Construction of tetrahydrofurans by PdII/PdIV-catalyzed aminooxygenation of alkenes.

Catalytic transformations involving Pd s-alkyl or s-aryl intermediates are widely used in organic synthesis and offer attractive routes to many valuable products. However, the vast majority of these reactions proceed by Pd/Pd mechanisms. As a result, the diversity of structures/bonds that can be constructed is constrained by the limitations of this redox cycle. Recent studies have explored the generation of Pd salkyl/aryl species in the presence of strong oxidants (e.g., PhI(OAc)2, oxone, N-halosuccinimides, iodine) to access alternative Pd/Pd reaction manifolds. Importantly, these oxidative transformations often yield highly complementary organic products to those formed by traditional Pd catalysis. Our group is interested in exploiting Pd/Pd catalytic cycles for the development of new organic transformations. As part of these efforts, we reasoned that Pd baminoalkyl species (generated by the aminopalladation of olefins) might be oxidatively intercepted with PhI(OAc)2 (Scheme 1). If successful, such reactions would provide an attractive Pd/Pd-catalyzed route from alkenes to aminooxygenated products, which are valuable building blocks in organic synthesis. Importantly, while this work was in progress, several other groups disclosed related transformations. We report herein the successful application of this strategy to the stereospecific and diastereoselective conversion of 3-alken-1-ols into 3-aminotetrahydrofurans. Mechanistic details are discussed and offer insights into the further design and development of Pd/Pd-catalyzed reactions. Our initial studies focused on generating Pd b-aminoalkyl species A by the intermolecular aminopalladation of 1octene with phthalimide (Scheme 1). Complex A would typically undergo b-hydride elimination; however, we anticipated that this species could react competitively with PhI(OAc)2 to generate a Pd IV intermediate. Reductive elimination from this intermediate should then provide aminoacetoxylated product 1a. We were pleased to find that treatment of 1-octene with 5 mol% Pd(OAc)2, one equivalent phthalimide, and two equivalents PhI(OAc)2 for 12 h at 60 8C afforded 1a in 41% yield. However, consistent with results recently disclosed by Liu and Stahl, the b-hydride product 1b was also obtained in 27% yield. We hypothesized that competing b-hydride elimination might be suppressed by tethering a hydroxyl group to the alkene. In a substrate like 3-buten-1-ol (2), the hydroxyl group could coordinate to the Pd center during/after aminopalladation to form palladacycle B (Scheme 2), thereby slowing bhydride elimination relative to oxidative functionalization. Gratifyingly, treatment of 2 with 5 mol% Pd(OAc)2, one equivalent phthalimide, and two equivalents PhI(OAc)2 did not produce any of the b-hydride elimination product 2d. However, surprisingly, the intermolecular aminoacetoxylated species 2c was not observed in this reaction. Instead, tetrahydrofuran product 2a, resulting from an intramolecular oxygenation, was formed in a modest 30% yield along with a second THF compound (2b). 9] A screening of reaction additives revealed that 10 mol%AgBF4 increased the yield of 2a to 37%. Two sequential additions of catalyst, silver salt, oxidant, and alcohol further improved the yield of 2a to 45% (based on phthalimide as the limiting reagent). Importantly, control reactions (in the absence of Pd or oxidant) did not afford any of the tetrahydrofuran products 2a or 2b. With these results in hand, we next sought to investigate the mechanism of the Pd-catalyzed formation of 2a. We initially hypothesized that 2a might be formed in a two-step sequence. In the first step, Pd-catalyzed reaction between 2 and PhI(OAc)2 would afford either 2b [9, 11] or 2c (Scheme 2). Product 2b could then undergo an intermolecular SN2 reaction with free phthalimide (Scheme 3, route a), or 2c could undergo intramolecular SN2 ring closure (Scheme 3, route b) to afford 2a. To test the viability of these pathways, Scheme 1. Pd-catalyzed aminoacetoxylation of 1-octene.