Difunctionalization of Conjugated Dienes

Palladium(II)-promoted oxidative 1,4-difunctionalization of conjugated dienes with various nucleophiles is a useful reaction [98], The reaction is stoichiometric with respect to Pd(II) salts, but it can be made catalytic by use of Pd(0) reoxidants. 1,4-Difunctionalization with the same or different nucleophiles has wide synthetic application. The oxidative diacetoxylation of butadiene with Pd(OAc)2 proceeds by acetoxypalladation to generate the 7i-allylpalladium 136, which is attacked by acetoxy anion as the nucleophile, and (E)-, 4-diacctoxy-2-butcnc (137) is formed with 3,4-diacetoxy-1-butene (138) as the minor product. The commercial process for 1,4-diacetoxy-2-butene (137) by the reaction of butadiene, AcOH and O2 has been developed using a supported Pd catalyst containing Te. 1,4-Butanediol (139) and THF are produced commercially from l,4-diacetoxy-2-butene (137) [99]. 

The stereoselective cis diacetoxylation of 5-carbomethoxy-l,3-cyclohexadiene (146) has been applied to the synthesis of /-shikimic acid (147). 

The following Pd-catalysed stereoselective transformations of 142 and 143 are possible. The Pd-catalysed reaction of the cis product 143 with malonate gives the coproduct 148 with retention of the stereochemistry. However, reaction of 143 without the Pd catalyst affords the trans product 149. The cis product 142 is a mesa form and can be converted to the chiral half ester 150 by enzyme-catalysed partial hydrolysis. 

By changing the relative reactivity of the allylic leaving groups, namely acetate and the more reactive carbonate, either enantiomer of 4-substituted cyclohexenyl acetate is accessible by choice. The Pd-catalysed reaction of the allylic acetate moiety of 150 with malonate affords 151. Acetylation of 151 and Pd-catalysed 1,4-elimination of 

followed by hydrolysis, gives the (/ )- , 3-dienecarboxylic acid 152. Then the acetoxylactone 153 can be prepared by the Pd-catalysed intramolecular trans-1,4-functionalization of the 1,3-cyclohexadiene 152. On the other hand, the acetate 155 is obtained by the Pd-catalysed chemoselective displacement of the allylic carbonate moiety in 154 with malonate under neutral conditions. The (5)-1,3-dienecarboxy 1ic acid 156 is obtained by Pd-catalysed 1,4-elimination of 155. The Pd-catalysed 1,4-functionalization of the 1,3-cyclohexadiene 156 and acetylation, afford 157, which is an enantiomer of 153 [101]. 

---

Reaction of conjugated dienes with aryl and alkenyl halides is treated in Section 3.2 and oxidative difunctionalization of conjugated dienes with Pd(II) is treated in Section 11.3. This chapter covers other reactions of conjugated dienes as major reactants. 

Addition to dienes. 1,4-Difunctionalization of conjugated dienes, especially proceeding with good regio- and stereoselectivity, is synthetically desirable. Access to 4-stannyl-2-alkenylboranes by the Pd(0)-catalyzed addition is such a process. 

Difunctionalization of conjugated dienes. Dienes are metallated by treatment with active Mg. A variety of compounds can be prepared by the subsequent reaction with electrophiles such as epoxides and CO2. 

Several types of Pd-catalyzed or -promoted reactions of conjugated dienes via TT-allylpalladium complexes are known. The Pd(II)-promoted oxidative difunctionalization reactions of conjugated dienes with various nucleophiles is treated in Chapter 3, Section 4, and Pd(0)-catalyzed addition reactions of conjugated dienes to aryl and alkenyl halides in this chapter. Section 1.1.1. Other Pd(0)-catalyzed reactions of conjugated dienes are treated in this section. 

---