Allylation palladium-catalyzed regioselective

Additions of carbon nucleophiles to vinylepoxides are well documented and can be accomplished by several different techniques. Palladium-catalyzed allylic alkylation of these substrates with soft carbon nucleophiles (pKa 10-20) proceeds under neutral conditions and with excellent regioselectivities [103, 104]. The sul-fone 51, for example, was cyclized through the use of catalytic amounts of Pd(PPh3)4 and bis(diphenylphosphino)ethane (dppe) under high-dilution conditions to give macrocycle 52, an intermediate in a total synthesis of the antitumor agent roseophilin, in excellent yield (Scheme 9.26) [115, 116]. 

Regioselectivities that are usually high to excellent have been reported in novel palladium-catalyzed Heck arylation reactions with a variety of allylic substrates. The //-stabilizing effect of silicon enhanced regiocontrol in the internal arylation of allyl-trimethylsilane (Eq. 11.5) [18], and coordination between palladium and nitrogen... 

Palladium complexes are general and versatile catalysts for allylic amination.1,la lh The palladium-catalyzed allylic aminations of 1,3-symmetrically disubstituted substrates, including enantioselective versions, have been widely studied.1, a h It has been important to control the regioselectivity in allylic amination of unsymmetrical substrates 1 or 2 (Equation (1)). In general, palladium-catalyzed allylic amination gives the ( )-linear product 3Tla lh regiocontrol in amination has recently attracted much attention in approaches toward the branched product 4. 

An unusually high regioselectivity was observed by Cook s group in palladium-catalyzed allylic amination of 5-vinyloxazolidinone 10 (Scheme 2).5 An imide-type nucleophile was directed to the internal carbon, whereas... 

The regioselectivity in palladium-catalyzed alkylations has been attributed to the dynamic behavior of trihapto pentadienyl metal complexes60. For example, competing electronic and steric effects influence product formation in dienyl epoxides, but in palladium-catalyzed reactions steric factors were often found to be more important. Thus, alkylation of dienyl epoxide 76 with bulky nucleophiles such as bis(benzenesulfonyl)me-thane in the presence of (Ph3P)4Pd occurred exclusively at the terminal carbon of the dienyl system producing allyl alcohol 77 (equation 39). However, the steric factors could be overcome by electronic effects when one of the terminal vinylic protons was replaced with an electron-withdrawing group. Thus, alkylation of dienyl epoxide 78 affords homoal-lylic alcohol 79 as the major product (equation 40). 

Concerning the lithium-zinc transmetallation from intermediate 331, it has been used (THF, room temperature) to perform a palladium-catalyzed Negishi cross-coupliug reaction with aryl bromides - and a 8 2 regioselective allylation in the presence of copper cyanide. 346 and 347 were, respectively, obtained (Scheme 101). 

A-Alkylhydroxylamines react with substituted allyl acetates (e.g. 15, equation 11) in palladium catalyzed addition-elimination reactions giving the corresponding A-alkyl, A-allylhydroxylamines 16. The reaction proceeds with high regioselectivity but complete racemization. A similar reaction with 0-acyl hydroxamic acids has been carried out using allylic a-alkoxycarbonyloxyphosphonates. ... 

As described in many reviews, Trost and his co-workers have carried out a pioneering work on the molybdenum-and tungsten-catalyzed allylic alkylation of allylic esters regioselectivity of the reaction is often complementary to the palladium-catalyzed allylic alkylation. The first asymmetric version was disclosed by Pfaltz and Lloyd-Jones in 1995 (Equation (63)). They used a catalytic amount of a novel tungsten complex, prepared from [W(CO)3(MeCN)3] or [W(cycloheptatriene) (COIs] and optically active (diphenylphosphino)phenyloxazolines 57, for the allylic alkylation of 3-aryl-2-propenyl phosphate with dimethyl sodiomalonate to isolate the corresponding branched alkylated compounds as a major isomer with an excellent enantioselectivity (96% ee). Unexpectedly, 3-aryl-2-propenyl carbonates are shown to be unreactive. It is worth noting that an isostructural molybdenum complex does not promote the catalytic alkylation under the same reaction conditions. In contrast, Lloyd-Jones and Lehmann reported the stereocontrolled... 

Cacchi, S. Fabrizi, G. Pace, P. Palladium-catalyzed cyclization of o-alkynyltrifluoroacetani-lides with allyl esters. A regioselective synthe-... 

