Kami L. hull group realizes palladium catalyzed anti Markovian regular selective oxidation amination

The author: Wan yanlang in organic chemistry, Markovnikov rule It is a regioselective empirical rule based on Zaitsev's rule Its content is: when the electrophilic addition reaction (such as the reaction of hydrogen halide and olefin) occurs, the positive group (such as hydrogen) in the electrophilic reagent is always added to the carbon atom with the most hydrogen (the least substitution), while the negative group (such as halogen) is added to the carbon atom with the least hydrogen (the most substitution) 1）。
Figure 1 takes alkene and hydrogen halide as examples to show that the orientation of addition reaction between asymmetric alkene and hydrogen halide is inconsistent with that predicted according to the rule of martensite, which is called anti martensitic rule (Figure 2) Figure 2 takes alkenes and boranes as examples to illustrate that in recent years, the synthesis of amines and other nitrogen-containing compounds has been the main field of organic chemistry research, because they are widely present in bioactive molecules The current strategy mainly depends on the multi-step synthesis method, which is easy to lead to low efficiency and functional group intolerance Recently, Kami L hull group from the University of Illinois Urbana Champaign published an article on palladium catalyzed selective oxidation amination of anti martensitic rules in nature Chemistry (DOI: 10.1038 / nchem 2904) In this paper, a palladium catalyzed oxidative amination reaction is introduced The reaction selectivity follows the anti Markovian rule The addition of nitrogen atom occurs on the carbon atom with less substitution in the double bond (Figure 3) Figure 3 palladium catalyzed oxidative amination of trans olefins, including hydrogenation and oxidative amination, is an atom economic method for the synthesis of C-N bonds Oxidative amination, also known as azawacker oxidation, is different from other hydroamination because it retains the unsaturation in the product Due to the widespread presence of terminal amines in drugs, especially in the far end of polar functional groups, the development of anti Markovian rule selective aza Wacker oxidation of unactivated olefins will be a significant progress This reaction provides a new method for the long-range anti Markovian regular selective amination of organic molecules and a new powerful cut-off method in organic synthesis At present, there are several strategies for amination of simple olefins by anti Markovian regular oxidation (Figure 4): A using activated olefins to produce stable alkyl PD intermediates provides the basis for anti Markovian regular selectivity b Allylic C-H bond activation can provide π - allylic intermediates, which can be substituted by nucleophiles to obtain allylamine c The connected guiding group can functionalize the terminal position by forming a more stable metal ring intermediate d E it is found in chemometrics that palladium salt can support the reaction of simple aliphatic alkenes and nucleophiles with steric hindrance to functionalize (d) according to the anti martensitic rule, and the catalysis in the author's work (E) Figure 4 strategy of regular oxidation amination of anti martensite L: nitrogen or oxygen; [M]: metal catalyst; R: alkyl chain; ts: Toluenesulfonyl (ch3c6h4so2); X: carbon, nitrogen or oxygen (source: nature Chemistry) based on the mechanism research, the author proposed the following catalytic cycle process (Figure 5): the order of reagents implies that the participation of olefins and catalysts is before or in the rapid control step, and the participation of o-phthalimide is excluded The results show that palladium binding to olefins after dissociation from associated ligands is a fast controlling step, while its nucleophilic attack on olefins is fast The requirement of the catalytic amount of acetate indicates that it may take part in the process as a catalytic base, capture the active protons of phthalimide to produce nucleophilic anions, and then eliminate them in the subsequent reduction to generate AcOH and Pd (0) from PD (H) OAC The H + of these two equivalents is finally used to oxidize PD (0) to PD (II) to produce H 2O 2 or H 2O, and regenerate ACO - After β - elimination and olefin isomerization, the most stable olefin isomer was produced, and then pd-h was oxidized to generate palladium salt Figure 5 conclusion of the catalytic cycle process (source: nature Chemistry) proposed by the author: the author shows a palladium catalyzed anti Markovian rule selective aza Wacker oxidation In addition, under the reaction conditions, olefins containing unsaturated units will undergo isomerization, leading to the shift of hydrogen atoms to form the most stable molecules Finally, the oxidative amination method in this paper also provides a new cut-off method for organic synthesis Corresponding author: Kami L hull