Oxypalladation alcohol additions

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... 

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. 

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). 

The oxidative addition reactions to alkenes promoted or catalyzed by PdCl2(CH3CN)2 have been classified based on the nature of the attacking species. Oxygen nucleophiles such as water, alcohols and carboxylic acids undergo oxypalladation, while ammonia, amines and their derivatives are typical nucleophiles for aminopalladation. Carbopalladation with active methylene compounds is also discussed The palladium-catalyzed intramolecular hetero- and carbopalladation of olefins is extensively used as the ring-forming step in the synthesis of a variety of heterocyclic and carbocyclic systems, and representative examples are provided. 

In addition, if a chiral secondary allylic alcohol is used, a stereospecific intramolecular oxypalladation and elimination can take place to give stereodeflned oxygen heterocycles such as tetrahy-drop)Tans (eq 11), 3,6-dihydro[2H]pyrans, dihydrofurans or spiroketals. ... 

Thereafter, a serial of palladium-catalyzed intramolecular C-ff activation of allylic C-H bonds (Scheme 2.4) was reported by White [9], who first developed a novel route for accessing chiral syn-l,2-amino alcohols enabled through the discovery of a Pd/sulfoxide-catalyzed diastereoselective allylic C-H activation reaction of chiral homoallylic Af-tosyl carbamates. The author discovered that the addition of bis-sulfoxide ligands (L-1) to Pd(OAc)2 promoted allylic C-H cleavage of a-olefins versus oxypalladation in the presence of weak oxygen nucleophiles (i.e., carboxylic acids). Evidences presented that the mechanism proceeds via Pd(ll)/sulfoxide-promoted allylic C-H cleavage to furnish a n-allylic palladium intermediate followed by counterion-promoted functionalization with the tethered Af-tosyl carbamate nucleophile. 

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