Carboxylic-phosphoric Anhydride Research Articles

Palladium-Catalyzed Decarbonylative Sonogashira Alkynylation of Carboxylic-Phosphoric Anhydrides.

We report the first palladium-catalyzed decarbonylative alkynylation of carboxylic-phosphoric anhydrides via highly selective C(O)-O bond cleavage. Carboxylic-phosphoric anhydrides are highly active carboxylic acid derivatives, which are generated through activating carboxylic acids using phosphates by esterification or direct dehydrogenative coupling with phosphites. Highly valuable internal alkynes have been generated by the present method, and the efficiency of this approach has been demonstrated through a wide substrate scope and excellent functional group tolerance.

Palladium-catalyzed Suzuki-Miyaura cross-coupling of carboxylic-phosphoric anhydrides via C-O bond cleavage.

A robust palladium-catalyzed Suzuki-Miyaura reaction of carboxylic-phosphoric anhydrides via highly selective C(O)-O bond cleavage under inorganic base-free conditions has been reported. Carboxylic-phosphoric anhydrides, generated through activating carboxylic acids using phosphates by esterification or direct dehydrogenative reaction with phosphites, have been employed as highly reactive electrophiles for Suzuki-Miyaura cross-coupling reactions. Broad substrate scope and excellent functional group tolerance have been demonstrated to be a general and practical approach for the synthesis of highly valuable ketones.

Carboxylic-Phosphoric Anhydrides as Direct Electrophiles for Decarbonylative Hirao Cross-Coupling of Carboxylic Acids: DFT Investigation of Mechanistic Pathway.

In this anniversary issue, we present a DFT study of the mechanism of decarbonylative Hirao cross-coupling of carboxylic-phosphoric anhydrides to afford aryl phosphonates. Traditionally, the direct activation of carboxylic acids to participate in decarbonylative couplings is performed in the presence of carboxylic acid anhydride activators. We discovered that direct dehydrogenative decarbonylative phosphorylation of benzoic acid can be performed in high yield via dehydrogenative and decarbonylative coupling in the presence of phosphite as dual activating and nucleophilic reagent, enabling direct decarbonylative phosphorylation. Control studies demonstrated that carboxylic-phosphoric anhydride (acyl phosphate) is an intermediate in this process. DFT studies were conducted to gain insight into this decarbonylative process and compare the selectivity of C-O and P-O bond activations. Considering the utility of ubiquitous carboxylic acids, this alternative activation pathway may find applications in decarbonylative coupling of carboxylic acids for the synthesis of valuable molecules in organic synthesis.

A COMPARISON OF THE STEREOISOMERIC PENTA-COORDINATED PHOSPHORUS INTERMEDIATES FORMED FROM 19 DIMETHOXYL N-PHOSPHORYL AMINO ACIDS BY DFT CALCULATIONS

N-phosphoryl amino acids (PAAs) are important species in the origin of life that self-catalyze and self-assemble into polypeptides and polynucleotides under mild conditions. Both experimental and theoretical studies have shown that a penta-coordinated phosphorus intermolecular mixed carboxylic-phosphoric anhydride (IMCPA) is formed as the common intermediate in these reactions. In this work, the mechanism for the formation of stereoisomeric IMCPAs from PAAs is investigated using density functional theory (DFT) calculations at the B3LYP/6-311+G(d,p) theoretical level. The molecular structures of the cis- and the trans-IMCPAs, as well as the transition states of the two stereochemical reaction pathways, were characterized in detail. The results showed that the hydroxyl groups of PAAs were situated in favorable positions for attacking the phosphorus atom from two sides of the phosphoryl group, resulting in the formation of the cis-IMCPA and the trans-IMCPA, respectively. The trans-isomers were predicted to be more likely to undergo a further reaction involving an ester exchange on the phosphorus than the cis-isomers. By comparing the relative energies of the IMCPAs and the activation energies, the trans-IMCPAs were computed to be more stable than the cis-IMCPAs, but the energy barriers for the formation of the trans- and the cis-isomers were similar. This work is expected to shed light on the stereochemical effect involved in the chemical evolution of biomolecules.

Carboxylic Phosphoric Anhydrides as a New Coupling Partner in Pd‐Catalyzed Coupling Reactions: A New Ketone Synthesis.

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Carboxylic Phosphoric Anhydrides as a New Coupling Partner in Pd-Catalyzed Coupling Reactions: A New Ketone Synthesis

The Pd-catalyzed cross-coupling reactions of carboxylic phosphoric anhydrides with organoboronic acids or organostannanes afforded the corresponding ketones. The intramolecular Heck reaction was successful with carboxylic phosphoric anhydrides as a coupling partner.

