Rh-Catalyzed [4+1] Reaction of Cyclopropyl-Capped Dienes (but not Common Dienes) and Carbon Monoxide: Reaction Development and Mechanistic Study

Transition-metal-catalyzed [4 + 1]reaction of dienesand carbonmonoxide (CO) is the most straightforward and easily envisioned cyclizationfor the synthesis of five-membered carbocycles, which are ubiquitouslyfound in natural products and functional molecules. Unfortunately,no test of this reaction was reported, and consequently, chemistsdo not know whether such kind of reaction works or not. Herein, wereport that the [4 + 1] reaction of common dienes and CO cannot work,at least under the catalysis of [Rh(cod)Cl](2). However,using cyclopropyl-capped dienes (also named allylidenecyclopropanes)as substrates, the corresponding [4 + 1] reaction with CO proceedssmoothly in the presence of [Rh(cod)Cl](2). This [4 + 1]reaction, with a broad scope, provides efficient access to five-memberedcarbocyclic compounds of spiro[2.4]hept-6-en-4-ones. The [4 + 1] cycloadductscan be further transformed into other molecules by using the uniquechemistry of cyclopropyl groups present in these molecules. The mechanismof this [4 + 1] reaction has been investigated by quantum chemicalcalculations, uncovering that cyclopropyl-capped dienes are straineddienes and the oxidative cyclization step in the [4 + 1] catalyticcycle can release this (angular) strain both kinetically and thermodynamically.The strain release in this step then propagates to all followed COcoordination/CO insertion/reductive elimination steps in the [4 +1] catalytic cycle, helping the realization of this cycloadditionreaction. In contrast, common dienes (including cyclobutyl-cappeddienes) do not have such advantages and their [4 + 1] reaction suffersfrom energy penalty in all steps involved in the [4 + 1] catalyticcycle. The reactivity of ene-allenes for the [4 + 1] reaction withCO is also discussed.

Automated summary

Transition-metal-catalyzed [4 + 1] reaction of dienes and carbon monoxide (CO) can efficiently synthesize five-membered carbocycles. However, the reaction does not work with common dienes, but it proceeds smoothly when using cyclopropyl-capped dienes as substrates under the catalysis of [Rh(cod)Cl](2). This reaction provides a versatile method to access spiro[2.4]hept-6-en-4-ones and the products can be further transformed by utilizing the unique chemistry of the cyclopropyl groups.