Diversity-oriented synthesis of 1,2,3,5-tetrahydrobenzo[e][1,2,4]oxadiazepines and 2,3-dihydro-1H-benzo[e][1,2,4]triazepines by base-induced [4 + 3] annulation reactions

Synthesis of Benzo[e][1,4]thiazepines by Base-Induced Formal [4+3] Annulation Reaction of Aza-o-quinone Methides and Pyridinium 1,4-Zwitterionic Thiolates

“…On the basis of the experimental results presented above and literature evidence, ,, a plausible reaction mechanism for this [4+3] annulation reaction is proposed in Scheme . Base-induced dehydrochlorination of N -( o -chloromethyl)­aryl amides 1 delivers aoQMs 1′ , which then reacted with pyridinium 1,4-zwitterionic thiolates 2 via S -Michael addition to form intermediates A .…”

“…The recently discovered [4+3] annulation reaction of in situ-generated aza- o -quinone methides (aoQMs) with 1,3-zwitterionic intermediates for the synthesis of seven-membered nitrogen-containing heterocycles has attracted a great deal of attention owing to the high efficiency and step economy (Scheme a) . AoQMs, which contained exocyclic alkylidene and an imine unit, were envisioned to be effective four-atom synthons for [4+ n ] annulation reactions due to the driving force of aromatization. , In 2015, the Chen group presented a facile approach for accessing an azaspirocycloheptane oxindole scaffold through a [4+3] cycloaddition reaction with aoQMs and isatin-derived Morita–Baylis–Hillman (MBH) adducts .…”

[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.…”

“…The Wang group also reported similar work almost at the same time (Scheme 28). 52 As part of their efforts to develop reactions of aza-o-QMs with N-alkoxy -halogenoacetamides, 25 Zhang, Jin and co-workers described [4+3] annulation reactions of aza-o-QMs 65 with unsubstituted haloamides 145 via a cascade aza-Mannich addition/intramolecular S N 2 domino reaction pathway (Scheme 29). 54 The reported methodology was concise and provided synthetically useful 1,2,4,5-tetrahydro-1,4-benzodiazepine-3-ones 146 in high yields and highlighted the use of unsubstituted haloamides, the dialkyl-substituted analogues of which reacted with aza-o-QMs via the aforementioned [4+2] annulation process (see Scheme 13).…”