Addition of Carbon and Oxygen

In a related reaction, tetraenes 32 underwent carbocyclization to give allylic ethers 33 (Eq. (11.24)) [50]. The reaction can be considered as an intramolecular telomerization reaction, and leads to the 1,4-addition of a carbon and an oxygen 

The use of the terminally hydroxy-substituted tetraene substrate 34 in this reaction made it possible to determine the stereochemistry of the overall 1,4-addition of the carbon and oxygen functions to the diene (Eq. (11.25)) [51]. Palladium-catalyzed reaction of 34 in THF under reflux afforded product 36 in which a net antt-1,4-addition had occurred. The stereochemistry was consistent with an intermediate 7i-allyl complex 35, in which carbon and palladium have added to the upper diene in a syn manner. Intramolecular attack by the hydroxy group from the face opposite to that of palladium would give the product observed. In this reaction, an interesting 1,2-stereoinduction by the methyl group occurred. 

In a reaction similar to those detailed in Eq. (11.19) and Eq. (11.22), Grigg et al. [43, 44] also employed lithium acetate as an oxygen nucleophile in place of the amine and stabilized carbon nucleophile, respectively, as presented in these equations. This led to a 1,4-addition of carbon and oxygen to the conjugated diene. 

Larock et al. [53] have studied the palladium-catalyzed arylation of 1,3-dienes followed by intramolecular attack by an oxygen nucleophile. o-Iodophenols and o-iodobenzyl alcohol were used as substrates. These reactions, which essentially are annelation reactions, lead to a 1,2-addition onto the conjugated dienes, and will not be discussed further here. Amides were also used as nucleophiles in these reactions. 

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The Michael reaction is addition of a carbon nucleophile to the /3 position of an a,/3-unsaturated carbonyl compound or its equivalent. It also may be called a 1,4-addition reaction (the carbonyl oxygen is counted as 1 and the )3-carbon as 4). The conjugation of the v bond with thp carbonyl group imparts positive character to the /3 position, making it susceptible to reaction with a nucleophile. The product of this reaction, an enolate ion, also is stabilized by resonance. 

Intramolecular reactions of allylic acetates with conjugated dienes catalyzed by Pd(0) lead to a 1,4-addition of a carbon and an oxygen nucleophile to the diene. The reaction, which is formally an isomerization, involves tw different yr-allyl complexes (Scheme 8-4) [44]. Reaction of 22 in the presence of the Pd(0) catalyst Pd2(dba)3-CHCl3 (dba = dibenzyl-ideneacetone) and LiOAc/HOAc in acetonitrile at reflux produces the cyclized isomer 25 in 62% yield. The double bond was exclusively of E stereochemistry, while the ring stereochemistry was a mixture of cis and tram isomers. Oxidative addition of the Pd(0) to the allylic acetate gives the intermediate jr-allyl complex 23. Subsequent insertion of a diene double bond into the allyl-palladium bond produces another jr-allyl intermediate (24), which is subsequendy attacked by acetate to give the product 25. 

The use of alcohol tetraene substrate 28 in this reaction made it possible to determine the stereochemistry of the overall 1,4-addition of the carbon and oxygen functions to the diene [Eq.(27)] [46]. Palladium-catalyzed reaction of 28 in THF at reflux afforded product 30 in... 

Intramolecular six-membered ring formation is also efficient. Treatment of bisdiene 62a with 0.05 equiv of a [Pd(OAc)2/3 PhjP] mixture in THF (65 °C, 24 h) affords the cyclized and intramolecularly trapped diene 63a in good chemical yield (82%) and with good diastereoselectivity (9 1 mixture of two diastereomers) (Scheme 20). The conversion of 62a to 63a is a unique cascade cyclization in that it constructs two new six-membered rings via the net 1,4-addition of the elements carbon and oxygen across a diene subunit. Three stereochemical elements are controlled in the cyclization of 62a to 63a. Two of these elements, the ( )-configuration of the double bond and the trans... 

Catalytic and stoichiometric additions of oxygen nucleophiles to coordinated dienes are summarized in Equations 11.33 and 11.34. Early studies involved 1,4-additions of two acetoxy or alkoxy groups across a diene. More recently, intermolecular additions of two different nucleophiles have been developed. The stereochemistry for additions across cyclic dienes makes this procedure particularly valuable. Conditions for either cis or trans additions have been developed. Cis addition is typically observed in the presence of added chloride, and trans addition occurs in the absence of chloride. Both intermolecular and intramolecular " 1,4 additions to dienes have been developed, and reactions of nitrogen and carbon nucleophiles have also been reported. More details on these processes are reported in Chapter 16. 

As shown in Scheme 23.2, oxygen-metalated enolate species (as opposed to carbon-bound keto tautomers) undergo 1,4-addition of a coordinated monomer, in a manner often likened to the Michael reaction, leading to the formation of the backbone carbon-carbon bond and the generation of a new enolate ligand capable of repeating the insertion process. As described later in this chapter, it has also been proposed that a bimetallic intermolecular version of this process might operate with certain zirconocene initiators, whereby attack occurs by a metal enolate at a monomer bound to a second metal. 

There are many examples of nucleophilic reagents that add to a, 3-unsaturated aldehydes and ketones in a manner in which the addition is formally 1,4. This result is called conjugate addition. Under basic conditions, these transformations involve initial attack by the nucleophile to the p-carbon atom, followed by electrophilic addition (normally of a proton) on the carbonyl oxygen the nucleophile and electrophile add at the 1 and 4 positions relative to one another. The enolate formed in the early stages of the reaction is generally quickly protonated to give an enol. The enol wiU subsequently tautomer-ize to the ketone. A general mechanistic scheme is shown below for the 1,4 addition of water to an a,p-unsaturated carbonyl system. 

Pd-catalyzed isomerization of l-acetoxy-2,7,9-decatrienes 10 to 11 formally involves a 1,4-addition of a carbon and an oxygen nucleophile to a conjugated diene moiety... 

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