The asymmetric synthesis of CF3- or –CF2-substituted tetrahydroquinolines by employing a chiral phosphoric acid as catalyst

Lin, Jin‐Hong; Zong, Guoqiang; Du, Ruo‐Bing; Xiao, Ji‐Chang; Liu, Shubin

doi:10.1039/c2cc18064b

Cited by 50 publications

(16 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, whether the reaction benefits from large proximal sterics or small depends on the sterics of the nucleophile. For smaller displaced nucleophiles, large proximal sterics are advantageous, disfavouring Type I E pathways . However, if the nucleophile is large, small proximal sterics are essential .…”

Section: Resultsmentioning

confidence: 99%

Selecting Chiral BINOL‐Derived Phosphoric Acid Catalysts: General Model To Identify Steric Features Essential for Enantioselectivity

Reid

Goodman

2017

Chemistry A European J

View full text Add to dashboard Cite

Choosing the optimal catalyst for a new transformation is challenging because the ideal molecular requirements of the catalyst for one reaction do not always simply translate to another. Large groups at the 3,3′ positions of the binaphthol rings are important for efficient stereoinduction but if they are too large this can lead to unusual or poor results. By applying a quantitative steric assessment of the substituents at the 3,3′ positions of the binaphthol ring, we have systematically studied the effect of modulating this group on enantioselectivity for a wide range of reactions involving imines, and verified this analysis using ONIOM calculations. We have shown that in most reactions, the stereochemical outcome depends on both proximal and remote sterics. Summarising detailed calculations into a simple qualitative model identifies and explains the steric features required for high selectivity. This model is consistent with seventy seven papers reporting reactions (over 1000 transformations in total), and provides a straightforward decision tree for selecting the best catalyst.

show abstract

Section: Resultsmentioning

confidence: 99%

Selecting Chiral BINOL‐Derived Phosphoric Acid Catalysts: General Model To Identify Steric Features Essential for Enantioselectivity

Reid

Goodman

2017

Chemistry A European J

View full text Add to dashboard Cite

show abstract

“…Very recently, Xiao and co‐workers reported the synthesis of difluoroalkyl‐substituted tetrahydroquinolines in the reaction of α‐difluorinated N ‐arylimines 73 with benzyl N ‐vinylcarbamate 74 catalyzed by chiral phosphoric acid 75 a 28. A variety of difluoroalkyl groups could be installed at the 2‐position of a tetrahydroquinoline framework in a highly enantioselective manner (Scheme ).…”

Section: Catalytic Asymmetric Methodsmentioning

confidence: 99%

Catalytic Asymmetric Construction of Stereogenic Carbon Centers that Feature a gem‐Difluoroalkyl Group

Liu

Zhou

2013

Asian J Org Chem

View full text Add to dashboard Cite

gem-Difluoroalkyl groups, characterized as a gem-difluoromethylene group substituted by a hydrogen atom or an alkyl or other functional group, are not only valuable for the modulation of the properties of organic compounds, but are also useful for the synthesis of various fluorine-containing compounds. Currently, the catalytic asymmetric construction of stereogenic carbon centers that feature a gem-difluoroalkyl group is in its infancy. This Focus Review summarizes the latest achievements and discusses the difficulties and challenges in this field. Scheme 1. Structural difference between a CF 3 group and a difluoroalkyl group. FG = functional group. Scheme 2. The presence of gem-difluoroalkyl groups in important compounds. Scheme 13. The catalytic asymmetric addition of TMSCF 2 SO 2 Ph to aldehydes. TBAF = tetrabutylammonium fluoride. Scheme 14. The catalytic asymmetric addition of TMSCF 2 SePh to ketones. Ar = 3,5-(CF 3 ) 2 C 6 H 3 . Scheme 15. The asymmetric hydrogenation of a-CF 2 R ketimines. Bn = benzyl. Scheme 16. The Mannich reaction of a-difluoromethyl aldimines 69.

show abstract

“…Another variation of the Povarov reaction with benzyl N-vinylcarbamate has been carried out with preformed imines derived from trifluoromethyl and 2,2difluoromethyl acetaldehydes (entry 5), reported by Xiao, Lu and co-workers. 42 This reaction, catalyzed by the (R)- BINOL-derived phosphoric acid catalyst 5, delivered as single 2,4-cis diastereoisomers and with very good yields and enantioselectivities the 2-fluoroalkyl-substituted THQs. This study was motivated by the relevance of fluoroalkyl compounds in medicinal chemistry.…”

Section: Vinyl Ethers As Dienophilesmentioning

confidence: 98%

“…The reactions with dienophiles other than vinyl ethers were also investigated. Interestingly, the benzyl Nvinyl carbamate, a very useful substrate for phosphoric acid catalyzed Povarov cycloadditions, 37,38,40,42,44 afforded a mixture of THQ cycloadduct, derived from a 'normal' Povarov reaction, and the benzopyran deriving from the cyclization of the phenolic moiety (Scheme 31). The ratio between these two products was found to be strongly dependent on the electronic properties of the substituents at the N-aryl moiety, with electron-withdrawing groups favoring the benzopyran, and electron-donating groups, the THQ.…”

Section: Scheme 30 Interrupted Povarov Reaction Between Salicylaldehymentioning

confidence: 99%

Catalytic Asymmetric Aza-Diels–Alder Reactions: The Povarov Cycloaddition Reaction

2013

View full text Add to dashboard Cite

The Povarov reaction provides a straightforward and modular entry to 1,2,3,4-tetrahydroquinolines (THQs). Despite its importance, it was only very recently that several highly efficient catalytic asymmetric protocols for this reaction have been developed, as summarized in this review which falls on the 50 th anniversary of Povarov's pioneering disclosure. Furthermore, this review collects and critically discusses the interrupted versions of the reaction, often featuring intriguing and still unclear mechanicistic pathways.

show abstract

The asymmetric synthesis of CF3- or –CF2-substituted tetrahydroquinolines by employing a chiral phosphoric acid as catalyst

Abstract: CF(3)- or -CF(2)-containing tetrahydroquinolines have been asymmetrically synthesized from the reaction of fluorinated N-arylimines with benzyl N-vinylcarbamate in the presence of a chiral phosphoric acid.

Cited by 50 publications

References 41 publications

Selecting Chiral BINOL‐Derived Phosphoric Acid Catalysts: General Model To Identify Steric Features Essential for Enantioselectivity

Selecting Chiral BINOL‐Derived Phosphoric Acid Catalysts: General Model To Identify Steric Features Essential for Enantioselectivity

Catalytic Asymmetric Construction of Stereogenic Carbon Centers that Feature a gem‐Difluoroalkyl Group

Catalytic Asymmetric Aza-Diels–Alder Reactions: The Povarov Cycloaddition Reaction

Contact Info

Product

Resources

About