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

Abstract

The selective functionalization of carbon-carbon s bonds is a synthetic strategy that offers uncommon retrosynthetic disconnections. Despite progress in CÀC activation and its great importance, the development of asymmetric reactions lags behind. Rhodium(I)-catalyzed selective oxidative additions into enantiotopic C À C bonds in cyclobutanones are reported. Even operating at a reaction temperature of 130 8C, 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.Scheme 1. Asymmetric reactions involving a CÀC bond cleavage step.

Cooperative activation of cyclobutanones and olefins leads to bridged ring systems by a catalytic [4 + 2] coupling

“…3b, 37% ee). 48–49 This result suggests that the “cofactor”-assisted C–C activation mode is amenable to asymmetric catalysis, and work on this topic is ongoing.…”

Catalytic enantioselective synthesis of quaternary carbon stereocentres

“…10d). 90 In an example exploiting enantioselective C–H activation, the Yu group reported palladium(II)-catalyzed group-selective functionalizations of diphenylacetic acid derivatives. 91 Utilizing a palladium catalyst containing protected-amino acid ligands, various diphenylacetic derivatives underwent selective alkenylation with acrylates or styrenes exemplified by the conversion of 100→101 (Fig.…”

“…d , The enantiotopic rhodium-catalyzed insertion into a C–C bond of cyclobutanone 98 , followed by intramolecular insertion of the rhodium-acyl intermediate to give bridged-tricyclic ketone 99 . 90 Bn, benzyl; Me, methyl; cod, 1,5-cyclooctadiene; t -Bu, tert -butyl. e , The palladium(II)-catalyzed enantiotopic C–H activation of sodium diphenylacetate 100 templated by the carboxylate group, followed by bimolecular Heck coupling with styrene to give product 101 .…”

Carbon–carbon bond activation of cyclobutenones enabled by the addition of chiral organocatalyst to ketone

“…Due to the high reactivities of the metal catalyst and the metal-bound intermediates, chemoselectivity is generally difficult to control. In addition, it still remains difficult to achieve high levels of enantioselectivity using the transition metal-catalysed C–C bond activation approach 6 7 8 9 10 11 . In many cases, intramolecular reactions were used to overcome the challenging selectivity issues.…”

“… 36 37 have pioneered the non-enantioselective C–C bond activation of four-membered cyclic ketones to react with olefins in an intramolecular fashion 38 39 40 41 42 . Recently, impressive enantioselective intramolecular reactions enabled by the metal-catalysed C–C bond activation of four-membered cyclo-ketones were reported by the groups of Dong 10 and Cramer 11 . The related cyclobutanol has also been used in the synthesis via C–C bond breaking to build sophisticated molecules, as illustrated by Trost, 43 Tu 44 45 and others 43 44 45 46 47 .…”