Catalytic addition of amine N-H bonds to carbodiimides by half-sandwich rare-earth metal complexes: efficient synthesis of substituted guanidines through amine protonolysis of rare-earth metal guanidinates

Reaction of [Ln(CH(2)SiMe(3))(3)(thf)(2)] (Ln=Y, Yb, and Lu) with one equivalent of Me(2)Si(C(5)Me(4)H)NHR' (R'=Ph, 2,4,6-Me(3)C(6)H(2), tBu) affords straightforwardly the corresponding half-sandwich rare-earth metal alkyl complexes [{Me(2)Si(C(5)Me(4))(NR')}Ln(CH(2)SiMe(3))(thf)(n)] (1: Ln = Y, R' = Ph, n=2; 2: Ln = Y, R' = C(6)H(2)Me(3)-2,4,6, n=1; 3: Ln = Y, R' = tBu, n=1; 4: Ln = Yb, R' = Ph, n=2; 5: Ln = Lu, R' = Ph, n=2) in high yields. These complexes, especially the yttrium complexes 1-3, serve as excellent catalyst precursors for the catalytic addition of various primary and secondary amines to carbodiimides, efficiently yielding a series of guanidine derivatives with a wide range of substituents on the nitrogen atoms. Functional groups such as C[triple chemical bond]N, C[triple chemical bond]CH, and aromatic C--X (X: F, Cl, Br, I) bonds can survive the catalytic reaction conditions. A primary amino group can be distinguished from a secondary one by the catalyst system, and therefore, the reaction of 1,2,3,4-tetrahydro-5-aminoisoquinoline with iPrN==C==NiPr can be achieved stepwise first at the primary amino group to selectively give the monoguanidine 38, and then at the cyclic secondary amino unit to give the biguanidine 39. Some key reaction intermediates or true catalyst species, such as the amido complexes [{Me(2)Si(C(5)Me(4))(NPh)}Y(NEt(2))(thf)(2)] (40) and [{Me(2)Si(C(5)Me(4))(NPh)}Y(NHC(6)H(4)Br-4)(thf)(2)] (42), and the guanidinate complexes [{Me(2)Si(C(5)Me(4))(NPh)}Y{iPrNC(NEt(2))(NiPr)}(thf)] (41) and [{Me(2)Si(C(5)Me(4))(NPh)}Y{iPrN}C(NC(6)H(4)Br-4)(NHiPr)}(thf)] (44) have been isolated and structurally characterized. Reactivity studies on these complexes suggest that the present catalytic formation of a guanidine compound proceeds mechanistically through nucleophilic addition of an amido species, formed by acid-base reaction between a rare-earth metal alkyl bond and an amine N--H bond, to a carbodiimide, followed by amine protonolysis of the resultant guanidinate species.     

Divalent lanthanide complexes: highly active precatalysts for the addition of N-H and C-H bonds to carbodiimides

Various divalent lanthanide complexes with the formula LnL2(sol)x (L = N(TMS)2, sol = THF, x = 3, Ln = Sm (I), Eu (II), Yb (III); L = MeC5H4, sol = THF, x = 2, Ln = Sm (IV); L = ArO(Ar = [2,6-((t)Bu)2-4-MeC6H2]), sol = THF, x = 2, Ln = Sm (V)), especially complexes I- III, serve as excellent catalyst precursors for catalytic addition of various primary and secondary amines to carbodiimides, efficiently providing the corresponding guanidine derivatives with a wide range of substrates under solvent-free condition. The reaction shows good functional groups tolerance. Complexes I- III are also excellent precatalysts for addition of terminal alkynes to carbodiimides yielding a series of propiolamidines. The active sequence of Yb < Eu < Sm for metal and MeC5H4 < ArO < N(TMS)2 for ligand around the metal was observed for both reactions. The first step in both reactions was supposed to include the formation of a bimetallic bisamidinate samarium species originating from the reduction-coupling reaction of carbodiimide promoted by lanthanide(II) complex. The active species is proposed to be a lanthanide guanidinate and a lanthanide amidinate.     

Alkali-metal-catalyzed addition of primary and secondary phosphines to carbodiimides. A general and efficient route to substituted phosphaguanidines

Organo alkali metal compounds such as (n)BuLi and (Me3Si)2NK act as excellent catalyst precursors for the addition of phosphine P-H bonds to carbodiimides, offering a general and atom-economical route to substituted phosphaguanidines, with excellent tolerability to aromatic C-Br and C-Cl bonds.     

