Catalytic transformations involving Pd II s-alkyl or s-aryl intermediates are widely used in organic synthesis and offer attractive routes to many valuable products. [1] However, the vast majority of these reactions proceed by Pd 0 /Pd II 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 II salkyl/aryl species in the presence of strong oxidants (e.g., PhI(OAc) 2 , oxone, N-halosuccinimides, iodine) to access alternative Pd II /Pd IV reaction manifolds. [3][4] Importantly, these oxidative transformations often yield highly complementary organic products to those formed by traditional Pd 0/II catalysis. [3][4] Our group is interested in exploiting Pd II /Pd IV catalytic cycles for the development of new organic transformations. [2a-e, 4a] As part of these efforts, we reasoned that Pd II baminoalkyl species (generated by the aminopalladation of olefins) [5] might be oxidatively intercepted with PhI(OAc) 2 (Scheme 1). If successful, such reactions would provide an attractive Pd II /Pd IV -catalyzed route from alkenes to amino-oxygenated products, which are valuable building blocks in organic synthesis. Importantly, while this work was in progress, several other groups disclosed related transformations. [3] 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 II /Pd IV -catalyzed reactions.
Our initial studies focused on generating Pd II b-aminoalkyl species A by the intermolecular aminopalladation of 1octene with phthalimide (Scheme 1). [3a] 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 1 a. 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 1 a in 41 % yield. However, consistent with results recently disclosed by Liu and Stahl, [3a] the b-hydride product 1 b 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 2 d. However, surprisingly, the intermolecular aminoacetoxylated species 2 c was not observed in this reaction. Instead, tetrahydrofuran product 2 a, resulting from an intramolecular oxygenation, was formed in a modest 30 % yield along with a second THF compound (2 b). A screening of reaction additives revealed that 10 mol % AgBF 4 increased the yield of 2 a to 37 %. Two sequential additions of catalyst, silver salt, oxidant, and alcohol further improved the yield of 2 a 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 2 a or 2 b.
With these results in hand, we next sought to investigate the mechanism of the Pd-catalyzed formation of 2 a. We initially hypothesized that 2 a might be formed in a two-step sequence. In the first step, Pd-catalyzed reaction between 2 and PhI(OAc) 2 would afford either 2 b or 2 c (Scheme 2). Product 2 b could then undergo an intermolecular S N 2 reaction with free phthalimide (Scheme 3, route a), or 2 c could undergo intramolecular S N 2 ring closure (Scheme 3, route b) to afford 2 a. To test the viability of these pathways, Scheme 1. Pd-catalyzed aminoacetoxylation of 1-octene.