How to Suppress C(<i>sp</i>²)–Rh–C(<i>sp</i>³) Reductive Elimination and Insert CO to Achieve Rhodium-Catalyzed [5 + 2 + 1] Cycloaddition of Yne-vinylcyclopropanes and CO: Answers from Experimental and Computational Investigatio

Rhodium-catalyzed [5 + 2 + 1] reaction of ene-vinylcyclopropanes (ene-VCPs) and CO is an efficient method for synthesizing eight-membered carbocycles (EMCs). However, the [5 + 2 + 1] reactions of yne-vinylcyclopropanes (yne-VCPs) are elusive. In theory, the direct reductive elimination for yne-VCPs is faster in forming C(sp2)–C(sp3) bonds, making the CO insertion disfavored. In this case, the [5 + 2] reaction instead of the [5 + 2 + 1] reaction would occur. In this study, we show that these hypotheses are corrected and supported by both experiments and quantum chemistry calculations. However, we found experimentally that the [5 + 2 + 1] reactions of yne-VCPs and CO can be realized for substrates with an ester or carbonyl tether and/or a substituent in their cyclopropane moiety. Further quantum chemistry calculations found that yne-VCPs with substituents in the cyclopropyl group adopt the [5 + 2 + 1] pathway, where alkyne insertion occurs ahead of CO insertion. The introduced substituents help the CO insertion and its followed reductive elimination, which consequently makes the [5 + 2 + 1] reaction dominate. However, yne-VCPs with an ester or carbonyl tether adopt a [5 + 1 + 2] pathway where CO insertion happens before alkyne insertion. The reason for this switch is that the carbonyl group in the tether coordinates with the Rh atom of the catalyst and assists CO insertion, which makes the generation of EMCs possible.