Oxypalladation alcohols

Propargylic alcohol, after lithiation, reacts with CO2 to generate the lithium carbonate 243, which undergoes oxypalladation. The reaction of allyl chloride yields the cyclic carbonate 244 and PdC. By this reaction hydroxy and allyl groups are introduced into the triple bond to give the o-allyl ketone 245[129]. Also the formation of 248 from the keto alkyne 246 with CO2 via in situ formation of the carbonate 247 is catalyzed by Pd(0)[130]. 

Reduced furans are formed in two types of oxypalladation processes on substrate a,ft- and y,<5-unsaturated alcohols. In an unusual reaction, allyl alcohol is converted into 4-methylenetetrahydrofurfuryl alcohol, among other products (Scheme 57)97 the formation of propene is thought to arise by reductive hydrogenolysis of allyl alcohol. 

When 1,3-dienes containing a tethered alcohol are subjected to Wacker-type reactions, the initial intramolecular oxypalladation event creates a 7r-allylpalladium species, which can then undergo an additional bond-forming process to effect an overall 1,4-difunctionalization of the diene with either cis- or // -stereochemistry (Scheme 18).399 An array of substrate types has been shown to participate in this reaction to generate both five- and six-membered fused or ro-oxacycles.435-437 Employing chiral benzoquinone ligands, progress toward the development of an asymmetric variant of this reaction has also been recorded, albeit with only modest levels of enantioselectivity (up to 55% ee).438... 

An interesting variant involves the use of an allylic alcohol as the alkene component. In this process, re-oxidation of the catalyst is unnecessary since the cyclization occurs with /Uoxygen elimination of the incipient cr-Pd species to effect an SN2 type of ring closure. Both five- and six-membered oxacycles have been prepared in this fashion using enol, hemiacetal, and aliphatic alcohol nucleophiles.439,440 With a chiral allylic alcohol substrate, the initial 7r-complexation may be directed by the hydroxyl group,441 as demonstrated by the diastereoselective cyclization used in the synthesis of (—)-laulimalide (Equation (120)).442 Note that the oxypalladation takes place with syn-selectivity, in analogy with the cyclization of phenol nucleophiles (1vide supra). 

Extensive studies on the Wacker process have been carried out in industrial laboratories. Also, many papers on mechanistic and kinetic studies have been published[17-22]. Several interesting observations have been made in the oxidation of ethylene. Most important, it has been established that no incorporation of deuterium takes place by the reaction carried out in D20, indicating that the hydride shift takes place and vinyl alcohol is not an intermediate 1,17]. The reaction is explained by oxypalladation of ethylene, / -elimination to give the vinyl alcohol 6, which complexes to H-PdCI, reinsertion of the coordinated vinyl alcohol with opposite regiochemistry to give 7, and aldehyde formation by the elimination of Pd—H. 

Cyclization of a variety of y-allenic alcohols with silver nitrate proceeds by 5-exo cyclization to form 2-alkenyltetrahydrofurans (equation 87).205c 206 Little stereoselectivity is seen in cyclizations of secondary alcohols. Cyclization by intramolecular oxypalladation/methoxycarbonylation or oxymercuration followed by transmetallation and methoxycarbonylation also showed no stereoselectivity (equation 88 and Table 24, entries 1 and 2).50 207 However, cyclization of the corresponding r-butyldimethylsilyl ether derivatives with mercury(II) trifluoroacetate followed by transmetallation/methoxycarbonylation pro-... 

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. 

In the presence of CO, terminal alkenes are oxidized by PdCl2 to RCH(C1)CH2C0C1. When the reaction is made catalytic in palladium by the addition of CuCl2 and oxygen, and carried out in alcohols, the products are a, /3-unsaturated esters, /3-alkoxy esters, and, under some conditions, succinate derivatives (equation 87). Two mechanisms are possible for this reaction. In the first, an oxypalladation can produce a Pd-CH2-CH2-X species, which can undergo CO insertion into the Pd-C bond. Alternatively, an XCOPd species can form and add across the double bond. Loss of Pd-H can generate the a, /3-unsaturated ester, or a second carbonylation step can lead to succinate derivatives. 

There is a precedent for the isomerization of oxypalladation adducts (Section III, A, 2a and b), but it is surprising that no allylic alcohol is formed simply by Pd(II)-hydride elimination from the original oxypalladation adduct. 

The first oxypalladation adducts from dienes were obtained by the reaction of dienes in basic alcohol media... 

There is, however, one problem which arises from the Pd(II)-hydrogen interaction picture of the decomposition of the oxypalladation adduct. Based on analogy with Pd (II)-alkyl chemistry, the most likely mode of decomposition of the oxypalladation adduct would be palladium (II) hydride elimination to give vinyl alcohol, which would re-... 

Arai et al. reported that asymmetric tandem cyclization of the dialkenyl alcohol 182 in the presence of Pd(II)— spiro bis(isoxazoline) catalyst gave the bicyclic heterocycle 183 in 89% yield with 82% ee (Scheme 61).132d The reaction proceeds through Wack-er-type oxypalladation, formation of the palladacycle 185 by carbopalladation of the resulting alkylpalla-dium intermediate 184, elimination of HX, and subsequent reductive elimination of Pd(0) to give the product 183. 

