Cited by 105Catalytic C–H Functionalization MethodsAsymmetric Synthesis and CatalysisSynthesis and Catalytic Reactions

Practical Alkoxythiocarbonyl Auxiliaries for Iridium(I)‐Catalyzed C−H Alkylation of Azacycles

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Tran, Anh T., Yu, Jin‐Quan·2017·Angewandte Chemie International Edition

Abstract

The development of new and practical 3‐pentoxythiocarbonyl auxiliaries for Ir I ‐catalyzed C−H alkylation of azacycles is described. This method allows for the α‐C−H alkylation of a variety of substituted pyrrolidines, piperidines, and tetrahydroisoquinolines through alkylation with alkenes. While the practicality of these simple carbamate‐type auxiliaries is underscored by the ease of installation and removal, the method's utility is demonstrated in its ability to functionalize biologically relevant l ‐proline and l ‐ trans ‐hydroxyproline, delivering unique 2,5‐dialkylated amino acid analogues that are not accessible by other C−H functionalization methods.

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  • Several of the enantiopure fragment recognition groups deployed herein are poised for direct modification using synthetic methodologies such as C-H bond activation chemistry.

    “Toward this end, we note that the enantioprobes offer a convenient target engagement assay for assessing competitive binding of elaborated analogues in cells, and that several of the enantiopure fragment recognition groups deployed herein are poised for direct modification using synthetic methodologies such as C-H bond activation chemistry44–46.”

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  1. [3]a Meyers AI Edwards PD Rieker WF Bailey TR J Am Chem Soc 1984 106 3270 b Cordier CJ Lundgren RJ Fu GC J Am Chem Soc 2013 135 10946 23869442 PMC3803154 c Liniger M Estermann K Altmann KH J Org Chem 2013 78 11066 24102677
  2. [6]a Booth SE Benneche T Undheim K Tetrahedron 1995 51 3665 b Bertrand S Glapski C Hoffmann N Pete JP Tetrahedron Lett 1999 40 3169 c Yoshikai N Mieczkowski A Matsumoto A Ilies L Nakamura E J Am Chem Soc 2010 132 5568 20361736 d Noble A MacMillan DWC J Am Chem Soc 2014 136 11602 25026314 PMC4140496 e Johnston CP Smith RT Allmendinger S MacMillan DWC Nature 2016 536 322 27535536 PMC5695702 f Qin T Cornella J Li C Malins LR Edwards JT Kawamura S Maxwell BD Eastgate MD Baran PS Science 2016 352 801 27103669 PMC4867118 g Xie J Yu J Rudolph M Rominger F Hashmi ASK Angew Chem, Int Ed 2016 55 9416 27351709 h Joe CL Doyle AG Angew Chem, Int Ed 2016 55 4040 PMC4807873 26890705

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Authors
Tran, A. T., & Yu, J.
Affiliations
Scripps Research Institute (US)
Corresponding author
Yu, Jin‐Quan
Venue
Angewandte Chemie International Edition
Publisher
Wiley
Published
2017-07-24
Volume
56
Issue
35
Pages
10530-10534
ISSN
  • 1433-7851 (ISSN-L)
  • 1521-3773
OpenAlex
W2625559439
Cited by
105
References
58
Citations by year
2026: 4 · 2025: 8 · 2024: 5 · 2023: 6 · 2022: 14 · 2021: 15 · 2020: 15 · 2019: 16 · 2018: 18 · 2017: 4
FWCI
6.05
Type
journal article
Language
en
Open access
Locations
  • Angewandte Chemie International Edition (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institutes of Health (NIGMS, 2R01GM084019)
Topics
  • Physical Sciences › Chemistry › Organic Chemistry › Catalytic C–H Functionalization Methods
  • Physical Sciences › Chemistry › Organic Chemistry › Asymmetric Synthesis and Catalysis
  • Physical Sciences › Chemistry › Organic Chemistry › Synthesis and Catalytic Reactions
Keywords
iridium(I) catalysis, C–H alkylation, azacycles, pyrrolidine, piperidine, tetrahydroisoquinolines, alkene alkylation, proline, C–H functionalization
MeSH terms
Alkylation, Aza Compounds, Catalysis, Iridium, Isoquinolines, Organometallic Compounds, Piperidines, Pyrrolidines, Molecular Structure

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