Investigation of a Late‐Stage Derivatiza­tion Approach to Isatogens: Discovery of New Reaction Pathways

Abstract

We have developed a new strategy for preparing 2‐substituted indolone N‐oxides (isatogens) by substitution reactions with aryl‐ and alkyl‐organometallic reagents. This approach allows a range of substituents to be incorporated at a late stage and complements existing methods that necessitate their early stage incorporation during substrate preparation. Further chemistry has been found to take place at the nitrone moiety; intramolecular dipolar cycloaddition provides access to angularly fused tricyclic heterocycles. More unusually however, these compounds are prone to further addition by organozinc reagents leading to 2,2‐disubstituted 3‐oxindole products.

Enantioselective Total Synthesis of (+)-Corymine and (−)-Deformylcorymine

“…We then converted (−)-12 to the more reactive triflate 13. However, the C2-alkylation 19 of 13 with less nucleophilic dialkylzinc or organocuprate also failed. Moreover, the carbonylative Sonogashira reaction 20 of 13 with a terminal alkyne turned out to be unsuccessful and only the C2alkynylation byproduct was observed.…”

“…However, the strategy required the removal of the oxo moiety at C14 and the introduction of a hydroxyl group at C3, rendering the synthetic route lengthy rather than concise. The Zu group described the synthesis of (±)-deformylcorymine in 19 protected indolin-3-one. 4g There have been no reports to date on the asymmetric synthesis of these two molecules.…”

Rhodium-Catalyzed Addition of Organozinc Iodides to Carbon-11 Isocyanates

“…Functionalized electron-rich arylzinc iodides were superior in reactivity, improving nucleophilicity of the reagent, as with 3m compared to those with electronwithdrawing groups such as products 3n and 3o. Alkyl organozinc iodides were prepared [17] and successfully coupled with isocyanates under similar conditions to prepare Calkyl amides. Notably, addition of [Rh(OH)(cod)]2 suppresses the previously reported carbamate formation.…”

“…Alkyl organozinc iodides were prepared and successfully coupled with isocyanates under similar conditions to prepare C-alkyl amides, with longer reaction times required for complete conversion. Notably, addition of [Rh­(OH)­(cod)] 2 suppresses the previously reported carbamate formation .…”