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Synlett 2016; 27(18): 2561-2566
DOI: 10.1055/s-0035-1562621
DOI: 10.1055/s-0035-1562621
letter
Synthesis of 4,4′-Disubstituted and Spiro-tetrahydroquinolines via Photochemical Cyclization of Acrylanilides and the First Synthesis of (±)-trans-Vabicaserin
Further Information
Publication History
Received: 17 June 2016
Accepted after revision: 28 July 2016
Publication Date:
16 August 2016 (online)
![](https://www.thieme-connect.de/media/synlett/201618/lookinside/thumbnails/st-2016-r0394-l_10-1055_s-0035-1562621-1.jpg)
Abstract
The synthesis of vabicaserin analogues bearing a quaternary center or spiro substitution at the 4-position has been studied via a [6π]-acrylanilide cyclization employing flow photochemistry in a mesoscale and microfluidic flow photoreactor. The method is also used to synthesize 4,4′-disubstituted tetrahydroquinolines and, furthermore, enables the first synthesis of (±)-trans-vabicaserin.
Key words
flow photochemistry - photocyclization - electrocyclization - electrocyclic reactions - tetrahydroquinoline - vabicaserinSupporting Information
- Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0035-1562621.
- Supporting Information
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References and Notes
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For recent relevant examples, see:
It is noteworthy, that the commonly employed approach, a Pd-catalyzed amidation of aryl halides, should allow the synthesis of dihydroquinolinones bearing a quarternary center in the 4-position if a suitable precursor is employed. Until now, this has not been shown. For the underlying chemistry, see:
For the synthesis of such precursors, the purposive Rh-based conjugate addition of ortho-halo-arylboronic acids onto β-substituted acrylamides, however, fails even if only a tertiary center is attempted, as stated in:
For a review on effective space time yields (STYeff) to compare efficiencies of reactors with different geometries see: