Asymmetric Hydroarylation of Enones via Nickel-Catalyzed 5-Endo-Trig Cyclization

Abstract

A nickel-catalyzed reductive cyclization of enones affords a wide array of indanones in high enantiomeric induction. The reaction is featured with an unprecedented broad scope of substrates. The versatility of the new method is demonstrated in several short stereoselective syntheses of medically valuable (R)-tolterodine, parent and deuterated (+)-indatraline, and an antitumor natural product, (+)-multisianthol. In comparison, these compounds cannot be prepared satisfactorily via analogous processes catalyzed by palladium.

Recent Advances of Catalytic Enantioselective Heck Reactions and Reductive‐Heck Reactions

“…In the reaction of ortho ‐bromochalcones, Zhou and co‐workers were able to achieve the desired products in excellent ee (up to 97%) with moderate to good yields by utilizing modified semicorrin ligands L37 or L38 (Scheme 63). [ 75 ] Manganese powder as reducing agent and H 2 O as protonation agent were again used in this reaction. Wang and co‐workers accomplished an intramolecular hydroarylation of unactivated alkenes by using Ni(BF 4 ) 2 as a catalyst, pyridine‐oxazoline L9 as chiral ligand, zinc powder as reducing agent, and i‐ PrOH as a proton…”

Nickel-Catalyzed Enantioselective Desymmetrizing Aza-Heck Cyclization of Oxime Esters

“…Since the β-H elimination from the alkyl Ni II intermediates is more difficult than Pd(II), 46,47 the intermediate III might be able to undergo protonolysis, leading to the minor product 2′, along with the aza-Heck-type product 2. 48,49 This process affords enantioenriched 2-substituted-3,7a-dihydro-3aH-indoles 2, incorporating two stereocenters and a diene subunit that provides a large chemical space for the subsequent diastereoselective transformations (Scheme 1c).…”

Efficient kinetic resolution in the asymmetric transfer hydrogenation of 3-aryl-indanones: applications to a short synthesis of (+)-indatraline and a formal synthesis of (R)-tolterodine

“…1). [4][5][6][7] Typical examples of this type are (+)-indatraline used for the treatment of depression and cocaine addiction, [8][9][10] the antihypertensive agent (+) irindalone, 11 the neuroprotective agent (+)-quadrangularin A, 12 (+)-isopaucioral F used for the treatment of osteoporosis 12 and a-diisoeugenol that has cytotoxic and antioxidant activities. 13 An example of a bioactive indane bearing a 3-alkenyl group is (+)-multisianthol, which has antitumor activity.…”

“…23 Bakers' yeast-promoted conjugate reduction of 3arylinden-1-ones to form enantioenriched 3-aryl-1-indanones has also been described. 24,25 Recent approaches devised to generate enantioenriched 3-aryl-1-indanones rely on metal (Pd or Ni)catalyzed asymmetric intramolecular reductive Heck reaction of 2 0 -halochalcones, 7,[26][27][28] and Rh-catalyzed asymmetric intramolecular 1,4-addition of aryl boronates to enones. 29 Asymmetric transfer hydrogenation (ATH) reactions, using hydrogen sources other than molecular hydrogen, have proven to be among the most powerful processes for asymmetric reduction of ketones to produce enantioenriched alcohols.…”