Copper-Catalyzed Regiospecific and 1,2-Regioselective Cyclopropanation of (1Z)-1-Amino- and (1Z)-1-Oxy-1,3-butadienyl Derivatives

Abstract

The copper-catalyzed regiospecific and 1,2-regioselective cyclopropanation of (1Z)-1-amino-and (1Z)-1-oxy-1,3-butadienyl derivatives, which could be prepared by Z-stereoselective 1,4-elimination with α-aryl diazoesters was successfully demonstrated. This successful regiospecific protocol enabled the preparation of the corresponding 1amino-and 1-oxy-2-vinylcyclopropane derivatives as almost single stereoisomers.

Generation of Tosyl Azide in Continuous Flow Using an Azide Resin, and Telescoping with Diazo Transfer and Rhodium Acetate-Catalyzed O–H Insertion

“… 22 Synthesis of each of the α-diazo aryl acetates ( 9 , 20 , 22 , and 24 ) has been previously reported diazo transfer under traditional batch conditions. 42 − 44 Most importantly, this study demonstrates that diazo transfer in flow is a practical synthetic route even with substrates with relatively high p K a , such as aryl acetates; the key step which makes this approach practical is the nonaqueous medium enabled through use of the azide resin.…”

“…The crude residue was purified by column chromatography, using 9:1 hexane/ethyl acetate as eluent, to afford the desired product 9 as a yellow oil (0.170 g, 69%) with spectral data consistent with that reported above and in the literature. 42 The used Dowex azide resin 16 was removed from the column and stirred in acetonitrile for 2 h and was filtered. The filtrate was then concentrated under reduced pressure to remove acetonitrile.…”

“…The crude residue was purified by column chromatography, using 9:1 hexane/ethyl acetate as eluent, to afford the desired product 9 as a yellow oil (0.251 g, 58%) with spectral characteristics consistent with those described above and in the literature. 42 …”

“…Methyl 2-(2-chlorophenyl)-2-diazoacetate (9). 42 Attempted Preparation of 9 in Flow Using DBU in Aqueous Acetonitrile. A solution of methyl 2-chlorophenylacetate (8) (0.83 g, 4.5 mmol) and DBU (0.75 g, 4.95 mmol) in acetonitrile (10 mL) was prepared, and a solution of tosyl chloride 13 (0.89 g, 4.5 mmol) was made up in acetonitrile (10 mL).…”

“…The crude residue was purified by column chromatography, using 9:1 hexane/ethyl acetate as eluent, to afford the desired product 9 as a yellow oil (0.314 g, 64%) with spectral characteristics consistent with those described above and in the literature. 42 Method B. A solution of methyl 2-(2-chlorophenyl)acetate (8) (0.480 g, 2.6 mmol) and DBU (0.455 g, 3.0 mmol, 1.15 equiv) in acetonitrile (10 mL) was prepared and a solution of tosyl chloride 13 (0.49 g, 2.6 mmol, 1 equiv) was made up in acetonitrile (10 mL).…”