Addition of two nucleophiles

In this reaction two carboxylate anions are added in a 1,4-fashion to a conjugated diene in an oxidation process involving removal of two electrons. The catalyst employed is a palladium(II) salt, usually Pd(OAc)2. The 1,4-diacyloxylation may be an intermolecular or 

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The 3,6-dehydro compound 4 undergoes an oxidative route of reaction resulting in addition of two nucleophiles from reagent or solvent to the strained C-C bond.92... 

Addition of two nucleophiles to an electron-rich double-bond ... 

The addition of two nucleophiles to a coordinated //6-arene is a synthetically important goal. A one-pot synthesis of 1,3-disubstituted cyclohexadienes involving an initial ipso addition to fluoroarene complexes is possible. Indeed, p-fluorotoluenetricarbonylchromium complex 22c reacts with isobutyronitrile carbanion (2 equiv.) in THF to give, after 5 days at —30 °C and acidic treatment under CO atmosphere, the cyclohexadiene 66 in 47 % yield (Scheme 31) [53] the yield can reach 75 % after several weeks Carbon monoxide was used in order to decoordinate the // -cyclohexadiene intermediate and to recover Cr(CO)6 needed for the preparation of the starting material [54]. 

An example of cis-addition of two nucleophiles to a 1,3-diene catalyzed by Pd(II) is shown in Scheme 21. Pd-H elimination is competitive with addition of the second nucleophile affording either mono or di-unsaturated bicyclic products. 

For simple triorganotin halides it has been established that the rate of the inversion process is accelerated if external nucleophiles, e.g., pyridine, are present (123). Based on the fact that the inversion process is second order in nucleophile, two possible mechanisms have been proposed (i) addition of a nucleophile to the metal center, followed by addition of a second nucleophile and displacement of the halogen atom giving the achiral transition state (A) (see Fig. 23) or (ii) addition of two nucleophiles without loss of the halogen atom to give the achiral transition state (B), Fig. 23 (123). 

The 1,4-addition of two nucleophiles to 1,3-dienes is an oxidation reaction and involves nucleophilic attacks on (jr-diene)- and (jr-allyl)palladium complexes. The principle and mechanism of this reaction are given in Eq.(32) and Scheme 8-6, and are exemplified with p-benzoquinone as the oxidant. 

Dienes can bind to metals in an t) or r fashion. Many metal complexes contain t) -diene ligands, and reactions of -ri -diene complexes are described in Section 11.7.2. However, other metals, particularly Pd(II), bind dienes and allenes in an t) fashion. The reactivity of these species has been exploited to develop useful synthetic methods and is described in this section. Backvall has developed chemistry based on nucleophilic addition to palladium-diene complexes to generate allyl products, which subsequently react with a second nucleophile to generate free organic products from 1,4-addition of two nucleophiles across the diene. The palladium(O) byproduct is then re-oxidized to Pd(II) with quinone. 

Often similar reactions proceed via the same intermediate. For example, the SnI solvolysis of f-butyl bromide and f-butyl iodide in water would both be presumed to proceed via the f-butyl cation. We could easily verify this conclusion by performing a competition experiment where the addition of two nucleophilic traps would give two products resulting from the same intermediate in the same ratio. Any deviation in products and ratios would indicate different intermediates. This is exactly the same concept that was used in our example of competition experiments, except now we compare the product ratio from two different reactants. 

Another example for the addition of two nucleophiles to 1,4-dimethoxycyclo-hexadienyliumiron complex salts is the sequential introduction of an aryl group and a malonitrile. In the first step, the aryllithium reagent adds to the 1-position of the 1,4-di-methoxycyclohexadienylium)iron complex salt (Scheme 4-172). Subsequent elimination of water or methanol under various conditions gives rise to l-aryl-4-methoxy-cyclohexadienyliumiron complexes. 

Having completed the intramolecular nitroso-Diels-Alder reaction, the shape of the bicyclic oxazinolactam 188 allowed for a diastereoselective successive addition of two nucleophiles (Scheme 41.40). The addition of methylmag-nesium bromide into 188 at 0°C because the carbonyl is activated by the N O bond, followed by sodium boro-hydride in acetic acid, delivers the cis-2,6 disubstituted piperidine precursor 190. The diastereoselectivity could be explained by the fact that the presence of the oxazino ring would force the C4a substituent of the N-alkoxypiperidi-nium unit 189 into a pseudoequatorial position, and the stereoelectronically axial attack of the hydride led diaster-eoselectively to the desired compound 190, which was eventually transformed into (-)-lepadin B 191. 

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