Catalytic addition of C-H bonds to multiple bonds with the aid of ruthenium complexes

Ruthenium complexes, e.g., RuH2(CO)(PPh3)3, have been found to catalyze the direct addition of ortho carbon-hydrogen bonds of aromatic ketones to olefins and acetylenes with high efficiency and selectivity. The C-H/olefin coupling reaction is applicable to not only C-H bonds in aromatic ketones but also to those in a,b-enones and aro-matic esters. Catalytic addition of ortho carbon-hydrogen bonds of aromatic imines to olefins is found to be catalyzed by Ru3(CO)12.     

Heterobimetallic dianionic guanidinate complexes of lanthanide and lithium: highly efficient precatalysts for catalytic addition of amines to carbodiimides to synthesize guanidines

A series of heterobimetallic dianionic guanidinate complexes of lanthanide and lithium, [Li(THF)(DME)]₃Ln[μ-η²η¹(ⁱPrN)₂C(NC₆H₄p-R)]₃ [R=Cl, Ln=Nd (I), Y (II), La (III); R=H, Ln=Nd (IV)] were synthesized and fully characterized. These complexes were found to be highly efficient precatalysts for the addition of various primary and secondary amines, and aromatic and aliphatic diamines to carbodiimides to give the corresponding monoguanidine and biguanidine derivatives under mild condition (at 25-60 °C), which provides an efficient way for the synthesis of biguanidines compounds. The activity depends on the central metals and ligands: La>Nd>Y for the metals and [(ⁱPrN)₂C(NC₆H₄p-Cl)]²⁻>[(ⁱPrN)₂C(NC₆H₅)]²⁻ for the ligands were observed.     

CeCl3-mediated addition of acetylenic bis-lithium salts to aldehydes and ketones: An efficient route to bis-substituted alkyne diols

An efficient, chemoselective protocol to access propargylic diols via a CeCl₃-mediated addition reaction is reported. Propargylic alcohols were transformed into the corresponding acetylenic bis-lithium salt intermediates, which react with aldehydes and ketones in the presence of dry CeCl₃ to furnish the corresponding bis-substituted alkyne diols. This protocol does not involve protection-deprotection or transmetallation steps, and allows the use of poorly reactive or highly enolizable substrates.     

Facile oxidative addition of N-C and N-H bonds to monovalent rhodium and iridium

An investigation of room-temperature oxidative addition of N-C and N-H bonds to RhI and IrI in solution and in the solid state is presented. The rigid, product-adapted framework of the pincer bis(ortho-phosphinoaryl)amine (PNP) ligand may contribute to the ease of the N-C and N-H cleavage. The migration of Me from N of the coordinated amine moiety to Rh proceeds with near-zero entropy of activation in solution. In the solid state, this transformation is a crystal-to-crystal reaction, transforming only one of the two independent molecules of (PN(Me)P)RhCl into (PNP)Rh(Me)Cl.     

Pd-catalysed synthesis of isoquinolinones and analogues via C-H and N-H bonds double activation

An atom economical synthesis of isoquinolinones and analogues via ligand-free Pd-catalysed C-H and N-H double activation has been developed. A series of isoquinolinones were obtained in good to excellent yields. Good regioselectivities were also observed during the activation reactions with unsymmetrical alkynes. A practical one-pot procedure for the preparation of N-H isoquinolinones is also described.     

GaCl_3催化胺与碳二亚胺的加成反应合成胍的研究

以路易斯酸Ga Cl3为催化剂,在无水、无氧、氮气保护无溶剂条件下催化胺与碳二亚胺合成胍的反应,得到一系列胍产物,研究了催化剂用量,反应温度和反应时间对催化反应的影响,研究发现Ga Cl3具有良好的催化活性,以5mol%催化剂用量,无溶剂条件下一级芳香胺与碳二亚胺反应在一小时内得到高于90%产率的胍产物,二级胺也能得到较好产率。     

Nickel-catalyzed addition of C-H bonds of terminal alkynes to 1,3-dienes and styrenes