A common intermediate for prebiotic synthesis of proteins and nucleosides: a density functional theory (DFT) study on the formation of penta-coordinate phosphorus carboxylic–phosphoric mixed anhydride from N-phosphoryl amino acids

N-phosphoryl amino acids (PAA) are a unique chemical species with many chemical reactivities and properties, including the ability to self-assemble into oligopeptides. Because of their chemical characteristics, they have been proposed as the common origin for both nucleic acids and proteins. In this paper, we discussed six intramolecular mixed carboxylic–phosphoric anhydrides (IMCPAs) as possible intermediates for the prebiotic synthesis of biopolymers from PAA. We also investigated the role of water molecules in the formation of IMCPA using density functional theory B3LYP quantum mechanical calculations at the 6-31G** and 6-311+G** levels. Our results showed that the energy barrier of IMCPA formation was reduced from 19.5 kcal mol −1 to 9.9 kcal mol −1 when water participation and solvent effects were considered. Thus, the direct participation of one water molecule and the bulk solvent effects both play important roles in the formation of IMCPA.

Mechanism of intramolecular mixed anhydride formation as intermediates in the reactions of N-phosphorylamino-acids —An MNDO research

N-phosphoryl-α-amino acids can react to form esters, peptides, phosphoryl ester-exchanged products and phosphoryl group migration products under mild conditions, which are very important in researches on arohebiont. It has been proposed that intramolecular mixed carboxylic-phosphoric anhydrides (IMCPAs) might be the common intermediates of the reactions, which are difficult to be experimentally observed because of their high activity. In this note, it has been revealed, by means of MNDO, that the IMCPAs arc situated at the relatively minimal points of the potential surface and can form in a non-synchronous concerted reaction pathway that passes through a transition state with a hydrogen-bond-bridge structure. The results give a successful explanation to the structure and formation of IMCPAs and their ability to promote the various reactions mentioned above.

Phosphoryl group participation leads to peptide formation from N-phosphorylamino acids.

N-phosphorylated amino acids without a side chain functional group can transfer themselves into peptides after prolonged standing in solvents at warm temperatures. Seven N-phosphorylpeptides and free peptides were isolated and their structures determined. The phosphoryl group participation is the key to the peptide formation. An intramolecular mixed carboxylic-phosphoric anhydride intermediate was proposed for this type of reaction which might provide a clue to the function of the phosphoryl group in the phosphorylated enzymes and in the prebiotic synthesis of protein.

Isolation and characterization of the carbohydrate moiety bound to N-7-mercaptoheptanoyl- O-threonine phosphate

Component B ( N-7-mercaptoheptanoyl-threonine- O-3-phosphate) (HS-HTP) which is an absolute requirement in the methylcoenzyme M methylreductase reaction was found to be part of a complex UDP-disaccharide when isolated carefully from cell-free supernant of Methanobacterium thermoautotrophicum. The site of attachment of HS-HTP to the UDP-disaccharide was through a carboxylic-phosphoric anhydride linkage of the C-6 mannosaminuronic acid to the phosphate group in HS-HTP. This bond is quite labile and this may account for the fact that the intact molecule, called methyl reducing factor (MRF) was not isolated previously. The structure of MRF was determined by combined fast atom bombardment mass spectrometry and 1H-, 13C-, and 31P-NMR spectroscopy and assigned as: uridine 5′-[ N-7-mercaptoheptanoyl- O-3-phosphothreonine(2-acetamido-2-deoxy- β-mannopyranuronosyl)acid anhydride]-(1 → 4)- O-2-acetamido-2-deoxy α-glucopyranosyl diphosphate.

Isolation and characterization of the carbohydrate moiety bound toN-7-mercaptoheptanoyl-O-threonine phosphate

Abstract Component B ( N -7-mercaptoheptanoyl-threonine- O -3-phosphate) (HS-HTP) which is an absolute requirement in the methylcoenzyme M methylreductase reaction was found to be part of a complex UDP-disaccharide when isolated carefully from cell-free supernant of Methanobacterium thermoautotrophicum . The site of attachment of HS-HTP to the UDP-disaccharide was through a carboxylic-phosphoric anhydride linkage of the C-6 mannosaminuronic acid to the phosphate group in HS-HTP. This bond is quite labile and this may account for the fact that the intact molecule, called methyl reducing factor (MRF) was not isolated previously. The structure of MRF was determined by combined fast atom bombardment mass spectrometry and 1 H-, 13 C-, and 31 P-NMR spectroscopy and assigned as: uridine 5′-[ N -7-mercaptoheptanoyl- O -3-phosphothreonine(2-acetamido-2-deoxy- β -mannopyranuronosyl)acid anhydride]-(1 → 4)- O -2-acetamido-2-deoxy α -glucopyranosyl diphosphate.

