Analysis of the Critical Step in Catalytic Carbodiimide Transformation: Proton Transfer from Amines, Phosphines, and Alkynes to Guanidinates, Phosphaguanidinates, and Propiolamidinates with Li and Al Catalysts

Abstract

While lithium amides supported by tetramethylethylenediamine (TMEDA) are efficient catalysts in the synthesis of substituted guanidines via the guanylation of an amine with carbodiimide, as well as the guanylation of phosphines and conversion of alkynes into propiolamidines, aluminum amides are only efficient catalysts for the guanylation of amides. Density functional theory (DFT) calculations were used to explain this difference in activity. The origin of this behavior is apparent in the critical step where a proton is transferred from the substrate to a metal guanidinate. The activation energies of these steps are modest for amines, phosphines, and alkynes when a lithium catalyst was used, but are prohibitively high for the analogous reactions with phosphines and alkynes for aluminum amide catalysts. Energy decomposition analysis (EDA) indicates that these high activations energies are due to the high energetic cost of the detachment of a chelating guanidinate nitrogen from the aluminum in the proton transfer transition state. Amines are able to adopt an ideal geometry for facile proton transfer to the aluminum guanidinate and concomitant Al-N bond formation, while phosphines and alkynes are not.

Synthesis of a Highly Water-Soluble Derivative of Amphotericin B with Attenuated Proinflammatory Activity

“…Although we had not anticipated finding an N -alkylguanidine adduct, reactions of amines and carbodiimides to furnish substituted guanidines have indeed been reported in the literature. 36;37 The other mono-adduct corresponding to the N -acylurea adduct ionized solely as singly charged proton adduct at higher fragmenter voltages (Fig. 3, Peak 3) and as +2H + doubly charged species at lower voltages (data not shown).…”

Insertion Reactions and Catalytic Hydrophosphination of Heterocumulenes using α-Metalated N,N-Dimethylbenzylamine Rare-Earth-Metal Complexes

“…The hydrophosphination of heterocumulenes has recently come under scrutiny as a convenient means to synthesize phosphorus analogues of guanidines, ureas, thioureas, and amidines. − Early investigations demonstrated that alkali-metal amides serve as catalysts for the hydrophosphination of carbodiimides, while recent work has shown that constrained-geometry lanthanide catalysts also effect this transformation but require elevated temperatures (80 °C) . The product phosphaguanidines are known to be a versatile ligand class for Al, Y, La, Ti, Zr, Nb, Cu, and Zn species with broadly tunable properties. − Direct synthesis of phosphaguanidines from phosphines and carbodiimides does not work; therefore, metal-catalyzed hydrophosphination of carbodiimides, in which the P–H bond is added across the diimine, reducing the bond order by 1, represents a useful new method to produce these compounds.…”

Alkali and alkaline-earth metals

“…73 The mechanism of catalytic guanylation as well as the guanylation of phosphines and conversion of alkynes into propiolamidines has been studied through DFT calculations and seen to involve carbodiimide insertion into a lithium-amide bond followed by a proton transfer from the amine to liberate the guanidine. 74,75 Metalation of the napthylamine-substituted secondary phosphane [{(Me 3 Si) 2 CH}(C 10 H 6 -8-NMe 2 )PH] with n-BuLi provided the lithium phosphanide [{[{(Me 3 Si) 2 CH}(C 10 H 6 -8-NMe 2 )P]Li} 2 (OEt 2 )] 2 which crystallised with the phosphanide ligands arranged in a head-to-head fashion and was subject to dynamic exchange in toluene solution. 76 Several X-ray structures resulting from the lithiation and alkylation of the triphosphaferrocenes, [Fe-Z 5 -(P 3 C 2 t Bu 2 )-Z 5 -(C 5 R 5 )], (R = H and Me) have been reported, 77 while protonation of Li[Fe-Z 5 78 A comparison between phosphine boranes and sulfides in their catalytic asymmetric deprotonation using organolithiums and sub-stoichiometric amounts of (À)-sparteine has revealed superior catalytic efficiency in the phosphine sulfide deprotonation.…”