Synthesis 2023; 55(13): 2037-2046
DOI: 10.1055/a-2019-1455
paper

Trifluoroethanol-Mediated Cyclization of Two-Carbon-Tethered Epoxide–N-Boc Pairs: Completely Regioselective Synthesis of 3,6-Disubstituted 1,3-Oxazinan-2-ones

Jonali Das
,
Raju Chouhan
,
Hemi Borgohain
,
Biraj Jyoti Borah
,
Sajal Kumar Das
This work was financially supported by the DBT-Twinning Project (BT/PR25173/NER/95/1055/2017) granted by the North Eastern Region Biotechnology Programme Management Cell (NER-BPMC), Department of Biotechnology, Ministry of Science and Technology, New Delhi, India.


Abstract

The regio- and diastereoselective construction of biologically relevant cyclic carbamates under operationally simple and mild transition-metal-free conditions is challenging and has led to a demand for efficient methods for their synthesis. The intramolecular ring-opening cyclization of N-Boc-tethered epoxides leading to the formation of cyclic carbamates is equipped with many favorable synthetic features, including easy accessibility of starting materials in a stereodefined form, high diversification points in the substrates, and a favorable entropy factor. However, its use in the construction of 1,3-oxazinan-2-ones remains largely neglected. Specifically, prior to 2020, only few 1,3-oxazinan-2-ones were successfully synthesized using this strategy. Moreover, our very own recent attempt to access these heterocycles using one-carbon-tethered N-Boc–epoxide pairs was met with little success as the process furnished either only 1,3-oxazolidin-2-ones or nearly equal amounts of 1,3-oxazolidin-2-ones and 1,3-oxazinan-2-ones. Herein, we demonstrate that when the epoxide and N-Boc moieties are connected by a two-carbon tether, the cyclization could deliver 1,3-oxazinan-2-ones containing vicinal stereocenters, as sole regioisomers and diastereomers in high yields (up to 95% yield), irrespective of whether the distal epoxide substituent is alkyl or aryl, or the epoxide is cis- or trans-configured.

Supporting Information



Publication History

Received: 01 April 2022

Accepted after revision: 24 January 2023

Accepted Manuscript online:
24 January 2023

Article published online:
02 March 2023

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