Structure of a novel cofactor containing N-(7-mercaptoheptanoyl)-O-3-phosphothreonine

The cofactor required in the methylcoenzyme M methylreductase reaction was shown to be a large molecule with an Mr of 1149.21 in the free acid form. The cofactor, named MRF for methyl reducing factor, was identified from analyses by fast atom bombardment mass spectrometry and 1H, 13C, and 31P NMR spectroscopy as uridine 5'-[N-(7-mercaptoheptanoyl)-O-3-phosphothreonine-P-yl(2-acetamido- 2-deoxy- beta-mannopyranuronosyl)(acid anhydride)]-(1----4)-O-2-acetamido-2-deoxy- alpha-glucopyranosyl diphosphate. MRF contains N-(7-mercaptoheptanoyl)threonine O-3-phosphate (HS-HTP) [No11, K. M., Rinehart, K. L., Tanner, R. S., & Wolfe, R. S. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 4238-4242] and is linked to C-6 of 2-acetamido-2-deoxymannopyranuronic acid of the UDP-disaccharide through a carboxylic-phosphoric anhydride linkage. It is postulated that this bond is responsible for the instability of the molecule and its hydrolysis during isolation. Analyses of Eadie and Hofstee plots of the methylcoenzyme M methylreductase reaction indicate that MRF has a 6-fold lower Km(app) than HS-HTP and a 50% greater Vmax. This suggests that the UDP-disaccharide moiety may be of importance in the binding of MRF to the enzyme active site.

A new peptide coupling reagent—Dialkyl phosphite

Eighteen N-protected dipeptide esters were synthesized using dialkyl phosphite as a coupling reagent. The reaction proceeded probably through a mixed carboxylic-phosphoric anhydride intermediate. The dipeptide esters were prepared in satisfactory yields and low racemization.

ChemInform Abstract: The Mechanism of Phosphoryl to Carbonyl Migration of Amino Groups in Mixed Anhydrides. A MNDO SCF‐MO Study

A MNDO SCF–MO study of the mechanism of acyl migration in mixed carboxylic–phosphoric anhydride systems supports the hypothesis that these reactions are concerted, involving no dipolar intermediates. The calculations reveal a marked specificity for migration to an amino group rather than to an alkoxy group. The stereoelectronic contributions to this effect are revealed by inspection of the SCF molecular orbitals. These show greater localisation along the axes of the forming/cleaving C–N and N–P bonds at the transition state for migration to N than for migration to O. The cyclic transition state for the latter also shows greater destabilising 1,3-interactions between the endocyclic heteroatoms. A more quantitative analysis in terms of localised orbitals also supports the bond localisation argument.

The mechanism of phosphoryl to carbonyl migration of amino groups in mixed anhydrides. A MNDO SCF-MO study

A MNDO SCF–MO study of the mechanism of acyl migration in mixed carboxylic–phosphoric anhydride systems supports the hypothesis that these reactions are concerted, involving no dipolar intermediates. The calculations reveal a marked specificity for migration to an amino group rather than to an alkoxy group. The stereoelectronic contributions to this effect are revealed by inspection of the SCF molecular orbitals. These show greater localisation along the axes of the forming/cleaving C–N and N–P bonds at the transition state for migration to N than for migration to O. The cyclic transition state for the latter also shows greater destabilising 1,3-interactions between the endocyclic heteroatoms. A more quantitative analysis in terms of localised orbitals also supports the bond localisation argument.

29] Carboxylic-phosphoric anhydrides isosteric with adenine nucleotides

Publisher Summary Adenine nucleotide analogs of this type are of interest as potential affinity labels because (1) they are structurally closely similar to the parent nucleotides, (2) after adsorption to the substrate site they can either acylate or phosphorylate amino acid residues, and (3) it is likely that binding of these analogs to the substrate site will frequently be accompanied by partial neutralization of negative charges on the phosphoryl groups that would increase the reactivity of the mixed anhydride function in the enzyme-bound analogs and thereby tend to increase the specificity of labeling of the substrate site. This chapter describes the synthesis of carboxylic-phosphoric mixed anhydride analogs of AMP (I) and ATP (II) and conditions under which they appear to react covalently at the adenine nucleotide sites of three enzymes.

Phosphorus in organic synthesis. IX. On the mechanism of esterification of malonic acid half esters by diphenyl phosphorazidate.

The mechanism of esterification of malonic acid half esters by diphenyl phosphorazidate (DPPA) was investigated by treatment of some possible intermediates, such as mixed carboxylic phosphoric anhydrides and carboxylic acid azides, under similar reaction conditions to esterification, which revealed these are really intermediates of the esterification. Ethyl hydrogen (3, 4-methylenedioxybenzyl) methylmalonate (XI), which has no α-hydrogen to ester group, smoothly underwent the Crutius rearrangement instead of esterification under usual reaction conditions for the modified Curtius reaction by DPPA. This demonstrates that esterification takes place if substrates have an acidic hydrogen at the α-position to electron-withdrawing groups, allowing the formation of ketene intermediates. The overall mechanism is summarized in Chart 3.