PMID- 37712624
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231020
IS  - 1520-5126 (Electronic)
IS  - 0002-7863 (Linking)
VI  - 145
IP  - 38
DP  - 2023 Sep 27
TI  - Methyl Ketones as Alkyl Halide Surrogates: A Deacylative Halogenation Approach 
      for Strategic Functional Group Conversions.
PG  - 21096-21103
LID - 10.1021/jacs.3c08176 [doi]
AB  - Alkyl halides are versatile precursors to access diverse functional groups (FGs). 
      Due to their lability, the development of surrogates for alkyl halides is 
      strategically important for complex molecule synthesis. Given the stability and 
      ease of derivatization inherent in common alkyl ketones, here we report a 
      deacylative halogenation approach to convert various methyl ketones to the 
      corresponding alkyl chlorides, bromides, and iodides. The reaction is driven by 
      forming an aromatic byproduct, i.e., 1,2,4-triazole, in which 
      N'-methylpicolinohydrazonamide (MPHA) is employed to form a prearomatic 
      intermediate and halogen atom-transfer (XAT) reagents are used to quench the 
      alkyl radical intermediate. The reaction is efficient in yielding primary and 
      secondary alkyl halides from a wide range of methyl ketones with broad FG 
      tolerance. It also works for complex natural-product-derived and 
      fluoro-containing substrates. In addition, one-pot conversions of methyl ketones 
      to various other FGs and annulations with alkenes and alkynes through deacylative 
      halogenation are realized. Moreover, an unusual iterative homologation of alkyl 
      iodides is also demonstrated. Finally, mechanistic studies reveal an intriguing 
      double XAT process for the deacylative iodination reaction, which could have 
      implications beyond this work.
FAU - Zhang, Zining
AU  - Zhang Z
AD  - Department of Chemistry, University of Chicago, Chicago, Illinois 60637, United 
      States.
FAU - Zhu, Qi
AU  - Zhu Q
AD  - Department of Chemistry, University of Chicago, Chicago, Illinois 60637, United 
      States.
FAU - Pyle, Daniel
AU  - Pyle D
AD  - Department of Chemistry, University of Chicago, Chicago, Illinois 60637, United 
      States.
FAU - Zhou, Xukai
AU  - Zhou X
AD  - Department of Chemistry, University of Chicago, Chicago, Illinois 60637, United 
      States.
FAU - Dong, Guangbin
AU  - Dong G
AUID- ORCID: 0000-0003-1331-6015
AD  - Department of Chemistry, University of Chicago, Chicago, Illinois 60637, United 
      States.
LA  - eng
PT  - Journal Article
DEP - 20230915
PL  - United States
TA  - J Am Chem Soc
JT  - Journal of the American Chemical Society
JID - 7503056
SB  - IM
EDAT- 2023/09/15 12:42
MHDA- 2023/09/15 12:43
CRDT- 2023/09/15 08:43
PHST- 2023/09/15 12:43 [medline]
PHST- 2023/09/15 12:42 [pubmed]
PHST- 2023/09/15 08:43 [entrez]
AID - 10.1021/jacs.3c08176 [doi]
PST - ppublish
SO  - J Am Chem Soc. 2023 Sep 27;145(38):21096-21103. doi: 10.1021/jacs.3c08176. Epub 
      2023 Sep 15.