Synthesis and inhibitory activities at mGluRs of 3-alkylated and N-alkylated cyclopentyl-glutamate analogues

Ung, Alison T.; Pyne, Stephen G.; Bischoff, François; Lesage, Anne; Skelton, Brian W.; White, Allan H.

doi:10.1016/j.tet.2013.01.054

Cited by 2 publications

(2 citation statements)

References 15 publications

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“…A thienyl ketone can be employed as a reactant (entry 4), as can alkyl ketones with alkyl groups which range from primary to tertiary (entries 5–7). The scope of the process is not limited to α‐cyano ketones, as both α‐cyano amides (including a diphenyl amide and a Weinreb amide) and an α‐cyano ester serve as useful substrates (entries 8–11) 26…”

Section: Phosphepine‐catalyzed Enantioselective [4+1] Annulation: Effmentioning

confidence: 99%

Biphenyl‐Derived Phosphepines as Chiral Nucleophilic Catalysts: Enantioselective [4+1] Annulations To Form Functionalized Cyclopentenes

et al. 2014

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Due to the frequent occurrence of cyclopentane subunits in bioactive compounds, the development of efficient catalytic asymmetric methods for their synthesis is an important objective. In this report, we introduce a new family of chiral nucleophilic catalysts, biphenyl-derived phosphepines, and we apply them to an enantioselective variant of a useful [4+1] annulation first described by Tong. A range of one-carbon coupling partners can be employed, thereby generating cyclopentenes that bear a fully substituted stereocenter (either all-carbon or heteroatom-substituted (sulfur and phosphorus)). Stereocenters at the other four positions of the cyclopentane ring can also be introduced with good stereoselectivity. An initial mechanistic study indicates that phosphine addition to the electrophilic four-carbon coupling partner is not the turnover-limiting step of the catalytic cycle.Correspondence to: Gregory C. Fu, gcfu@caltech.edu. Supporting information for this article is given via a link at the end of the document. [1] but also as enantioselective nucleophilic catalysts for a broad spectrum of useful transformations. [2,3] Studies by our lab and by others have established that 1,1′-binaphthyl-derived phosphepines (e.g., 1) are effective for a diverse array of interesting processes; [4,5,6] in contrast, to the best of our knowledge, there have been no applications of axially chiral biphenyl-derived phosphepines (e.g., 2) as asymmetric nucleophilic catalysts. [7] The use of chiral phosphines as nucleophilic catalysts for the synthesis of five-membered rings has been a focus of particular interest, [8] due in part to the occurrence of cyclopentane subunits in a wide range of bioactive molecules, [9] and Lu's powerful methods for convergent [3+2] annulation have been especially well-explored. [10,11] With regard to the enantioselective construction of quaternary stereocenters, [12] nearly all reports have described the generation of spirocyclic structures. [8,13,14] One complication in some of these [3+2] reactions is the formation of regioisomeric products. [10] In 2010 approach obviates the formation of regioisomeric products. [16,17] As part of an ongoing program to demonstrate the utility and the versatility of asymmetric nucleophilic catalysis, [18] we embarked on the development of an enantioselective variant of this [4+1] annulation. At the point that we completed our study, [19] we were not aware of any progress by others toward this objective. However, this year Lu has described asymmetric reactions that furnish spirocyclic products in good ee [(Eq. 2)], [20] which has prompted us to disclose our independent investigation. Herein, we report the first use of biphenyl-derived phosphepines (3 and 4) as enantioselective nucleophilic catalysts, specifically, their application in [4+1] annulations that generate cyclopentenes that bear nonspirocyclic, fully substituted stereocenters (either all-carbon or heteroatom-substituted; Eq. 3). [21,22] Ziegler et al. HHS Public AccessUpon determining that an arra...

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Section: Phosphepine‐catalyzed Enantioselective [4+1] Annulation: Effmentioning

confidence: 99%

Biphenyl‐Derived Phosphepines as Chiral Nucleophilic Catalysts: Enantioselective [4+1] Annulations To Form Functionalized Cyclopentenes

et al. 2014

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“…to a-cyano ketones, as both a-cyano amides (including a diphenyl amide and a Weinreb amide) and an a-cyano ester serve as useful substrates (entries [8][9][10][11]. [26] However, when we applied this method with either an acyano sulfone or an a-cyano phosphonate as the nucleophilic partner, the target cyclopentene was produced with moderate enantioselectivity (< 80 % ee). In contrast, by employing a related biphenyl-derived phosphepine [(R)-4] as the chiral catalyst, we were able to achieve asymmetric [4+1] annulations with improved ee values, thereby enabling the efficient synthesis of enantioenriched a-cyano sulfones, [27] phosphine oxides, and phosphonates ( Table 3).…”

mentioning

confidence: 99%

Biphenyl‐Derived Phosphepines as Chiral Nucleophilic Catalysts: Enantioselective [4+1] Annulations To Form Functionalized Cyclopentenes

Ziegler¹,

Riesgo²,

Ikeda³

et al. 2014

Angew Chem Int Ed

111

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Synthesis and inhibitory activities at mGluRs of 3-alkylated and N-alkylated cyclopentyl-glutamate analogues

Cited by 2 publications

References 15 publications

Biphenyl‐Derived Phosphepines as Chiral Nucleophilic Catalysts: Enantioselective [4+1] Annulations To Form Functionalized Cyclopentenes

Biphenyl‐Derived Phosphepines as Chiral Nucleophilic Catalysts: Enantioselective [4+1] Annulations To Form Functionalized Cyclopentenes

Biphenyl‐Derived Phosphepines as Chiral Nucleophilic Catalysts: Enantioselective [4+1] Annulations To Form Functionalized Cyclopentenes

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