Lee SH, Kim IS, Li QR, Dong GR, Jeong LS, Jung YH * Sungkyunkwan University, Suwon, University of Ulsan and Ewha Womans University, Seoul, Republic of Korea
Stereoselective Amination of Chiral Benzylic Ethers Using Chlorosulfonyl Isocyanate: Total Synthesis of
(+)-Sertraline.
J. Org. Chem. 2011;
76: 10011-10019
Key words
sertraline - stereoselective amination - benzylic ethers - chlorosulfonyl isocyanate
Significance
Key steps in this small-scale, six-step synthesis of (+)-sertraline (19% overall yield) are (1) the kinetic resolution of the racemic ketone E using the (R)-(+)-2-methyl-CBS-oxazaborolidine catalyst D and N,N-diethylaniline borane as reducing agent, and (2) the reaction of benzyl ether F with chlorosulfonyl isocyanate to give carbamate I.
Comment
The retention of configuration observed in the latter reaction arises from the formation of the tight ion pair H that allows front-side attack by an SN
i mechanism involving a four-center transition state. A further 11 examples of the reaction are reported all proceeding with good yield (70–89%) and high ee (88 to >99%). Benzylic methyl ethers give the corresponding methyl carbamates.
