PMID- 30542595
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240403
IS  - 2041-6520 (Print)
IS  - 2041-6539 (Electronic)
IS  - 2041-6520 (Linking)
VI  - 9
IP  - 44
DP  - 2018 Nov 28
TI  - Regio- and chemoselective Csp(3)-H arylation of benzylamines by single electron 
      transfer/hydrogen atom transfer synergistic catalysis.
PG  - 8453-8460
LID - 10.1039/c8sc02965b [doi]
AB  - We present a highly regio- and chemoselective Csp(3)-H arylation of benzylamines 
      mediated by synergy of single electron transfer (SET) and hydrogen atom transfer 
      (HAT) catalysis. Under well precedented SET catalysis alone, the arylation 
      reaction of N,N-dimethylbenzylamine proceeded via aminium radical cation 
      formation and selectively targeted the N-methyl group. In contrast, addition of 
      PhC(O)SH as a HAT catalyst precursor completely switched the regioselectivity to 
      Csp(3)-H arylation at the N-benzylic position. Measurement of oxidation 
      potentials indicated that the conjugate base of PhC(O)SH is oxidized in 
      preference to the substrate amine. The discovery of the thiocarboxylate as a 
      novel HAT catalyst allowed for the selective generation of the sulfur-centered 
      radical, so that the N-benzyl selectivity was achieved by overriding the inherent 
      N-methyl and/or N-methylene selectivity under SET catalysis conditions. While 
      visible light-driven alpha-C-H functionalization of amines has mostly been 
      demonstrated with aniline derivatives and tetrahydroisoquinolines (THIQs), our 
      method is applicable to a variety of primary, secondary and tertiary benzylamines 
      for efficient N-benzylic C-H arylation. Functional group tolerance was high, and 
      various 1,1-diarylmethylamines, including an alpha,alpha,alpha-trisubstituted amine, were 
      obtained in good to excellent yield (up to 98%). Importantly, the reaction is 
      applicable to late-stage functionalization of pharmaceuticals.
FAU - Ide, Takafumi
AU  - Ide T
AD  - School of Pharmaceutical Sciences , University of Shizuoka , 52-1 Yada, Suruga-ku 
      , Shizuoka 422-8526 , Japan . Email: hamashima@u-shizuoka-ken.ac.jp.
FAU - Barham, Joshua P
AU  - Barham JP
AUID- ORCID: 0000-0003-1675-9399
AD  - School of Pharmaceutical Sciences , University of Shizuoka , 52-1 Yada, Suruga-ku 
      , Shizuoka 422-8526 , Japan . Email: hamashima@u-shizuoka-ken.ac.jp.
FAU - Fujita, Masashi
AU  - Fujita M
AD  - School of Pharmaceutical Sciences , University of Shizuoka , 52-1 Yada, Suruga-ku 
      , Shizuoka 422-8526 , Japan . Email: hamashima@u-shizuoka-ken.ac.jp.
FAU - Kawato, Yuji
AU  - Kawato Y
AD  - School of Pharmaceutical Sciences , University of Shizuoka , 52-1 Yada, Suruga-ku 
      , Shizuoka 422-8526 , Japan . Email: hamashima@u-shizuoka-ken.ac.jp.
FAU - Egami, Hiromichi
AU  - Egami H
AUID- ORCID: 0000-0002-7784-4987
AD  - School of Pharmaceutical Sciences , University of Shizuoka , 52-1 Yada, Suruga-ku 
      , Shizuoka 422-8526 , Japan . Email: hamashima@u-shizuoka-ken.ac.jp.
FAU - Hamashima, Yoshitaka
AU  - Hamashima Y
AUID- ORCID: 0000-0002-6509-8956
AD  - School of Pharmaceutical Sciences , University of Shizuoka , 52-1 Yada, Suruga-ku 
      , Shizuoka 422-8526 , Japan . Email: hamashima@u-shizuoka-ken.ac.jp.
LA  - eng
PT  - Journal Article
DEP - 20180912
PL  - England
TA  - Chem Sci
JT  - Chemical science
JID - 101545951
PMC - PMC6244453
EDAT- 2018/12/14 06:00
MHDA- 2018/12/14 06:01
PMCR- 2018/09/12
CRDT- 2018/12/14 06:00
PHST- 2018/07/05 00:00 [received]
PHST- 2018/09/10 00:00 [accepted]
PHST- 2018/12/14 06:00 [entrez]
PHST- 2018/12/14 06:00 [pubmed]
PHST- 2018/12/14 06:01 [medline]
PHST- 2018/09/12 00:00 [pmc-release]
AID - c8sc02965b [pii]
AID - 10.1039/c8sc02965b [doi]
PST - epublish
SO  - Chem Sci. 2018 Sep 12;9(44):8453-8460. doi: 10.1039/c8sc02965b. eCollection 2018 
      Nov 28.