Oxadiazepine Synthesis by Formal [4+3] Cycloaddition of o‐Chloromethyl Arylsulfonamides with Nitrones Promoted by NaHCO₃

Abstract

An effective and facile method for the synthesis of highly substituted 1,2,3,5‐tetrahydrobenzo[e][1,2,4]‐oxadiazepines is described. A formal [4+3] cycloaddition of N‐(2‐(chloromethyl) phenyl) amides with nitrones afforded benzo[e][1,2,4]‐oxadiazepine derivatives with high atom economy and excellent yields (up to 97%).magnified image

Recent Advances in Transition-Metal-Free (4+3)-Annulations

“…It was also determined that the formation of the desired seven-membered product 2.9d was kinetically favored. 21 In 2018, both Li and Liu 22 and Shao 23 published similar base-mediated (4+3)-annulations between o-chloromethyl arylsulfonamides 2.10a and nitrones 2.10b for the synthe-sis of benzooxadiazepines 2.10c (Scheme 2.10). The former employed Na 2 CO 3 whereas the latter employed NaHCO 3 .…”

A [4+3] Cycloaddition Reaction of Aza-ortho-quinone Methides with C,N-Cyclic Azomethine Imines for Synthesis of 1,2,4-Triazepines

“…15 The Shao research group reported a method for the synthesis of 1,2,3,5-tetrahydro-4,1,3-benzoxadiazepines in excellent yields through [4+3] cycloaddition of [o-(chloromethyl)aryl]sulfonamides with nitrones (Scheme 2c). 16 To construct functionalized 1,2,4-…”

“…Because the influence of the base was crucial for the reaction, various bases were then screened. The yield was not improved by using other bases such as Na 2 CO 3 , Cs 2 CO 3 , NaHCO 3 , KOH, or DIPEA instead of K 2 CO 3 (entries [10][11][12][13][14][15][16]; in the presence of Et 3 N or DBU, the reaction failed to work and no product was obtained (entries 15 and 16). Endeavors to improve the efficiency of the reaction by varying the ratio of 1a and 2a proved to be in vain (entries 17 and 18).…”

[4+n] Annulation Reactions Using ortho-Chloromethyl Anilines as Aza-ortho-Quinone Methide Precursors

“…49 Nitrones are also well-known 1,3-dipoles due to their high reactivity and facile preparation. In 2018, the groups of Liu and Li, 50 Shao, 51 and Wang 52 independently published elegant work on the same annulation process involving N-(o-chloromethyl)aryl amides 47 and nitrones 137 in the presence of various bases and solvents. Using the developed protocol, a variety of oxygen-containing seven-membered N-heterocycles 138 were smoothly prepared in high yields under mild conditions.…”