Palladium(II)-Catalyzed Annulation of Alkynes with 2-(Cyanomethyl)phenylboronates Leading to 3,4-Disubstituted 2-Naphthalenamines

Abstract

1,2-Bis(diphenylphosphino)ethane (dppe)-ligated palladium(II) complexes catalyze the annulation of internal alkynes with 2-(cyanomethyl)phenylboronates to provide 3,4-disubstituted-2-naphthalenamines in good yields. The annulation reaction proceeds under mild and neutral conditions and requires methanol as an essential solvent. In addition to symmetrical alkynes, unsymmetrical alkynes substituted by aryl, alkyl, and alkynyl groups participate in the annulation to afford the corresponding 2-naphthalenamines with electron-withdrawing sp(2)- and sp-carbons preferentially located at the C-3 position. Substituents including an alkyl or alkoxy group on the cyanomethyl moiety and a halogen atom on the benzene ring in the boronates are compatible with the reaction conditions. The annulation proceeds through the transmetalation of the palladium(II) complexes with the boronates and alkyne insertion followed by nucleophilic addition of the generated alkenylpalladium(II) species to the intramolecular cyano group. Stoichiometric reactions revealed that the methanol solvent was effective for both transmetalation and catalyst regeneration.

Asymmetric Synthesis of Axially Chiral 2‐Aminobiaryls by Rhodium‐Catalyzed Benzannulation of 1‐Arylalkynes with 2‐(Cyanomethyl)phenylboronates

“…The reaction with KOH as a base or those in THF/H 2 O and toluene/H 2 O did not give better results than that under the optimized reaction conditions (entries 15–17). The palladium complex Pd(OCOCF 3 ) 2 (dppe) efficiently catalyzed the reaction of 1 a with 2 , giving a high yield of 3 a in MeOH at 65 °C under the conditions reported by Tsukamoto (entry 18), but the reaction was very sluggish with chiral bisphosphine ligands in place of dppe and the enantioselectivity was not high (entries 18–20).…”

“…Recently Tsukamoto reported that the palladium complex Pd(OCOCF 3 )(dppe) catalyzes the reaction of internal alkynes with 2‐(cyanomethyl)phenylboronate to give 3,4‐disubstituted 2‐aminonaphthalenes (Scheme b). This report inspired us to apply this annulation reaction to asymmetric synthesis of axially chiral biaryls.…”

“…We have examined rhodium catalysts coordinated with chiral bisphosphines and chiral dienes, as they have been shown to be active catalysts for the asymmetric reactions where the catalytic cycle involves addition of aryl‐rhodium intermediates to alkynes, for the reaction of 1‐(1‐naphthyl)‐1‐propyne ( 1 a ) with the 2‐(cyanomethyl)phenylboronate 2 (Table ). The benzannulation was found to proceed smoothly at 22 °C in most cases with chiral diene ligands to give high yields of the axially chiral 1,2′‐binaphthyl 3 a together with the 1,1′‐binaphthyl 4 a as a minor product.…”

“…[e] In MeOH (0.50 mL) at 65 °C (Ref. ). [f] In situ generation from Pd(OCOCF 3 ) 2 and ( R )‐segphos.…”

Palladium(II)-Catalyzed Redox-Neutral Cyclizations of Alkynes Containing Alkenyl or Electrophilic Functional Groups: A Convenient Synthesis of Carbocycles and Heterocycles

“…also took place successfully to provide 2-naphthols 138 or 2-naphthylamines 140, respectively. 53,54 Stoichiometric reactions revealed that the use of methanol as a solvent was effective for both transmetalation and catalyst regeneration.…”