Described herein is a protocol for visible-light-induced consecutive synthesis of gem-difluorinated spiro-γ-lactam oxindoles under mild conditions by means of a process involving sequential radical difluoromethylative dearomatization, hydroxylation, and oxidation. The protocol features high chemoand regioselectivity, good functional group tolerance, and easy scalability. Several of the functionalized spirooxindole products showed good fungicidal activity, suggesting that they have potential agrochemical applications. The gem-difluoromethylene (CF2) group has found many applications in the life sciences because it is a bioisostere of hydroxyl, thiol, and carbonyl groups. Therefore, the development of methods for introducing a CF2 group into organic molecules, especially heterocycles, has been a hot topic of research among chemists. Heterocycles containing a trifluoromethyl group have been synthesized by means of onepot processes involving trifluoromethylation combined with dearomatization, which is a well-known, efficient method for constructing molecules with complex heterocyclic and spirocyclic skeletons. However, there have been only a few reports of the use of tandem difluoromethylation and dearomatization strategy to afford CF2-containing heterocyclic compounds. [4g,6] In addition, most of the known examples involve dearomatization of a phenol moiety. Thus, this transformation should be explored more thoroughly with the aim of developing methods for constructing a wider variety of gem-difluoromethylated heterocycles. Scheme 1. Synthetic compounds and natural products with a 3,3spirooxindole scaffold. The 3,3-spirocyclic oxindole moiety is common in drugs and drug candidates, as well as in various bioactive natural products (Scheme 1). Owing to the unique three-dimensional structure and broad biological activity of spirooxindoles, they have been identified as privileged chemotypes for the development of antiviral drugs, and great effort has been directed toward the synthesis of this versatile scaffold. One general method for the preparation of C-3 spirooxindoles is organocatalytic cyclization of oxindole derivatives (Scheme 2a). In addition, selective intramolecular dearomatization of C-3substituted indoles, coupled with an oxidation step, has the potential to be an attractive route to 3,3-spirocyclic oxindole. However, the existing examples of this transformation are limited to tryptophan derivatives and proceed through a two-electron process (Scheme 2b). Construction of 3,3-spirocyclic oxindole by means of a radical process is very limited and require the use of hazardous radical initiators. We hypothesized that combining a difluoromethylation step with a dearomatization/oxidation process would provide an efficient, step-economical route to gem-difluoromethylated spirocyclic oxindoles. Because photoredox reactions are mild and operationally simple and have wide substrate scopes, and because the XCF2 (X = Br or I) group can serve as a difluoromethyl radical precursor upon visible-light irradiation, we designed an indole substrate with a C-3 bromodifluoroacetamide moiety as a difluoromethyl radical precursor to test our hypothesis (Scheme 2c). Our strategy was to carry out sequential regioselective radical difluoromethylative dearomatization, hydroxylation, and oxidation reactions in a consecutive process. In fact, we found that after optimization of the reaction conditions, our strategy worked as we expected and afforded the gem-difluorinated spiro-γ-lactam oxindole products. To our knowledge, this is the first report of intramolecular difluoromethylative dearomatization of indoles, and the first use of a cascade radical reaction strategy for the synthesis of functionalized 3,3-spirocyclic oxindole. [a] Q. Wang, Y. Qu, Q. Xia, H. Song, H. Song, Y, Liu, Prof. Q. Wang State Key Laboratory of Elemento-Organic Chemistry Research Institute of Elemento-Organic Chemistry College of Chemistry Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin 300071 (China) Fax: (+86) 22-23503952 E-mail: wangqm@nankai.edu.cn 10.1002/chem.201802141 A cc ep te d M an us cr ip t Chemistry A European Journal This article is protected by copyright. All rights reserved.