Diastereoselective Synthesis of CF<sub>3</sub>-Containing Vicinal Diamines

Huang, Qiuxia; Zheng, Qutong; Duan, Yaya; Lin, Jin‐Hong; Xiao, Ji‐Chang; Zheng, Xiaohui

doi:10.1021/acs.joc.7b01261

Cited by 12 publications

(6 citation statements)

References 35 publications

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“…While β-fluorine elimination from ylide Ph 2 S + CH – CF 3 may readily occur, the Johnson–Corey–Chaykovsky reaction of aldehydes, imines, and α,β-unsaturated ketones with this ylide proceeded smoothly to afford the cyclization products with high diastereoselectivity when CsF was used as the base to suppress the β-fluorine elimination (Scheme a) . The cyclization of imines was applied to a one-pot synthesis of CF 3 -containing vicinal diamines (Scheme b) …”

Section: Sulfonium Saltsmentioning

confidence: 99%

“…54 cyclization of imines was applied to a one-pot synthesis of CF 3containing vicinal diamines (Scheme 19b). 55 The successful development of the fluorinated sulfonium ylide reagent (Ph 2 S + CH 2 CF 3 TfO − ) prompted us to further examine whether trifluoromethylcarbene (:CHCF 3 ) can be produced from ylide Ph 2 S + CH − CF 3 . It was found that the direct thermal S−CH bond cleavage to form :CHCF 3 cannot occur.…”

Section: Sulfonium Saltsmentioning

confidence: 99%

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Fluorinated Ylides/Carbenes and Related Intermediates from Phosphonium/Sulfonium Salts

Lin

Xiao

2020

Acc. Chem. Res.

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Metrics & MoreArticle Recommendations CONSPECTUS: Owing to the special effects of the fluorine element, including high electronegativity and small atomic radius, the incorporation of a fluorinated group into organic molecules may modify their physical, chemical, and biological properties.Fluorine-containing compounds have found widespread application in a variety of areas, and thus, the development of efficient reagents and methods for the incorporation of fluorinated groups has become a subject of significant interest. Described in this Account are our recent discoveries in the chemistry of fluorinated ylides/carbenes and related intermediates generated from phosphonium/sulfonium salts. Initially, we obtained the (triphenylphosphonio) difluoroacetate, Ph 3 P + CF 2 CO 2 − (PDFA), which was proposed as a reactive intermediate but had never been successfully synthesized. PDFA, shelf-stable and easy to prepare, is not only a mild ylide (Ph 3 P + CF 2 − ) reagent, but also an efficient difluorocarbene source. It can directly generate difluorocarbene, via the first generation of ylide Ph 3 P + CF 2 − , simply under warming conditions without the need for any additive. Interestingly, difluorocarbene chemistry was then discovered by using PDFA as a reagent. Difluorocarbene can be oxidized to CF 2  O, can react with elemental sulfur to afford CF 2 S, and can be trapped by NaNH 2 or NH 3 to give CN − . The development of these processes into synthetic tools allowed us to achieve various reactions, including the challenging 18 F-trifluoromethylthiolation and cyanodifluoromethylation. It was found that a substituent on the cation of a phosphonium salt can be directly transferred as a nucleophile despite the cation's high electrophilicity. This transfer process is like an "umpolung" of the cation, which may provide more opportunities for the synthetic utilities of phosphonium salts. The investigation of this transfer process led us to find that iodophosphonium salts, active intermediates which can be easily generated, may efficiently promote deoxygenative functionalizations of aldehydes and alcohols. Dehydroxylative substitution of alcohols by this protocol permits the use of unprotected amines with higher pK a values as nucleophiles, which is an attractive feature compared with the Mitsunobu reaction. On the basis of the ylide-tocarbene process (Ph 3 P + CF 2 − → :CF 2 ), we further developed sulfonium salts as precursors of fluorinated ylides and fluorinated methyl carbenes. In particular, the studies on difluoromethylcarbene, remaining largely unexplored, may deserve more attention. The discoveries may find utility in the synthesis of biologically active fluorine-containing molecules.

