Highly Enantioselective Rhodium(I)‐Catalyzed Activation of Enantiotopic Cyclobutanone CC Bonds

Abstract

The selective functionalization of carbon-carbon σ bonds is a synthetic strategy that offers uncommon retrosynthetic disconnections. Despite progress in C-C activation and its great importance, the development of asymmetric reactions lags behind. Rhodium(I)-catalyzed selective oxidative additions into enantiotopic C-C bonds in cyclobutanones are reported. Even operating at a reaction temperature of 130 °C, the process is characterized by outstanding enantioselectivity with the e.r. generally greater than 99.5:0.5. The intermediate rhodacycle is shown to react with a wide variety of tethered olefins to deliver complex bicyclic ketones in high yields.

Cycloaddition of cyclobutenone and azomethine imine enabled by chiral isothiourea organic catalysts

“…It has been observed that both chemo- and stereo-selectivities are difficult to control in these otherwise elegant reactions, likely due to the high reactivity of the metal catalyst and the metal-bound intermediates. 6 , 7…”

Rhodium-Catalyzed Enantioselective Cycloisomerization to Cyclohexenes Bearing Quaternary Carbon Centers

“…Carbometallation could occur with the opposite regioselectivity to generate 5 , which upon reductive elimination would yield bicyclic heptanones 6 (Figure 1c-route B). 15a On the basis of our previous study, 13 we realized that the key challenge would be to identify a catalyst to favor the proposed cycloisomerization, in preference to the known hydroacylation and carboacylation 15 pathways.…”

Modular Access to Substituted Azocanes via a Rhodium-Catalyzed Cycloaddition–Fragmentation Strategy

“…This observation is likely to have wider implications given the emerging family of processes that are dependent upon this key mechanistic step. 8b , 13 , 14 Current studies are focused upon the development of other medium-ring methodologies inspired by the mechanistic insights gained here.…”