Alkene expanded substrate scope

As shown above, the PKR has tremendous synthetic potential due to a rapid increase in synthetic complexity from simple starting materials. The frequent presence of five-membered rings in synthetic targets has led to numerous applications. In turn, these applications have inspired improved conditions that allow the PKR to occur under mild conditions with with predictable regiocontrol and stereocontrol. Efforts continue to optimize the reaction for improved alkene regiocontrol, absolute stereocontrol, expanded substrate scope (especially for unreactive alkenes and medium-size ring formation) and catalytic turnover. 

More specifically, 3,5-di-ferf-butylphenyl substitution on the 3,3 -position of the binaphthol backbone (260) provided overall best yields and selectivities. Using catalyst 260, the authors expanded the scope of substrates to include aliphatic and aromatic nitro-alkenes, and a-substituted P-ketoesters, while maintaining good yields and enantiomeric ratios (Scheme 71). 

In the proposed mechanism, the Rh catalyst selectively reacts with the diyne moiety of 525 to form metallacycle A. Alkene insertion to the Rh-C bond and CO coordination gives metallacycle B. From metallacycle B, CO insertion to the Rh-C bond gives metallacycle C or C , and subsequent reductive elimination affords cycloadduct 526. Reductive elimination of Rh from metallacycle B prior to CO insertion gives the [2+2+2] cycloadduct 527. Kaloko et al. forther expanded the scope of this novel [2+2+2+1] cycloaddition process to cyclohexene-diyne substrates 528, which gave the corresponding tetracyclic products 529 as single diastereomers in high yields (Scheme 2-78). 

For a long time, rhodium catalysts were privileged for the transformation of carbonyl functions into olefins [82]. Nevertheless, as copper became more successful, a new methodology based on this inexpensive metal has been welcome. Lebel et al. developed a process, similar to the one based on the Willdnson catalyst using [Cu(Cl)(NHC)] (Scheme 8.30) [83]. Using these copper complexes, they were able to expand the scope to a large variety of substrates. Aliphatic alkenes, dienes, styrenes and heteroarenes were successfully functionalized. Whereas the rhodium systems underwent decomposition in the case of substrates with a nitro moiety, copper complexes showed high tolerance and... 

Later, they expanded the substrate scope of the reaction using different electron-deficient alkenes such as maleimides... 

A number of recent examples have served to expand the scope of chiral Cu(II) catalysts and substrates applicable in 1,3-dipolar cycloadditions of nitrones to electron-deficient alkenes. Saito and coworkers demonstrated Cu(OTf)2/bis(imine) (310) to be an efficient catalyst for highly endo and enantioselective cycloaddition of nitrones (309) with (253) [100]. Interestingly, the substitution of the aromatic imine subunit of the bis(imine) ligands (314a-c) was found to have a dramatic effect on chemical yields and the levels of enantioselectivity observed (Scheme 17.69). 

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