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Section: Sulfonium Saltsmentioning

confidence: 99%

Section: Sulfonium Saltsmentioning

confidence: 99%

Fluorinated Ylides/Carbenes and Related Intermediates from Phosphonium/Sulfonium Salts

Lin

Xiao

2020

Acc. Chem. Res.

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“…The aziridine ring was synthesized from N ‐tosyl‐ or N ‐mesyl‐imines, whereas N ‐Boc or N ‐Cbz‐imines proved to be unreactive under their experimental conditions. A few years later Xiao [64] and co‐workers applied the same process to N ‐tosyl vinyl‐imines leading to various vinyl aziridines (13 examples), which served as intermediates to the synthesis of CF 3 ‐containing vicinal diamines (Scheme 42, Eq. (b)).…”

Section: Fluoro‐ Monofluoromethyl‐ Difluoromethyl‐ and Trifluoromementioning

confidence: 99%

Synthesis of Fluoro‐, Monofluoromethyl‐, Difluoromethyl‐, and Trifluoromethyl‐Substituted Three‐Membered Rings

Decaens

Couve‐Bonnaire

Charette

et al. 2020

Chemistry A European J

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“…The synthesis of vicinal diamines is currently an interesting topic, as the molecules with the 1,2‐diamino structural unit not only are characteristic structural features of many nature products and drugs, but also play an important role in ligand design and organic chemistry . For instance, vicinal diamines are valuable synthetic intermediates that are extensively used in the preparation of nitrogen‐containing heterocyclic compounds (piperazines, imidazolines, imidazolidines, etc) as well as aliphatic amines (amino acids, amino alcohols, etc).…”

Section: Introductionmentioning

confidence: 99%

Diastereoselective Synthesis of Vicinal Diamines by Aza‐Michael Addition of Chiral Phenethylamine to Nitroalkenes

Liang

et al. 2018

ChemistrySelect

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An efficient aza‐Michael addition of (R or S)‐α‐phenethylamine, a chiral nitrogen nucleophile to (E)‐nitroalkenes 2 a‐f permits the synthesis of vicinal diamines (or 1, 2‐di‐amine) after reduction of the 1, 4‐adducts 3 a‐f (or 3’a‐f). The key adducts 3 a‐f (or 3’a‐f) can be obtained in good yields (up to 78%) and excellent diastereoselectivities (up to > 98:2 dr (diastereomeric excess ratio)). In addition, this is one of the scarce examples where chiral phenethylamine and nitroalkenes have been used in catalyst‐free aza‐Michael additions. Our developed strategy opens an efficient entry to synthetic building blocks of vicinal diamines for natural products and drugs.

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Diastereoselective Synthesis of CF₃-Containing Vicinal Diamines

Abstract: The highly diastereoselective synthesis of CF-containing vicinal diamines by a convenient two-step procedure without the need to isolate the intermediate products is described.

Cited by 12 publications

References 35 publications

Fluorinated Ylides/Carbenes and Related Intermediates from Phosphonium/Sulfonium Salts

Fluorinated Ylides/Carbenes and Related Intermediates from Phosphonium/Sulfonium Salts

Synthesis of Fluoro‐, Monofluoromethyl‐, Difluoromethyl‐, and Trifluoromethyl‐Substituted Three‐Membered Rings

Diastereoselective Synthesis of Vicinal Diamines by Aza‐Michael Addition of Chiral Phenethylamine to Nitroalkenes

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Diastereoselective Synthesis of CF3-Containing Vicinal Diamines

Abstract: The highly diastereoselective synthesis of CF-containing vicinal diamines by a convenient two-step procedure without the need to isolate the intermediate products is described.

Cited by 12 publications

References 35 publications

Fluorinated Ylides/Carbenes and Related Intermediates from Phosphonium/Sulfonium Salts

Fluorinated Ylides/Carbenes and Related Intermediates from Phosphonium/Sulfonium Salts

Synthesis of Fluoro‐, Monofluoromethyl‐, Difluoromethyl‐, and Trifluoromethyl‐Substituted Three‐Membered Rings

Diastereoselective Synthesis of Vicinal Diamines by Aza‐Michael Addition of Chiral Phenethylamine to Nitroalkenes

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Diastereoselective Synthesis of CF₃-Containing Vicinal Diamines