Regioselective polycondensations with transition-metal catalysts were also reported. Nomura et al. developed palladium-catalyzed allylation polycondensation, in which nucleophile predominantly reacted with jt-allyl palladium at the terminal allylic carbon to give fi-linear products [122,123]. On the other hand, polymerization with an iridium catalyst selectively proceeded at the internal allylic carbon to yield branched polymers with pendant vinyl groups (Scheme 30). These polycondensations demonstrate that polymers having different structures can be synthesized from the same monomers by changing the catalyst [124],... 

In the palladium-catalyzed allylic amination reaction, primary and secondary amines can be used as nucleophiles, whereas ammonia does not react. Therefore, many ammonia synthons have been developed, and a variety of protected primary allyl amines can now be prepared using azide, sulphonamide, phthalimide, di-f-butyl iminocarbonate ((Boc)2NLi), and dialkyl A-(rerr-butoxycarbonyl)phosphoramide anions as the nucleophile [20], An example of the use of ((Boc)2NLi) 30 as the amine nucleophile in the palladium-catalyzed allylic amination reaction is shown in Eq. (9). This reaction also illustrates the problem with the regioselectivity in the reaction as a mixture of the products 31-33 are obtained [21]. 

Vinyl epoxides can also be used as substrates for formation of optically active allyl amines catalyzed by the same type of chiral palladium complexes as in Eq. (10). By reaction of simple vinyl epoxides with phthalimide as the nitrogen source in the presence of the chiral palladium complexes as the catalyst, very high ee (> 98 %) and regioselectivity (> 97 %) were obtained [26]. A variety of different applications of the use of the palladium-catalyzed approach for the formation of allyl amines and the use of this in total synthesis has been pursued by several research groups, and further details can be obtained in a review by Trost et al. [19d]. 

C-3 of the naphthalene nucleus that controls the electrophilic ring-closure of the vinyl ketene intermediate moreover, the degree of aromaticity of the angular rings in the phenanthrene skeleton exceeds that in the anthracene analogues. This regioselectivity observed in the benzannulation of chromium carbenes is paralleled by results observed for 2-naphthyl cyclo-butenones [77] and for the palladium-catalyzed cyclocarbonylation of 2-naphthyl allyl acetates [78]. 

A combination of molecular mechanics, based on the dummy atom technique described above, with a QSAR-type treatment and a linear free energy relationship (LFER)-based model was used successfully to analyze the relative importance of steric influences on regioselectivity and stereoselectivity in the palladium-catalyzed allylation reaction[453]. 

The palladium-catalyzed decarboxylative coupling of allyl 2-(benzo[c(jthiazol-2-yl)acetates 118 provides a facile approach to 2-(but-3-enyl)benzo[c(jthiazoles 122 <07JA4138>. The reaction is initiated by nucleophilic attack of Pd(0) on the allyl ester to give Pd-7t-allyl complex 119, which undergoes nucleophilic attack at the less substituted allylic carbon from the benzothiazole nitrogen to produce 120. Decarboxylative dearomatization leads to intermediate 121, and a subsequent aza-Cope rearrangement driven by rearomatization affords the final product 122 and accounts for the unusual regioselectivity. This appears to be the first report of a tandem allylation/aza-Cope reaction driven by decarboxylative dearomatization/ rearomatization. 

Palladium-catalyzed Stille cross-coupling of furanylstannanes to an allyl bromide was also regioselective. An example, as employed in the total synthesis of 6/3-hydroxyeuryopsin, is depicted in Equation (38) <2004CC44>. This type of reaction could also be performed by using a catalytic amount of CuCl, rather than a palladium catalyst <1999SL1942>. 

In the oxidation of 2-octenyl acetate, in addition to the normal oxidation, palladium-catalyzed allylic rearrangement and subsequent oxidation took place to give a small amount of 3-acetoxy-2-octanone as a byproduct. Ethers of secondary allylic alcohols also underwent the regioselective oxidation to give the corresponding 3-alkoxy ketones in 30-40% yields. But in this case too, by-products derived from the allylic reanangement a subsequent oxidation were also detected. Results of the oxidation of some allyl ethers are shown in Table 3. °... 

Vinyloxazolidin-2-ones 224 were used as substrates for palladium catalyzed allylic substitutions showing an unexpected regioselectivity towards the branched product 226. This effect was rationalised on the basis of an hydrogen bond interaction<03JA5115>. 

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