The C-H bond of a terminal alkyne adds to a carbon-carbon double bond of 1,3-dienes, styrenes, and norbornene at room temperature in the presence of a nickel catalyst in regio- and stereoselective manners. Reaction of triisopropylsilylacetylene with 1-substituted 1,3-butadiene derivatives afforded hydroalkynylation products via introduction of a hydrogen atom and a triisopropylsilylethynyl group to 4- and 3-positions of the dienes, respectively. Likewise, 1-triisopropylsiloxy-1,3-butadiene, 1,3-pentadiene, 1-cyclohexen-1-yl-1,3-butadiene, and 1,3-cyclohexadiene underwent the hydroalkynylation reaction, giving the corresponding 1,4-enyne derivatives in good yields at room temperature. Reaction of p-substituted styrene with triisopropylsilylacetylene also proceeded in the presence of the nickel catalyst, giving the branched hydroalkynylation products in good yields. Norbornene gave a exo-addition product in good yield under the same reaction conditions.     

Variable coordination of amine functionalised N-heterocyclic carbene ligands to Ru, Rh and Ir: C-H and N-H activation and catalytic transfer hydrogenation

Chelating amine and amido complexes of late transition metals are highly valuable bifunctional catalysts in organic synthesis, but complexes of bidentate amine-NHC and amido-NHC ligands are scarce. Hence, we report the reactions of a secondary-amine functionalised imidazolium salt 2a and a primary-amine functionalised imidazolium salt 2b with [(p-cymene)RuCl(2)](2) and [Cp*MCl(2)](2) (M = Rh, Ir). Treating 2a with [Cp*MCl(2)](2) and NaOAc gave the cyclometallated compounds Cp*M(C,C)I (M = Rh, 3; M = Ir, 4), resulting from aromatic C-H activation. In contrast, treating 2b with [(p-cymene)RuCl(2)](2), Ag(2)O and KI gave the amine-NHC complex [(p-cymene)Ru(C,NH(2))I]I (5). The reaction of 2b with [Cp*MCl(2)](2) (M = Rh, Ir), NaO(t)Bu and KI gave the amine-NHC complex [Cp*Rh(NH(2))I]I (6) or the amido-NHC complex Cp*Ir(C,NH)I (7); both protonation states of the Ir complex could be accessed: treating 7 with trifluoroacetic acid gave the amine-NHC complex [Cp*Ir(C,NH(2))I][CF(3)CO(2)] (8). These are the first primary amine- or amido-NHC complexes of Rh and Ir. Solid-state structures of the complexes 3-8 have been determined by single crystal X-ray diffraction. Complexes 5, 6 and 7 are pre-catalysts for the catalytic transfer hydrogenation of acetophenone to 1-phenylethanol, with ruthenium complex 5 demonstrating especially high reactivity.     

The silver salt of 12-tungstophosphoric acid: an efficient catalyst for the three-component coupling of an aldehyde, an amine and an alkyne

A three-component coupling of an aldehyde, an alkyne and an amine to prepare propargylamines was performed using the silver salt of 12-tungstophosphoric acid (Ag₃PW₁₂O₄₀) as a heterogeneous catalyst under mild reaction conditions in the absence of any co-catalyst. A variety of aldehydes and amines were converted to the corresponding propargylamines demonstrating the versatility of the reaction. The Ag₃PW₁₂O₄₀ (AgTPA) catalyst was recovered quantitatively by a simple filtration and reused several times.     

Catalytic addition of terminal alkynes to carbodiimides by half-sandwich rare earth metal complexes

The catalytic addition of terminal alkynes to carbodiimides has been achieved for the first time by use of half-sandwich rare earth metal complexes, such as {Me2Si(C5Me4)(NPh)}Y(CH2SiMe3)(THF)2, which offers a straightforward, atom-economic route to the N,N'-disubstituted propiolamidines which contain a conjugated C-C triple bond, a new family of amidines which were difficult to prepare by other means. A rare earth metal amidinate species was confirmed to be a true catalytic species in this process, thus demonstrating for the first time that an amidinate unit, though being often used as an ancillary ligand for various organometallic complexes, can itself participate in a catalytic reaction under appropriate conditions.     

