Xiaoxing Wu

Abstract: The trifluoromethyl (CF3) group is an important structural motif in many pharmaceutically relevant molecules because of its unique chemical and metabolic stability, lipophilicity, and binding selectivity. Consequently, much effort has been directed toward the development of efficient methods for the introduction of the trifluoromethyl group into small molecules. While a variety of processes have been reported to generate aromatic C(sp) CF3 bonds, the analogous direct trifluoromethylation of alkenes and their derivatives has received less attention. In 2011, the groups of Buchwald, Liu, and Wang independently reported efficient allylic trifluoromethylation of unactivated alkenes with copper catalysts under mild conditions. The trifluoromethylation of allylsilanes, vinyltrifluoroborates, and enamides has since been disclosed by several groups, allowing the effective formation of compounds with a CF3 group in an allylic or vinylic position. Furthermore, oxytrifluoromethylation, carbotrifluoromethylation, and hydrotrifluoromethylation of alkenes have been achieved with and without transition-metal catalysis. These reactions provide a valuable array of highly regioselective C CF3 bond-forming methods under mild conditions. However, the mechanism of these copper-catalyzed trifluoromethylation reactions is not fully understood. Addition of both the trifluoromethyl cation or radical have been suggested as routes to the observed products. Buchwald reported the efficient formation of CF3-containing epoxides from secondary allylic alcohols, possibly via intermediate A [Eq. (1)]. Thus, we envisioned that the trifluoromethylation of a,a-diaryl allylic alcohols 2 with the Togni reagent (1) would lead to the analogous intermediates B, which could undergo 1,2-aryl migration to provide btrifluoromethyl ketones 3 [Eq. (2)]. Importantly, electronrich aryl groups migrate preferentially in cationic (semipinacol) rearrangements, whereas electron-poor aryl groups migrate preferentially in radical (“neophyl”) rearrangements. Therefore, the structures of the products from unsymmetrical substrates would provide important insight into the reaction mechanism. b-Trifluoromethyl ketones such as 3 are difficult to prepare. Nucleophilic trifluoromethylating reagents typically undergo 1,2-addition to enones, affording trifluoromethyl allylic alcohols rather than b-trifluoromethyl ketones by 1,4addition. Only a few cyclic b-trifluoromethyl ketones have been prepared by 1,4-addition of a nucleophilic CF3 group to cyclic enones. The use of radical or electrophilic CF3 reagents for this challenging task has been rarely described. Consequently, we wanted to develop new C(sp) CF3 bond-forming reactions to prepare b-trifluoromethyl ketones, and to probe the mechanism of the copper-catalyzed trifluoromethylation of alkenes as discussed above. We report herein an unprecedented trifluoromethylation-initiated radical 1,2-aryl migration(“neophyl rearrangement”) in a,adiaryl allylic alcohols utilizing 1, leading to a wide variety of acyclic b-trifluoromethyl a-aryl ketones 3. We commenced our study with the reaction of 2a with the Togni reagent (1) and [(MeCN)4Cu]PF6 as catalyst (Table 1). To our delight, the reaction in methanol at 50 8C for 14 h afforded the desired rearranged product 3a in 27% yield (entry 1). It also provided 48% of compound 4a, which was probably derived by trapping of the allylic cation of 2a by MeOH. Complex product mixtures were obtained when the reaction was performed in the less nucleophilic alcohols trifluoroethanol or hexafluoroisopropanol (HFIP; entries 2 and 3, respectively). In acetonitrile and dichloromethane, mixtures of the desired ketone 3a (22% and 9%, respectively) and substitution product 4b (23% and 76%, respectively, entries 4 and 5) were formed. In DMSO, the yield of 3a increased to 51%, but the conversion was not complete (entry 6). In DMF, the yield of 3a increased further to 69% [*] X. Liu, F. Xiong, X. Huang, Prof. Dr. X. Wu Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences 190 Kaiyuan Avenue, Guangzhou 510530 (China) E-mail: wu_xiaoxing@gibh.ac.cn

Abstract: An efficient, general palladium catalyst for C–O bond-forming reactions of secondary and primary alcohols with a range of aryl halides has been developed. Use of a catalyst based on a single bulky biarylphosphine ligand L4 (RockPhos, soon to be commercially available) has expanded this chemistry to allow the transformation of a variety of heteroaryl halides, and for the first time, allows for the coupling of electron-rich aryl halides with secondary alcohols. Additionally, this new catalyst system provides the ability to effect these reactions with a diverse set of substrate combinations, while employing a single ligand. Thus the need to survey mutiple ligands, as was previously the case, is obviated.

Abstract: An extremophilic challenge: Stereospecific condensation of a fully functionalized ketal aldehyde and a 2,6-dihydroxybenzoic acid is the key step in the synthesis of (-)-berkelic acid confirming Furstner's reassignment of the stereochemistry at C18 and C19, establishing the absolute stereochemistry, and tentatively assigning the stereochemistry at C22.

Abstract: Primary alcohols were selectively tetrahydropyranylated in good to excellent yields at room temperature using PdCl 2 (CH 3 CN) 2 as catalyst in tetrahydrofuran (THF) in the presence of phenols, secondary, and tertiary alcohols. The tetrahydropyranyl (THP) group could be efficiently removed using PdCl 2 (CH 3 CN) 2 as catalyst in CH 3 CN, while other protection groups such as p -toluenesulfonyl (Ts), tert -butyldiphenylsilyl (TBDPS), benzyloxycarbonyl (Cbz), allyl, benzyl (Bn), and benzoyl (Bz) remained intact under these conditions.

Abstract: The tricyclic hydroxy imidazolidinone was converted to chaetominine in seven steps in 22% overall yield The key step was the construction of the δ-lactam by heating an amino ester with a catalytic amount of DMAP in toluene at reflux

Abstract: Research and industrial interest in radical C–H activation/radical cross-coupling chemistry has continuously grown over the past few decades. These reactions offer fascinating and unconventional approaches toward connecting molecular fragments with high atom- and step-economy that are often complementary to traditional methods. Success in this area of research was made possible through the development of photocatalysis and first-row transition metal catalysis along with the use of peroxides as radical initiators. This Review provides a brief and concise overview of the current status and latest methodologies using radicals or radical cations as key intermediates produced via radical C–H activation. This Review includes radical addition, radical cascade cyclization, radical/radical cross-coupling, coupling of radicals with M–R groups, and coupling of radical cations with nucleophiles (Nu).

Abstract: New developments of various reactions of α-diazocarbonyl compounds have been reviewed in this report, which primarily focuses on the literatures published since 2003.

Abstract: In the last few years, the efficient introduction of trifluoromethyl groups in organic molecules has become a major research focus. This review highlights the recent developments enabling the incorporation of CF3 groups across unsaturated moieties, preferentially alkenes, and the mechanistic scenarios governing these transformations. We have specially focused on methods involving the simultaneous formation of C–CF3 and C–C or C–heteroatom bonds by formal addition reactions across π-systems, as such difunctionalization processes hold valuable synthetic potential.