Palladium(II)‐Catalyzed Enantioselective Azidation of Unactivated Alkenes

Abstract

The first Pd‐catalyzed enantioselective azidation of unactivated alkenes has been established by using readily accessible 1‐azido‐1,2‐benziodoxol‐3(1H)‐one (ABX) as an azidating reagent, which affords a wide variety of structurally diverse 3‐N3‐substituted piperidines in good yields with excellent enantioselectivity. The reaction features good functional‐group compatibility and mild reaction conditions. Notably, both an electrophilic azidating reagent and the sterically bulky chiral pyridinyl‐oxazoline (Pyox) ligand are crucial to the successful reaction.

Efficient Synthesis of Bulky 2,2’‐Bipyridine and (S)‐Pyridine‐Oxazoline Ligands

“…This result indicated that the sterically hindered 1‐naphthyl group retarded the second arylation under these conditions. Compared to the synthetic routes [4e–g] described in the Introduction involving 4–6 steps, this work provides an efficient method to synthesize bulky and enantioenriched ( S )‐pyridine‐oxazoline ligands in two steps starting from commercially available 6‐methyl‐2‐pyridinecarbonitrile and β‐amino alcohols [9] with reasonable to good yields. Although it was viewed as unlikely that the stereocenter in the pyridine oxazoline‐based ligands would be racemized by the base under these mild conditions, we viewed it as prudent to verify this hypothesis using chiral phase SFC (see Supporting Information for details).…”

“…While many transformations have been introduced with commercially available bidentate 2,2’‐bipyridine derivatives (bpy), the use of bulky NN’ ‐bidentate ligands [4] has been gaining attention. For example, bulky N , N ’‐bidentate ligands derived from 2,2′‐bipyridine and enantioenriched pyridine‐oxazolines have been used in metal‐catalyzed carbon dioxide reduction [4c,d] (Scheme 1a), enantioselective alkene difunctionalization reactions [4e–g,i] (Scheme 1b) and enantioselective electrochemical homocoupling reactions [4h] (Scheme 1c) with enhanced catalytic activity. In these reactions, the bulky ligands were implemented to prevent undesirable catalyst dimerization [4c,5] or to increase the metal center's electrophilicity toward binding olefin substrates [4f] .…”

Transition Metal Catalyzed Azidation Reactions

“…The possible mechanism starts with the coordination of the Pd(II)-catalyst to the alkenyl double bond giving the π-olefin complex I-39, followed by the generation of the σ-alkyl-complex II-39. The latter was oxidized to the In 2020, an enantioselective Pd-catalyzed azidation of unactivated alkenes in oxidative conditions has been reported by Liu and co-workers [97].…”

Catalytic, Enantioselective Diamination of Alkenes

“…Recently, Liu and co-workers described an L6-Pd-catalyzed diamination of N-Ts tethered terminal alkenes to provide 6-endo-cyclized product with 1-azido-1,2-benziodoxol-3(1H)-one 23 as amination reagent and oxidant (Scheme 11). 31 This process diverges from Michael and co-worker's 5-exo-aminopalladation most likely because of the different protecting groups on the nitrogen nucleophile. 3-Azidopiperidines are obtained in variable yields with excellent enantioselectivities.…”