An efficient alternative to DBU in the oxathiaphospholane (OTP) method for the solid phase synthesis of P-stereodefined phosphorothioate analogs

This work was financially supported by National Centre of Science, Poland, grant UMO-2021/43/D/ST4/02433 (to K. J.). An Avance Neo 400 NMR spectrometer was purchased using funds provided by the EU Regional Operational Program of the Lodz Region RPLD.01.01.00-10-0008/18.

National Science Centre, Poland; UMO-2021/43/D/ST4/02433 EU Regional Operational Program of the Lodz Region; RPLD.01.01.00-10-0008/18

This study presents a modified (extended) 1,3,2-oxathiaphospholane (OTP) method for the synthesis of P-stereodefined phosphorothioate analogs in the presence of previously unused organic bases. TBD (5,7-triazabicyclo[4.4.0]dec-5-ene) and Verkade's proazaphosphatrane (2,8,9-trimethyl-2,5,8,9-tetraaza-1-phosphabicyclo[3.3.3]undecane) are herein used for the first time as efficient organic bases compared to DBU, which is commonly used in the OTP approach. OTP method for the synthesis of P-stereodefined phosphorothioate has been extended to use activators TBD and Verkade base, which can be used interchangeably with DBU.