Question

1. November 4, 2014 (12 pts) An article published in the current issue of Organic Letters reports the esterification of alcohols using amides under a sulfuryl fluoride atmosphere (Org. Lett. 2019, 21, 8657-8661). Draw a reasonable mechanism for the scheme below and provide a brief summary to explain each step. Droomly serious OH SOF, Cs2CO3 DMF, r.1., 12h and * HN +

Answer 1

0: HN-3 H -CH3 CH3 1 (1) CH3 70 Ph Phố (3) HNP3 H CHE il + FS-F on (4) HN ☺ н ” || 1 + HN CHA • Phi HN CH PVHOCH(7) CH3 (6)

Amide nitrogen has lone pair and it is in conjugation with amide carbonyl hence the amide is always in equilibrium with (dimethylamino)methanolate (1). This (1) can act as a nucleophile.
On the other hand, alcohol attacks as a nucleophile on SO2F2 to give intermediate (2). This makes the hydroxyl group as a very good leaving group. And hence, via the SN2 pathway, the nucleophile (1) attacks to give new C-O bond formation with intermediate (3) and (4). Intermediate (4) is unstable and hence it regenerates the SO2F2 along with releasing strong nucleophilic hydroxyl ions. This hydroxyl ion attacks on an intermediate (3) at the sp2 carbon-bearing O and =N. The intermediate (5) contains sterically hindered sp3 carbon and hence cleavage of C-N bond becomes energetically more favorable to give ester (6) and amine (7).