1.4- Cyclohexadiene, homoallylic

The homoallylation product 16a presumably stems from oxidative cycloaddition of a Ni(0) species across the diene and aldehyde moieties of 15, leading to an oxanickellacycle intermediate 17 (path A, Scheme 5), which undergoes 0-bond metathesis with triethylsilane giving rise to a o-allylnickel 19. On the other hand, formation of 16b may start with addition of a Ni - H species upon the diene followed by intramolecular nucleophilic allylation as described in Eqs. 4-6 (path B). Alternatively, allylic transposition of the NiH group providing 20 from 19 may be related to the formation of 16b. The different reactivity between cyclohexadiene and many other acyclic dienes is also observed for the reaction undertaken under typical homoallylation conditions (see Scheme 14). 

Another advantage of the Et2Zn-Ni catalysis over the Et3B-Ni catalysis is that only the former can promote the reductive coupling of 1,3-cyclohexadiene with aldehydes (c.f., run 8, Table 3). For example, under the Et2Zn-Ni catalysis, 1,3-cyclohexadiene smoothly reacts with benzaldehyde at room temperature and provides 53 in 61% isolated yield (Scheme 13). Curiously, however, the product 53 is not the expected homoallylation product, but an allylation product. 

A rationale for the exceptionally low reactivity and the unusual reductive coupling pattern, allylation not homoallylation, associated with 1,3-cyclohexadiene is outlined in Scheme 13. In contrast to syn-trans dienes... 

Scheme 13 Ni-catalyzed allylation (not homoallylation) of benzaldehyde with 1,3-cyclohexadiene promoted by Et2Zn...

It has been demonstrated that the intramolecular Diels-Alder reaction is a simple and efficient entry to different tricyclic 2-azetidinones, with a six-membered ring fused to the (3-lactam nucleus. Homoallylic mesylate 60 was used for the stereoselective preparation of fused tricyclic 2-azetidinone 61 through a tandem one-pot elimination-intramolecular Diels-Alder reaction (Scheme 21) [68, 69]. In a similar way, starting from mesylate 62, elimination and intramolecular Diels-Alder reaction have allowed the preparation of enantiopure fused tetracyclic (3-lactam 63 (Scheme 22) [70]. 1,4-Cyclohexadiene 63 is prone to undergo aromatization to afford the tetracyclic p-lactam 64 containing a benzene ring, as illustrated in Scheme 22. 

Pancratistatln. The first total synthesis of ( )-pancratistatin (94) (Scheme 14), the structurally most complex of narciclasine alkaloids, was achieved by Danishefsky [27]. The requisite starting material, the substituted benzaldehyde 95 prepared from pyrogallol in six steps in 18% overall yield, was converted via the homoallylic alcohol 96 into the diene 97. Reaction of 97 with 2-nitrovinylsulphone yielded the cycloadduct 98, which on treatment with tributyltinhydride and 2,2 -azobisisobutyronitrile furnished the cyclohexadiene 99. Whilst the cyclisation of the silylether 99 or the derived phenol, under the influence of iodine, could not be accomplished, the more nucleophilic stannylether did participate in the desired ring closure and provided via the iminium salt, the iodolactone 100 on aqueous work-up. 

Nucleophilic attack occurs at C(2) of the diene. The 1,3-cyclohexadiene complex 66 is converted to the homoallyl anionic complex 67 by nucleophilic attack, and the 3-alkyl-1-cyclohexene 68 is obtained by protonation. Insertion of CO to 67 generates the acyl complex 69, and its protonation and reductive elimination afford the aldehyde 70 [20]. Reaction of the butadiene complex 56 with an anion derived from ester 71 under CO atmosphere generates the homoallyl complex 72 and then the acyl complex 73 by CO insertion. The cyclopentanone complex 74 is formed by intramolecular insertion of alkene, and the 3-substituted cyclopentanone 75 is obtained by reductive elimination. The intramolecular version, when applied to the 1,3-cyclohexadiene complex 76 bearing an ester chain at C(5), offers a good synthetic route to the bicyclo[3.3.1]nonane system 78 via intermediate 77 [21]. 

It was determined that carbon nucleophiles derived from carbon acids with p/fa > 22 or so are sufficiently reactive to combine with the diene ligand rapidly at —78°C to produce an anionic intermediate (Scheme 25). With a few exceptions, the regioselectivity favors formation of the homoallyl anionic complex from addition at C-2, by kinetic control. This intermediate can be quenched with protons to give the terminal alkene, or can react with excess CO to produce an acyl iron intermediate. Following the recipes of Collman s reaction, the acyl iron intermediate can lead to methyl ketones, aldehydes, or carboxylic acids. The processes are illustrated with the 1,3-cyclohexadiene complex (Scheme 25). ... 

Interaction between even more remote spins is possible in conjugated systems such as alkynes and allenes. is also commonly observed in homoallylic fragments (H-C-C=C-C-H). Large couphngs of this type are observed in in l,4-cyclohexadienes. Small homoallylic coupling is also observed across amides. Its magnitude is a function of conformations across peptide bonds (Figure 12.81)." ... 

This method has not yet found widespread use for the preparation of allylboronates. In fact, uncatalyzed hydroborations of dienes tend to provide the undesired regioiso-mer with the boron atom on a terminal carbon, i.e., homoallylic boranes. By making use of certain transition metal catalysts, however, Suzuki and co-workers found that (Z)-allylic catecholboronates such as 22 can be obtained in high yield from various substituted butadienes (e.g., isoprene. Equation 11) [44]. Whereas a palladium catalyst is the preferred choice for acyclic dienes, a rhodium catalyst (Rh4(CO)i2) was best for the hydroboration of cyclohexadiene. A suitable mechanism was proposed to explain the high regioselectivity of this process. In all cases, a reaction quench with benzaldehyde afforded the expected homoallylic alcohol product from a tandem hy-droboration/allylation (Section 6.4.1.4). 

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