Interception of Secondary Amide Ylide with Sulfonamides: Catalyst-Controlled Synthesis of N-Sulfonylamidine Derivatives

Abstract

A novel, secondary amide activation strategy has been developed through the in situ generation of ylides from amides and diazoacetates. Under the developed reaction conditions, Mn-catalyzed ylide formation and interception reaction by sulfonamide delivered a variety of N-sulfonylamidines. Notably, when highly active Zn(OTf) was used as the catalyst, further N-H insertion products were obtained. In contrast with traditional methods, our amide activation strategy is distinguished by accessible starting material, inexpensive catalyst, and broad substrate scope.

Selective Functionalization of Aliphatic Amines via Myoglobin-Catalyzed Carbene N–H Insertion

“…Following the general procedure B with N,N-dioctylamine 18a, the title compound 18b was obtained as a slowly crystallizing colorless oil in 82% yield. Following a previously reported procedure, [1] isopropyl alcohol (5.00 mmol, 1 equiv.) and NaHCO3 (1.26g, 15.0 mmol, 3 equiv.)…”

“…Following a previously reported procedure, [1] cyclohexyl alcohol (5.00 mmol, 1 equiv.) and NaHCO3 (1.26g, 15.0 mmol, 3 equiv.)…”

“…The crude product was used without further purification as a colorless oil in 60% yield. 1 H NMR (CDCl3, 500 MHz): δ 4.82 (m, 1H), 3.81 (s, 2H), 1.86-1.29 (m, 10H).…”

“…Rf (5% EtOAc/hexanes) = 0.16. GC-MS m/z (% relative intensity): 120(100), 106(36.0), 121(9.3), 118(4.4) 164(3.5), 247(1.3) 1. H NMR (CDCl3, 500 MHz): δ 7.37 -7.27 (m, 5H), 4.83 (m, 1H), 3.81 (s, 2H), 3.39 (s, 2H), 1.88 -1.24 (m, 10H).13 C NMR (CDCl3, 125 MHz): δ 172.0, 1397, 128.6, 128.5, 127.3, 73.4, 53.4, 50.5, 31.8, 25.4, 23.9.…”

“…Rf (10% EtOAc/hexanes) = 0.10. GC-MS m/z (% relative intensity): 120(100), 106(27.0), 164(22.0), 121(9.9), 118(6.0) 1. H NMR (CDCl3, 500 MHz): δ 7.38-7.32 (m, 10H), 5.18 (s, 2H), 3.81 (s, 2H), 3.47 (s, 2H), 1.87 (br).…”