Doctoral thesis
Open access

Mechanistic investigations and development of Rh(II)-catalyzed [3+6+3+6] macrocyclization reactions

ContributorsPoggiali, Daniele
Defense date2016-03-11

In 2010 the group of Professor Jérôme Lacour disclosed a new [3+6+3+6] reactivity leading to the formation of macrocyclic structures, closely related to 18C6 crown ethers. This reaction was achieved using a combination of alpha-diazo-beta-ketoesters reagents, 6-membered cyclic ethers and Rh(II) complexes as catalysts. The project of this PhD thesis was to disclose the kinetic and mechanistic parameters governing the formation of these macrocyclic structures and to optimize the process to readily scale up the reactions with low catalyst loading. These conditions were then applied on nitrogen containing substrates which were challenging at the time, such as morpholines. Moreover, an in-depth analysis of the key reaction parameters will be provided, with a focus on the role of the dirhodium catalysts and the diazo decomposition kinetics. The studies were also dedicated to an extensive analysis of the mechanism generating the macrocyclic structures, with a particular care on the characterization (reactivity and structure) of key oxonium ylide intermediate. Several achiral dirhodium complexes were synthetized, structurally analyzed, and applied in the reaction, showing, for some of them, such as novel Rh2(TCPTCC)4, a better catalytic activity. A scale up process (20 g of diazo) with a catalyst loading as low as 0.001 mol% was then generalized to increase the scope of the reaction. Challenging substrates such as protected morpholines were successfully used, generating aza-polyether macrocycles.

  • Macrocyclic structures
  • Acceptor-acceptor diazo
  • Rhodium catalyst
  • Kinetics studies
  • Oxonium ylide
  • Scale-up reaction
  • Low catalyst loading
  • Aza-polyether macrocycles.
Research group
Citation (ISO format)
POGGIALI, Daniele. Mechanistic investigations and development of Rh(II)-catalyzed [3+6+3+6] macrocyclization reactions. 2016. doi: 10.13097/archive-ouverte/unige:84833
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Technical informations

Creation06/26/2016 12:35:00 PM
First validation06/26/2016 12:35:00 PM
Update time03/15/2023 12:29:49 AM
Status update03/15/2023 12:29:48 AM
Last indexation01/29/2024 8:45:57 PM
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