Tertiary Carbinamine Synthesis by Rhodium‐Catalyzed [3+2] Annulation of N‐Unsubstituted Aromatic Ketimines and Alkynes

Abstract

A convenient and waste-free synthesis of indene-based tertiary carbinamines by rhodium-catalyzed imine/alkyne [3+2] annulation is described. Under the optimized conditions of 0.5-2.5 mol % [{(cod)Rh(OH)}(2)] (cod=1,5-cyclooctadiene) catalyst, 1,3-bis(diphenylphosphanyl)propane (DPPP) ligand, in toluene at 120 degrees C, N-unsubstituted aromatic ketimines and internal alkynes were coupled in a 1:1 ratio to form tertiary 1H-inden-1-amines in good yields and with high selectivities over isoquinoline products. A plausible catalytic cycle involves sequential imine-directed aromatic C-H bond activation, alkyne insertion, and a rare example of intramolecular ketimine insertion into a Rh(I)-alkenyl linkage.

Cationic Palladium Complex‐Catalyzed Diastereoselective Tandem Annulation of 2‐Iminoarylboronic Acids with Substituted Alkynes: Enantioselective Synthesis of Aminoindene Derivatives by Double Asymmetric Induction

“…[8] Very recently, Zhao and Sun reported an alternative approach of rhodium-catalyzed [3 + 2] annulation of N-unsubstituted aromatic ketimines and internal alkynes based on imine-directed aromatic C À H bond activation. [9] Unfortunately, the asymmetric version has not been explored to give the more important chiral aminoindene derivatives.…”

Ruthenium(II)/N‐Heterocyclic Carbene Catalyzed [3+2] Carbocyclization with Aromatic NH Ketimines and Internal Alkynes

“…[9,10] By contrast, our recent report on Rh(I)-catalyzed C-H coupling of aromatic N-H ketimines ( 1 ) with alkynes ( 2 ) involves a selective [3+2] carbocyclization to form indenamines ( 3 ). [11–13] We proposed a catalytic cycle initiated by imine-directed aromatic C–H bond activation to form rhodacycle A (Scheme 1, M = Rh(I)). [2] Subsequent alkyne insertion gives a cyclometalated Rh(I) alkenyl intermediate B , [10] which undergoes carbocyclization via intramolecular imine insertion into the Rh-C linkage to form an amido intermediate C , [10,12] and releases indenamine 3 upon protonation.…”

“…[(cod)Rh(OH)] 2 and DPPP ligand failed to react with 1a at 80 °C, which was consistent with the high reaction temperatures for corresponding Rh(I) catalysis. [11,14] By contrast, a Ru(II) π-allyl complex [(cod)Ru(η 3 -methallyl) 2 ] [21] ( 5a ) reacted with 1a at room temperature quantitatively to form a doubly cyclometalated Ru(II) bis(imine) complex {Ru(cod)[η 2 -HNC(C 6 H 5 )C 6 H 4 ] 2 } ( 6 ). The solid-state structure of complex 6 was determined by single crystal X-ray diffraction, which shows a near-octahedral Ru(II) center with two N atoms from imine ligands trans to each other, as well as two Ru–C bonds at cis positions.…”

“…Such electronic effect on regioselective C–H bond activation was most pronounced with product 3p , which was formed with exclusive reactivity at the phenyl ring with meta -CF 3 substituent over the one with meta -methoxy substituent. [11] …”

“…Formation of product 3r represents a very rare example of mild C–H functionalization with unactivated and unprotected aryl-alkyl N-H ketimines . [11,14] In another preliminary study (Eq. 2), a mild [3+2] ketone/alkyne annulation was achieved using [( p -cymene)RuCl 2 ] 2 catalyst, IPr ligand, and catalytic amount of NaOAc at 60 °C.…”