Synthesis and hetero-Diels–Alder reactions of enantiomerically pure dihydro-1H-azepines

Abstract

Thermolysis of enantiomerically pure 3-substituted 7,7-dihalo-2-azabicyclo[4.1.0]heptanes in the presence of K2CO3 gives in good yields 2-alkyl-6-halo-1-tosyl-2,3-dihydro-1H-azepines. These undergo highly stereoselective [4+2] cycloaddition reactions with heterodienophiles and arylation/alkenylation under Suzuki conditions

Bicyclic N-dihalocyclopropylamide derivatives as precursors of nitrogen-containing fused polycyclic systems

“…The other diastereoisomer exo - 11 had been left unreacted under the same conditions, which is consistent with the Woodward–Hoffmann–DePuy rule. 1 a The production of 12 can readily be interpreted as the result of the loss of a proton from the iminium intermediate 13 , 13 rather than the desired cyclisation to the tricyclic system 14 .…”

Diels‐Alder Cycloaddition of Azepino[4,5‐b]indoles Towards Hydrocarbazole Derivatives and Related Heterocycles

“…To further expand the scope of dienophiles in the cycloaddition of azepino[4,5‐ b ]indoles, 4‐phenyl‐3 H ‐1,2,4‐triazole‐3,5(4 H )‐dione (PTAD), a reactive dienophile was used to perform the hetero‐Diels‐Alder reaction [11,16] . It was found that all the reactions underwent smoothly with no catalyst, affording the endocyclic hetero‐Diels‐Alder cycloaddition products in high yields (Table 4).…”

“…reaction. [11,16] It was found that all the reactions underwent smoothly with no catalyst, affording the endocyclic hetero-Diels-Alder cycloaddition products in high yields (Table 4). [17] This result implied that the occurance of retro-aza-Michael reaction could be tuned by changing the type of the dienophiles.…”

“…Previously we developed a strategy for the syntheses of azepino[4,5‐ b ]indoles via cycloisomerization of tryptamine‐ynamides [10b] . The diene moiety in azepino[4,5‐ b ]indoles enabled the syntheses of hydrocarbazoles via a [4+2] cycloaddition [11] . In this study, a Diels‐Alder cycloaddition/retro‐aza‐Michael addition cascade strategy was proposed aiming for the preparation of hydrocarbazole scaffold, a key molecular motif in natural products and potent RMAs.…”

“…[10b] The diene moiety in azepino [4,5-b]indoles enabled the syntheses of hydrocarbazoles via a [4 + 2] cycloaddition. [11] In this study, a Diels-Alder cycloaddition/retro-aza-Michael addition cascade strategy was proposed aiming for the preparation of hydrocarbazole scaffold, a key molecular motif in natural products and potent RMAs. It was envisioned that a Diels-Alder cycloaddition of azepino [4,5-b]indoles (A) and commercially available dienophiles (B) would provide the congested tetracyclic intermediates (C), followed by a subsequent retro-aza-Michael addition driven by releasing the strain of endocyclic structure to yield hydrocarbazoles (E) after isomerization of intermediates (D) (Scheme 1).…”