Regio- and Enantioselective Synthesis of 1,2-Diamines by Formal Hydroamination of Enamines : Scope, Mechanism, and Asymmetric Synthesis of Orthogonally Protected Bis-Piperazines as a Privileged Scaffold
(2024) In Chemistry - A European Journal- Abstract
We have previously reported the first formal hydroamination of enamines for the synthesis of chiral 1,2-diamines. Here, we describe: (i) the discovery, optimization, and substrate expansion of this reaction; (ii) a novel and straightforward protocol for the “click-type” synthesis of enamines in quantitative yield utilizing sodium sulfate in a dual role as an ancillary and dehydrating agent without the need for workup or purification; (iii) the application of this methodology to the first enantioselective synthesis of orthogonally protected 1,1′-(1-(4-fluorophenyl)ethane-1,2-diyl) piperazines, a scaffold for rapid lead optimization in drug discovery; (iv) a computational investigation into the mechanism and rationalization of the... (More)
We have previously reported the first formal hydroamination of enamines for the synthesis of chiral 1,2-diamines. Here, we describe: (i) the discovery, optimization, and substrate expansion of this reaction; (ii) a novel and straightforward protocol for the “click-type” synthesis of enamines in quantitative yield utilizing sodium sulfate in a dual role as an ancillary and dehydrating agent without the need for workup or purification; (iii) the application of this methodology to the first enantioselective synthesis of orthogonally protected 1,1′-(1-(4-fluorophenyl)ethane-1,2-diyl) piperazines, a scaffold for rapid lead optimization in drug discovery; (iv) a computational investigation into the mechanism and rationalization of the enantioselectivities of the reaction.
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- author
- Mohiti, Maziar LU ; Lu, Yu LU ; He, Hui ; Ni, Shao Fei and Somfai, Peter LU
- organization
- publishing date
- 2024
- type
- Contribution to journal
- publication status
- epub
- subject
- keywords
- asymmetric catalysis, computational study, diamines, enamines, hydroamination
- in
- Chemistry - A European Journal
- publisher
- Wiley-Blackwell
- external identifiers
-
- pmid:38205968
- scopus:85183917616
- ISSN
- 0947-6539
- DOI
- 10.1002/chem.202303078
- language
- English
- LU publication?
- yes
- id
- 68ad81e5-3117-4ff5-92ff-296203f27646
- date added to LUP
- 2024-02-27 15:08:33
- date last changed
- 2024-04-26 18:56:08
@article{68ad81e5-3117-4ff5-92ff-296203f27646, abstract = {{<p>We have previously reported the first formal hydroamination of enamines for the synthesis of chiral 1,2-diamines. Here, we describe: (i) the discovery, optimization, and substrate expansion of this reaction; (ii) a novel and straightforward protocol for the “click-type” synthesis of enamines in quantitative yield utilizing sodium sulfate in a dual role as an ancillary and dehydrating agent without the need for workup or purification; (iii) the application of this methodology to the first enantioselective synthesis of orthogonally protected 1,1′-(1-(4-fluorophenyl)ethane-1,2-diyl) piperazines, a scaffold for rapid lead optimization in drug discovery; (iv) a computational investigation into the mechanism and rationalization of the enantioselectivities of the reaction.</p>}}, author = {{Mohiti, Maziar and Lu, Yu and He, Hui and Ni, Shao Fei and Somfai, Peter}}, issn = {{0947-6539}}, keywords = {{asymmetric catalysis; computational study; diamines; enamines; hydroamination}}, language = {{eng}}, publisher = {{Wiley-Blackwell}}, series = {{Chemistry - A European Journal}}, title = {{Regio- and Enantioselective Synthesis of 1,2-Diamines by Formal Hydroamination of Enamines : Scope, Mechanism, and Asymmetric Synthesis of Orthogonally Protected Bis-Piperazines as a Privileged Scaffold}}, url = {{http://dx.doi.org/10.1002/chem.202303078}}, doi = {{10.1002/chem.202303078}}, year = {{2024}}, }