Base‐Mediated Generation of Ketenimines from Ynamides: Direct Access to Azetidinimines by an Imino‐Staudinger Synthesis

Abstract

Ynamides were used as precursors for the in situ generation of highly reactive ketenimines that could be trapped with imines in a [2+2] cycloaddition. This imino‐Staudinger synthesis led to a variety of imino‐analogs of β‐lactams, namely azetidinimines (20 examples), that could be further functionalized through a broad range of transformations.

Synthesis of Halogenated Cyclic Enamines from Cyclic N‐2‐En‐4‐ynyl‐N‐1‐ynylamides and N‐Propargyl‐N‐1‐ynylamides via a Tandem Iron Halide Promoted N‐to‐C Shift‐Aza‐Prins Cyclization Sequence

“…The low yield was also found with substrate 9 m bearing an electron-donating methoxy group at C3 of the phenyl ring on the ynamide terminus (33%, Table 1, entry 13). Unfortunately, running the reaction with substrates bearing a methoxy group at C2 or C4 of the phenyl ring on the ynamide moiety led to complete decomposition upon treatment with FeBr 3 ( Table 3, entries [14][15]. Moreover, substrates with an alkyl substitution at the ynamide terminus, 9 p and 9 q, were also reactive, providing the desired compounds 10 p and 10 q, albeit with diminished yields (33-40%, Table 3, entries 16-17).…”

“…A formal [2 + 2] cycloaddition of the allene with the ketenimine gives an imine, which then undergoes hydrolysis and tautomerization to generate 10 a (path b, Scheme 4). [15] 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 Six-membered ring N-propargyl-N-1-ynylamides 13 also reacts with FeBr 3 under the same reaction conditions to produce spiro compounds 14 and 15 (Scheme 5). Thus, treatment of 13 a with 2.2 equiv.…”

“…It must be mentioned that Fe(III) halides are known to promote alkynes aza-Prins-type cyclization. [15] 16 9 p n-hexyl Ph 10 p 33 17 9 q 3-Cl-propyl Ph 10 q 40 A formal [2 + 2] cycloaddition of the allene with the ketenimine gives an imine, which then undergoes hydrolysis and tautomerization to generate 10 a (path b, Scheme 4).…”

Ketenimines Generated from Ynamides: Versatile Building Blocks for Nitrogen‐Containing Scaffolds

“…[21] Subjecting N-tert-butylcarbamate ynamide 74 to lithium tert-butoxide in dimethylformamide in the presence of an imine under microwave heating led to azetidinimines 76 in moderate to good yields (Scheme 26). [21] Subjecting N-tert-butylcarbamate ynamide 74 to lithium tert-butoxide in dimethylformamide in the presence of an imine under microwave heating led to azetidinimines 76 in moderate to good yields (Scheme 26).…”

“…In order to furthere xpand the potentialo ft his straightforward access to phenylethenimine, Dodd and Cariou soughtt o trap it in a[ 2 + +2] cycloaddition. [21] Subjecting N-tert-butylcarbamate ynamide 74 to lithium tert-butoxide in dimethylformamide in the presence of an imine under microwave heating led to azetidinimines 76 in moderate to good yields (Scheme 26). This imino-Staudinger synthesis using arylethenimines 75 is complementary to Fokin's method that provides Nsulfonyl-azetidinimines.…”