Nickel-catalyzed hydrocarboxylation of ynamides with CO₂ and H₂O: observation of unexpected regioselectivity

Abstract

We describe the nickel-catalyzed hydrocarboxylation of ynamides with CO 2 and H 2 O to afford a variety of α-amino-α,β-unsaturated esters with high regioselectivities. Selective α-carboxylation of ynamide with this catalytic protocol is unexpected in view of the electronic bias of ynamide and is in sharp contrast to our previous study in which a stoichiometric amount of Ni(0) was used to form a β-carboxylated product exclusively. We revealed that this unexpected C−C bond formation was induced by the combination of Zn and MgBr 2 .Homogeneous nickel catalysis has emerged in the past few decades as a highly efficient tool for organic synthesis.1 The intrinsic chemical properties of some nickel catalysts to construct a C−C bond have been applied to incorporation of CO 2 , which is an abundant, non-toxic and renewable carbon source. 2 Especially, reactions using compounds bearing a C−C double bond or triple bond as a coupling partner of CO 2 enable transformation of these building blocks into carboxylic acid derivatives without prefunctionalization such as halogenation or metalation. [3][4][5] Since all carbons constituting an unsaturated bond are potentially reactive, controlling the regioselectivity is a common concern of these promising reactions employing CO 2 . Recently, Martin's group has developed regioselective hydrocarboxylation of alkyl aryl acetylenes with CO 2 employing alcohol as a proton source. 4f They speculated that an equilibrium would exist between two possible nickelalactones derived from alkyne and CO 2 and that steric repulsion between an alkyl group and alcohol would be a key factor for preferential formation of carboxylic acid A behind B (Scheme 1). Their proposed mechanism let us assume another strategy for nickel-catalyzed regioselective hydrocarboxylation of a C−C triple bond with CO 2 in which the selectivity would be engendered by taking advantage of an electronic factor. Herein, we report a nickel-catalyzed regioselective hydrocarboxylation of ynamide, which is known to have an electronic bias on the C−C triple bond, by use of H 2 O and CO 2 .6 Consequently, we observed an interesting selectivity switching triggered by additives. Scheme 2. Our previous work: Nickel-mediated hydrocarboxylation of ynamide with CO2We previously described a nickel-mediated regioselective synthesis of functionalized β-amino-α,β-unsaturated esters from ynamides 1 and CO 2 .7 The selectivity was controlled by a regioselective oxidative cyclization step in which a negative β-carbon of an ynamide forms a C−C bond with CO 2 on Ni(0) (Scheme 2). The resulting β-carboxylated products were shown to be precursors of enantio-enriched β-amino acid derivatives by conducting Rh-catalyzed asymmetric hydrogenation. As a next step, we commenced to develop a regioselective catalytic hydrocarboxylation of ynamides. Recently, Sakaki and Tsuji et al. reported a nickel-catalyzed double carboxylation of alkyne by the use of CO 2 in the presence of Zn/MgBr 2 as reducing agents. 4g We applied their reaction conditions to catalytic ...

Alkylative Carboxylation of Ynamides and Allenamides with Functionalized Alkylzinc Halides and Carbon Dioxide by a Copper Catalyst

“…[5b,d,e,i, 6c, 10] In this context, we have achieved the alkylativec arboxylation of ynamides with dialkylzinc reagents (R 2 Zn) and CO 2 which affords a,b-dehydro-a-amino acid esters bearing ab ranched alkyl group introduced by the addition of dialkylzinc reagents. Herein, we report our studies on the alkylativec arboxylationso fy namides and allenamides [13][14][15][16][17][18] with alkylzinch alides and CO 2 ,w hich afford various a,b-dehydro-a-a nd b-amino acid esters with well-controlled configuration. [5i] Although these methods can afford av ariety of a,b-dehydroamino acid esters with well-controlled configurations, the introducible alkyl groups are limitedt omethyl, ethyl, or butyl due to the accessibility of dialkylzincr eagents.…”

“…These features of alkylzinc halides prompted us to develop an ew alkylative carboxylation protocol fory namides and allenamides by using alkylzinc halides as the alkylating agentsb yt he combination of carbozincation with alkylzinc halides and the subsequent carboxylation of the resulting alkenylzinc halide species with CO 2 (Scheme1). Herein, we report our studies on the alkylativec arboxylationso fy namides and allenamides [13][14][15][16][17][18] with alkylzinch alides and CO 2 ,w hich afford various a,b-dehydro-a-a nd b-amino acid esters with well-controlled configuration.…”

Nickel‐Catalyzed Tandem Reaction of Functionalized Arylacetonitriles with Arylboronic Acids in 2‐MeTHF: Eco‐Friendly Synthesis of Aminoisoquinolines and Isoquinolones

“…High-resolution mass spectrometry (HRMS) was recorded on an ESI-Q-TOFm ass spectrometer.2 -(Cyanomethyl)benzonitriles and methyl 2-(cyanomethyl)benzoates were synthesized according to the literature procedures. [12] Other commercially obtained reagents were used without further purification. Column chromatography was performed using EM silica gel 60 (300-400 mesh).…”

Syntheses of α‐Amino Acids by Using CO2 as a C1 Source

“…In 2017, we reported the hydrocarboxylation of ynamides by using aN i/bpy complexi nt he presence of Zn, MgBr 2 ,a nd water to afford a-dehydroamino acids (Scheme25). [27] Opposite regioselectivity (b-dehydroamino acid) was observed when as toichiometric amount of [Ni(cod) 2 ]a nd 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as al igand were used throught he formation of an ickelalactone intermediate, [28] thus suggesting that this reaction proceeded through hydronickelation, followed by carboxylation with CO 2 .W ater was found to be acritical additivef or accelerating the desired carboxylation reaction. The obtained product was hydrogenated in the presence of Pd/C to afford the corresponding a-amino acid in quantitative yield.…”