Ni-Catalyzed HDA reaction

Our studies on the Ni-catalyzed HDA reaction of acyclic and cyclic enones provided some additional information. The reaction of MVK with NBD is highly exo selective (Scheme 7, Table 3(a)), whereas the cyclic enones and lactones give endo adducts (Eq. 9). Two differences are immediately evident for these substrates the presence of the P-cw-sub-stituent and the frozen s-trans geometry for cyclic dienophiles (Fig. 3). 

A detailed study of the effect of the nature and the size of phosphine ligands on the exo/endo selectivities of Ni-catalyzed HDA reactions was carried out by Yoshikawa and co-workers. The audiors attempted to correlate the cone angle of the phosphines and the observed exo/endo selectivities, but no clear trend emerged from these studies. Thus, many details of the mechanism in the metal-catalyzed HDA reaction still remain unsolved. 

Figure 5. Two possible metallocycles in the Ni-catalyzed HDA reaction of NBD and a cyclic enone.

Based on the proposed mechanism for the Ni-catalyzed HDA reaction described in Section IIB, reaction pathways leading to these different regioisomers are summarized as in Scheme 11. Unfortunately, we do not yet have a good e, planation to rationalize our observations on the regioselectivities. Detailed mechanistic studies have to be carried out to understand these results fully. 

Scheme 64 Early- and late-stage applications of Cr(ni)-catalyzed HDA reactions to leucascandrolide A and phorboxazole A [117, 118]...

Similar studies of the regioselectivity in the HDA reaction between 2-substituted norbomadienes and unactivated terminal acetylenes catalyzed by a cobalt catalyst were also undertaken. Unfortunately, 2-sub-stituted norbomadienes are much less reactive with unactivated acetylenes in the cobalt-catalyzed HDA reaction than with electron-deficient olefins in the Ni-catalyzed HDA cycloadditions. When an electron-withdrawing group (Y = COOMe) or an electron-donating group (Y = OMe) is attached to the 2-position of the NBD, no desired [2 + 2 + 2] cycloadduct is observed with 1-hexyne, even in refluxing toluene for three days under the usual cobalt-catalyzed conditions (Scheme 12). Instead, some NBD dimers and acetylene trimers are detected. With a... 

Similar studies on the cobalt-catalyzed HDA reaction between various 7-substituted norbomadienes and an unactivated terminal acetylene, 1-hexyne, were also investigated (Scheme 16, Table 11). Although the yields remain high, the anti/syn selectivities are poor compared with the corresponding Ni-catalyzed cycloadditions. 

During the studies of the nickel-catalyzed HDA reactions between substituted norbomadienes with various dienophiles, we noticed that some dienes undergo a [2 + 2] cycloaddition instead of a [2 + 2 + 2] cycloaddition. As shown earlier (Section IID, Eq. 14), 2-TMS-substi-tuted NBD reacts with acrylonitrile in the presence of Ni(COD)2/2PPh3, to afford a mixture of [2 + 2 + 2] and [2 -i- 2] adducts. In some cases, the... 

Table 6. HDA Reaction of 19 with Different Dienophiles Catalyzed by Ni(COD)2/PPh3...

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