Anti-Selective [3+2] (Hetero)annulation of Non-Conjugated Alkenes via Directed Nucleopalladation

Abstract

2,3-Dihydrobenzofurans and indolines are common substructures in medicines and natural products. Herein, we describe a method that enables direct access to these core structures from non-conjugated alkenyl amides and <i>ortho</i>-iodoanilines/phenols. Under palladium(II) catalysis this [3+2] heteroannulation proceeds in an <i>anti</i>-selective fashion and tolerates a wide variety of functional groups. <i>N</i>-Acetyl, -tosyl, and -alkyl substituted <i>ortho</i>-iodoanilines, as well as free –NH<sub>2</sub> variants, are all effective. Preliminary results with carbon-based coupling partners also demonstrate the viability of forming indane core structures using this approach. Experimental and computational data with phenols support a mechanism involving turnover-limiting, endergonic directed oxypalladation, followed by intramolecular oxidative addition and reductive elimination.

Nickel-Catalyzed 1,2-Carboamination of Alkenyl Alcohols

“…This result rules out a stepwise mechanism consisting of oxidative Heck arylation followed by hydroamination of the resulting styrenyl intermediate. Finally, a radical clock experiment using 1,6-heptadien-4-ol (11) was performed to probe the generation of a carbon-centered radical intermediate (Figure 3C). Interestingly, acyclic carboaminated product 12 was observed as the major product, and no evidence of the cyclized product was observed.…”

“…Additionally, several groups independently demonstrated heteroannulations in which alkenes are coupled with bifunctional coupling partners using different transition metal catalysts [7][8][9][10][11] .…”

Stereospecific nickel-catalyzed [4+2] heteroannulation of alkynes with aminophosphanes

“…These approaches, however, require complicated multistep substrate synthesis and only formation of one chemical bond during reactions. Metal-catalyzed annulation of unsaturated hydrocarbons is a valuable tool to substituted heterocycles and carbocycles by constructing several chemical bonds simultaneously (43)(44)(45)(46)(47)(48)(49). Among them, Larock indole synthesis through palladium-catalyzed reaction of internal alkynes and o-haloanilines is particularly important (50)(51)(52)(53), which has been widely applied for the construction of indole skeletons in natural products and pharmaceutically active compounds (Fig.…”

Regioselective 1,2-carbosulfenylation of unactivated alkenesviadirected nickel catalysis

“…[22][23][24][25][26][27][28] While signi cant progress has been made in recent years, most of these transformations are largely focused on alkene dicarbofunctionalization. [29][30][31][32][33][34][35][36][37][38][39] Carboheterofunctionalizations with concomitant formation of C-N, [40][41][42][43] C-O, [44][45] C-B, 46-48 and C-Si 48 have been explored, directed ole n carbosulfenylation remains untouched. 49 Recently, our group described a method for Ni(II)-catalyzed dicarbofunctionalization 37 and carboamination 43 of unactivated alkenes bearing picolinamide (PA) directing group via a Ni(I)/Ni(III) cycle rather than a Ni(0)/Ni(II) cycle, thus resulting in reversed regioselectivity that incorporate nucleophiles distal to the directing group.…”