Catalytic intermolecular amination of C-H bonds: method development and mechanistic insights

Reaction methodology for intermolecular C-H amination of benzylic and 3 degrees C-H bonds is described. This process uses the starting alkane as the limiting reagent, gives optically pure tetrasubstituted amines through stereospecific insertion into enantiomeric 3 degrees centers, displays high chemoselectivity for benzylic oxidation, and enables the facile preparation of isotopically enriched 15N-labeled compounds. Access to substituted amines, amino alcohols, and diamines is thereby made possible in a single transformation. Important information relevant to understanding the initial steps in the catalytic cycle, reaction chemoselectivity, the nature of the active oxidant, and pathways for catalyst inactivation has been gained through mechanistic analysis; these studies are also presented.     

Microwave-promoted three-component coupling of aldehyde, alkyne, and amine via C-H activation catalyzed by copper in water

[reaction: see text] An efficient three-component coupling of aldehyde, alkyne, and amine to generate propargylamines has been effected under microwave irradiation in water using only CuI catalyst without the noble metal cocatalyst. This method has proved to be applicable to a wide range of substrates. In addition, the preliminary experiment using (S)-proline methyl ester as a chiral source demonstrated that it could be developed to be a direct and highly diastereoselective method for construction of chiral propargylamines.     

CuBr-catalyzed efficient alkynylation of sp3 C-H bonds adjacent to a nitrogen atom

A simple and effective catalytic method to construct propargylamine was developed by using copper bromide and tert-BuOOH via a combination of sp3 C-H bond and sp C-H bond activations followed by C-C bond formation.     

Catalytic enantioselective addition of propionate units to imines: an efficient synthesis of anti-alpha-methyl-beta-amino acid derivatives

Optically active anti-alpha-methyl-beta-amino acid derivatives have been prepared based on catalytic enantioselective addition of propionate units to simple and inert imines using a chiral zirconium complex. High reactivity and selectivity with wide substrate scope were attained by using a new chiral ligand, (R)-6,6'-bis(pentafluoroethyl)-1,1'-bi-2-naphthol ((R)-6,6'-C(2)F(5)BINOL). The reactions using geometrically isomeric ketene silyl acetals gave excellent anti-selectivity with high enantiomeric excess in both cases. Synthetic utility of this reaction has been demonstrated by the preparation of various anti-alpha-methyl-beta-amino acid and trans-3,4-disubstituted beta-lactam derivatives.     

Very strong C-H...O, N-H...O, and O-H...O hydrogen bonds involving a cyclic phosphate.

Very short C-H...O, N-H...O, and O-H...O hydrogen bonds have been generated utilizing the cyclic phosphate [CH2(6-t-Bu-4-Me-C6H2O)2]P(O)OH (1). X-ray structures of (i) 1 (unsolvated, two polymorphs), 1...EtOH, and 1...MeOH, (ii) [imidazolium](+)[CH2(6-t-Bu-4-Me-C6H2O)2PO2](-)...MeOH [2], (iii) [HNC5H4-N=N-C5H4NH](2+)[(CH2(6-t-Bu-4-Me-C6H2O)2PO2)2](2-)...4CH3CN...H2O [3], (v) [K, 18-crown-6](+)[(CH2(6-t-Bu-4-Me-C6H2O)2P(O)OH)(CH2(6-t-Bu-4-Me-C6H2O)2PO2)](-)...2THF [4], (vi) 1...cytosine...MeOH [5], (vii) 1...adenine...1/2MeOH [6], and (viii) 1...S-(-)-proline [7] have been determined. The phosphate 1 in both its forms is a hydrogen-bonded dimer with a short O-H...O distance of 2.481(2) [triclinic form] or 2.507(3) A [monoclinic form]. Compound 2 has a helical structure with a very short C-H...O hydrogen bond involving an imidazolyl C-H and methanol in addition to N-H...O hydrogen bonds. A helical motif is also seen in 5. In 3, an extremely short N-H...O hydrogen bond [N...O 2.558(4) A] is observed. Compounds 6 and 7 also exhibit short N-H...O hydrogen bonds. In 1...EtOH, a 12-membered hydrogen-bonded ring motif, with one of the shortest known O-H...O hydrogen bonds [O...O 2.368(4) A], is present. 1...MeOH is a similar dimer with a very short O(-H)...O bond [2.429(3) A]. In 4, the deprotonated phosphate (anion) and the parent acid are held together by a hydrogen bond on one side and a coordinate/covalent bond to potassium on the other; the O-H...O bond is symmetrical and very strong [O...O 2.397(3) A].