Conjugated diene, 1,2-addition synthesis

Diacetoxylation of various conjugated dienes including cyclic dienes has been extensively studied. 1,3-Cyclohexadiene was converted into a mixture of isomeric l,4-diacetoxy-2-cyclohexenes of unknown stereochemistry[303]. The stereoselective Pd-catalyzed 1,4-diacetoxylation of dienes is carried out in AcOH in the presence of LiOAc and /or LiCI and beiizoquinone[304.305]. In the presence of acetate ion and in the absence of chloride ion, /rau.v-diacetox-ylation occurs, whereas addition of a catalytic amount of LiCl changes the stereochemistry to cis addition. The coordination of a chloride ion to Pd makes the cis migration of the acetate from Pd impossible. From 1,3-cyclohexadiene, trans- and ci j-l,4-diacetoxy-2-cyclohexenes (346 and 347) can be prepared stereoselectively. For the 6-substituted 1,3-cycloheptadiene 348, a high diaster-eoselectivity is observed. The stereoselective cij-diacetoxylation of 5-carbo-methoxy-1,3-cyclohexadiene (349) has been applied to the synthesis of dl-shikimic acid (350). 

Diels-Alder reaction (Section 10 12) Conjugate addition of an alkene to a conjugated diene to give a cyclohexene denva tive Diels-Alder reactions are extremely useful in synthesis... 

In addition to the synthetic applications related to the stereoselective or stereospecific syntheses of various systems, especially natural products, described in the previous subsection, a number of general synthetic uses of the reversible [2,3]-sigmatropic rearrangement of allylic sulfoxides are presented below. Several investigators110-113 have employed the allylic sulfenate-to-sulfoxide equilibrium in combination with the syn elimination of the latter as a method for the synthesis of conjugated dienes. For example, Reich and coworkers110,111 have reported a detailed study on the conversion of allylic alcohols to 1,3-dienes by sequential sulfenate sulfoxide rearrangement and syn elimination of the sulfoxide. This method of mild and efficient 1,4-dehydration of allylic alcohols has also been shown to proceed with overall cis stereochemistry in cyclic systems, as illustrated by equation 25. The reaction of trans-46 proceeds almost instantaneously at room temperature, while that of the cis-alcohol is much slower. This method has been subsequently applied for the synthesis of several natural products, such as the stereoselective transformation of the allylic alcohol 48 into the sex pheromone of the Red Bollworm Moth (49)112 and the conversion of isocodeine (50) into 6-demethoxythebaine (51)113. 

Nickel-bpy and nickel-pyridine catalytic systems have been applied to numerous electroreductive reactions,202 such as synthesis of ketones by heterocoupling of acyl and benzyl halides,210,213 addition of aryl bromides to activated alkenes,212,214 synthesis of conjugated dienes, unsaturated esters, ketones, and nitriles by homo- and cross-coupling involving alkenyl halides,215 reductive polymerization of aromatic and heteroaromatic dibromides,216-221 or cleavage of the C-0 bond in allyl ethers.222... 

Reaction of iodine with non-conjugated dienes has been applied to the synthesis of cyclic compounds100. Although the reactions of 1,5-hexadiene, 1,6-heptadiene and 1,7-octadiene with I2 in CCI4 gave exclusively products arising from addition to the two double bonds, the introduction of dialkyl substituents into the 4-position of 1,6-heptadiene completely changed the reaction course in favor of cyclization (equation 85). 

Since the oxidative addition occurs with retention of configuration and the transmetallation is also stereospecific with retention, the method is extremely valuable for the stereoselective synthesis of conjugated dienes. The... 

An unusual synthesis of acyldienes from conjugated dienes, carbon monoxide, and alkyl or acyl halides using cobalt carbonylate anion as a catalyst should be mentioned here (57). The reaction apparently involves the addition of an acylcobalt carbonyl to a conjugated diene to produce a l-acylmethyl-7r-allylcobalt tricarbonyl, followed by elimination of cobalt hydrocarbonyl in the presence of base. The reaction can thus be made catalytic. Since the reaction was discussed in detail in the recent review by Heck (59), it will not be pursued further here. 

Complexes of unsymmetrically substituted conjugated dienes are chiral. Racemic planar chiral complexes are separated into their enantiomers 84 and 85 by chiral HPLC on commercially available /f-cyclodextrin columns and used for enantioseletive synthesis [25]. Kinetic resolution was observed during the reaction of the meso-type complex 86 with the optically pure allylboronate 87 [26], The (2R) isomer reacted much faster with 87 to give the diastereomer 88 with 98% ee. The complex 88 was converted to 89 by the reaction of meldrum acid. Stereoselective Michael addition of vinylmagnesium bromide to 89 from the opposite side of the coordinated Fe afforded 90, which was converted to 91 by acetylation of the 8-OH group and displacement with EtjAl. Finally, asymmetric synthesis of the partial structure 92 of ikarugamycin was achieved [27],... 

Addition to unsaturated centres (C=0, C=N, C=C) adjacent to the diene can occur in a diastereoselective fashion, and asymmetric synthesis can be carried out if the diene complex is optically active. As Fe(CO)3 coordinates from one face of the unsymmetrically substituted conjugated dienes, the complexes are chiral and can be resolved to the optically active forms 93 and 94, which are used for asymmetric synthesis. The optically active acetyldiene complex 95, obtained by the acetylation of the optically active diene complex 94, reacts diastereoselectively with PhLi to give 96. The optically active tertiary alcohol 97 is obtained by its decomplexation. The enantiomer 100 can be synthesized by the opposite operation namely the benzoylation of 94 to give 98, and subsequent reaction of MeLi gives 99. The enantiomer 100 is obtained by decomplexation [16]. 

Conjugated dienes have alternating single and double bonds. They may undergo 1,2- or 1,4-addition. Allylic carbocations, which are stabilized by resonance, are intermediates in both the 1,2- and 1,4-additions (Sec. 3.15a). Conjugated dienes also undergo cycloaddition reactions with alkenes (Diels-Alder reaction), a useful synthesis of six-membered rings (Sec. 3.15b). 

Acetoacetic Ester Synthesis Section 20.4 Addition of an Alcohol to an Aldehyde or a Ketone Section 18.9 Figure 18.5 Addition of a Carbene to an Alkene Section 11.8 Addition to a Conjugated Diene Section 11.13 Addition of a Grignard Reagent to an Aldehyde or a Ketone Section 18.6... 

The ruthenium-catalyzed addition of diazo compounds to alkynes has led to the selective synthesis of functional 1,3-dienes by the combination of two molecules of diazoalkane and one of alkyne [106] (Eqs. 82,83). The stereoselective formation of these conjugated dienes results from the selective creation of two C=C double bonds rather than leading to the cyclopropene derivative. This is expected to be due to the possibility for the C5Me5RuCl moiety to accomodate two cis carbene ligands. 

As discussed in the last sections, addition of sodium methoxide-alkenylborane complexes to copper bromide-dimethyl sulfide at 0 °C immediately gives conjugated dienes. However, if the temperature is lowered to —15 °C, the dark blue-black complex formed is stable and can be trapped by allylic halides to afford a stereochemically defined synthesis of (4 )-1,4-dienes (Eq. 93) 148). 

The usual reaction of alkenes with conjugated dienes is the Diels-Alder synthesis. This addition does not apply, with a few exceptions, to cycloaddition of fluorinated alkenes. The presence of fluorine atoms, especially if there are more of them around the double bond, retards the cycloadditions forming six-membered rings, and accelerates the (2 + 2) cycloaddition to form four-membered rings. 

---