinylcyclopropane (43) undergoes smooth cyclization with methyl acrylate in the presence of a palladium catalyst to give vinylcyclopentane (44) as a mixture of diasteroisomers (equation 35). The cycloaddition probably proceeds through the zwitterionic ( ir-allyl)palladium intermediate (45) and its stepwise reaction with the acrylate (equation 36). Enones such as cyclopentenone and methyl vinyl ketone will also react. Reaction of the same vinylcyclopropane with phenyl isocyanate produces vi-nyllactam (46) (equation 37).Some cycloaddition reactions with (cyclopropyl)Fp complexes have also been reported. However, the substrates are limited to SO2 and TCNE and the yields have not been disclosed (equation 38). ... 

Allene carboxylic acids have been cyclized to butenolides with copper(II) chloride. Allene esters were converted to butenolides by treatment with acetic acid and LiBr. Cyclic carbonates can be prepared from allene alcohols using carbon dioxide and a palladium catalyst, and the reaction was accompanied by ary-lation when iodobenzene was added. Diene carboxylic acids have been cyclized using acetic acid and a palladium catalyst to form lactones that have an allylic acetate elsewhere in the molecule. With ketenes, carboxylic acids give anhydrides and acetic anhydride is prepared industrially in this manner [CH2=C=0 + MeC02H (MeC=0)20]. 

Vinyl halides add to allylic amines in the presence of Ni(cod)2 where cod=l, 5-cyclooctodine, followed by reduction with sodium borohydride. Aryl iodides add to alkynes using a platinum complex in conjunction with a palladium catalyst. A palladium catalyst has been used alone for the same purpose, and the intramolecular addition of a arene to an aUcene was accomplished with a palladium or a GaCl3 catalyst, " AUcyl iodides add intramolecularly to aUcenes with a titanium catalyst, or to alkynes using indium metal and additives. The latter cyclization of aryl iodides to alkenes was accomplished with indium and iodine or with Sml2. " ... 

Intermolecular hydroamination of alkynes, which is a process with a relatively low activation barrier, has not been used for the synthesis of chiral amines, since the achiral Schiff base is a major reaction product. However, protected aminoalkynes may undergo an interesting intramolecular allylic cyclization using a palladium catalyst with a chiral norbomene based diphosphine ligand (Eq. 11.9) [115]. Unfor tunately, significantly higher catalyst loadings were required to achieve better enantioselectivities of up to 91% ee. 

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