Toward Replacing Ethylene Oxide in a Sustainable World: Glycolaldehyde as a Bio-Based C2 Platform Molecule.

Fossil-based platform molecules such as ethylene and ethylene oxide currently serve as the primary feedstock for the C2 -based chemical industry. However, in the search for a more sustainable chemical industry, fossil-based resources may preferentially be replaced by renewable alternatives, provided there is realistic economic feasibility. This Review compares and critically discusses several production routes toward bio-based structural analogues of ethylene oxide and the required adaptations for their implementation in state-of-the-art C2 -based chemical processes. For example, glycolaldehyde, a structural analogue obtainable from carbohydrates by atom-economic retro-aldol reactions, may replace ethylene oxide's leading role. This alternative chemical route may not only allow the carbon footprint of conventional chemicals production to be lowered, but the introduction of a bio-based pathway may also contribute to safer production processes. Where possible, challenges, drawbacks, and prospects are highlighted.

Low-Temperature Reductive Aminolysis of Carbohydrates to Diamines and Aminoalcohols by Heterogeneous Catalysis.

Short amines, such as ethanolamines and ethylenediamines, are important compounds in today's bulk and fine chemicals industry. Unfortunately, current industrial manufacture of these chemicals relies on fossil resources and requires rigorous safety measures when handling explosive or toxic intermediates. Inspired by the elegant working mechanism of aldolase enzymes, a novel heterogeneously catalyzed process-reductive aminolysis-was developed for the efficient production of short amines from carbohydrates at low temperature. High-value bio-based amines containing a bio-derived C2 carbon backbone were synthesized in one step with yields up to 87 C%, in the absence of a solvent and at a temperature below 405 K. A wide variety of available primary and secondary alkyl- and alkanolamines can be reacted with the carbohydrate to form the corresponding C2-diamine. The presented reductive aminolysis is therefore a promising strategy for sustainable synthesis of short, acyclic, bio-based amines.

Synthesis of tricyclic phosphonopyrrolidines via IMDAF: experimental and theoretical investigation of the observed stereoselectivity.

During the synthesis of tricyclic phosphonopyrrolidines via intramolecular Diels-Alder reactions of 1-acylamino(furan-2-yl)methyl phosphonates, two isomers are formed in most cases. The presence of a short three-atom tether together with spectroscopic data, including difference NOE, revealed that the cycloaddition occurred exo, but the phosphonate substituent on the tether had an exo or endo orientation. This was confirmed via X-ray analysis. A thermodynamic preference for the product with the phosphonate function in the endo position was observed experimentally and was confirmed theoretically. Density functional theory methods and several high-level post Hartree-Fock procedures were used to rationalize the observed isomer ratio of the IMDAF-reactions. This was done for two different types of reagents: with the activating carbonyl group in the tether or as a substituent on the tether. For the first type of molecules there is a large steric hindrance of the bulky tether substituents that disfavors the exo-isomer. In the latter case, there was a very small energy difference between the transition states causing a mixture of epimers being formed.

Selective catalytic amination of halogenated aldehydes with calcined palladium catalysts.

This work focuses on understanding the influence of the conditions used in the calcination step of palladium catalysts on the performance of this catalyst in the reductive amination of halogen-containing substrates. The results show that increasing the calcination temperatures (from 100 °C to 400 °C) has a detrimental effect on catalytic activity but a strong positive effect on the selectivity (from 45 to 96%), avoiding the undesired dehalogenation reaction. TEM investigation showed that the reason for the different selectivity can be addressed to different Pd mean particles size and particle size distribution. In particular, larger Pd particles obtained at the highest calcination temperature (400 °C) showed the best selectivity to halogenated benzylamines (96%), with a good stability in terms of both activity and selectivity as confirmed by performing recycling tests.

Enyne metathesis-oxidation sequence for the synthesis of 2-phosphono pyrroles: proof of the "yne-then-ene" pathway.

A new tandem reaction sequence has been developed for the synthesis of 2-phosphono pyrroles. The sequence consists of ring-closing enyne metathesis of a substituted aminophosphonate, containing a terminal alkyne and an internal alkene, in combination with in situ oxidation of the produced 3-pyrrolines using tetrachloroquinone. By analyzing the formation of the end and certain byproducts, taking into account the difference in reactivity of different substrates and carefully studying spectroscopic data, it was found that the reaction proceeds by means of the "yne-then-ene" pathway. During the initiation phase, a new ruthenium carbene is formed which continues the propagation cycle.

Synthesis of 2-phosphonopyrroles via a one-pot RCM/oxidation sequence.

A four-step synthesis of 2-phosphonopyrroles is presented starting from suitable aldehydes. The key step in the synthesis involves a one-pot ring-closing metathesis/oxidation sequence of a functionalized alpha-aminoalkenyl phosphonate. Notwithstanding the presence of a nucleophilic nitrogen atom and high substitution patterns in the substrate, the results of the RCM reaction are excellent using mild reaction conditions. Furthermore, a synergism is observed between the RCM catalyst and the oxidizing agent, causing higher oxidation rates and allowing reaction for substrates that normally fail to ring close under standard RCM conditions.

Tandem addition of trialkyl phosphites to alpha,beta-unsaturated imines: a comparison with silylated phosphites.

Trialkyl phosphites were evaluated for addition reactions to alpha,beta-unsaturated imines. An acidic medium is required to allow consecutive 1,4- and 1,2-addition to occur. In this manner, 3-phosphonyl-1-aminophosphonates, phosphonic acid analogues of glutamate, are obtained in good yields (32-90%). The reaction is mainly influenced by the steric bulk of the nitrogen substituent: less steric N-substituents lead to better yields of the tandem adducts.

Unexpected four-membered over six-membered ring formation during the synthesis of azaheterocyclic phosphonates: experimental and theoretical evaluation.

The cyclization of functionalized aminophosphonates is studied on both experimental and theoretical grounds. In a recently described route to phosphono-beta-lactams [Stevens C. V.; Vekemans, W.; Moonen, K.; Rammeloo, T. Tetrahedron Lett. 2003, 44, 1619], it was found that starting from an ambident allylic anion only four-membered rings were formed without any trace of six-membered lactams. New anion trapping experiments revealed that the gamma-anion is highly reactive in intermolecular reactions. Ab initio calculations predict higher reaction barriers for the gamma-anion due to restricted rotation about the C-N bond and due to highly strained transition states during ring closure. The sodium or lithium counterion, explicit dimethyl ether solvent molecules, and bulk solvent effects were properly taken into account at various levels of theory.