Many bi-and multi-cyclic natural products with sevenmembered carbocycles (Figure ) have significant biological activities. However, synthesizing these molecules and their analogs is still posing challenges to chemists. One of the major reasons is that the available reactions, methods, and strategies to build seven-membered carbocycles are limited. Therefore, developing new reactions to synthesize sevenmembered carbocycles with different substituents and stereochemistry, compared to those obtained by the known methods, is important to change this backwater in the science of synthesis. In our opinion, one of the most efficient and straightforward reactions, needed to be developed for the synthesis of sevenmembered carbocycles, is the transition metal-catalyzed [4+2+1] cycloaddition of diene-enes/diene-ynes/diene-allenes and carbon monoxide (CO), considering that these substrates are readily accessible and CO is cheap and abundant. However, realization of this reaction has obstacles, since [4+2], [2+2+1] cycloadditions and other side reactions could overwhelm the desired [4+2+1] cycloaddition. It was reported by that the [2+2+1] reactions were usually the outcomes for the reactions of diene-enes/diene-ynes/dieneallenes and CO under the rhodium catalysis. Only in one example, the [4+2+1] product was observed as a side product (Scheme 1a). 4a This observation prompted us to propose two strategies to overcome the regiochemistry issue in the future design of [4+2+1] reactions. The first strategy named as catalyst-searching strategy (CDS) is to find appropriate catalysts (and ligands). The second strategy is substratedesigning strategy (SDS), which involves of designing substrates of diene-enes/diene-ynes/diene-allenes with special substituents to favor the [4+2+1] reactions.