Carboamination: Additions of Imine CN Bonds Across Alkynes Catalyzed by Imidozirconium Complexes

Abstract

The development of new reactions employing imidozirconium complexes or their derivatives as catalysts is an elusive goal in organometallic chemistry. To date, the imidozirconocene-catalyzed hydroamination of alkynes and allenes to yield new enamines (and, on tautomerization, imines) is the lone example of such a process. [1,2] We recently reported that aldehydes and electron-deficient imines insert into the carbon-zirconium bond of azazirconacyclobutene 1 to afford new six-membered ring metallacycles 2 and 3 (see Scheme 1). On heating, these expanded zirconacycles undergo a retro-[4+2] cycloaddition to afford a,b-unsaturated imine 4 and oxozirconium complex 5 or electron-poor imidozirconocene dimer 6, both of which are unreactive (Scheme 1; EWG = electron-withdrawing group, Cp = C 5 H 5 ). [3,4] We reasoned that insertion of an aldimine 7 with N-substitution identical to that of the nitrogen group in the metallacyclobutene, followed by subsequent retro-cycloaddition, would not only afford a,b-unsaturated imine 4 but would also generate imidozirconocene complex 8 previously used to prepare the starting azazirconacyclobutene (see Scheme 2). [5] Carrying out the reaction in the presence of the necessary alkyne would regenerate the starting metallacycle and close the catalytic cycle (Scheme 2).[6] This reaction is deemed a carboamination, because it results in the overall cleavage of an imine C = N bond and addition of the resulting C and N fragments across an alkyne, forming a new carbon-carbon double bond and a new ketimine carbon-nitrogen double bond. [7][8][9] Herein, we present the development of a novel, high-yielding imidozirconocene-catalyzed carboamination reaction that also represents the best method for preparing the highly arylated a,b-unsaturated imine co-products.The most frequently studied imidozirconium complexes bear sterically bulky groups on the nitrogen atom to prevent competitive dimerization of the imido compound.[5] As such, N-2,6-dimethylphenyl-and N-tert-butyl-substituted azazirconacyclobutenes 1 and 9 (see Scheme 3) were explored in the desired insertion chemistry. Unfortunately, even at high concentrations of substrate and temperatures up to 165 8C, neither of these zirconium compounds was an effective catalyst as no imine insertion products were observed. In the case of metallacycle 1 and imine 10, it appears that the combined steric bulk of the zirconacycle and imine Nsubstituents prohibits insertion; with metallacycle 9 and Ntert-butyl imine 11, we began to observe CÀD bond activation of the [D 6 ]benzene solvent. Presumably, this pathway arises from [2+2]-cycloreversion to afford the free imidozirconocene complex 12, which had been shown to activate benzene CÀH bonds at a minimum temperature of 75 8C (Scheme 3).

Understanding the role of an easy-to-prepare aldimine–alkyne carboamination catalyst, [Ti(NMe2)3(NHMe2)][B(C6F5)4]

“…To a solution of 7 (171 mg, 0.167 mmol) in C 6 H 5 F was added a solution of [2, ]N]CHtol (46.92 mg, 0.167 mmol) in C 6 H 5 F. The solution was stirred for 20 h and filtered through Celite. The solution was then layered with pentane and cooled at À35 C, and crystals formed overnight.…”

“…In the absence of the alkyne such an intermediate would dimerize thereby killing its catalytic activity. Despite this attractive entry to these new organic frameworks, typical reaction conditions involving the metallocene system required extensive time frames, high temperatures using 10e20 mol% of catalyst, as well as the system had also limited range of functional group tolerance at both the aldimine and alkyne substrates [2]. The reaction also suffered from not being atomeconomical when the imido group on zirconium was inequivalent to the aldimine N-aryl group given the ability of [Cp 2 Zr]NAr] to undergo imine metathesis with the aldimine and hence afford a mixture of a,b-unsaturated imines when R 2 s R 1 (Scheme 1) [3].…”

“…This interesting transformation was made possible via the use of a transient, mononuclear zirconocene imido precursor, [Cp 2 Zr]NAr] (Ar ¼ p-substituted aryl where the p-group is H, OMe, or Me), which could reversibly [2 þ 2]-cycloadd the alkyne, then insert the aldimine into the ZreC bond of the azametallacyclobutene species (Scheme 1) [1,2]. A [4 þ 2] retrocycloaddition stemming from the six-membered metallacycle resulted in extrusion of a,b-unsaturated imine concurrent with regeneration of the imido thereby closing the cycle for carboamination of alkynes with aldimines (Scheme 1).…”

“…In 2004 the Bergman group discovered a catalytic reaction where an aldimine can be added across an internal alkyne to form an a,b-unsaturated imine (denoted as the carboamination of alkynes with aldimines, Scheme 1) [1,2]. This interesting transformation was made possible via the use of a transient, mononuclear zirconocene imido precursor, [Cp 2 Zr]NAr] (Ar ¼ p-substituted aryl where the p-group is H, OMe, or Me), which could reversibly [2 þ 2]-cycloadd the alkyne, then insert the aldimine into the ZreC bond of the azametallacyclobutene species (Scheme 1) [1,2].…”

Zirconium‐Mediated Conversion of Amides to Nitriles: A Surprising Additive Effect

“…A related paper describing catalytic imine insertions into azazirconacyclobutenes also appears in this issue. [15] Received: June 24, 2004 . Keywords: additive effects · amides · kinetics · nitriles · zirconium…”