Intramolecular cyclization of alcohols to 1,3-dienes can lead to fused tetrahydrofurans and tetrahydropyrans. In this reaction, using 5 mol% Pd(0Ac)2, the first step involves a trans oxypalladation to form the heterocyclic ring and a jr-allyl palladium complex. In the presence of 0.2 equiv. of LiCl, AcO adds trans to the r-allyl, leading to a net cA-l,4 addition of oxygen nucleophiles to the diene. When LiCl is omitted, the AcO adds to the same face of the r-allyl as the palladium, giving net tra/ 5-1,4-addition of oxygen groups to the diene (Scheme 41). 

Asymmetric domino cyclization of the unsaturated alcohol 71 proceeded smoothly to give the bicyclic compound 72 with 82% ee in 89% yield as a single diastereomer using a spiro bis(oxazoline) ligand which has a chiral spiro skeleton and two oxazoline rings. The reaction proceeds via the formation of 73 and 74 as oxypalladation products. BQ was used as a reoxidant [36],... 

Carbonylation of alkenes having an amino or hydroxy group (AH or BH = OH or NHR) 140, 142 and 144 offers interesting synthetic methods for cyclic compounds. The 4-pentenylamine or alcohol 140 is converted to 141 via amino or oxypalladation, followed by carbonylation. The amino alcohol 142 gives 143 by palladation and carbonylation by path a. The homoallylic amine or alcohol 144 is converted to lactone or lactam ester 145 by path c [60]. 

Upon treatment with a Pd(II) catalyst, keto allylic diols or derivatives deliver the corresponding spiroketal through oxypalladation on the activated double bond of the intermediate lactol (2013CEJ11613). Borrero and Apo-nick used this method to form the spiroketal core of acortatarin A from keto alcohol 16 that bears an aUylic methyl ether moiety. When alcohol 16 was treated with Pd(PhCN)2Cl2 in CH2CI2 at 0 °C, a spiroketahzation took place albeit with no diastereoselectivity as compounds 17 and 17 were obtained in a 1 1 ratio. After separation, spiroketal 17 was transformed into acortatarin A in five steps (Scheme 11) (2012JOC8410). 

A similar experiment with an unsaturated alcohol reported by Stoltz also implies that syn oxypalladation occurs. Again, the observation of deuterium in the product implies that the alkoxyalkylpalladium intermediate contains the palladium cis to the alkoxo group and trans to the deuterium label. The stereochemical outcome of catalytic cyclizations reported by Wolfe also imply that cis oxypalladation occurs during certain transformations, as shown in Equation 9.82. 

The Wacker reaction of ethylene or terminal aUcenes proceeds via nncleophilic attack of water to coordinated alkenes to give oxypalladation intermediates from which /3-Pd-H elimination takes place. This process produces vinyl alcohols, which, nnder the influence of palladium, lead to acetaldehyde or methyl ketones as the final prodnct (Scheme 1). 

The use of other oxygen nncleophiles such as acetic acid or alcohols also results in oxypalladation. Subsequent 8-Pd-H elimination produces vinyl acetates or vinyl ethers. However, these are not necessarily the final products. When acetic acid is used as the nucleophile, ally lie acetates often become the major product. In the case of alcohols, another alcohol reacts with the resulting vinyl ether to give an acetal (Scheme 2). Focusing on such product compositions, the oxypalladation of alkenes with carboxylic acids and alcohols followed by dehydropalladation is described here. 

D. OXYPALLADATION OF ALKYNES WITH CARBOXYLIC ACIDS AND ALCOHOLS... 

In summary, oxypalladation of unsaturated carbon-carbon bonds followed by Pd—H elimination has been studied extensively with aUcenes using carboxylic acids and alcohols, but not much with alkynes. The chirality generated by this type of... 

Oxygen nucleophiles such as water, alcohols, and acetic acid react with alkenes coordinated to PdXj (X = Cl, OAc, etc.) to give oxypalladation adducts. In general, a subsequent pathway is /3-Pd—elimination from the intermediate as shown in Scheme 1. 

As shown in Scheme 32, when allylilc alcohols are allowed to react with vinyl ethers, the resulting a--bond in oxypalladation intermediate adds intramolecularly to the C=C bond of allylic moiety.f Subsequent (3-Pd—elimination leads to cyclic acetals. With this method, albeit stoichiometric in palladium(II), a unique approach to the synthesis of prostaglandins was attained by Larock and Lee as shown in Scheme 33.1 ... 

Cyclization of homoallylic alcohols bearing an OH group at the allylic position gives an oxypalladation intermediate in which the OH group is in the adjacent position of Pd—C bond. In such cases, elimination of Pd—OH predominates to give dihydrofurans as shown in Scheme 34.The same type of cyclization and elimination occurs with /3-diketones bearing allylic alcohol moiety. The cyclization proceeds via keto-enol tautomerism (Scheme 35). 

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