Non-bonding 1,5-S•••O interactions govern chemo- and enantioselectivity in isothiourea-catalyzed annulations of benzazoles
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Isothiourea-catalyzed annulations between 2-acyl benzazoles and α,β-unsaturated acyl ammonium intermediates are selectively tuned to form either lactam or lactone heterocycles in good yields (up to 95%) and high ee (up to 99%) using benzothiazole or benzoxazole derivatives, respectively. Computation gives insight into the significant role of two 1,5-S•••O interactions in controlling the structural preorganization and chemoselectivity observed within the lactam synthesis with benzothiazoles as nucleophiles. When using benzazoles the absence of a second stabilizing non-bonding 1,5-S•••O interaction leads to a dominant CH•••O interaction in determining structural preorganization and lactone formation.
Robinson , E R T , Walden , D M , Fallan , C , Greenhalgh , M D , Cheong , P H-Y & Smith , A D 2016 , ' Non-bonding 1,5-S•••O interactions govern chemo- and enantioselectivity in isothiourea-catalyzed annulations of benzazoles ' Chemical Science , vol 7 , no. 12 , pp. 6919-6927 . DOI: 10.1039/C6SC00940A
This is an Open Access article, which is licensed under a Creative Commons Attribution 3.0 Unported Licence.
We thank the Royal Society (URF to ADS), the EPSRC (ERTR – grant code EP/J500549/1) and the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013) ERC grant agreement n° 279850 (CF). We also thank the EPSRC UK National Mass Spectrometry Facility at Swansea University. PHYC is the Vicki & Patrick F. Stone Scholar of Oregon State University and gratefully acknowledges financial support from the Stone Family & the National Science Foundation (NSF, CHE-1352663), and the computing infrastructure in part provided by the NSF Phase-2 CCI, Center for Sustainable Materials Chemistry (NSF CHE-1102637). DMW also acknowledges financial support from the Johnson Research Fellowship.