Achieving Site Selectivity in Metal-Catalyzed Electron-Rich Carbene Transfer Reactions from N-Tosylhydrazones

Abstract

Catalyst control of the site-selectivity of electron-rich alkyl, aryl disubstituted carbenes generated in situ from o-alkenyl-substituted N-tosylhydrazones was achieved in this study. Exposure of these substrates to copper iodide triggered the formation of α-alkoxy 2H-naphthalenones. This investigation established that changing the catalyst to a rhodium(II) carboxylate turned off cyclization and migration of the electron-rich metal carbene with the β-carboxylate and turned on allylic C-H bond functionalization to diastereoselectively afford 1H-indenes. Examination of the scope of this reaction revealed that ethereal, aminomethylene, and unactivated 2° C-H bonds could be functionalized.

Transition Metal Catalyzed Insertion Reactions with Donor/Donor Carbenes

“…Driver and co-workers reported several examples of polycyclic indanes,i ndolines,a nd benzodihydrofurans using Du Bois Rh 2 (esp) 2 catalyst 18 from acetophenone-derived [51] 3H Ar, [a] alkyl Ar, [a] alkyl, H, allylic [d] [a] Ar, [a] Angewandte Chemie Minireviews tosylhydrazones (Figure 10). [55] This work highlights catalyst control of carbene reactivity:while copper(I)-based aryl/alkyl carbenes were previously found to undergo cyclization/alkyl migrations, [56] rhodium carbenes in this work cleanly furnish allylic insertion products 80 while avoiding cyclopropanation reactions.I nterestingly,w hen the available bond for C sp 3 ÀH insertion is at abridgehead, the preferred pathway is the vinyl C sp 2 ÀHinsertion reaction to afford 84.Itisalso notable that in all cases the carbene is appended with amethyl group,which is capable of undergoing aBamford-Stevens type elimination that is not observed. [57] Thes ynthesis of saturated monocyclic five-membered heterocycles is also enabled using ruthenium porphyrin catalyst 27 (Figure 11).…”

Transition Metal Catalyzed Insertion Reactions with Donor/Donor Carbenes

“…Driver and co-workers reported several examples of polycyclic indanes,i ndolines,a nd benzodihydrofurans using Du Bois Rh 2 (esp) 2 catalyst 18 from acetophenone-derived [51] 3H Ar, [a] alkyl Ar, [a] alkyl, H, allylic [d] [a] Ar, [a] Angewandte Chemie Kurzaufsätze tosylhydrazones (Figure 10). [55] This work highlights catalyst control of carbene reactivity:while copper(I)-based aryl/alkyl carbenes were previously found to undergo cyclization/alkyl migrations, [56] rhodium carbenes in this work cleanly furnish allylic insertion products 80 while avoiding cyclopropanation reactions.I nterestingly,w hen the available bond for C sp 3 ÀH insertion is at abridgehead, the preferred pathway is the vinyl C sp 2 ÀHinsertion reaction to afford 84.Itisalso notable that in all cases the carbene is appended with amethyl group,which is capable of undergoing aBamford-Stevens type elimination that is not observed. [57] Thes ynthesis of saturated monocyclic five-membered heterocycles is also enabled using ruthenium porphyrin catalyst 27 (Figure 11).…”

“…Driver and co‐workers reported several examples of polycyclic indanes, indolines, and benzodihydrofurans using Du Bois’ Rh 2 (esp) 2 catalyst 18 from acetophenone‐derived tosylhydrazones (Figure 10). [55] This work highlights catalyst control of carbene reactivity: while copper(I)‐based aryl/alkyl carbenes were previously found to undergo cyclization/alkyl migrations, [56] rhodium carbenes in this work cleanly furnish allylic insertion products 80 while avoiding cyclopropanation reactions. Interestingly, when the available bond for C −H insertion is at a bridgehead, the preferred pathway is the vinyl C −H insertion reaction to afford 84 .…”

Rhodium-Catalyzed B–H Bond Insertion Reactions of Unstabilized Diazo Compounds Generated in Situ from Tosylhydrazones

“…To our delight, we found that in the presence of a copper, palladium, or rhodium complex, the reaction smoothly afforded desired B–H bond insertion product (1-(naphthalen-2-yl)­ethyl)­borane ( 3aa ) in moderate to good yield (entries 1–3 and 6–10). CuI, Rh 2 (TPA) 4 , and Rh 2 (piv) 4 gave yields over 70%, with Rh 2 (piv) 4 giving the highest yield (92%, entry 10) . The amount of Rh 2 (piv) 4 could be reduced to as low as 1 mol % without substantially compromising the yield (entries 10–12).…”

“…We next evaluated B–H bond insertion reactions of tosylhydrazones 4 derived from various other carbonyl compounds as carbene precursors (Table ). Tosylhydrazones derived from aromatic aldehydes ( 4a and 4l ; entries 1 and 12), aryl alkyl ketones with linear or branched R groups ( 4b , 4c , and 4j ; entries 2, 3, and 10), and diaryl ketones ( 4e – 4i ; entries 5–9) were all suitable carbene precursors for B–H bond insertion reactions with borane adduct 2a or 2f . , Reaction of an aryl alkyl ketone with a sterically hindered R group ( 4d ) was achieved with CuI as a catalyst (entry 4). Moreover, the tosylhydrazone derived from cyclic ketone 4k reacted smoothly with 2a to afford the desired product 5ka in good yield (entry 11).…”