Tetrazine Assists Reduction of Water by Phosphines: Application in the Mitsunobu Reaction

Abstract

Reaction of 3,6-disubstituted-1,2,4,5-tetrazines with water and PEt forms the corresponding 1,4-dihydrotetrazine and OPEt . Thus PEt , as a stoichiometric reductant, reduces water, and the resulting two reducing equivalents serve to doubly hydrogenate the tetrazine. A variety of possible initial interactions between electron-deficient tetrazine and electron-rich PR , including a charge transfer complex, were evaluated by density functional calculations which revealed that the energy of all these make them spectroscopically undetectable at equilibrium, but one of these is nevertheless suggested as the intermediate in the observed redox reaction. The relationship of this to the Mitsunobu reaction, which absorbs the components of water evolved in the conversion of alcohol and carboxylic acid to ester, with desirable inversion at the alcohol carbon, is discussed. This enables a modified Mitsunobu reaction, with tetrazine replacing EtO CN=NCO Et (DEAD), which has the advantage that dihydrotetrazine can be recycled to tetrazine by oxidation with O , something impossible with the hydrogenated DEAD. For this tetrazine version, a betaine-like intermediate is undetectable, but its protonated form is characterized, including by X-ray structure and NMR spectroscopy.

Application of Silicon‐Initiated Water Splitting for the Reduction of Organic Substrates

“…Despite enormous efforts made over the last century, the direct use of water as a hydrogen donor in organic synthesis remains a challenging and unsolved task. According to the known data, the splitting of water can follow the following three pathways: 1) oxidative splitting generating O 2 ; 2) reductive splitting generating H 2 ; 3) direct splitting into elements (O 2 +H 2 ) . Most of the presently known strategies of water splitting are photocatalytic or photoelectrochemical processes .…”

“…Subsequently, the development of novel reductive water splittings used in catalytic hydrogenations remains one of the “holy grails” of modern organic synthesis. In this connection, the research made within the last few years indicates that reductive water splitting can be initiated by various diboron compounds, phosphines, DMF/Cu system, iron powder, SmI 2 , and Ti III complexes…”

A Redox‐Active Tetrazine‐Based Pincer Ligand for the Reduction of N‐Oxyanions Using a Redox‐Inert Metal

“…Furthermore, zinc pincer complexes have recently shown promise for metal‐ligand cooperation to promote catalytic hydrogenation, [16] as well as an H 4 Zn pincer complex catalyzing the dehydrogenation of alcohols [17] . We have previously shown the ability of tetrazines to assist in the reduction of water by phosphines, where H 4 btzp is quantitatively generated [18] . We have now found that a conversion of tetrazine to dihydrotetrazine can be accomplished simply with H 2 as the reductant, using catalytic Pd/C, which alleviates the need for removal of phosphine oxides.…”

Seeking Redox Activity in a Tetrazinyl Pincer Ligand: Installing Zerovalent Cr and Mo

“…Figure compares the 1 H NMR spectra of relevant complexes together with those of btzp Et and H 4 btzp Et , the latter showing the effect on 1 H NMR of tetrazine reduction (hydrogenation). If reduction is occurring at the tetrazine ring in M­(btzp) 2 , the CH 2 1 H NMR chemical shift should be most sensitive.…”

“…Scheme 1). The pattern of single-and double-bond intra-tetrazine distances in the fully reduced (hydrogenated) bis-dihydrotetrazinyl pincer 13 serves as a comparison. Scheme 2 shows anticipated bond length changes, upon reduction.…”