Cycloisomerization

These cyclizations are able to be performed with excellent levels of selectivity in numerous cases and have transformed cycloisomerization into a powerful tool for unique and complex molecular construction.

[2] Thiourea catalysts with pendant chiral backbones have shown to activate systems with tethered nitroalkane and ester motifs to induce asymmetric IMA.

[3] A functional stereodivergent organocatalyzed IMA/lactonization transformation in the synthesis of substituted dihydrofurans and tetrahydrofurans has been studied for its ability to construct important structural motifs in numerous natural products (figure 2).

[7] The synthesis of (–)–isopulo'upone demonstrated the utility of cationic Cu(II)bis(oxazoline) complex catalyzed IMDA reactions to give bicyclic products with as many as four neighboring stereogenic centers (figure 3).

[8] N–heterocyclic carbenes (NHCs) are an emerging class of organocatalysts that are able to induce Umpolung reactivity as well as normal polarity transformations, however until recently these have not been broadly used in total synthesis due to limited substrate scope.

[2] As synthesis quarrels to build complex structural motifs in the presence of inductive, stereoelectronic and steric demands this rearrangement has recently been developed as a robust method for constructing carbo– and heterocyclic scaffolds with excellent chemo–, regio– and diastereoselective outcomes.

[16] A versatile function of Au(I) catalyzed enyne cycloisomerization is the construction of asymmetric medium–sized rings, which is a challenge in the synthesis of ornamented molecular design.

[17] Computational studies show that the syn–intermediate, 29, is formed under kinetic control and it is suggested that it is in equilibrium with the thermodynamically favorable cis–intermediate which may be intercepted by a nucleophile leading to vinyl cyclopropane diene products, however this is beyond the scope of this article.

[20] It is suggested through DFT calculations that the 5–exo–dig cyclization is favored for Au(I) complexes as it has a lower activation barrier relative to the 6–endo–dig and indeed numerous examples of vinylcycloalkenes products produced via an initial 5–exo–dig are given (figure 11).

[20] The divergent reactivity of these transition metal catalyzed cycloisomerizations further demonstrates their synthetic utility in building unique molecular skeletons.